WO2007110611A1

WO2007110611A1 - Composite material

Info

Publication number: WO2007110611A1
Application number: PCT/GB2007/001067
Authority: WO
Inventors: Malcolm Brown; Ben Alcock; Michael Andrew Hall; De Oca Horacio Montes; Mark Bonner
Original assignee: Smith & Nephew, Plc
Priority date: 2006-03-24
Filing date: 2007-03-26
Publication date: 2007-10-04
Also published as: GB0605885D0

Abstract

A high strength composite material for orthopaedic applications comprising amorphous polymer and large amounts of inorganic filler, where the material has been highly oriented to increase the strength and modulus of the composite.

Description

COMPOSITE MATERIAL

BACKGROUND OF THE INVENTION FIELD OF THE INVENTION

[0001] The present invention relates to composite polymeric materials and methods for making the same. In particular the present invention relates to the orientation of highly filled polymeric materials resulting in improved mechanical properties such as tensile strength, ductility and strength retention.

RELATED ART

[0002] Orthopaedic surgery involves the implantation of materials that must be both biocompatible and capable of bearing high loads. Traditionally metals such as titanium and titanium alloys have been used, but these suffer a number of disadvantages, for example they can cause stress shielding and require a second medical procedure to remove them from the body.

[0003] In recent years particulate fillers (i.e. buffers, radiopaque agents, and osteoconductive agents etc) have been incorporated into medical devices to improve x-ray visibility, biocompatibility, strength retention profile and to facilitate bone replacement of polymeric implants. It has also been reported that the optimum buffering or osteoconductive properties of these polymeric composites are often achieved by incorporating filler in excess of 35 wt/wt%. However the incorporation of these fillers is known to have a detrimental effect on the mechanical properties (i.e. strength and ductility) of the final material. It is also known that these materials would find applications in medium - high loading bearing applications if the polymer composites had sufficiently high strength & ductility. Improvements of the mechanical properties of particulate filled polymer composites have been achieved by orientating the material. However processing of these particulate composites has been only been achieved for composites containing filler at 20 wt% and below.

[0004] It is an object of the present invention to provide a polymeric material suitable for use in load bearing orthopaedic applications that has optimal strength, strength retention and biological properties.

SUMMARY OF THE INVENTION

[0005] According to the present invention there is provided a composite material comprising amorphous polymer and 25-50% by weight inorganic filler where the composite material has been orientated to improve its mechanical properties.

[0006] In an embodiment there is provided a composite material comprising amorphous polymer and 25-50% by weight inorganic filler where the composite material has been orientated to a draw ratio of at least two. Draw ratio can be defined as the final sample length divided by the initial sample length.

[0007] Amorphous polymer is defined herein to be any polymer with less than 10% crystallinity. Suitable polymers include resorbable and non-resorbable polymers.

[0008] In an embodiment the non-resorbable polymers may be polystyrene, polymethyl methacrylate (PMMA), polybutylmethyl acrylate (PBMA) polyethyl methy acrylate (PEMA) and copolymers or blends thereof.

[0009] In an embodiment the resorbable polymers may be polylactide and copolymers thereof where the lactide component comprises at least 50% by weight; polyglycolide and copolymers thereof where the glycolide comprises at least 50% by weight and polydioxanone and copolymers thereof where the dioxanone comprises at least 50% by weight. Other copolymer components may comprise lactide, glycolide, caprolactone, dioxanone, trimethylene carbonate or dimethyltrimethylene carbonate. The amorphous polymer may also be a blend of two or more polymers. The amorphous polymer may further comprise a non-buffering inorganic material such as hydroxyapatite. The amorphous polymer may further comprise one or more bioactive agents that would promote tissue repair in the body, for example angiogenic agents, antimicrobial agents, osteoinductive agents or osteoconductive agents.

[0010] The inorganic fillers of the present invention may be buffers, radiopaque agents, and/or osteoconductive agents.

[0011] The inorganic fillers are typically particulates and may be crystalline particulates.

