AU4764199A - Contact lens material - Google Patents

Description

WO 00/04065 PCT/AU99/00575 CONTACT LENS MATERIAL INTRODUCTION 5 The invention relates to a polymer having high oxygen permeability and to hydrated compositions including such polymer particularly in the form of a contact lens. BACKGROUND 10 For optimal performance, hydrogel contact lens materials must possess optical clarity, resistance to tear and high oxygen permeability. Poly(2-hydroxyethylmethacrylate) is used for hydrogel contact lenses as it is hard enough to be easily fabricated by machining and polishing in the dry state yet soft and comfortable to wear in the water swollen state. Other 15 hydrophilic monomers are also used, such as dimethylacrylamide (DMA) polymers and N-vinylpyrrolidone (NVP) polymers with methacrylates. The oxygen permeability of such hydrogel contact lenses is determined by the water content and thickness of the lens and can be improved by increasing the water content or decreasing the thickness. Both strategies, however, can 20 lead to lenses with insufficient strength which are easily damaged. The incorporation of either siloxane or fluorinated groups improves oxygen permeability without loss of good mechanical properties. While siloxane groups give slightly higher oxygen permeability, fluorinated groups are especially desirable as they allow the manufacture of polymers with 25 higher dry hardness and therefore better niachineability while at the same time reducing lipophilicity and deposit formation on the hydrated polymer. The fluorine has been introduced into polymeric materials by polynerising hydrophilic monomers such as N-vinylpyrrolidone (NVP) and 2-hydroxyethyl methacrylate (HEMA) with fluorinated styrenes and 30 methacrylates. In these cases the range of clear compositions is limited and the fluorinated monomers can only be incorporated in relatively small amounts. In some cases, fluorine containing monomers have been specially synthesised to achieve better solubility in NVP and HEMA. US Patent No 5011275 by Mueller discloses a hydrogel based on a 35 polymer of 15 - 85% dimethylacrylamide and 15 - 85% fluorine containing monomer and optionally other acrylates or methacrylates and a polyvinyl WO 00/04065 PCT/AU99/00575 2 functional cross-linking agent. The polymers form clear hydrogels with about 25 - 75% water content. Polymerisation between DMA and methacrylates in general proceeds 5 smoother than for NVP polymers because of more favourable reactivity ratios leading to a more random polymer structure for DMA polymers. The fluorine containing monomers of US patent no 5011275 are selected from the group consisting of: acrylate or methacrylate esters of the formula B1 10 CH 2 =C-COO (CHz)n(CF 2 )m 1

CF

2 X (B1) R1 wherein

R

1 is hydrogen or methyl, 15 n is an integer from 1 - 4, m is an integer from 0 - 11, X is hydrogen or fluorine with the proviso that, when m is 0. X is fluorine; hexafluoroisopropyl acrylate, hexafluoroisopropyl methacrylate, 20 undecafluoro cyclohexyl-methyl methacrylate and 2, 3, 4, 5, 6 pentafluorostyrene. DISCLOSURE OF INVENTION The present inventors have found a group of fluorine-containing 25 sulfanomido monomers which when polymerised with dimethylacrylamide give high water content and unexpectedly high oxygen permeability. The present invention consists in a polymer including the polymerisation product of (a) N, N-dimethylacrylamide, and 30 (b) a monomer of the formula (I) R' R"f (I)

C,

1

F

2

,

1 +1SO 2

N(CH

2 )2COOC = CH 2 WO 00/04065 PCT/AU99/00575 3 wherein n is an integer from 1 to 8, preferably 4 to 8, R' is an alkyl group, preferably a lower alkyl group containing up to 4 5 carbon atoms. more preferably ethyl or butyl, and R" is hydrogen or an alkyl group which may be the same as or different from R', preferably hydrogen or a lower alkyl group containing up to 4 carbon atoms, more preferably hydrogen or methyl. Preferred polymers are those containing 40 - 90% by weight of 10 component (a) and 10 - 60% by weight of component (b), based on the total weight of the monomers (a) and (b). A second aspect of the present invention consists in a hydrated composition in the form of a contact lens which includes a polymer including the polymerisation product of 15 (a) N. N-dimethylacrylamide, and (b) a monomer of the formula (I) as shown above. Preferably the hydrated composition in the form of a contact lens has an oxygen permeability of at least 30 Dk. A third aspect of the present invention consists in a hydrated 20 composition in the form of an ophthalmic prosthetic device, a drug delivery device or bandage which includes a polymer, said polymer including the polymerisation product of: (a) N, N-dimethylacrylamide, and (b) a monomer of the formula (I) as shown above. 25 The polymer may include additional monomers, preferably in an amount of from 2 to 50% by weight based on the total weight of the polymer. In conjunction with DMA monomer and monomer(s) of the formula (I), one or more additional monomers may be included selected from the group consisting of: styrene and styrene derivatives, methacrylates - especially 3 30 [tris(trimethylsilyloxy)silyl] propyl methacrylate (TRIS), acrylates, acrylamides, methacrylamides, vinyl pyrrolidone, vinyl monomers containing phosphoryl choline functional groups, and partly or fully fluorinated derivatives of the foregoing.

