GB2171106A - Hydrogel-forming polymers - Google Patents

Abstract

Hydrogel-forming polymers for contact lenses and intraocular lenses having increased toughness despite high equilibrium water content comprise a hydrophilic monomer (e.g. N-vinyl pyrrolidone or hydroxyethyl methacrylate) together with a monomer having a UV-absorbing group (e.g. 4-benzoyl-3-hydrexyphenyl methacrylate) and/or a polyunsaturated polymeric cross-linking agent (e.g. cellulose acetate acrylate or an isophthalate-based polyunsaturated polyester). The polymers may also contain hydrophobic monomers (e.g. methyl methacrylate or pentafluorostyrene) and non-polymeric cross-linking monomers (e.g. diallyl maleate, diallyl phthalate, allyl methacrylate or ethoxylated Bisphenol A dimethacrylate).

Description

SPECIFICATION Hydrogel-forming polymers This invention relates to cross-linked polymers which can be hydrated to form hydrogels having improved mechanical properties despite a generally high equilibrium water content. The polymers of the invention are particularly, but not exclusively, useful in the field of optical prostheses (ie contact lenses and intraocular implants) as well as in reverse osmosis membranes and in controlled-release devices for controlled discharge of an active ingredient, particularly in a physiological environment.

Soft contact lenses are made of hydrogel, a hydrated cross-linked polymer containing hydrophilic monomer units. In use, these lenses coverthe cornea, a body of avasculartissue which requires a continuous supply of oxygen from the air in order four itto function. If starved of adequate oxygen supply, the cornea swells and becomes hazy, producing dangerous impairment of vision. Oxygen supply to the cornea in a normal eye takes place by diffusion through thetearfluid and thus the supply when the cornea is covered by a contact lens musttake place by diffusion through the lens and by tear circulation to the area beneath the lens. In practice, the latter route is inadequate alone so that contact lenses must be oxygen-permeable if they are to be worn for any length oftime.

The oxygen permeability of a hydrogel is a property of its material and depends primarily on the equilib rium watercontent, high water contents producing a lens of high oxygen permeability and low water contents lower oxygen permeability. Forthis reason, high equilibrium water content hydrogels are used for extended wear lenses whilst hydrogels of low water content are limited to use for daily wear lenses.

Extended wear lenses are normally also made in considerably smallerthicknesses than daily wear lenses. This is largely becausethickness determines the actual oxygen transmissibility of the finished lens.

However, another major reason for use of small thicknesses is the additional wearer comfort resulting from the low volume ofthe lens in the eye as well as the reduced level oftear production which such lenses require for their surface to be covered with a continuous permanenttearfilm which enables the lens to function as an efficient optical device and to remain reasonably clear.

Both methods, either of increasing the water content, or of reducing the lens thickness, suffer nevertheless from a serious drawback. In both cases the lens loses physical strength and its firmness. It becomes too soft for positive eyelid interaction and thus loses the ability to keep clean. It becomes too soft to centre properly in the eye and thus it loses stability of vision. The ultra thin lenses also become fragile and tend to break easily. The lens a Iso tends to adhere to the eyeball and thus prevents adequate tear circula- tion. It also tends to buckle and becomes difficultto handle. The soft contact lens and especiallythethin and the ultra thin lens tends therefore to lose most of the advantages they were initially designed to gain.

The main reason for that is the adequate modulii of the hydrogels used for these devices. The modern hydrogelspossess low moduli to enablethem to function properly in the eye. Formation of hydrogels with higher modulii could overcome most of the existing drawbacks of modern soft contact lenses, which drawbacks have been mentioned earlier.

However, raising the hydrogels modulii would result in rendering them brittle and the lenses made out of them even more fragile. Improving the hydrogels modulii oughtthereforeto go hand in hand with maintaining their other physical properties and even further improving them. While the higher modulus is required to form efficient thin or ultra thin lenses that can supply enough oxygen to the cornea for extended wear use, improvement of the toughness is also required to extend the life ofthe lens and to make it suitable for daily wear use too.

Only the hydrogels which possess the combination of higher mods liy with physical strength would qualify to form the desirable thin or ultra thin lens for both daily and extended wear.

Improved hydrogel-forming polymers need to further possess good machining and moulding characteristics, improved hydrogel surface properties and improved UV absorption characteristics which are imperative in cases of aphakia.

Attempts to improve the toughness of hydrogels have been proposed in the past butthese have been unsatisfactory for various reasons. US Patent 4327202 (Foley), for example, addresses the lack oftoughness in polyhydroxyalkylated (meth) acrylic esters such as polyhydroxyethylmethacrylate (HEMA). In Foley, styrene or a styrene derivative is included in the polymer to provide toughness, thus producing a hydrophilic-hydrophobic system typified by HEMAstyrene. HEMA has an equilibrium water content of only 38.5% at 20"C and this is, of course, lowered by the styrene to a level which is not adequate to provide the oxygen transmissibiiity needed for extended wear.Methacrylic acid is included to raise the water content to a reasonable level but this use of an acidic material gives rise to dimensional and optical instability depending on local pH conditions. Foley's lenses were also not ultra-thin, Foley reporting onlythicknesses down to 0.5mm.

Similar approaches to Foley are described in US Patents 3070348 and 3983083, although in the latter case the polymers concerned were soft at room temperature and needed to be machined at low temperature.

Intraocularlenses (1OL's) are bioimplants implanted surgically into the eye in patients whose natural crystalline lens has been surgically removed in a cataract operation.

It is of prime importance to reduce the size of the incision made in the eye during this operation. Forthis reason it is specially importantthatthe 10should possess high equilibrium water content. The higher thewatercontentoftholensthe more itwould shrink on drying.

The high water content 1OLcould be partially dried before the cataract operation. Thus itwould shrink considerably enabling a small size incision for insert ing the lens into the eye. Once in position the semi-dried iOLwould gain its water content from the liquids of the eye and swell back to its original parameters.

Intraocular lenses are also required to possess good mechanical properties such as high tensile strength and modulus sincethey are implanted as permanent prostheses which cannot easily be replaced should they suffer mechanical damage. They also need to possess improved surface properties so as to avoid deposit on the lens which could cause impairment of vision.

As in the case ofthe natural crystalline lens, the 1 0L needs to absorb UV light in the solar region (290400nm) so asto filterthis damaging light out of the human sight.

It has now been found that hydrogel-forming polymers of improved modulii can be produced in a way that eliminates deterioration ofthe physical strength ofthe hydrogels. Furthermore, the method according to the invention may result in hydrogels of both improved modulii and physical strength at the sametime. It may also improve the machinability and the moulding properties of the polymers, the surface properties of the hydrogols and their UV absorption characteristics.

According to the invention, a cross-linked hydrngel forming polymer comprises one ore more hydrophilic monomers (eg a vinyl monomer such as a ring saturated or ring unsaturated heterocyclic vinyl monomer) and is given improved tensile modulus without deterioration of strength and toughness by inclusion of one or more polyunsaturated (eg having vinyl orallyl unsaturation such as methacrylic or acrylic unsaturation) polymeric cross-linking agents.

In preferred embodiments of the invention, the hydrophilic monomer is a nitrogen-containing monomer, preferably a heterocyclic monomer.

Heterocyclic N-vinyl monomers are especially preferred,forexample N-vinyl lactams.

Preferred N-vinyl lactams are pyrrolidone, piperidone and caprolactam derivatives, such as N -vinyl - 2 - piperidone, N - vinyl - 2 - pyrrolidone, N - vinyl caprolactam orderivativesthereof.