[0012] Typically inorganic fillers that act as buffers improve strength retention of degradable systems by reacting with the acidic breakdown products of the amorphous polymer.

[0013] In an embodiment the inorganic filler comprises calcium, sodium, potassium, magnesium, barium, zirconium, bismuth, silver, gold, copper, zinc elements, compounds or any combination thereof.

[0014] In a preferred embodiment the inorganic filler is a crystalline calcium, sodium, zirconium, bismuth, barium, silicon, tungsten or magnesium salt.

[0015] In an embodiment the inorganic filler is calcium carbonate, calcium hydrogen carbonate, calcium phosphate, dicalcium phosphate, tricalcium phosphate, magnesium carbonate, sodium carbonate, hydroxyapatite, bone, phosphate glass, silicate glass, magnesium phosphate, sodium phosphate, barium sulphate, barium carbonate, zirconium sulphate, zirconium carbonate, zirconium dioxide, bismuth trioxide, bismuth oxychloride, bismuth subcarbonate, tungsten oxide or any combination thereof. [0016] The filler may be a particulate that can have a range of sizes and geometries. For example the particulate shapes may be needles, cubes, platelets, fibres or spheres. Preferably the filler particulates are shaped to enhance the mechanical properties of the composite material. The particulate size is typically between lOnm and 1mm.

[0017] Typically inorganic fillers that act as radiopaque agents are barium sulphate, barium carbonate, zirconium sulphate, zirconium carbonate, zirconium dioxide, bismuth trioxide, bismuth oxychloride, bismuth subcarbonate or tungsten oxide

[0018] The filler particulates may be pre-treated with a coupling agent such as a fatty acid, fatty acid anhydride or siloxane in order to enhance the properties of the composite.

[0019] Typically inorganic fillers that act as osteogenic agents are calcium carbonate, calcium phosphate, dicalcium phosphate, tricalcium phosphate, hydroxyapatite, bone, phosphate glasses, silicate glasses, magnesium phosphate, sodium phosphate,

[0020] The unoriented composite material can be made by blending the inorganic filler into the amorphous polymer by, for example, solution casting methods, melt compounding methods or by in situ polymerizing the polymer around the inorganic filler.

[0021] A number of orientation methods are suitable for creating the orientated composite material. These include both thermal_, and solution methods. Suitable methods include die drawing, fibre drawing, oven drawing, zone drawing, zone annealing, ram extrusion, hydrostatic extrusion, rolling, gel spinning, shear controlled orientation in injection moulding, roll drawing, biaxial drawing and solid state extrusion. These orientation methods can be carried out under constant load or constant extension.

[0022] Following orientation the orientated composite material may be at least 20% higher strength than the unoriented composite material. Preferably it has at around 50% higher strength than the unoriented composite material. Most preferably it has at least 100% higher strength than the unoriented composite material.

[0023]- Following orientation the orientated composite material may be at least 100% more ductile than the unoriented composite material, preferably it is at least 200% more ductile than the unoriented material.

[0024] The orientated composite material can be used to generate second generation composite, for example a fibre-reinforced composite, or further processed to generate a medical device, hi one embodiment the orientated composite material is forged or machined into a fixation plate, hi another embodiment the orientated composite material is forged or machined into a screw. Ih another embodiment the orientated composite material is forged or machined into a suture anchor. In another embodiment the orientated composite material is used as a bone graft substitute.

[0025] Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0026] The following description of the preferred embodiment(s) is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses. [0027] Example 1. Method for Production and Zone Drawing of Oriented Polymers Containing 35^w/w CaCO₃

[0028] 60Og of poly(DL-lactide-co-glycolide) (PDLGA) was vacuum dried at 50°C, lOmbar for 48hours. 30Og of calcium carbonate was vacuum dried at 150°C, 10 mbar for 48hours. 162.5g of dried PDLGA was dry blended with 87.5g of dried CaCO₃, and fed into a twin screw extruder, operating at 225rpm and 200⁰C. The output of the extruder was a lmm diameter PDLGA fibre containing dispersed CaCO₃ particles. A 30cm length of this extruded PDLGA fibre was drawn by locally applying a non-contact "zone" heater and applying a constant extension of 0.5mm.min^"1 to the fibre. The "zone" heater was moved along the fibre as the fibre was extended and local deformation occurred causing a drawing effect. The tensile mechanical properties of drawn and undrawn PDLGA fibre are shown in table 1.