WO 00/04065 PCT/AU99/00575 4 The polymer may be formed in the presence or absence of crosslinking agents. Where crosslinking agents are used these may be multi-functional vinyl compounds such as ethylene glycol dimethacrylate or 1,1,1 5 trimethylolpropane trimethacrylate, although a wide range of commercial crosslinkers are available and any polymerizable crosslinker is suitable for use in these compositions. Crosslinking agents are preferably included in an amount of up to 8% by weight based on the total weight of the polymer. A fourth aspect of the present invention consists in a hydrogel having 10 an equilibrium water content in the range of from 30 to 90% by weight, the hydrogel being suitable for use as a contact lens and including a polymer having a fluorine and/or siloxane rich hydrophobic phase separated from a hydrophilic phase. Preferably, the equilibrium water content of the hydrogel is in the range of from 40 to 80% by weight. The fluorine and/or siloxane 15 rich hydrophobic phase preferably includes units of the monomer of formula (I) shown above, more preferably units of 2-(N-butyl perfluoro octane sulfonamido) ethyl acrylate, 2-(N- ethyl perfluoro octane sulfonamido) ethyl acrylate, 2-(N- ethyl perfluoro octane sulfonamido) ethyl methacrylate or mixtures of two or more of the foregoing. The hydrophobic phase preferably 20 includes units of DMA. In addition to DMA, the hydrophilic phase may include other monomers known to those skilled in the art, for example, methacrylic/acrylic acids and their ester derivatives, N-Vinyl-2 pyrrolidone, acrylamides, methacrylamides and functional zwitterionic monomers introduced to confer biocompatibility such as phosphoryl choline 25 derivatives. The polymers are prepared by free radical polymerization, either in bulk, solution, suspension or emulsion using heat- or UV activated initiators or redox systems. Alternatively gamma radiation can be used to initiate polymerisation. A variety of initiators can be used based on azo-or peroxy 30 compounds for thermally initiated systems or photoinitiators based on benzoin derivatives or other compounds capable of generating radicals which absorb in the UV or visible regions.

WO 00/04065 PCT/AU99/00575 5 The polymers can be produced in sheet form or films by casting monomer solutions and subsequently carrying out the polymerization or by casting polymer solutions into moulds. The polymers can also be fabricated 5 in a spin-casting process. For contact lens manufacture, the polymer may be formed as a rod, button or sheet and subsequently machined, cut and polished to the finished article. For use as a hydrogel material the polymer is often made as a crosslinked material. Any organic solvent may be used for the polymerization process 10 provided it prevents polymer precipitation and inhomogeneity of the polymer product. BRIEF DESCRIPTION OF THE DRAWINGS 15 Figure 1: Structure of fluorine sulphonamide acrylic monomers used in the examples. Figure 2: Photographs of uncrosslinked xerogels where A is N,.N Dimethylacrylamide (DMA) homopolymer and (a) B-G are 2-(N- butyl 20 perfluoro octane sulfonamido) ethyl aciylate (BFA) /DMA copolymers containing (sequentially), 10, 20, 30, 40, 50 and 60wt% BFA (b) H-M are 2 (N- ethyl perfluoro octane sulfonamido) ethyl acrylate (EFA) /DMA copolymers containing (sequentially), 10, 20, 30, 40, 50 and 60wt% EFA (c) N-S are 2-(N- ethyl perfluoro octane sulfonamido) ethyl methacrylate (EFMA) 25 /DMA copolymers containing (sequentially), 10, 20, 30, 40, 50 and 60wt% EFMA. Figure 3: Thermograms for uncrosslinked BFA/DMA xerogels. The solid vertical lines indicate the T. values for the two glass transition 30 homopolymers where A is DMA homopolymer, B is BFA-20/DIVIA-80, C is BFA-40/DMA-60, D is BFA-60/DMA-40 and E is BFA homopolymer. Figure 4: Structure of BFA/DMA copolymer showing the origin of the two 35 distinct regions giving rise to the two glass transition temperatures.

WO 00/04065 PCT/AU99/00575 6 MODES FOR CARRYING OUT THE INVENTION Example 1 5 Synthesis hydrogels based on copolymers of dimethylacrylamide and fluoro sulphonamide (meth)acrylates Materials N,N-Dimethylacrylamide (DIA) (supplied by Sigma-Aldrich Pty. Ltd) 10 was purified by passing over a short column of basic alumina to remove the inhibitor. Fluorinated monomers were selected as follows: 2-(N- butyl perfluoro octane sulfonamido) ethyl acrylate (BFA) (FX189 supplied by 3M Chemical Co) 15 2-(N- ethyl perfluoro octane sulfonamido) ethyl acrylate (EFA) (FX13 supplied by 3M Chemical Co) 2-(N- ethyl perfluoro octane sulfonamido) ethyl methacrylate (EFMA) (FX14 supplied by 3M Chemical Co). The structure of these monomers is shown in Figure 1. BFA was distilled 20 under reduced pressure and EFA and EFMA were both recrystallised twice from ethanol. Ethyleneglycol dimethacrylate (EDMA) was purified by column chromatography using silica gel as absorbent and n-hexane/ethyl acetate (7/3 vol/vol) as eluant. Normal (1N) saline was used for all swelling measurements. 25 Polymerisation Monomer mixtures were made up gravimetrically. deoxygenated with nitrogen for 10mins and irradiated in sealed polypropylene ampoules. In all cases the y-irradiation dose was 1 Mrad obtained from a bOCo source , the 30 dose rate being 0.01 Mrad h as determined by Fricke dosimetry. The resultant solid rods of xerogel were post-cured at 90 0 C for 24 hrs and then lathe cut to produce thin discs (diameter 10mm; thickness 1mm) for swelling measurements and thin discs (diameter 10mm; thickness 0.1-0.5mm) for oxygen permeability measurements.

