EP1109846A1

EP1109846A1 - Contact lens material

Info

Publication number: EP1109846A1
Application number: EP99930948A
Authority: EP
Inventors: Thomas Paul Davis
Original assignee: Unisearch Ltd
Current assignee: Unisearch Ltd
Priority date: 1998-07-13
Filing date: 1999-07-13
Publication date: 2001-06-27
Also published as: JP2002520456A; KR20010074704A; WO2000004065A1; CA2337173A1; AUPP463998A0

Abstract

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. The invention consists in a polymer including the polymerisation product of (a) N,N-dimethylacrylamide, and (b) a monomer of formula (I) 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 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. In conjunction with the DMA monomer and monomer(s) of formula (I), one or more additional monomers may be included selected from the group consisting of: styrene and styrene derivatives, methacrylates - especially 3-[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.

Description

CONTACT LENS MATERIAL

INTRODUCTION 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 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 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 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 higher dry hardness and therefore better machineability while at the same time reducing lipophilicity and deposit formation on the hydrated polymer.

The fluorine has been introduced into polymeric materials by polymerising hydrophilic monomers such as N-vinylpyrrolidone (NVP) and 2-hydroxyethyl methacrylate (HEMA) with fluorinated styrenes and 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. TS Patent No 5011275 by Mueller discloses a hydrogel based on a polymer of 15 - 85% dimethylacrylamide and 15 - 85% fluorine containing monomer and optionally other acrylates or methacrylates and a polyvinyϊ functional cross-linking agent. The polymers form clear hydrogels with about 25 - 75% water content.

Polymerisation between DMA and methacrylates in general proceeds 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 Bl- CH₂=C— COO(CH₂)„(CF₂)_πICF₂X (Bl)

wherein

Ri is hydrogen or methyl, n is an integer from 1 - 4, in 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, undecafluoro cyclohexyl-methyl methacrylate and 2, 3, 4, 5, 6- pentafluorostyrene.

DISCLOSURE OF INVENTION

The present inventors have found a group of fluorine-containing 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 (b) a monomer of the formula (I) :

R^* R"

I I (i)

C_nF_{2lJ+ 1}S0₂N(CH₂)₂COOC=CH₂ 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

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 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 (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 composition in the form of an ophthalmic prosthetic device, a drug deliveiy 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. 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- [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. 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- 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 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 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 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 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 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. 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 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 provided it prevents polymer precipitation and inhomogeneity of the polymer product.

BRIEF DESCRIPTION OF THE DRAWINGS

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 perfluoro octane sulfonamido) ethyl acrylate (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) /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_g values for the two glass transition homopolymers where A is DMA homopolymer. B is

BFA-20/DMA-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 distinct regions giving rise to the two glass transition temperatures. MODES FOR CARRYING OUT THE INVENTION

Example 1 Synthesis hydrogels based on copolymers of dimethylacrylamide and fluoro sulphonamide (meth)acrylates

Materials

N.N-Dimethylacrylamide (DMA) (supplied by Sigma-Aldrich Pty. Ltd) 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) 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 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 (IN) saline was used for all swelling measurements.

Polymerisa tion

Monomer mixtures were made up gravimetrically. deoxygenated with nitrogen for lOmins and irradiated in sealed polypropylene ampoules. In all cases the γ-irradiation dose was 1 Mrad obtained from a ^oαCo source , the dose rate being 0.01 Mrad If ¹ as determined by Fricke dosimetry. The resultant solid rods of xerogel were post-cured at 90°C for 24 firs 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. 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 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.

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 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 ~} '"" x 100 [1] m_s where m_s = mass of swollen sample mo = mass of dry sample

This EWC measurement needs to be based on the xerogel weight after sol fraction extraction, in the brine medium. % sol fraction = ^/W" ^{~ /Wg} _x ioo [2] m₎ where m_E = the dry mass of extracted sample.

The volume fraction of polymer within a hydrogel is given as

*. = { y w

Where D and D₀ are the diameters of the hydrogel and xerogel respectively. Oxygen Permeability

Measurements were made on swollen samples over a range of thicknesses (at least three) on a JDF DklOOO^{I M} coulometric oxygen permeation instrument under wet cell conditions.

Thermal Analyses

The glass transition temperatures (T_g) of the xerogels were determined using a TA Instruments DSC 2010 Differential Scanning Calorimeter, at a heating rate of 10°C min^"1 using sample weights in the range 5-10 mg. The reported T measurements were taken from the second heating run.

Results & Discussion

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 this copolymer may be unsuitable for contact lens applications. However, the addition of a crosslinker (l%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 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 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 deformation of the discs and pellets. The xerogel rods often appeared to contain residual stresses (clearly shown via observation between cross- polarising lenses) which may be due to either inhomogeneities in the original monomer mixing and/or a substantial gel effect observed in these reactions. 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.