[0029]

[0030]

_[003i_] Table 1. Mechanical properties of polymer fibres containing 35%^w/w CaCO₃

[0032]

[0033] Example 2. Method for Production and Die Drawing of Oriented Polymers Containing 357w CaCO^

[0034] 60Og of poly(DL-lactide-co-glycolide) (PDLGA) was vacuum dried at 50°C, lOmbar for 48 hours. 300g of calcium carbonate was vacuum dried at 15O⁰C, lOmbar for 48hours. 162.5g of dried PDLGA was dry blended with 87.5g of dried CaCO₃, and fed into a twin screw extruder, operating at 225rpm and 200°C. The output of the extruder is a lmm diameter PDLGA fibre containing dispersed CaCO₃ particles. This fibre is chopped into 2mm lengths, melted and moulded into a 10mm diameter cylindrical rod. This rod was drawn by pulling through a conical die (heated to 70⁰C) at a rate of lOmm-min^"1. The rod experiences local deformation causing a drawing effect. The tensile mechanical properties of 5 specimens of drawn and undrawn filled PDLGA rod and the results are shown in table 2.

Table 2. Mechanical properties of polymer fibres containing 35%^w/w CaCO₃

[0035] Example 3. Method for Drawing and Production of Oriented Polymers Containing 35^w/w CaCO₃ and a Fatty Acid Anhydride

[0036] 60Og of poly(DL-lactide-co-glycolide) (PDLGA) was vacuum dried at 5O⁰C, 10 mbar for 48 hours. 30Og of calcium carbonate was vacuum dried at 150⁰C, 10 mbar for 48 hours. 4Og of dried CaCO₃ and 0.571g of Dodecenylsuccinic anhydride (DSA) were placed •together in 40ml CH₂Cl₂. The contents were thoroughly mixed and air dried for 72hours, followed by oven drying at 200⁰C for 5 minutes. 96.75g of dried PDLGA was dry blended with 53.25g of dried DSA coated CaCO₃, and fed into a twin screw extruder, operating at 225rpm and 200⁰C. The output of the extruder was a lmm diameter PDLGA fibre containing dispersed DSA coated CaCO₃ particles. A 30cm length of this extruded. PDLGA fibre was drawn by locally applying a non-contact "zone" heater and applying a constant extension of 0.5mm.min^"1 to the fibre. The "zone" heater was moved along the fibre as the fibre was extended and local deformation occurred causing a drawing effect. The tensile mechanical properties of drawn PDLGA fibre are shown in table 3.

[0037]

[0038] Table 3. Mechanical properties of PDLGA fibres containing 35%^w/w CaCO₃ and 0.5%^w/w DSA '

[0039]

[0040] Example 4: Method for production and drawing of polymer fibres containing 50%^w/w CaCO3

[0041] 50.0g of CaCO₃ and 50.0g of Poly (DL-Lactide-co-Glycolide) 85:15 were solution blended in 400 ml of CH₂Cl₂ to produce a suspension of CaCO₃ particles. The solution was cast to produce a block of filled polymer. The block was ground to produce granules suitable for feeding into an extruder and then vacuum dried to remove residual solvent. The granules were compounded using a twin screw extruder with all zones set at 200°C except the feed zone and die which were set at 140°C and 210°C respectively to produce fibres. A Im length of 0.43 mm diameter fibre was zone drawn at a speed of 50 mm min^"1 at 7O⁰C with a mass of 54.27 g attached to the fibre. A draw ratio of 4.62 was achieved, the drawn fibre having a diameter of 0.20 mm. The tensile mechanical properties of fibre pre-zone drawing and post zone drawing were tested; the results are shown in table 4. [0042]

Table 4. Mechanical properties of polymer fibres containing 50%^w/w CaCO₃

[0043]