As an alterative to N - vinyl lactams, the heterocyclic N -vinyi monomer may be N -vinyl imidazole, N -vinyl succinamide or N - vinyl glutarimide.

Alternative nitrogen-containing monomers to the heterocyclic monomers referred to above are amido derivatives of (meth) acrylic compounds, for example a (meth) acrylamide or an N-substituted derivative thereof. Preferred arethosowhich are mono-ordisubstituted with, for example alkyl, hydroxyalkyl or aminoalkyl substituents. Specific examples of such materials are N-methyl acrylamide, N-isopropyl acrylamide, N-diacetone acrylamide, N, N-dimethyl acrylamide, N, N - dimethyiaminomethyl acrylamide, N, N - dimethylaminoethylacrylamide N -methylami noisopropyl acrylamide or a methacrylamide analog of any one ofthe foregoing.

The hydrophilic monomer may alternatively be any othervinyl orallyl monomer.

Examples are a monovinyl ether, a monovinyl polyester, a hydroxylated vinyl ether, an aminoaikyl (meth) acrylate, a hydrozyalkyl (meth) acrylate or an alkoxy derivative thereof.

The hydroxyalkyl (meth) acrylate may be, for example, mono-, di- or tri-hydroxylated, with the alkyl moiety in any event preferably being of one to four carbon atoms (especially ethyl and propyl). Specific hydroxyalkyl (meth) acrylates are 2 - hydroxyethyl methacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate,2,3 - dihydroxypropyl methacrylate and their alkoxy derivatives.

The aminoalkyl (meth) acrylate may conveniently be one in which the amino group thereof is either unsubstituted or is mono- or d-alkyl substituted, for example aminoethyl (meth) acrylate, dimethylaminoethyl methacrylate, methylaminoethyl methacrylate and diethylaminoethyl methacrylate. Other (meth) acrylic acid derivatives are also envisaged.

The hydrophilic monomers are conveniently present in an amount of at least 35% by weight based on the weight of the polymer, a proportion of 50% by weight or more on the same basis being preferred.

Proportionsarevaried depending primarily on the desired equilibrium water content ofthe hydrogel, proportions within the ranges specified above nor mally providing acceptably high water contents for hydrogels suitable for use in extended wear contact lenses.

Whilstthe polymers of the invention may contain low molecular weight cross-linking agents (ie monomers containing at leasttwo olefinic bonds per molecule), it is crucial to the invention that one or more polyunsaturated polymeric cross-linking agents (ie polymers having multiple unsaturation along the polymeric backbone) are included in the hydrogelforming polymers. The chains constituted bythese polymeric cross-linking agents serve to provide reinforcement, somewhatanalogouslytothefibre-reinforcement provided by incorporating, for example, glass or carbon fibres in polymer compositions for other applications. They thus produce an improvement in both toughness and stiffness which facilities production of thin and ultra-thin lenses as well as lens durability. The resilience of the hydrogel-forming polymers was also improved to enable lenses made therefrom to have high recovery speed when resiliently deformed in use (for example, in the eye).

The polyunsaturated polymeric cross-linking agent (preferably present in an amount of 0.5% by weight or more) mayconveniently boa polyunsaturatedpolyos- ter resin of average molecular weight 1500 to 10000 such as 2000 to 8000 (eg about 3500). The polyunsatu- rated polyester resin may be aliphatic or aromatic type and in particular may be a terephthalate- or isoph- thaalate-based polyunsaturated polyester resin such as phenylterephthalate- or phenylisophthalate-containing polyunsaturated polyester resin.

Terephthalate-based resins are preferred in terms ofthe properties of the resulting hydrogels but is ophthalate-based resins are preferred on cost grounds. Polyunsaturated polyester resins may be used as such or as a mixture in which a polyu nsaturated polyester resin is dissolved in one or more monomers required in polymerization to produce the hydrogel-forming polymer.

As an alternative to polyunsaturated polyester resins, the polymeric cross-linking agent may be any unsaturated derivative of a natural or synthetic homopolymer or copolymer containing multiplefunctional groups along its chain, the derivative typically having an average molecularweightof 25000to 100000 (eg about 50000). Such functional groups include, for example, hydroxy, amino, carboxy, sulphonic and chloromethylene groups as well as their activated derivatives. The natural or synthetic polym ers referred to may thus be, for example, polyvinyl alcohol, cellulose or a cellulose ester such as cellulose acetate, cellulose butyrate or a mixed ester such as cellulose acetate butyrate, PVA-vinyl acetate copolymer or polymethyl-methacrylate - 2 - hyroxyethylmethacrylate copolymer.Multiple pendant unsaturation produced in the above homo/co-polymers may be allyl or vinyl (eg acrylic or methacrylic), examples of polyunsaturated polymeric cross-I inking agents accordingly being cellulose acetate acrylate, cellulose acetate methacrylate, other (meth) acrylic esters of cellulose or a cellulose ester, and polyvinyl alcohol (meth) acrylic esters.

Further alternative polyunsaturated polymeric cross-linking agents are (Meth) acrylic amido derivatives of polyamines ("Meth) acrylic" used throughout means acrylic or methacrylic).

The polymeric cross-linking agent need not be a homopolymor but could be a copolymer of two or more monomers the only requirement being that is has the requisite multiple unsaturation and, in practice, that it be soluble in the reaction mixtures used to produce the hydrogel-forming polymers ofthe invention. Typical unsaturation degree in the case of cellulose esters may be one to three unsaturations per recurring glucose unit (two glucose groupings have a molecularweight of 534 in the case of a typical cellulose acetate methacrylate) down to one per eight our twelve glucose units (eg. one unsaturation perthree to five glucose units). In the case of polyester the unsaturation is usually one per recurring unit and may be as low as one for each of two orthree recurring unfits.Expressed as a ratio unsaturations: molecular weight typical degree on unsaturation ranges from 1:2000 or 3000 upwards (eg. 1:2000 to 1:500 or 1:200 such as 1 :1000 or 1 : about300or350).

Any ofthe polymeric cross-linking agents mentioned herein, especially the polyesters, may be fluorinated (or substituted with other substituents) and it has been found that, when used in fluorinated form, it becomes more efficient and improved on the machinability ofthe polymer and the surface properties ofthe hydrogel after hydration.

Non-polymeric cross-linking agents which may be used in the invention in addition to polyunsaturated polymeric cross-linking agents include any monomer containing two or more olefinic unsaturations per molecule. Specific examples are ethylene glycol dimethacrylate, diethyleneglycol dimethacrylate, tri, tetra or polyethyleneglycol dimethacrylate, and also divinylbenzene, divinylethylene urea, divinypropylene urea, allyl methacrylate, trimethylol propane trimethacrylate, diallyl phthalate, fumarate or maleate, diethylene glycol bis (Allyl carbonate) and ethoxylated disphenol A dimethacrylate or dipentaerythritol monohydroxy pentacrylate or pentamethacrylate.

The non-polymeric cross-linking agent may, of course, contain three or more olefinic unsaturations per molecule, specific examples being trimethylolpro panetrimethacrylate, diallyl fumarate, diallyl maleate and dipentaerythritol monohydroxy penta (meth) acrylate.