Glass Transition Temperatures

The T_g values for the xerogels were determined and are shown in Table 1. In all three copolymer systems, two T_gs were observed. The thermograms for the BFA/ DMA series are shown in Figure 3. The higher T_g is assumed to originate from the DMA component and the lower T_g from the BFA side-chain. Random copolymers usually exhibit only one T_g . given by the weighted average of the T_gs of the two polymeric components. The T_g 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 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 T_g (corresponding to DMA) is seen to reduce as the concentration of fluoro-monomer increases, there is also a concomitant reduction in the lower glass transition. The reduction in both T_gs is possibly explicable as follows. The structure of the copolymer is shown in Figure 4. The high T_g corresponds to the backbone polymer chain region which comprises both DMA and fluoro-monomer segments. Thus the high DMA T_g is mediated by a contribution from the fluoro-monomer component. The low T_g originates solely from the flexible side-chain most distant from the polymer backbone forming icrodomains this value is lower than the T_g 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. The pure fluoro-monomers used in this current study are in fact a mixture of monomers with different length side-chains and thus the extent of incompatibility of the perfluoro sidechains with DMA rich areas may be tempered by a contribution from the smaller side-chains acting as 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 Un crosslinked 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 achieve high water contents whilst maintaining a reasonable fluorine content. This is clearly demonstrated by comparison of these new materials with PHEMA 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 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 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.

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 materials. This can be clearly demonstrated by comparing those hydrogels with about 60wt% fluoro-monomer that have water contents around 40wt% (similar to PHEMA). The oxygen permeability is about five times higher than PHEMA. This indicates that oxygen transmission in these hydrogels occurs 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 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 permeability that occurs when the DMA 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. 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

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, but this can be minimised 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. Captions to Tables

Table 1: Glass transition temperatures for uncrosslinked xerogels.

Table 2: Swelling properties of uncrosslinked hydrogels at 296K.

Table 3: Swelling properties of crosslinked hydrogels at 296K.

Table 4: Oxygen permeabilities of uncrosslinked hydrogels.

Table 1

Material Low T_e fC) High T„ (°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

Table 2

Material EWC (wt%) Φ2 Sol fraction (wt%)

BFA-20/DMA-80 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-80 83 0.17 5.12

EFMA-40/DMA-60 68 0.32 5.68

EFMA-60/DMA-40 50 0.48 3.92 Table 3

Material EWC (wt%) φ₂ Sol fraction (wt%) lwt%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 Table 3 (Continued)

Material EWC (wt%) Φ2 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

Table 4

Material Dk

(barrers)

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) Example 2

Synthesis hydrogels based on terpolymers of dimethylacrylamide, fluoro sulphonamide acrylates and 3-[tris(trimethylsiloxy)silyl] propyl methacrylate

Materials

N,N-Dimethylacrylamide (DMA) (supplied by Sigma-Aldrich Pty. Ltd) and 3- [tris (trimethylsilyloxy)] propyl methacrylate (TRIS) (also supplied by Sigma- 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 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 (IN) saline was used for all swelling measurements.

Polymerisation

Monomer mixtures were made up gravimetrically, deoxygenated with nitrogen for lOmins and irradiated in sealed polypropylene ampoules. In all cases the γ-irradiation dose was 1 Mrad obtained from a ⁶⁰Co source, the dose rate being O.OlMrad h^"1 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.

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. Equilibrium water content

The equilibrium water content (EWC) of the hydrogels is defined as:

where m_s = mass of swollen sample n ₀ = mass of dry sample This EWC measurement needs to be based on the xerogel weight after sol fraction extraction, in the brine medium.

777 — 777

% sol fraction = — x 100 [5]

777_υ where m_E = the dry mass of extracted sample

The volume fraction of polymer within a hydrogel is given as φ₂ J^ [6]

Where D and D₀ are the diameters of the hydrogel and xerogel respectively

Oxygen Permeability

Measurements were made on swollen samples over a range of thicknesses (at least three) on a JDF DklOOO™ coulometric oxygen permeation instrument under wet cell conditions. Results & Discussion Xerogel synthesis and properties The xerogel rods were lathe cut into discs. All of the xerogels maintained their transparency on swelling.

Fluorinated Hydrogels with Added TRIS Swelling properties 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 + BFA) and TRIS is present at a concentration of 1.4 mol.-% of (MMA + BFA

+ TRIS).

Table (5) shows the swelling data obtained for the different copolymer systems at selected compositions, prepared in the absence of a crosslinker 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). 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 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 oxygen permeability results for the current TRIS-containing terpolymers are given in Table 6. Each reported value is an average of at least three 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 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 veiy 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 secondaiy transmission route via 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 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 terpolymer.

Hydrogels Containing a Constant DMA Concentration 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 example, the designation DMA-96/BFA-3/TRIS-1 now means that DMA 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 (MMA + BFA + TRIS). It is also pertinent to note that compositions containing 96 mol.-% and 90 mol.-% DMA correspond to compositions of 80 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. 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. 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 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 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 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 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. Captions to Tables

Table 5: Swelling properties of hydrogels with added TRIS at 296K.

Table 6: Oxygen permeabilities of hydrogels with added TRIS.

Table 7: Swelling properties of hydrogels with constant DMA at 296K.

Table 8: Oxygen permeabilities of hydrogels with constant DMA.