[0044] Example 5. Method for Production and Drawing of Non-Resorbable Polymer Fibres Containing 35%^w/w CaCO3

[0045] 70.03g of CaCO₃ and 130.01g of polystyrene were tumble blended to produce a homogenous mixture. The mixture was compounded using a twin screw extruder with all zones set at 18O⁰C except the feed zone and die which were set at 14O⁰C and 190⁰C respectively to produce fibres. A Im length of 0.47mm diameter fibre was zone drawn at a speed of 50mm min^" ¹ at 12O⁰C with a mass of 44.84g attached to the fibre. A draw ratio of 2.63 was achieved, the drawn fibre having a diameter of 0.29 mm. The tensile mechanical properties of extruded and drawn fibre were tested; the results are shown in table 5.

[0046]

[₀₀₄₇] Table 5 Mechanical properties of polystyrene fibres containing 35%^w/w CaCO₃

[0048]

[0049] Example 6: Method for Drawing and Production of Oriented Polymers Containing 35^w/w CaSQ_4.

[0050] 60Og of poly(DL-lactide-co-glycolide) (PDLGA) was vacuum dried at 5O⁰C, 10 mbar for 48 hours. 300g of calcium sulphate was vacuum dried at 150°C, 10 mbar for 48 hours. 162.5g of dried poly (DL-lactide-co-glycolide) was dry blended with 87.5g of dried CaSO₄, and fed into a twin screw extruder, operating at 225rpm and 200⁰C. The output of the extruder is a lmm diameter polymer fibre containing dispersed CaSO₄ particles. A 30cm length of this extruded polymer fibre was drawn by locally applying a non-contact "zone" heater and applying a constant extension of 25mm.min^"1. The "zone" heater is moved along the fibre as the fibre is extended and local deformation occurs causing a drawing effect. The tensile mechanical properties of drawn and undrawn polymer fibre are shown in table 6.

Table 6. Mechanical properties of poly(DL-lactide-co-glycolide) polymer fibres containing

[0051]

[0052] Example 7: Zone drawing of PDLLA-co-DL f70/30) CaCO₁ f35%wAv) [0053] Amorphous poly(D,L Lactide-co-DL) with 35% w/w CaCO₃ fibres lmm in diameter were prepared using a twin screw extruder. The fibres were drawn using the zone drawing technique. A fibre approximately 40cm long is attached at the top of the Zwick materials testing apparatus while the bottom end of the fibre is attached to a load (10Og). The fibre is passed through a local heater held at the draw temperature (7O⁰C) which moves upwards at lOmm/min while the fibre is drawn due to the hanged load. The tensile mechanical properties of drawn and undrawn polymer fibre are shown in table 7. [0054]

Table 7. Mechanical properties of PDLA-co-DL polymer fibres containing 35%^w/_w CaCO₃ Example 8: Die drawing of PDLLA-co-DL f70/30V CaCO₁ f35%w/w> Amorphous poly(D,L Lactide-cb-DL) with 35% w/w CaCO₃ fibres were prepared using a twin screw extruder. The fibres were palletised and consolidated into an isotropic long cylindrical rod with diameter of 5mm using a ram extrusion technique. Oriented rods 3mm in diameter were prepared by die drawing were the isotropic rod is pulled through a conical die at 7O⁰C and lOrnm/min. The tensile mechanical properties of drawn and undrawn polymer rod are shown in table 8.

Table 8. Mechanical properties of PDLA-co-DL polymer rod containing 35%^w/_w CaCO₃

[0055] As various modifications could be made to the exemplary embodiments, as described above with reference to the corresponding illustrations, without departing from the scope of the invention, it is intended that all matter contained in the foregoing description and shown in the accompanying drawings shall be interpreted as illustrative rather than limiting. Thus, the breadth and scope of the present invention should not be limited by any of the above- described exemplary embodiments, but should be defined only in accordance with the following claims appended hereto and their equivalents.

Claims

CLAIMS What is claimed is:

1. A composite material comprising amorphous polymer and 25-50% by weight inorganic filler where the composite material has been orientated to improve its mechanical properties.