WO 00/04065 PCT/AU99/00575 7 In this example, hydrogels are referred to on the basis of the corresponding xerogels. Compositions are expressed percentage by weight. For example, the designation BFA-20 / DMA-80 means that crosslinker is 5 absent and that BFA/DMA is 20/80 (w/w). The same ratio of BFA to DMA obtains in a terpolymer designated BFA-20 / DMA-80 / EDMA-5. However, here EDMA comprises 5wt% of the total monomers (BFA + DMA + EDMA). As conversion in these polymerizations is close to 100%, the compositions of xerogels are virtually identical to those of the feed mixtures. 10 Equilibrium water content Dimensions of the dry discs and pellets were measured with Vernier calipers and the weighed samples were equilibrated in normal saline at room temperature, the times to attain equilibrium being 2-4 weeks. During this 15 time the saline was changed at frequent intervals to allow for the removal of water-soluble material from the samples. The equilibrium water content (EWC) of the hydrogels is defined as: EWC = /s Inx,1 [1] Is 20 where ms = mass of swollen sample m = 0 mass of dry sample This EWC measurement needs to be based on the xerogel weight after sol fraction extraction, in the brine medium. in - in 25 % sol fraction = x 100 [2] rn., where mE = the dry mass of extracted sample. The volume fraction of polymer within a hydrogel is given as 30 0, =D, [31 ~a D Where D and Do are the diamieters of the hydrogel and xerogel respectively.

WO 00/04065 PCT/AU99/00575 8 Oxygen Permeability Measurements were made on swollen samples over a range of thicknesses (at least three) on a JDF Dk1000m coulometric oxygen 5 permeation instrument under wet cell conditions. Thermal Analyses The glass transition temperatures (Tg) of the xerogels were determined 10 using a TA Instruments DSC 2010 Differential Scanning Calorimeter, at a heating rate of 10'C min' using sample weights in the range 5-10 mg. The reported T measurements were taken from the second heating run. Results & Discussion 15 Xerogel synthesis and properties The xerogel rods were lathe cut into discs; the visual appearance of the discs is shown in Figure (2a-c). The polymers containing EFMA, the methacrylate derivative, proved to be either hazy or opaque indicating that 20 this copolymer may be unsuitable for contact lens applications. However, the addition of a crosslinker (1%wt. EDMA, for example) enabled the production of transparent materials. All of the xerogels maintained their transparency on swelling. It is theorised that the differences in optical appearance of the xerogels 25 may possibly be attributable to compositional drift. and subsequent phase separation between fluorine and non-fluorine rich areas. One surprising feature of these copolymer systems is the fact that the transparency is maintained on swelling with water. This is despite the presence of long perfluorinated side-chains which may be expected to 30 aggregate in an aqueous environment. This suggests that aggregation if it occurs (which seems highly likely) forms domains which are sufficiently small to avoid scattering visible light and /or are virtually isorefractive with the water rich areas. It was noted that anisotropic swelling sometimes occurred causing 35 deformation of the discs and pellets. The xerogel rods often appeared to WO 00/04065 PCT/AU99/00575 9 contain residual stresses (clearly shown via observation between cross polarising lenses) which may be due to either inhoiogeneities in the original monomer mixing and/or a substantial gel effect observed in these reactions. 5 It was found that the dominant cause of the residual stresses was the gel (or Trommsdorf) effect. By careful control of the polymerization rate and molecular weight evolution the production of samples which would swell isotropically - suitable for lens manufacture, could be achieved. 10 Glass Transition Temperatures The T9 values for the xerogels were determined and are shown in Table 1. In all three copolymer systems, two Ts were observed. The thermograms for the BFA/ DMA series are shown in Figure 3. The higher T9 is assumed to originate from the DMA component and the lower Tg from the 15 BFA side-chain. Random copolymers usually exhibit only one T. , given by the weighted average of the Tes of the two polymeric components. The Tg behaviour observed is relatively unusual for random copolymers and is normally associated with graft copolymers, where the grafted chain is incompatible with the backbone polymer, or with incompatible polymer 20 blends. It may be that the long perfluorinated side-chains are sufficiently long and flexible to form domains with a sub-ambient glass transition. The high Tg (corresponding to DIVIA) is seen to reduce as the concentration of fluoro-monomner increases, there is also a concomitant reduction in the lower glass transition. The reduction in both Tes is possibly explicable as follows. 