In addition to the presence of hydrophilic monomers, the polymers according to the invention may contain one or more hydrophobic monomers, usually to enable the equilibrium water content ofthe hydrogel to be adjusted two a predetermined level (and sometimes also to affect other prnperties). (Meth) acrylic alkyl esters (eg Cl alkyl esters) aretypical hydrophobic monomers for use in the invention, specific examples being methyl acrylate, methyl methacrylate, ethyl acrylate and ethyl methacrylate.

Other vinyl or allyl hydrophobic monomers may be used, for example vinyl esters such as vinyl acetate, vinyl propionate, styrene, styrene derivatives and maleate esters such as alkyl maleates.

The polymers of the invention may conveniently contain a fluorinated aromatic carbocyclic monomer.

These monomers have been found to enable reduction in the amount of polymeric cross-linking agent required for a hydrogel-forming polymer with particular desired strength and toughness qualities.

Similarly, they improve on the machinability of the polymer and the surface properties ofthe hydrogols.

A particularly useful class of such carbocyclic monomers are those of the general formula:-

wherein R, is an optionallyfluorinated unsaturated moiety, R2 is fluorine, R3to R6 each represent identical or different substituents, n to rare, each independent lyzero or one, mis zero oran integer up to a value 5-(n+p+q+r) with the proviso that mis zero only when R1 isafluorinated unsaturated moiety. The monomer may, for example, be di-,tri- or penta- fluorinated on the aromatic ring.

R1 may be ethylenically unsaturated optionally halogonated hydrocarbon moiety of, for example, 2 to 6 carbon atoms, for example, optionally halogenated vinyl, allyl or homologue thereof.

R3 to R5 may be identical or different substituents other than fluorine (eg other halogen substituents or hydrocarbon substituents such as alkyl groups of, for example, 1 to4carbon atom).

Inan embodiment of the invention, the carbocyclic monomer is one in which R1 isafluorinated ethylencally unsaturated hydrocarbon moiety and m to rare zero.

The fluorinated carbocyclic monomer may in particular be a fluorinated styrene (including at least parafluoro substitution), penta fluoro styrene being preferred.

As mentioned above,thefluorinatedcarbocyclic monomer enables a desirable level of strength and toughness to be achieved with decreased contents of polymeric cross-linking agents, although this is generally to some extent at expense of tensile modulus or recovery speed. Itwill thus be appreci ated thatthe capacity to varythe amount and type of both the polymeric cross-linking agent and the fluorinated monomer represents a tool by means of which the polymer can be produced with tailored mechanical properties. In addition to mechanical properties, optical properties can similarly be varied and, moreover, the fluorinated monomer has been found to improve the surface properties of lenses made from polymers according to the invention.This obviously has an influence on the tendency ofthe lensto suffersurface soiling,thus providing another factor determining the use ofthefluorinated monomers. The fluorinated monomer also improves casting ofthe polymerto a lens configuration (an aspect of surface property improvements) and hard polymer machinability.

The fluorinated carbocyclic monomer is conve niontlyusedin an amountof notmorethan 25% by weight of all the materials used to form the polymer, a preferred proportion being 15% or less. The most preferred range of proportion is 0.5% to 10% (eg 3% to 10%).

UV light has long been recognised to be hazardous to human sight. This is especially so after a cataract operation when the natural crystalline lens with its capacityto filter UV light in the solar region (wavelengths 290 -- 400n m) has been removed.

It is thus generally desirable for intraocular lenses to absorb UV light in the same region and this is equally desirable in the case ofthe polymer materials ofthe present invention.

To prevent leaching out, it is preferred that the polymer should contain UV-absorbing components polymerizedichemically bound therein. For example, the polymer may include at least one monomer containing a UV absorbing moiety which in the final polymer networkwill be located as a side group attached to the polymer backbone so as to be bound inextractable UV-absorber. The UV-absorbing monomer, which may be used in small amounts, eg 0.1 to 10% (preferably 0.1 to 2%) by weight ofthe materials used to form the polymer, may be a monoethylenicallyunsaturated monomer, for exam ple4- benzoyl -3- hydroxy phenyl(meth)acrylate.

Alternatively, the UV-absorbing moiety may be part of a cross-linking monomer. Cross-linking agents which are oligomeric may also be used in incorporate UV-absorbing components into the polymerstructure. Residues of chromophores such asthefollowing may be employed to provide the UV-absorbing moieties, namely hydroxybenzophenones and benzotriazoles such as 2 - hydroxybenzophenone; 2,4 dihydroxybenzophenone; 2,2',4-trihydroxyben- zophonone; ?,2',4,4' -tetrahydroxybenzophenone; 2 - (2H - benzotriazol - 2 - yl) phenol; or derivatives thereof.

Alternatively, the chromophone may be UVabsorbing substituted cinnamic acid or a derivative thereof.

The chromophore may also be a derivative of phenyl or other aryl esters capable of photo-Fries re-arrangement to form 2 - hydroxybenzophenone derivates bound in the polymer, for example resorcinol monobenzoate, phenyl salicylate, diaryl terephthalate, diaryl isophthalate or other derivatives.

It has been found that certain ofthe polymeric cross-linking agents referred to earlier possess UVabsorption characteristics in the solar region. Thus, for example, terephthalate- and isophthalate-based polyunsaturated polyester resins possess UVabsorption maxima in the solar range. Phenyltherephthalate-containing and phenyl-isophthalato- containing polyunsaturated polyester resins undergo Fries re-arrangement on exposure to UV-radiation to form 2-hydroxybenzophenone which functions as a UV-absorption moiety bound in the structure ofthe hydrogel-forming polymer.The Fries re-arrangement is illustrated below:

It will be appreciated that UV-absorbing moieties bound in the polymer structure as mentioned above are of advantage since the UV-absorbing components are not leached from the polymer in the optical environment and therefore there is no loss of UV-absorbing properties and no risk of toxic effects due to materials leaching into the eye.

The polymers of the invention may be prepared by radiation polymerization or by heating a polymerization mixture in the presence of one or more chemical initiators.

In the case of radiation polymerization, the radiation will preferably be ionizing gamma-radiation, for example from a cobalt 60 source. Otherforms of radiation, such as electron beams and photon beams, may however, be used as an alternative.

Examplesofchemical initiators are those which generate free radials, such as hydroperoxides or organic peroxides such as the benzoyl peroxide, a percarbonate such as di-isopropyl percarbonate or di-cyclohexyl percarbonato, a redox system or an azo compound such as azobisispbutyronitrile.

Heating attemperatures in the range of 30-95"C is generally suitable to polymerize the mixture. It is desirableto conductthe heating in a cycle, ie in a series of stages at increasing temperatures, the early stages (30-60 C) being conveniently carried out in a water bath or oven, while the latter stages may be preferably carried out in an oven; the last stage is a post-curetreatmentand may be conducted at85-95'C possibly under vacuum.

Apart fro monomers, cross-linking agents and any required initiators, the monomer mixture may contain one or more solvents to help dissolve the polymers or monomers, orto affect one or more of the physical and mechanical properties of the final product.

The polymerisation is preferably effected in a mould. The mould will convenientlytakethefinal shape of a desired article or may be as close as possible to it, so that subsequent machining is either not necessary or is minimized. The mould may also provideasimpleshapeega rod orsheetwhich could be used to provide blanks. The blanks may then be machined to produce a desired article such as a contact lens or an intraocular lens.