2. A composite material according to claim 1 where the composite material has been orientated to a draw ratio of at least two.

3. A composite material according to claim 1 or 2 that has at least 20% higher strength than the unoriented material.

4. A composite material according to claim 3 that has at least 50% higher strength than the unoriented material.

5. A composite material according to claim 1 or 2 that is at least 100% more ductile than the unoriented composite material.

6. A composite material according to claim 5 that is at least 200% more ductile than the unoriented composite material.

7. A composite material according to any of claims 1 to 6 comprising non-resorbable polymer.

8. A composite material according to claim 7 wherein the non-resorbable polymer comprises polystyrene, polymethyl methacrylate (PMMA), polybutylmethyl acrylate (PBMA) polyethyl methy acrylate (PEMA) or copolymers or blends thereof.

9. A composite material according to any of claims 1 to 6 comprising resorbable polymer.

10. A composite material according to claim 9 that comprises at least 50% polylactide by weight.

11. A composite material according to claim 10 further comprising glycolide, caprolactone, dioxanone, trimethylene carbonate or dimethyltrimethylene carbonate.

12. A composite material according to claim 9 that comprises at least 50% polyglycolide by weight.

13. A composite material according to claim 12 further comprising lactide, caprolactone, dioxanone, trimethylene carbonate or dimethyltrimethylene carbonate.

14. A composite material according to claim 9 that comprises at least 50% polydioxanone by weight.

15. A composite material according to claim 14 further comprising lactide, glycolide caprolactone, trimethylene carbonate or dimethyltrimethylene carbonate.

16. A composite material according to any preceding claim where the amorphous polymer is a blend or copolymer of two or more polymers.

17. A composite material according to any preceding claim where the inorganic filler is a buffer, a radiopaque agent, an osteoconductive agent or any combination thereof.

18. A composite material according to any preceding claim where the inorganic filler comprises calcium, sodium, potassium, magnesium, barium, zirconium, bismuth, silver, gold, copper, zinc elements, compounds or any combination thereof.

19. A composite material according to claim 17 where the inorganic filler is selected from the following list: calcium carbonate, calcium hydrogen carbonate, calcium phosphate, dicalcium phosphate, tricalcium phosphate, magnesium carbonate , sodium carbonate, hydroxyapatite, bone, phosphate glass, silicate glass magnesium phosphate, sodium phosphate, barium sulphate, barium carbonate, zirconium sulphate , zirconium ' carbonate, zirconium dioxide, bismuth trioxide, bismuth oxychloride, bismuth subcarbonate, tungsten oxide.

20. A composite material according to any preceding claim wherein the inorganic filler is a particulate.

21. A composite material according to any preceding claim wherein the inorganic filler is a crystalline particulate

22. A composite material according claim 20 or 21 where the particulates are shaped to enhance the mechanical properties of the composite material.

23. A composite material according to any of claims 20 to 22 where the particulate size is between lOnm and 1mm.

24. A composite material according to any of claims 20 to 23 where the particulates are pre- treated with coupling agent.

25. A composite material according to any of claims 20 to 24 where the particulates are pre- treated with a fatty acid, fatty acid anhydride or siloxane.

26. A composite material according to any preceding claim further comprising a non- buffering inorganic material.

27. A composite material according to any preceding claim further comprising a bioactive agent.

28. A composite material according to any preceding claims where, following orientation, the orientated composite material is at least 20% stronger than the unoriented composite material.

29. A composite material according to claim 28 where, following orientation, the orientated composite material is at around 50% stronger than the unoriented composite material.

30. A composite material according to claim 28 where, following orientation, the orientated composite material is at least 100% stronger than the unoriented composite material.

31. A fibre-reinforced article comprising a composite material according to any preceding claim and a resorbable fibre component.

32. An orthopaedic fixation plate comprising a composite material according to any of claims 1 to 31.

33. An orthopaedic screw comprising a composite material according to claims 1 to 31.

34. A suture anchor comprising a composite material according to claims 1 to 31.