25 The structure of the copolymer is shown in Figure 4. The high TP corresponds to the backbone polymer chain region which comprises both DMvLA and fluoro-monomer segments. Thus the high DMA T. is mediated by a contribution from the fluoro-monomer component. The low Tg originates solely from the flexible side-chain most distant from the polymer backbone 30 forming microdomains this value is lower than the Tg obtained for the pure fluoropolymer as it excludes contributions from the fixed polymer backbone. Once again, it seems surprising that these copolymers manifest transparency, as it is evident that the materials are inhomogeneous. It may be conjectured that some compatibility may be introduced from two sources. 35 The pure fluoro-monomers used in this current study are in fact a mixture of WO 00/04065 PCT/AU99/00575 10 monomers with different length side-chains and thus the extent of incompatibility of the perfluoro sidechains with DIVIA rich areas may be tempered by a contribution from the smaller side-chains acting as 5 compatibilisers. It is also conceivable that the sulphonamide group in the perfluoro side-chains acts to some extent as a compatibilizer via favourable interactions with the tertiary amide group in DMA. Swelling properties 10 Uncrosslinked Samples Table 2 shows the swelling data obtained for the three different copolymer systems at selected compositions, prepared in the absence of a crosslinker. As expected the presence of higher fluorine concentrations induces a decrease in the equilibrium swelling. Despite this, it is possible to 15 achieve high water contents whilst maintaining a reasonable fluorine content. This is clearly demonstrated by comparison of these new materials with PHEIMA with an EWC of about 40wt% - a similar water content is achieved with 60%wt of the fluoro- monomers in these new materials. The sol fractions are all fairly low indicating that most of the DMA has 20 copolymerized. There appears to be no significant differences among the swelling behaviours of the three different copolymer sets. Crosslinked Samples Table 3 shows the swelling characteristics of the same copolymer 25 systems prepared with 1, 2 and 5wt% EDMA crosslinker. Increasing concentrations of crosslinker lead to lower EWC values and (generally) lower sol fractions consistent with previous observations made on hydrogel materials. 30 Oxygen Permeability The oxygen permeabilities obtained on the uncrosslinked hydrogels are given in Table 4. Each reported value is an average of at least three independent measurements. The important factor is the large oxygen permeability of these hydrogel materials compared with non-fluorinated 35 materials. This can be clearly demonstrated by comparing those hydrogels WO 00/04065 PCT/AU99/00.575 11 with about 60wt% fluoro-monomer that have water contents around 40wt% (similar to PHEMA). The oxygen permeability is about five times higher than PHEIvIA. This indicates that oxygen transmission in these hydrogels occurs 5 not only via the dissolved oxygen in the aqueous phase but also by another route (which predominates) and which is assumed to be via a co-continuous polymeric phase, which is rich in fluorine. This indicates that the morphology of these gels is an important determinant factor in the attainment of high oxygen permeability. A further hypothesis leads from this 10 discussion, viz., that the water plays two important roles in these materials, firstly as a direct source of oxygen flux via dissolved oxygen (as with conventional hydrogel materials) and secondly by inducing a co-continuous hydrophobic network (via hydrophobic interactions) which provides a secondary mechanism for oxygen transmission. The slight rise in oxygen 15 permeability that occurs when the DIVIA content (and hence the water content) is raised may simply result from the increased contribution to the oxygen flux from water-dissolved oxygen. If this is the case then it indicates that the secondary transmission route (via a fluorine rich network) is maintained despite a reduction in the overall fluorine content of the gel. 20 Alternatively, it may indicate that increased ordering of the hydrophobic regions compensates for a loss of oxygen transmission caused by the reduction in fluorine content. Conclusions 25 Materials have been developed that are suitable for use as contact lenses. In the dry state these materials are easily turned on a lathe to produce xerogels which can be subsequently swollen into hydrogels. A substantial gel effect may induce residual stresses in the xerogels leading to anisotropic swelling, 30 but this can be mninimised by adopting an appropriate polymerization regime. The hydrogel materials exhibit high oxygen permeabilities at high water contents and mechanical properties comparable with literature values given for existing contact lens materials. Cytotoxicity testing indicated that these materials are safe for contact lens applications. 35 WO 00/04065 PCT/AU99/00575 12 Captions to Tables Table 1: Glass transition temperatures for uncrosslinked xerogels. 5 Table 2: Swelling properties of uncrosslinked hydrogels at 296K. Table 3: Swelling properties of crosslinked hydrogels at 296K. 10 Table 4: Oxygen permeabilities of uncrosslinked hydrogels.