The hydrogel-forming polymers of the present invention are suitable for use in contact with living tissueandarethussuitableformaking (by moulding and/or machining) into bioimplantable devices such as intraocular lenses and contact lenses of various thicknesses (eg. thick, thin or ultra thin) as they combine flexibility with improved tensile modulus and adequate toughness. They are particularly suit ablefor making into intraocular lenses asthey can be madeto possess any required equilibrium water contentandtoabsorb UVlightinthesolarregion.

Dyes may be incorporated in the monomer mix before polymerisation or may be used to colour the soft article at a later stage. Pharmaceutically effective substances may be incorporated into the microporous structure ofthe polymers and then be released into the human body on a controlled slow-release basis. For example, the polymers according to this invention may be formed into a bandage lens for an eye and drugs such as antibiotic substances may be incorporated into the lens for gradual diffusion into the eye. The polymers may be used to form other slow release materials for administering active ingredients such as drugs to a physiological environment and may also be used for example, as fallopian tube closures. They may also be swollen with oil or organic solventtoform organogels.

As will be appreciated from the Examples which follow, one class of preferred polymers according to the invention comprises (i) methyl methacrylate, (ii) ethoxylated bisphenol A dimethacryrate, (iii) polyethylene glycol dimethacrylate, (iv) methacrylate, (v) 2-hydroxyethyl methacrylate, (vi) cellulose acetate methacrylate, allyl, (vii) diacetone acrylamide and (viii) N-vinyl pyrrolidone in the preferred by weightamounts30 parts (i), 0.3 parts (ii), 0.25 parts (iii), 0.25 parts (iv), 2.5 parts (v), 1.5 parts (vi), 0.25 parts (vii), and 65 parts (viii).

In a second aspect, the invention provides crosslinked hydrogel-forming polymers comprising a fluorinated aromatic carbocyclic monomer and such a proportion of such a strongly hydrophilic comonomerthat a body of hydrogel formed by hydration thereof has an equilibrium water content at 20"C of preferably more than 50%, especially more than 60%, as well as lOLs and contact lenses made of such polymers. A preferred such contact lens for extended wear, the lens has a thickness and water content such that its oxygen transmissibility on the Fatt scale is at least 200 x 10-1 (cm/sec) (ml 02/ml x mm Hg) at 35" C.

The invention further provides a UV-absorbing hydrogel-forming polymer comprising at least one hydrophilic monomer and optionally at least one non-hydrophilic monomer characterized in that the polymer includes units containing a UV-absorbing moiety which in the final polymer network is bound as part of the polymerstructure. The polymer may include a polyunsaturated polymeric cross-linking agent.

The hydrophilic monomer may be acrylate of the general formula:-

wherein R is H or alkyl (eg C1-C4 alkyl such as methyl) and R1 is hydroxy- or alkoxy-alkyl, for example hydroxyethyl (meth)acrylate, dihydroxypropy Imethacrylate, ethoxyethylmethacrylate, an N-vinyl lactam, N-vinyl imidazole, N-vinyl succinamide, Nvinyl glutarimide, a vinyl orally ether, (meth)acrylamide, aminoacrylate, and derivatives thereof.

The units containing the UV-absorbing moiety may be monomer units or molecules of an oligomeric or polymeric cross-linking agent. The monomer units may be units of a comonomer ora monomeric cross-linking agent. The monomer units may contain any ofthe chromophores specified earlier, in particu lar a chromophore which undergoesphoto-Fries re-arrangement on exposure to UV-radiation to form a re-arrangement product which absorbs UV-radiation, such as an aryl ester which undergoes UV-Fries rearrangomenttoform 2-hydroxybenzophenone derivatives bound in the polymer.

The following specific Examples are intended to illustrate the invention.

In the Examples, MW means the approximate weight average molecular weight. Degree of unsaturation is expressed as number of u nsatu rations per segment of molecular weight 1000 and is necessarily approximate.

Example 1 A mixture of 1 0g freshly distilled pentafluoros tyrene, 17.6g freshly distilled methyl methacrylate, 0.29 diallyl phthalate, 0.2g dially maleate and 79 of purified cellulose acetate acrylate of Example 16 (MW = 50,000; degree of unsaturation = 1/1000)was thoroughly shaken then dissolved in 165g of N-vinyl2-pyrrolidone. Then 0.49 azobisisobutyronitrile was added and the solution was thoroughly mixed, filtered and degassed undervacuum. Part of it was then sealed in a low density polythenetube. The tube was subjected to a heating cylce of 40hrs at 400C, 6hrs at 60"C and 1 6hrs at 900C and then left to cool slowly to room temperature.Discs of 1 m m th ickness were machined from the hard polymer produced by the above method and then immersed in normal saline at 200for hydration until reaching equilibrium (3-7 days). The equilibrium water content was 70.5% and the hydrated discs were clear, tough and flexible with high tensile modulus.

The restofthe polymerisation mixture was cast into films between glass plates, sealed with silicon rubber gaskets and then subjected to the same heating cylce as above. The glass plates were then opened and the hard film was hydrated as before.

Similarly, the equilibrium water content was 70.5% and the mechanical properties of the hydrated film were measured using ASTM D638-77a and D1004-66 for tensile properties and initial tear resistance, respectively. The tensile modulus at 40% strain was 19.5kg/cm2, the tensile strength 19kg/cm2 and the initial tear resistance was 400g/mm.

Discs ofthe material could be machined into contact lenses thinnerthan 0.1 mm in their hydrated state, allowing an oxygen transmissibility on the Fatt scale of more than 360 x 10-1 (cm/sec)(ml 02/my x mm Hg) at35 C.

Example2 A mixture of 10g freshly distilled pentafluoros tyrene,13.6g freshly distilled methyl methacrylate, 0.29 diallyl phthalate,0.2g diallyl maleate, 2g Scott Bader Crystic 181 LV, a commercial, clear isophthalate based polyunsaturated polyester resin (which con tains 36% styrene; MW = 3,500; degreeofunsatura- tion = 1/363) and 7g of purified cellulose acetate acrylate, referred to in Example 1 was thoroughly shaken and then dissolved in 1679 of N-vinyl-2pyrrolidone. Then 0.49 azobisisobutyronitrile was added and the solution was thoroughly mixed, filtered and degassed undervacuum.Part of it was then sealed in a lowdensitytube.Thetubewas subjected to a heating cycle of 40hrs at 40"C, Ghrs at 60;C and 1 6hrs at 90"C and then left to cool slowly at room temperature. Discs of 1 mm thickness were machined from the hard polymer obtained by the above procedure and then immersed in normal saline at 20 Cfor hydration until reaching equilibrium (3-7 days). The equilibrium water content was 70.2% and the hydrated discs were clear, stifferthan those of Example 1; howevertheywere still tough and flexible. The hydrated discs showed UV absorption bands between 190 to 300nm.

The restofthe polymerisation mixture was cast into films between glass plates, sealed with silicon rubber gaskets and then subjected to the same heating cycle as above. The glass plates were then opened and the hard film was hydrated as before, giving rise to the same equilibrium water content.

The mechanical properties of the hydrated films were measured as in Example 1. The tensile modulus at 40% strain was 22kg/cm2, the tensile strength was 15kg/cm2 and the initial tear resistance was 320o/mm.

Discs of the material could be machined into contact lenses thinner than 0.1 mm in their hydrated state, allowing an oxygen transmissibility on the Fatt scale of more than 360 x 10-70 (cm/sec)(ml 02/mI x mm Hg) at35 C.