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-10/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-4TRIS-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-10 TRIS-1.7 62 0.38 6.80

DMA-90/EFA-10/ RIS-3.4 59 0.39 1.26

DMA-90/EFA-10/TRIS-6.6 53 0.45 2.87

Table 6

Material Dk (barrers)

DMA-96/BFA-4 /TRIS-0 47.43 (±6.33)

DMA-96BFA-4/ RIS-1.4 26.60 (± 9.44)

DMA-96/BFA-4/TRIS-2.7 41.13 (±5.47)

DMA-96BFA-4/TRIS-5.3 40.37 (±6.96)

DMA-90/BFA-10/ RIS-0 43.59 (± 1.60)

DMA-90/BFA-10/TRIS-1.7 39.85 (± 1.14)

DMA-90/BFA-10/TRIS-3.4 36.90 (±2.74)

DMA-90/BFA-10/TRIS-6.6 40.81 (±4.06)

DMA-96/EFA-4/TRIS-0 51.46 (± 3.06)

DMA-96/EFA-4/TRIS-1.4 45.11 (±6.54)

DMA-96/EFA-4/TRIS-2.7 42.60 (± 2.69)

DMA-96EFA-4/TRIS-5.3 41.66 (±4.66)

DMA-90/EFA-10/TRIS-0 43.23 (±5.24)

DMA-90/EFA-10/ RIS-1.7 33.36 (±5.59)

DMA-90/EFA-10TRIS-3.4 40.79 (±5.93)

DMA-90/EFA-10/TRIS-6.6 44.95 (±5.25)

Table 7

Material EWC Φ2 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/ RIS-3 85 0.17 6.02

DMA-96/BFA-0/TRIS-4 86 0.15 8.75

DMA-90/BFA-10/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-0/TRIS-10 70 0.34 4.31

DMA-96/EFA-4/ RIS-0 82 0.18 4.62

DMA-96/EFA-3/ RIS-1 80 0.22 6.66

DMA-96/ΕFA-2/TRIS-2 83 0.19 7.69

DMA-96/EFA-1/TRIS-3 85 0.15 6.95

DMA-96/EFA-0/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-0/TRIS-10 70 0.34 4.31

Table 8

Material Dk (barrers)

DMA-96/BFA-4/TRIS-0 47.43 [±6.33)

DMA-96/BFA-3/TRIS-1 34.98 (± 0.49)

DMA-96BFA-2/TRIS-2 32.23 [±0.42)

DMA-96/BFA-1/TRIS-3 29.80 [±2.62)

DMA-96/BFA-0/TRIS-4 18.01 [±5.97)

DMA-90/BFA-10 RIS-0 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/ RIS-7 29.25 ± 4.04)

DMA-90/BFA-0/TRIS-10 22.62 ±1.25)

DMA-96/EFA-4/TRIS-0 51.46 ( ± 3.06)

DMA-96/EFA-3/TRIS-1 32.89 ± 1.51)

DMA-96EFA-2TRIS-2 30.79 ( ±4.28)

DMA-96/EFA-1/TRIS-3 26.55 ±0.82)

DMA-96/EFA-0TRIS-4 18.01 ( ±5.97)

DMA-90/EFA-10/TRIS-0 43.23 ( ±5.24)

DMA-90/EFA-7/TRIS-3 31.62 ( ±5.35)

DMA-90EFA-5 RIS-5 29.53 ( ±0.68)

DMA-90/EFA-3/TRIS-7 30.08 ( ±2.16)

DMA-90/EFA-O/TRIS-lO 22.62 ( ±1.25)

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 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 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

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS :-

1. 1. A polymer including the polymerisation product of

(a) N. N-dimethylacrylamide, and (b) a monomer of the formula:

R' R"

C_uF_{2ll+ 1}SO₂N(CH₂)₂COOC=CH₂ wherein n is an integer from 1 to 8, preferably 4 to 8,

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.

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 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 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 dimethacrylate based on the total weight of the polymer.

7. A polymer including the polymerisation product of (a) 40-90% by weight of N, N-dimethylacrylamide. and

(b) 10-60% by weight of a monomer of the formula:

R' R"

I I

CΓÇ₧F_{2n+ 1}S0₂N(CH₂)₂COOC=CH₂ wherein n is an integer from 1 to 8. preferably 4 to 8. R' is ethyl, and 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.

8. A polymer including the polymerisation product of

(a) N. N-dimethylacrylamide. and

(b) a monomer of the formula:

R' R"

I I C_nF_{2n+ 1}SO₂N(CH₂)₂COOC=CH₂ 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 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. 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.

10. A polymer according to claims 8 or 9 wherein monomer (c) is

3-[tris(trimethylsilyloxy)silyl] propyl methacrylate.

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: R' R"

C_nF_{2u+ 1}S0₂N(CH₂)₂COOC=CH₂ wherein n is an integer from 1 to 8, preferably 4 to 8, 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.

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.

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.

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 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.

20. A hydrogel according to any one of claims 17 to 19 wherein the hydrophobic phase includes monomer units of the formula:

R' R"

C_uF_2ll+1S0₂N(CH₂)₂COOC=CH₂ 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

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.

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