WO 00/04065 PCT/AU99/00575 13 Table 1 Material Low T,("C) High T 0 ("C) DMA-100 - 104.1 BFA-20/DMA-80 -8.2 82.7 BFA-40/DMA-60 -9.1 81.8 BFA-60/DMA-40 -13.2 64.6 BFA-100 2.4 EFA-20/DMA-80 -2.3 113.7 EFA-40/DMA-60 -16.3 100.2 EFA-60/DMA-40 24.5 71.9 EFMA-20/DMA-80 -14.4 101.9 EFMA-40/DMA-60 -3.2 92.4 EFMA-60/DMA-40 -0.9 80.2 5 Table 2 Material EWC (wto) #2 Sol fraction (wt%) BFA-20/DMA-8o 77 0.24 2.41 BFA-40/DMA-60 64 0.37 3.97 BFA-60/DMA-40 42 0.56 1.80 EFA-20/DMA-80 82 0.18 4.62 EFA-40/DMA-60 62 0.34 2.05 EFA-60/DMA-40 41 0.57 1.79 EFMA-20/DMA-8o 83 0.17 5.12 EFMA-40/DMA-60 68 0.32 5.68 EFMA-60/DMA-40 50 0.48 3.92 WO 00/04065 PCT/AU99/00575 14 Table 3 Material EWC (wt%) <2 Sol fraction (wt%) 1wt%EDMA BFA-20/DMA-80/EDMA-1 71 0.28 6.94 BFA-40/DMA-60/EDMA-1 55 0.40 1.61 BFA-60/DMA-40/EDMA-1 37 0.60 1.02 EFA-20/DMA-80/EDMA-1 66 0.31 2.19 EFA-40/DMA-60/EDMA-1 52 0.44 1.47 EFA-60/DMA-40/EDMA-1 34 0.64 0.85 EFMA-20/DMA-80/EDMA-1 72 0.26 2.79 EFMA-40/DMA-60/EDMA-1 57 0.39 2.97 EFMA-60/DMA-40/EDMA-1 43 0.53 2.86 2wt% EDMA BFA-20/DMA-80/EDMA-2 64 0.39 11.79 BFA-40/DMA-60/EDMA-2 51 0.48 2.72 BFA-60/DMA-40/EDMA-2 34 0.66 4.12 EFA-20/DMA-80/EDMA-2 64 0.39 8.75 EFA-40/DMA-60/EDMA-2 51 0.51 4.90 EFA-60/DMA-40/EDMA-2 34 0.67 2.63 EFMA-20/DMA-80/EDMA-2 63 0.37 5.81 EFMA-40/DMA-60/EDMA-2 54 0.47 4.86 EFMA-60/DMA-40/EDMA-2 31 0.65 1.83 5wt% EDMA BFA-20/DMA-80/EDMA-5 52 0.47 8.66 BFA-40/DMA-60/EDMA-5 39 0.61 5.01 BFA-60/DMA-40/EDMA-5 29 0.72 4.55 WO 00/04065 PCT/AU99/00575 15 Table 3 (Continued) Material EWC (wt%) < 2 Sol fraction (wt%) EFA-20/DMA-80/EDMA-5 57 0.47 11.62 EFA-40/DMA-60/EDMA-5 42 0.56 2.65 EFA-60/DMA-40/EDMA-5 28 0.72 2.38 EFMA-20/DMA-80/EDMA-5 56 0.42 5.52 EFMA-40/DMA-60/EDMA-5 40 0.57 3.95 EFMA-60/DMA-40/EDMA-5 25 0.70 2.56 5 Table 4 Material Dk barrelss) BFA-20/DMA-80 47.43 ( 6.33) BFA-40/DMA-60 43.59 ( 1.60) BFA-60/DMA-40 41.05 ( 6.62) EFA-20/DMA-80 51.46 ( 3.06) EFA-40/DMA-60 43.23 ( 5.24) EFA-60/DMA-40 34.29 ( 5.64) EFMA-20/DMA-80 51.75(± 4.11) EFMA-40/DMA-60 43.47 (± 6.53) EFMA-60/DMA-40 47.29 (± 18.06) WO 00/04065 PCT/AU99/00575 16 Example 2 Synthesis hydrogels based on terpolymers of dimethylacrylamide, fluoro sulphonamide acrylates and 3-[tris(trimethylsiloxy)silyl] propyl 5 methacrylate Materials N,N-Dimethylacrylamide (DMA) (supplied by Sigma-Aldrich Pty. Ltd) and 3 [tris (trimethylsilyloxy)] propyl methacrylate (TRIS) (also supplied by Sigma 10 Aldrich Pty. Ltd) were purified by passing over a short column of basic alumina to remove the inhibitor. Fluorinated monomers were selected as follows: 2-(N- butyl perfluoro octane sulfonamido) ethyl acrylate ( "BFA") (FX189 supplied by 3M Chemical Co) and 15 2-(N- ethyl perfluoro octane sulfonamido) ethyl acrylate ( "EFA") (FX13 supplied by 3M Chemical Co). The structure of these monomers is shown in Figure (1). BFA was distilled under reduced pressure and EFA was recrystallised twice from ethanol. Normal (1N) saline was used for all swelling measurements. 20 Polymerisation Monomer mixtures were made up gravimetrically, deoxygenated with nitrogen for 10mins and irradiated in sealed polypropylene ampoules. In all cases the y-irradiation dose was 1 Mrad obtained from a""Co source, the dose 25 rate being 0.OlMrad h- as determined by Fricke dosimetry. The resultant solid rods of xerogel were post-cured at 90'C for 24 hrs and then lathe cut to produce thin discs (diameter 10mm; thickness 1mm) for swelling measurements and thin discs (diameter 10mm; thickness 0.1-0.5mm) for oxygen permeability measurements. 30 In this example, hydrogels are referred to on the basis of the corresponding xerogels. As conversion in these polymerizations is close to 100%, the compositions of xerogels are virtually identical to those of the feed mixtures.