Example 3 A mixture of 1 .6g freshly distilled pentafluoros tyrene, 3.3g freshly distilled methyl methacrylate, 0.029 diallyl phthalate, 0.02g diallyl maleate, 0.06g ethyoxylated bisphenol A dimethacrylate,0.8g of the isophthalate-based polyunsaturated polyester resin referred to in Example 2 and 0.89 of purified cellulose acetate methacrylate of Example 15 (MW = 50,000; degree ofunsaturation = 1/1000) was thoroughly shaken and then dissolved in 33.49 of N-vinyl-2pyrrolidone.Then 0.089 azobisisobutyronitrilewas added and the solution was thoroughly mixed, filtered and degassed undervacuum, and then sealed ion a low density polythene tube.Thetube was subjected to a heating cycle of 40hrs at 43'C, 6hrs at 60C and 1 6hrs at 90C and then left to cool slowly to room temperature. Discs of 1 mm thickness were machined from the hard polymer obtained by the above procedure and then immersed in normal saline at21 Cforhydration until reaching equilibrium (3-7 days). The equilibrium water contentwas74.2% and the hydrated discs were clear, stiff yet tough and flexible. in addition, the hydrated discs showed strong UVabsorption bands in the solar region, between 190 to 300nm.

Discsofthe material could be machined into contact lenses thinnerthan 0.06mm in their hydrated state, allowing an oxygen transmissibility on the Fatt scale of more than 420 x 1 0-'0 (cm/sec)(ml Odml x mm hg) at35 C.

Example 4 A mixture of 1 g freshly distilled pentafluoros tyrene,3.5g freshly distilled methyl methacrylate, 0.1 g diallyl phthalate, 0.75g of the isophthalate-based polyunsaturated polyester resin referred to in Exam ple 2, 1.59 of purified cellulose acetate methacrylate of Example 3 and 0.059 of4-benzoyl-3-hydroxy- phenyl methacrylate was thoroughly shaken and then dissolved in 43.19 of N-vinyl-2-pyrrolidone, 0.1 g of azobisisobutyronitrile was then added and the solution was thoroughly mixed, filtered and degassed under vacuum, and then sealed in a low density polythene tube.Thetube was subjected to a heating cycle of 40hrs at 400C, 6hrs at 60"C and 16hrs at 90 C and then left to cool slowly to room temperature.

Discs of 1 mm thickness were machined from the hard polymerthus produced and then immersed in normal saline at20"Cfor hydration until reaching equilibrium (3-7 days). The equilibrium water content was 78% and the hydrated discs were still tough and stiff enough fortheir high water content. The hydrated discs, after extraction with ethanol (3 times over night) and boiling in distilled waterfor 8hrs, still absorbed UV light in the solar region indicating the presence of a bound UV absorber in the hydrogel.

Discs ofthe material could be machined into contact lenses thinner than 0.2mm in their hydrated state, allowing an oxygen transmissibility on the Fatt scale of more than 250 x 10-1 (cm/sec)(ml 02/ml x mm Hg) at35 C.

Example5 Amixture of 69 freshly distilled methylmethacry late,0.1 diallyl phthalate, 0.75g of the polyunsaturated polyester resin of Example 2 and 1.59 of the purified cellulose acetate methacrylate of Example3 was thoroughly shaken and then dissolved in 41.659 of N-vinyl-2-pyrrolidone. 0.1 g of azobisobutyronitrile was then added and the solution was thoroughly mixed, filtered and degassed under vacuum and sealed in a low density polythenetube. The tube was subjected to a heating cycle of 40hers at 40"C. 6 hrs at 60and 16hrs at 90 C and then leftto cool slowlyto room temperature. Discs of 1 mm thickness were machined from the hard polymerthus produced and then immersed in normal saline at 200Cfor hydration until reaching equilibrium (3-7 days). The equilibrium water contentwas 78% and the hydrated discs were tough and stiff enough for such a high water content.

They also showed UV absorption bands between 190 to 300nm.

Discs ofthe material could be machined into contact lenses thinner than 0.2mm in their hydrated state, allowing an oxygen transmissibility on the Fatt scale of more than 250 x 10-1 (cm/sec)(ml 02(ml x mm Hg) at 35"C.

Example 6 A solution of 1 .129 of the solid isophthalate based polyunsaturated polyester resin referred to in Example2 but dissolved in 14g freshly distilled methyl methacrylate, 0.15g ethoxylated bisphenol A dimethacrylate, 0.1 g diallyl maleate and 1.259 2hydroxyethylmethacrylate was added to a mixture of solids which contained 0.759 cellulose acetate methacrylate of Example 3 and 0.129 diacetone acrylamide, thoroughly shaken and then dissolved in 32.519 on N-vinyl-2-pyrrolidone. 0.1g of azobisisobutyronitrile was then added and the solution was thoroughly mixed, filtered and degassed under vacuum, and then sealed in a low density polythene tube.The tube was subjected to a heating cycle of 40 hrsat40"C,6hrsat60"Candl6hrsat90"Candthe left to cool slowlyto room temperature. Discs of 1 mm thickness were machined from the hard polymer thus produced and then immersed in normal saline at 20"C for hydration until reaching equilibrium (3-7 days).

The equilibrium water content was 60% andthe hydrated discs were clear, stiff, tough yet still flexible.

They also showed strong UV absorption bands between 190 and 300nm and this property remained after attempting absorber extraction in boiling water and organic solvents.

Discs ofthe material could be machined into contact lensesthinnerthan O.lmm intheir hydrated state, allowing an oxygen transmissibility on the Fatt scale of more than 250 x 10-1 (cm/sec) (ml02/ml x mm Hg) at35 C.

Example 7 A solution of 1.129 of the solid isophthalate-based polyunsaturated polyester resin of Example 6 in 1 3.96g freshly distilled methyl methacrylate, 0.15g ethoxylated bisphenol Adimethacrylate,0.1g diallyl my leats and 1 .259 2-hydroxyethyl methacrylate, was added to a mixture of solids which contained 0.759 cellulose acetate methacrylate of Example 3,0.129 diacetone acrylamide and 0.05g 4-benzoyl-3-hydroxyphenyl methacrylate, thoroughly shaken and then dissolved in 32.59 of N-vinyl-2-pyrrolidono. 0.1 g of azobisisobutyronitrile was then added and the solution was thoroughly mixed, filtered and degassed undervacuum, and then sealed in a low density polythene tube.The tube was subjected to a heating cycle of 40 hrs at 40"C, 6 hrs at60 C and 16 hrs at90 C andthen Iefttocoolslowlyto room temperature.

Discs of 1 mm thickness were machined from the hard polymerthus produced and then immersed in normal saline at 20"C for hyd ration until reaching equilibrium (3-7 days). The equilibrium water contentwas 59% and the hydrated discs were clear, stiff, tough yet flexible and capable of absorbing UV in the sola r region, after extractions with ethanol, other and boiling water Discs could be machined into contact lenses with similar dimensions and properties to those of Exam ple6.

Examples 0.759 ofthe purified cellulose acetate methacrylate of Example 3 and 0.5g of crystallised diacetone acrylamide was added to a mixture of 1 2.6g offreshly distilled methyl methacrylate, 0.15g ethoxylated bisphenol A dimethacrylate, 0.1 3g polyethylene glycol dimethacrylate, 0.12g allyl methacrylate and 59 2-hyd roxyethyl methacrylate, and was thoroughly shaken. It was then dissolved in 30.759 of N-vinyl-2pyrrolidone, filtered and degassed under vacuum, and then sealed in a low density polythene tube. The tube was subjected to a dose of 2.5 MegaRads of ionising radiation from a Cobalt 60 source.Discs of 1 mm thickness were machined from the hard polymerthus produced and then immersed in normal saline at 20 Cfor hydration until reaching equilibrium (3-7 days). The equilibrium water contentwas 63% and the hydrated discs were flexible, stiffyottough and clear.