WO 00/04065 PCT/AU99/00575 17 Equilibrium water content Dimensions of the dry discs and pellets were measured with Vernier calipers and the weighed samples were equilibrated in normal saline at room 5 temperature, the times to attain equilibrium being 2-4 weeks. During this time the saline was changed at frequent intervals to allow for the removal of water-soluble material from the samples. The equilibrium water content (EWC) of the hydrogels is defined as: 10 EWC = Ills "'0 x 100 [4] Is wherems = mass of swollen sample me= mass of dry sample This EWC measurement needs to be based on the xerogel weight after sol 15 fraction extraction, in the brine medium. % sol fraction = Me -ME X 100 [5] wheremE = the dry mass of extracted sample The volume fraction of polymer within a hydrogel is given as 20 [6] SD Where D and Do are the diameters of the hydrogel and xerogel respectively 25 Oxygen Permeability Measurements were made on swollen samples over a range of thicknesses (at least three) on a JDF Dk1000N" coulometric oxygen permeation instrument under wet cell conditions.

WO 00/04065 PCT/AU99/00575 18 Results & Discussion Xerogel synthesis and properties 5 The xerogel rods were lathe cut into discs. All of the xerogels maintained their transparency on swelling. Fluorinated Hydrogels with Added TRIS Swelling properties 10 The terpolymer compositions in Tables (5) and (6) are expressed on a mole percentage basis,. relative to the total moles of (EFA or BFA + DMA) for the principal monomers and to the total moles of the whole for TRIS. For example. the designation DMA-96/BFA-4/TRIS-1.4 means that DMA comprises 96 mol.-% of (DMA + BFA), BFA comprises 4 mol wt.-% of (DMA 15 + BFA) and TRIS is present at a concentration of 1.4 mol.-% of (IMMA + BFA + TRIS). Table (5) shows the swelling data obtained for the different copolymer systems at selected compositions, prepared in the absence of a crosslinker 20 with ~ 5, 10 and 20 wt.-% TRIS. As expected, higher concentrations of TRIS, increase the total amount of hydrophobic monomer in the terpolymer compositions causing lower EWC values. However, it should be noted that the addition of 20wt.-% (5.3 mol.-%) TRIS has a similar impact on the EWC as the inclusion of only lwt.-% ethylene glycol dimathacrylate (EDMA). 25 There appears to be no significant differences among the swelling data for the different terpolymer systems. Oxygen Permeability TRIS is often used as a monomer to increase the oxygen permeability of 30 polymeric materials. Consequently, it was assumed that the incorporation of TRIS would ameliorate the oxygen permeability of these hydrogels. In example 1 the high oxygen permeability of these hydrogels (without TRIS) was attributed to two mechanisms for oxygen transmission: via the aqueous phase and through a fluorine-rich co-continuous polymeric phase. The 35 oxygen permeability results for the current TRIS-containing terpolymers are given in Table 6. Each reported value is an average of at least three WO 00/04065 PCT/AU99/00575 19 independent measurements. It is evident from these results that when the fluorinated monomer (BFA or EFA) is present at 4 mol.-% (20 wt.-%) the addition of TRIS induces a decrease in the Dk value. This is consistent with 5 a decrease in oxygen transmission that can be attributed solely to a decrease in the EWC. The oxygen permeability result for BFA-96/DMA-4/TRIS-1.4 appears to be very low in comparison with the other data and may simply be an anomalous result. Overall this oxygen permeability data may indicate that the TRIS is having no influence on the secondary transmission route via 10 the F-rich polymeric phase and is simply acting as a hydrophobic comonomer. When the fluorinated monomer (BFA or EFA) is present at 40 wt.-% there is an initial small decrease in the Dk value on addition of TRIS. As more TRIS is added the Dk slowly recovers back to the initial value obtained for the base copolymer formulation without TRIS. In this case it 15 may indicate that an initial loss in Dk caused by a lower EWC is compensated, to some extent, by the increasing siloxane content of the terpolyiner. Hydrogels Containing a Constant DMA Concentration 20 In order to study the relative contributions of the siloxane and fluorinated components in the gel to the oxygen transmission mechanism. terpolymer compositions were prepared with a constant DMA concentration, whilst varying the molar ratio of TRIS to EFA or BFA. Thus in Tables (7) and (8) the terpolymer compositions are defined in a slightly different way. For 25 example, the designation DMA-96/BFA-3/TRIS-1 now means that DIVIA comprises 96 mol.-% of (DMA + BFA + TRIS), BFA comprises 3 mol.-% of (DMA + BFA + TRIS) and TRIS is present at a concentration of 1 mol.-% of (MA + BFA + TRIS). It is also pertinent to note that compositions containing 96 mnol.-% and 90 mol.-% DMA correspond to compositions of 80 30 wt.-% and 60 wt.-% DMA respectively. Swelling As can be seen from the swelling data in Table (7) the inclusion of TRIS induces increases in the EWC and in the aqueous sol fraction.

WO 00/04065 PCT/AU99/00575 20 Oxygen Permeability It is quite evident from Table (8) that the primary route for oxygen transmission through these hydrogels is via the fluorine-rich polymer phase. 5 As the fluorine-containing monomer is systematically replaced by TRIS the oxygen permeability of the hydrogels declines quite substantially. This is despite the known propensity for high oxygen solubility in TRIS-based polymers. This situation should also be viewed in the light that the TRIS based hydrogels have a higher water content and this should in fact increase 10 the oxygen transmission via dissolved oxygen in the aqueous phase. These results indicate the importance of a secondary mechanism for oxygen transmission via a co-continuous polymeric phase. TRIS is known to impart high oxygen permeability to polymeric materials - however. this can only be effective if an unimpeded passage for oxygen transmission is present. In a 15 hydrophilic polymer matrix this can only be achieved by phase separation. Conclusions Materials have been developed that are suitable for use as contact lenses. In the dry state these materials are easily turned on a lathe to produce xerogels 20 which can be subsequently swollen into hydrogels. The hydrogel materials exhibit high oxygen permeabilities at high water contents and mechanical properties comparable withexisting contact lens materials. The data obtained indicates the importance of optimising phase separation in designing hydrogels with high oxygen permeabilities. Limited oxygen 25 permeability can be attained via the aqueous phase (the current route for commercial hydrogel materials) - however,. this can be substantially increased by designing a polymer morphology which provides a co continuous polymeric phase (based on siloxane or F-rich polymer) to provide a complementary route for oxygen transmission.

WO 00/04065 PCT/AU99/00575 21 Captions to Tables Table 5: Swelling properties of hydrogels with added TRIS at 296K. 5 Table 6: Oxygen permeabilities of hydrogels with added TRIS. Table 7: Swelling properties of hydrogels with constant DMA at 296K. 10 Table 8: Oxygen permeabilities of hydrogels with constant DMA.

WO 00/04065 PCT/AU99/00575 22 Table 5 Material EWC (2 Sol fraction (wt%) (wt%) DMA-96/BFA-4 /TRIS-0 77 0.24 2.41 DMA-96/BFA-4/TRIS-1.4 76 0.25 9.96 DMA-96/BFA-4/TRIS-2.7 74 0.25 6.21 DMA-96/BFA-4/TRIS-5.3 69 0.31 4.93 DMA-90/BFA-10/TRIS-0 64 0.37 3.97 DMA-90/BFA-10/TRIS-1.7 63 0.38 6.91 DMA-90/BFA-1O/TRIS-3.4 60 0.38 1.29 DMA-90/BFA-10/TRIS-6.6 54 0.47 3.23 DMA-96/EFA-4/TRIS-0 82 0.18 4.62 DMA-96/EFA-4/TRIS-1.4 77 0.24 9.34 DMA-96/EFA-4/TRIS-2.7 74 0.26 6.13 DMA-96/EFA-4/TRIS-5.3 69 0.31 4.12 DMA-90/EFA-10/TRIS-0 62 0.34 2.05 DMA-90/EFA-1o/TRIS-1.7 62 0.38 6.80 DMA-90/EFA-10/TRIS-3.4 59 0.39 1.26 DMA-90/EFA-10/TRIS-6.6 53 0.45 2.87 WO 00/04065 PCT/AU99/00575 23 Table 6 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Material Dk (barrers) DMA-96/BFA-4 /TRJS-O 47.43 (±6.33) DMA-96/BFA-4/TRJS-1.4 26.60 (±9.44) DMA-96/BFA-4/TRIS-2.7 41.13 (±5.47) DMA-96/BFA-4/TRIS-5.3 40.37 (±6.96) DMA-90/B3FA-lO/l'RIS-o 43.59 (±1.60) DM.A-90/1BFA-1O/TRIS-1.7 39.85 (±1.14) DMlA-90/B3FA-lO/TRIS-3.4 36.90 (±2.74) DMA-90/BFA-1o/TRIS-6.6 40.81 (±4.06) DMA-96/E FA-4/TRIS-0 51.46 (±3.06) DMA-96/EFA-4/TRJS-1.4 45.11 (6.54) DMA-96/]EFA-4/TRJS-2.7 42.60 (±2.69) DMA-96/]EFA-4/TRIS-5.3 41.66 (±4.66) DMIA-90/EFA-lO/TRIS-o 43.23 (±5.24) DMA-90/EFA-1O/TRIS-1.7 33.36 (±5.59) DMA-90/EFA-1O/TRIS-3.4 40.79 (±5.93) DMA-90/EFA-1Ofl'RIS-6.6 44.95 (±5.25) WO 00/04065 PCT/AU99/00575 24 Table 7 Material EWC ( Sol fraction (wt%) (wt%) DMA-96/BFA-4/TRIS-0 77 0.24 2.41 DMA-96/BFA-3/TRIS-1 79 0.22 7.18 DMA-96/BFA-2/TRIS-2 82 0.20 7.59 DMA-96/BFA-1/TRIS-3 85 0.17 6.02 DMA-96/BFA-O/TRIS-4 86 0.15 8.75 DMA-90/BFA-1o/TRIS-0 64 0.35 3.97 DMA-90/BFA-7/TRIS-3 66 0.35 6.09 DMA-90/BFA-5/TRIS-5 68 0.34 5.31 DMA-90/BFA-3/TRIS-7 71 0.32 5.58 DMA-90/BFA-O/TRIS-10 70 0.34 4.31 DMA-96/EFA-4/TRIS-0 82 0.18 4.62 DMA-96/EFA-3/TRIS-1 80 0.22 6.66 DMA-96/EFA-2/TRIS-2 83 0.19 7.69 DMA-96/EFA-1/TRIS-3 85 0.15 6.95 DMA-96/EFA-o/TRIS-4 86 0.15 8.75 DMA-90/EFA-10/TRIS-0 62 0.34 2.05 DMA-90/EFA-7/TRIS-3 64 0.37 5.00 DMA-90/EFA-5/TRIS-5 67 0.37 5.04 DMA-90/EFA-3/TRIS-7 68 0.36 5.61 DMA-90/EFA-O/TRIS-10 70 0.34 4.31 WO 00/04065 PCT/AU99/00575 25 Table 8 Material Dk (barrers) DMA-96/BFA-4/TRIS-o 47.43 ( 6.33) DMA-96/BFA-3/TRIS-1 34.98 ( 0.49) DMA-96/BFA-2/TRIS-2 32.23 ( 0.42) DMA-96/BFA-1/TRIS-3 29.80 ( 2.62) DMA-96/BFA-O/TRIS-4 18.01 ( 5.97) DMA-90/BFA-1O/TRIS-o 43.59 ( 1.60) DMA-90/BFA-7/TRIS-3 27.35 ( 2.22) DMA-90/BFA-5/TRIS-5 27.86 ( 6.57) DMA-90/BFA-3/fRIS-7 29.25 ( 4.04) DMA-90/BFA-OffRIS-1o 22.62 ( 1.25) DMA-96/EFA-4/TRIS-o 51.46 ( 3.06) DMA-96/EFA-3/TRIS-1 32.89 ( 1.51) DMA-96/EFA-2/TRIS-2 30.79 ( 4.28) DMA-96/EFA-1/TRIS-3 26.55 ( 0.82) DMA-96/EFA-OffRIS-4 18.01 ( 5.97) DMA-90/EFA-1O/TRIS-o 43.23 ( 5.24) DMA-90/EFA-7/TRIS-3 31.62 ( 5.35) DMA-90/EFA-5/TRIS-5 29.53 ( 0.68) DMA-90/EFA-3/TRIS-7 30.08 ( 2.16) DMA-90/EFA-O/TRIS-10 22.62 ( 1.25) WO 00/04065 PCT/AU99/00575 26 INDUSTRIAL APPLICABILITY The polymers of this invention are useful for ophthalmic devices such as soft contact lenses. They are also useful for a variety of other applications 5 which benefit from the hydrophilic nature and high oxygen permeability of the polymer, such as oxygen permeable wound dressings or bandages, carriers for controlled delivery of drugs either as dermal patches, orally taken beads, body implants or eye inserts and gas separation membranes. It will be appreciated by persons skilled in the art that numerous 10 variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims (22)

1. 1. A polymer including the polyierisation product of (a) N, N-dimethylacrylamide, and 5 (b) a monomer of the formula: R' R"f CRF 2 11 - IS0 2 N(CH2)2COOC=CH 2 wherein 10 n is an integer from 1 to 8, preferably 4 to 8, R' is an alkyl group, preferably a lower alkyl group containing up to 4 carbon atoms, more preferably ethyl or butyl, and R" is hydrogen or an alkyl group which may be the same as or different from R', preferably hydrogen or a lower alkyl group containing up to 4 carbon 15 atoms, more preferably hydrogen or methyl.