Example 9 Asolution of 0.48g the isophthalate based polyunsaturated polyester resin of Example 2 in 0.27 styrene was added to a mixture of 209 purified 2-hydroxyethyl methacrylate, 8.958 freshly distilled methyl methacrylate, O.lg ethoxylated bisphenol A dimethacrylate,0.1g diallyl phthalate, O.lg diallyl maleate, 1 g purified diacetone acrylamide and 199 N-vinyl-2-pyrrolidone. The mixture was shaken and 0.19 of azobisisobutyronitrilo was added. Thesolu- tion was then thoroughly mixed, filtered and degassed under vacuum and sealed in a low density polythene tube.The tube was subjected to a heating cycle the same as that of Example 7 above then left to cool slowly to room temperature. Discs of 1 mm thickness were machined from the hard polymer thus obtained and hydrated in normal saline at200C until equilibrium (3-7 days). The equilibrium water content was 42.7% and the hydrated discs were resilient, stiff and yettough. The discs also showed UV absorption bands between 190 to 300nm.

Example 10 2.59 of freshly distilled pentafluorostyrene was added to a mixture of 47.259 2-hydroxyethyl methacrylate and 0.259 of allyl methacrylate and thoroughly shaken together.0.1 of azobisisobutyronitrile was added and the solution was mixed, degassed and sealed in a low density polythene tube as in Example 8. The tube was subjected to the same heating cycle and discs from the hard polymer obtained were hydrated to equilibrium as in the previous example. The equilibrium water content was 28.9% and the hydrated discs were stiff and white in colour.

Example ii Asolution of 12.6g offreshly distilled methyl methacrylate, 0.159 ethoxylated bisphenol A dimethacrylate, 0.13g polyethylene glycol dimethacrylate, 0.1 2g allyl methacrylate and 5.09 2-hyd roxyethyl methacrylate was added to a mixture of 0.75g ofthe purified cellulose acetate methacrylate of Example 3 and 0.5g diacetone acrylamide. The whole mixture was shaken and then dissolved in 30.759 of N-vinyl-2-pyrrolidone. 0.1 g of azobisisobutyronitrile was added and the solution was thoroughly mixed, filtered and degassed undervacuum and sealed in a low density polythene tube. The tube was subjected to a heating cycle of 40 hrs at40"C, 6 hrs at60 C and 16 hrs at90 C andthen leftto cool slowly to room temperature. Discs of 1 mm thickness were machined from the hard polymerthus produced and then immersed in normal saline at 200C for hydration until reaching equilibrium (3-7 days). The equilibrium water content was 60.0% and the hydrated discs were flexible yet stiff, tough and clear.

Example 12 A solution of 15.3759 freshly distilled methyl methacrylate, 0.15g ethoxylated bisphenol A dimethacrylate, 0.125g polyethylene glycol dimethacrylate,0.125g allyl methacrylate and 1 .259 2-hydroxyethyl methacrylate was added to a mixture of 0.759 ofthe purified cellulose acetate methacrylate of Example 3 and 0.1259 diacetone acrylamide The whole mixture was shaken and then dissolved in 32.1 g of N-vinyl-2-pyrrolidone. 0.1 g of azobisisobuty ronitrile was added and the solution was thoroughly mixed, filtered and degassed undervacuum and sealed in a low density polyethylene tube.The tube was subjected to a heating cycle of 40 hrs at 400C. 6 hrs at60OC and 16 hrs at 90 C and then leftto cool slowlyto room temperature. Discs of 1 mm thickness were machined from the hard polymer thus produced and then immersed in normal saline at 20"C for hydration until reaching equilibrium (3-7 days). The equilibrium watercontentwas 60.5% andthehy- drated discs were stiff, tough and clear. It was found to be suitable for the production of soft intraocular lenses.

Example 13 Plano lenses of hydrated parameters of 9.0mm in radius, 14.5mm in diameter and 0.2mm in thickness were manufactured from the polymer of Example 11.

They were thoroughly cleaned, sterilized and then soaked in preservative-free 1% pilocorpine hydroch loride drops for 2 hrs. Then the lenses were used to treat the eyes of patients who suffer from acute closed-angled glaucoma. The presoaked lenses re leased in the eye over 90% of the pilocorpine in 4.0 hrsand reductionoftheintraocularpressurewas obtained.

Example 14 Crystallized 4-benzoyl-3-hydroxyphenyl methacrylate was dissolved in 2-hydroxyethylmethacrylate, cross-linking agent (allylmethacrylate) and other monomers in different formulations asspecified in the Table.

0.29 ofazobisisobutyronitrile was then added to each formulation and the different solutions were thoroughly mixed, filtered and degassed under vacuum. Each formulation was then sealed in low density polythene tube. The tubes were subjected to a heating cycle of 40 hrs at 500C, 6 hrs at 600C and 16 hrs at 90"C and then left to cool slowly to room temperature. Discs of about 0.1 mm in thickness were machined from the hard polymers thus produced and then hydrated in saline as in Example 1.The equilibrium water contents ofthe differentformulations were ranged between 34to 43% as indicated in the Table. The hydrated discs were clear and they absorbed UV light between 190to400mm before and after extraction with ethanol, ether and boiling water.

Example 15 1.25 litres petroleum other 40-60 is placed in a 3 litre round flask in a fume cupboard. 1 00g offreshly distilled methacryloyl chloride is added and the mixture isthoroughly stirred. 500g of cellulose acetate (Eastman Kodak No.4650) is now added slowly, while stirring constantly. Then the flask is sealed, covered and left to stand at room temperature overnight The mixture is then refluxed for 8 hours at 45"C sealed and cooled in the fridge overnight.The solid is subsequently transferred into a thimble placed beforehand in a fume cupboard and extracted with ether in a soxh let forth ree days, 8 hrs a day. 200g of granulated NaOH is placed in the flask of the soxhletto decompose the acid chloride and to convert the orga nic acid formed into its solid sodium salt:

The solids are removed every daytogethorwith the ether and replaced by new portions of NaOH (2009) and diethyl ether. In the fourth day the cellulose acetate methacrylate is placed between layers of filter paperinthefume cupboardfor5to 6 hours in orderto evaporate the ether. The resulting dry powder is then sieved in a 50 mesh sieve, placed in a dark bottle and kept in the freezer.

Example 16 1 00g offreshly distilled acryloyl chloride and 5009 of cellulose acetate are added one by one through constant stirring to 1.25 litres of petroleum ether 40-60 as in Example 15. The flask is then sealed and placed in the fridge for one week. The solid is subsequentlytransferred into a thimble and extracted with ether in a soxhlet forth ree days as in Example 15. In the fourth daythe cellulose acrylate thus formed is dried between sheets offilter paper, sieved and bottled as before (Example 15).

The invention includes within its scope all hydrogelforming polymers, for use in optical prostheses, containing UV-absorbing components bound therein,forexample HEMA-based and other polymers containing monomers such as 4-benzoyl-3-hydroxy- phenyl (meth)acrylate, orthecorrespondingtriazole derivative, polymerized therein.