2. A polymer according to claim 1 containing 40 - 90% by weight of component (a) and 10 - 60% by weight of component (b), based on the total weight of the monomers (a) and (b).

3. A polymer according to claims 1 or 2 wherein the polymerisation 20 product is formed in the presence of a crosslinking agent.

4. A polymer according to claim 3 wherein the crosslinking agent is included in an amount of up to 8% by weight based on the total weight of the polymer.

5. A polymer according to claim 3 wherein the crosslinking agent is 25 ethylene glycol dimethacrylate or 1,1,1-trimethylolpropane trimethacrylate.

6. A polymer according to claims 1 or 2 wherein the polymerisation product is formed in the presence of 1-5% by weight ethylene glycol dimnethacrylate based on the total weight of the polymer.

7. A polymer including the polymerisation product of 30 (a) 40-90% by weight of N, N-dimethylacrylamide. and (b) 10-60% by weight of a monomer of the formula: R' R" C,,F2.m+SO2N(CH2)2COOC=CH2 WO 00/04065 PCT/AU99/00575 28 wherein n is an integer from 1 to 8, preferably 4 to

8, R' is ethyl. and 5 R" is methyl based on the total weight of the monomers (a) and (b), wherein the polymerisation product is formed in the presence of 1-5% by weight ethylene glycol dimethacrylate based on the total weight of the polymer. 10 8. A polymer including the polymerisation product of (a) N, N-dimethylacrylamide., and (b) a monomer of the formula: R' R" 15 CF 2 m,+ lSO 2 N(CH2) 2 COOC=CH 2 wherein n is an integer from 1 to 8, preferably 4 to 8, R' is an alkyl group, preferably a lower alkyl group containing up to 4 carbon atoms, more preferably ethyl or butyl, and 20 R" is hydrogen or an alkyl group which may be the same as or different from R', preferably hydrogen or a lower alkyl group containing up to 4 carbon atoms, more preferably hydrogen or methyl, and (c) one or more monomers selected from the group consisting of: styrene, styrene derivatives, methacrylates, acrylates, acrylamides, 25 methacrylamides, vinyl pyrrolidone, vinyl monomers containing phosphoryl choline functional groups, and partly or fully fluorinated derivatives of the foregoing.

9. A polymer according to claim 8 wherein monomer (c) is included in an amount of from 2 to 50% by weight based on the total weight of the polymer. 30

10. A polymer according to claims 8 or 9 wherein monomer (c) is 3-[tris(trimethylsilyloxy)silyl] propyl methacrylate. WO 00/04065 PCT/AU99/00575 29

11. A polymer including the polymerisation product of (a) 60-80% by weight of N, N-dimethylacrylamide,. and (b) 40-60% by weight of a monomer of the formula: 5 R' R" CG 1 F 2 mi+ ISO 2 N(CH 2 ) 2 COOC=CH 2 wherein n is an integer from 1 to 8, preferably 4 to 8, 10 R' is ethyl or butyl, and R" is hydrogen based on the total weight of the monomers (a) and (b) and (c) 5-20% by weight of 3-[tris(trimethylsilyloxy)silyl] propyl methacrylate based on total weight of the polymer. 15

12. A hydrated composition in the form of a contact lens which includes a polymer according to any one of the preceding claims.

13. A hydrated composition in the form of a contact lens which includes a polymer according to any one of claims 1 to 11 having an oxygen permeability of at least 30 Dk. 20

14. A hydrated composition in the form of an ophthalmic prosthetic device, a drug delivery device or bandage which includes a polymer according to any one of claims 1 to 11.

15. A hydrogel which includes a polymer according to claim 1 as hereinbefore defined with reference to example 1. 25

16. A hydrogel which includes a polymer according to claim 8 as hereinbefore defined with reference to example 2.

17. A hydrogel having an equilibrium water content in the range of from 30 to 90% by weight, the hydrogel being suitable for use as a contact lens and including a polymer having a fluorine and/or siloxane rich hydrophobic 30 phase separated from a hydrophilic phase.

18. A hydrogel according to claim 17 having an equilibrium water content in the range of from 40 to 80% by weight.

19. A hydrogel according to claim 17 or 18 wherein the polymer has at least two glass transition temperatures. WO 00/04065 PCT/AU99/00575 30

20. A hydrogel according to any one of claims 17 to 19 wherein the hydrophobic phase includes monomer units of the formula: 5 R' R" CG 1 F 2 m+lSO 2 N(CH 2 ) 2 COOC=CH 2 wherein n is an integer from 1 to 8, preferably 4 to 8, 10 R' is an alkyl group, preferably a lower alkyl group containing up to 4 carbon atoms, more preferably ethyl or butyl. and R" is hydrogen or an alkyl group which may be the same as or different from R', preferably hydrogen or a lower alkyl group containing up to 4 carbon atoms, more preferably hydrogen or methyl. 15

21. A hydrogel according to any one of claims 17 to 19 wherein the hydrophobic phase includes units selected from the group consisting of 2-(N butyl perfluoro octane sulfonamido) ethyl acrylate, 2-(N- ethyl perfluoro octane sulfonamido) ethyl acrylate, 2-(N- ethyl perfluoro octane sulfonamido) ethyl methacrylate and mixtures of two or more of the foregoing. 20

22. A hydrogel according to any one of claims 17 to 21 wherein the hydrophilic phase includes units of NN-dimethylacrylamide. 25