(Meth)acrylate and other monomers including therein a chromophoresuch as hydroxybenzophenones and benzotriazoles are per se included within the scope ofthe invention since they are thoughtto be novel compounds.

The invention also encompasses slow-release devices comprising a polyunsaturated crosslinker- reinforced or fluorinated monomer-containing hydrogel ororganogel containing a biologically-active material such as an antibiotic or other drug within its microporous structure.

Formulation Formulation Formulation Formulation Formulation Compounds I II III IV V (grams) (grams) (grams) (grams) (grams) methacrylate 99.06 88.06 88.06 88.06 88.06 4-genzoyl-3-hydroxyphenyl 0.63 0.56 0.56 0.56 0.56 methacrylate Allyl methacrylate 0.31 0.28 0.28 0.28 0.28 N-vinyl-2-pyrrolidone - 11.10 - - - méthacrylate ~ ~ 11.10 ~ 5. 55 methacrylate Diacetone acrylamide - - - 11.10 5.55 Equilibrium Water Content % 38.10 43.10 41.80 34.90 39.00

Claims (82)

1. Ahydrogel-forming polymer wherein UVabsorbing moieties are bound chemically in the polymer structure so as to be inextractable by solvents.

2. Apolymerasclaimed in Claim 1 and comprising polymerised hydroxyethylmethacrylate.

3. A UV-absorbing hydrogel-forming polymer substantially as hereinbefore described with refer once to the specific Examples.

4. An intraocular lens comprised of a polymer as claimed in any one of Claims 1 to 3.

5. A UV-absorbing hydrogel-forming polymer comprising at least one hydrophilic monomer and optionally at least one non-hydrophilic monomer characterized in that the polymer includes units containing a UV-absorbing moiety which inthefinal polymer network is bound as part ofthe polymer structure.

6. A polymer as claimed in Claim 5 wherein the hydrophilic monomer is an acrylate ofthe general formula:

wherein R is H or alkyl and R1 is hydroxy - or alkoxy alkyl.

7. A polymer as claimed in Claim 6wherein R is hydrogen or Cl alkyl.

8. A polymer as claimed in Claim 6 wherein R is hydrogen or methyl.

9. A polymer as claimed in Claim 5 wherein the hydrophilic monomer is a hydroxyethyl(meth) acry- late.

10. A polymer as claimed in Claim 5 wherein the hydrophilic monomer is hydroxyethyl methacrylate, dihydroxypropyl methacrylate, ethoxyethyl- methacrylate, (meth) acrylamide, aminoacrylate, or derivatives thereof.

11. A polymer as claimed in Claim 5 wherein the hydrophilic monomer comprises an N-vinyl lactam, N-vinyl imidazole, N-vinyl succinamide, N-vinyl glu ta ri m ide o r a vi nyl or allyl other.

12. A polymer as claimed in any one of Claims 5 to 11 wherein the units containing the UV-absorbing moiety are monomer units.

13. A polymer as claimed in Claim 12 wherein the monomer units are units of a monomer.

14. A polymer as claimed in Claim 12 wherein the monomer units are units of a monomeric cross linking agent.

15. A polymer as claimed in any one of Claims 12 to 14 wherein the monomer units each contain one of the chromophores specified hereinbefore.

16. A polymer as claimed in anyone of Claims 5to 11 wherein the units containing the UV-absorbing moiety are molecules of an oligomeric or polymeric cross-linking agent.

17. A polymer as claimed in any one of Claims 5to 11 wherein the UV-absorbing moiety ofthe units is one which undergoes photo-Fries re-arrangement on absorbing UV-radiation to form a re-arrangement product which absorbs UV-radiation.

18. A polymer as claimed in Claim 17 wherein the chromophore is an aryl ester which undergoes UV-Fries re-arrangement to form 2-hydroxyben zophenone derivatives bound in the polymer.

19. A polymer as claimed in Claim 18 wherein the aryl ester is resorcinol monobenzoate, phenyl salicylate, diaryl terephthalate, diaryl isophthalate or a derivative of one of the foregoing.

20. A polymer as claimed in any one of Claims 5 to 11 wherein the units containing the UV-absorbing moiety are units of a polymeric cross-linking agent.

21. A polymer as claimed in Claim 20wherein the polymeric cross-linking agent is a terephthalate- or isophthalate- based polyunsaturated polyester resin.

22. A polymer as claimed in Claim 20 or 21 wherein the polymeric cross-linking agent is polyun saturatred and has a degree of unsaturation expressed as the ratio numberof unsaturations: molecular weight of from 1:300 to 1:3000.

23. Across-linked hydrogel-forming polymer comprising at least one hydrophilic monomer and at least one polyunsaturated polymeric cross-linking agent.

24. A polymer as claimed in Claim 22 wherein the hydrophilic monomer is a nitrogen-containing monomer.

25. A polymer as claimed in Claim 22 or Claim 23 wherein the hydrophilic monomer is a vinyl monomer.

26. A polymer as claimed in any one of Claims 23 to 25 wherein the hydrophilic monomer is a ring saturated or ring unsaturated heterocyclicvinyl monomer.

27. A polymer as claimed in any preceding claim wherein the hydrophilic monomer is a heterocyclic vinyl monomer.

28. A polymer as claimed in Claim 27 wherein the heterocyclic N-vinyl monomer is an N-vinyl lactam.

29. A polymer as claimed in Claim 28 wherein the N-vinyl lactam is a pyrrolidone, piperidone orcaprolactam derivative.

30. A polymer as claimed in Claim 28 or Claim 29 wherein the N-vinyl lactam is N - vinyl - 2 pyrrolidone, N -vinyl -2- piperidone, N -vinyl caprolactam ora derivative thereof.

31. A polymer as claimed in Claim 27 wherein the heterocyclic N-vinyl monomer is N -vinyl imidazole, N -vinyl succinamide or N - vinyl glutarimide.

32. A polymer as claimed in Claim 24 wherein the nitrogen-containing monomer is an amido derivative of a (meth) acrylic compound.

33. A polymer as claimed in Claim 32 wherein the amido derivative is a (meth) acrylamide compound or an N-substituted derivative thereof.

34. A polymer as claimed in Claim 32 or Claim 33 wherein the amido derivative is N - methyl acrylamidge, N - isopropyl acrylamide, N -diacetone acrylamide, N, N - dimethyl acrylamide, N, N - dimethylaminomethyl acrylamide, N, N - dimethylaminoethyl acrylamide, N -methylaminoisopropyl acrylamide or a methacrylamideanalog of any one of the foregoing.

35. A polymer as claimed in Claim 23 wherein the hydrophilic monomer is a monovinyl ether monovinyl polyether, a hydroxylated vinyl ether, an aminoalkyl (meth) acrylate, a hydroxyalkyl (meth) acrylate oran alkoxy derivative thereof.

36. A polymer as claimed in any preceding claim wherein the hydrophilic monomer(s) constitutues at least 35% by weight based on the weight ofthe polymer.

37. A polymer as claimed in Claim 36 wherein the hydrophilic monomer(s) constitutes at least 50% by weight based on the weight of the polymer.

38. A polymer as claimed in any preceding claim wherein the unsaturation ofthe polymeric crosslinking agent is vinyl or allyl unsaturation.

39. A polymer as claimed in any preceding claim wherein the unsaturation ofthe polymeric cross linking agent is (meth) acrylic.

40. A polymer as claimed in any preceding claim wherein the polyunsaturated polymeric cross-linking agent is a polyunsaturated polyester rosin.

41. A polymer as claimed in Claim 40 wherein the polyunsaturated polyester resin is an aliphatic or an aromatic based polyunsaturated polyester resin our a mixture thereof.

42. A polymer as claimed in Claim 40 or Claim 41 wherein the polyunsaturated polyester resin is a terephthalate- or isophthalate-based polyunsaturated polyester resin.

43. A polymer as claimed in Claim 42 wherein the polyunsaturated polyester resin is a phenylisophtha- late-containing or phenylterephthalate-containing polyunsaturated polyester resin.

44. A polymer as claimed in any one of Claims 22 to 39 wherein the polyunsaturated polymeric crosslinking agent is a polyunsaturated derivative of a natural orsynthetic homopolymeror copolymer containing multiple functional groups along its chain.

45. A polymer as claimed in Claim 44 wherein the multiple functional groups are selected from hydroxy, amino, carboxy, sulphonic or chloromethylene or an activated derivative thereof.

46. A polymer as claimed in Claim 44 or Claim 45 wherein the homopolymer or copolymer is polyvinyl alcohol (PEAS, cellulose, a cellulose ester, PVA-vinyl acetate copolymer or polymethyl methacrylate - 2 hydroxyethylmethacrylate copolymer.

47. A polymer as claimed in Claim 46 wherein the polyunsaturated polymeric cross-linking agent is a (meth) acrylic ester of polyvinyl alcohol or a (meth) acrylicesterof cellulose orof a cellulose ester.

48. A polymer as claimed in Claim 47 wherein the (meth) acrylic ester of cellulose or of a cellulose ester is cellulose (meth) acrylate, cellulose acetate (meth) acrylate, cellulose butyrate (meth) acrylate orcellulose acetate butyrate (meth) acrylate.

49. A polymer as claimed in any one of Claims 22 to 39 wherein the polyunsaturated polymeric crosslinking agent is a (meth) acrylic amido derivative of a polyamine.

50. A polymer as claimed in any preceding claim wherein the polyunsaturated polymeric cross-linking agent contains fluorine.

51. A polymer as claimed in any preceding claim wherein the polyunsaturated polymeric cross-linking agent is present in an amount of not more than 20% based on the weight of the polymer.

52. A polymer as claimed in any preceding claim and containing a non-polymeric cross-linking agent.

53. A polymer as claimed in Claim 52 wherein the non-polymeric cross-linking agent is ethylene glycol dimethacrylate, divinyl benzene, divinylethylene urea, divinylpropylene urea, allyl meth acrylate, di alkyl phthalate, diethyleneglycol bis (allylcarbonate), ethoxylated bisphenol A dimethacrylate, trimethylol propanetrimethacrylate, diallyl fumarate, diallyl maleate, dipentaerythritol monohydroxy pentacrylate or pentamethacrylate or di, tri- tetra- or polyethyleneglycol dimethacrylate.

54. A polymer as claimed in any preceding claim and containing one or more hydrophobic comonomers.

55. A polymer as claimed in Claim 54 wherein the hydrophobic comonomer is styrene, a vinyl ester, a maleate ester oran alkyl (meth) acrylate.

56. A polymer as claimed in any preceding claim and containing a UV-absorber.

57. A polymer as claimed in Claim 56 wherein the UV-absorberisa UV-absorbing monomercopolymerized in the polymer structure.

58. A polymer as claimed in Claim 57 wherein the UV-absorbing monomer is a monomer containing oneofthefollowingchromophores,namelya residue of 2-hydroxybenzophenone; 2,4-dihydroxyben- zophenono; 2,2',4-trihydroxybenzophenone; 2,2',4,4'-tetrahydroxybenzophenone; 2-(2H-benzotriazol-2-yl) phenol; resorcinol monobenzoate; phenyl salicylate; diaryl terephthalate; diaryl isophthalate or a derivative thereof; or UV-absorbing substituted cinnamic acid or a derivative thereof.

59. A monomer as claimed in Claim 57 or Claim 58 wherein the UV-absorbing monomer is a nonpolymeric cross-linking agent.

60. A polymer as claimed in any preceding claim and containing a fluorinated aromatic carbocyclic monomer.

61. A polymer as claimed in Claim 60 wherein the fluorinated monomer is ofthe general formula:-

wherein R1 is an optionallyfluorinated, unsaturated moiety, R2 is fluorine, R2to R6 each represent identical or different substituents, n to rare, each independently, zero or one, mis zero or an integer up to a value 5-(n+p+ q+ r) with the proviso that mis zero only when R1 is a fluorinated unsaturated moeity.

62. A polymer is claimed in Claim 61 wherein R1 is a fluorinated ethylenically unsaturated hydrocarbon moeityand mto rare zero.

63. A polymer is claimed in Claim 65 wherein the fluorinated monomer is a fluorinated styrene.

64. A polymer is claimed in Claim 63 wherein the fluorinated monomer is di-, tri, tetra- or pentafluorinated on the aromatic ring.

65. A polymer is claimed in Claim 63 or Claim 64 wherein the fluorinated monomer is pentafluorostyrene.

66. A polymer is claimed in any one of Claims 61 to 65 wherein the fluorinated monomer is present in an amount of not more than 25% by weight based on the weight of the polymer.

67. A polymer is claimed in Claim 66wherein the fluorinated monomerispresentinanamountoffrom 0.5% to 10% byweight based on the weight of the polymer.

68. A polymer as claimed in Claim 23 and comprising methyl methacrylate, ethoxylated bisphenol A dimethacrylate, polyethylene glycol dimethacrylate, allyl methacrylate,2-hydroxyethyl methacrylate, cellulose acetate methacrylate, diacetone acrylamide and N-vinyl pyrrolidone.

69. A polymer as claimed in Claim 68 wherein the N-vinyl-2-pyrrolidone constitutes about 60% by weight based on the weight ofthe polymer.

70. A polymer as claimed in Claim 69 and made by polymerizing a mixture having the following composition by weight:- methyl methacrylate 30 parts ethoxylated bisphenol A dimethacrylate 0.3 parts polyethylene glycol dimethacrylate 0.25 parts allyl methacrylate 0.25 parts 2-hydroxyethyl methacrylate 2.5 parts purified cellulose acetate methacrylate 1.5 parts diacetone acrylamide 0.25 parts N-vinyl-2-pyrrolidone 65 parts

71. Across-linked hydrogel-forming polymer substantially as hereinbefore described in any one of the foregoing specific Examples.

72. An optical prosthesis comprising a body of a hydrogel formed by hydrating a body of a polymer as claimed in any preceding claim.

73. Across-linked hydrogel-forming polymer comprising a fluorinated aromatic carbocyclic monomer and such a proportion of such a strongly hydrophilic comonomerthat a body of a hydrogel formed by hydration thereof has an equilibrium water content at 20"C of preferably more than 50%.

74. A polymer as claimed in Claim 73 wherein the hydrogel has an equilibrium water content of more than 60%.

75. An intraocular lens comprising a polymeras claimed in Claim 73 or Claim 74.

76. An ultra-thin contact lens for extended wear and comprising a polymer as claimed in Claim 73 or Claim 74, the lens having a thickness and water content such that its oxygen transmissibility on the Fattscale is at least x 1010(cm/sec)(ml0/ml x mm Hg) at 35 C.

77. An intraocular lens comprising a moulded and/or machined body of polymer in hydrated form and comprising the components specified in Claim 70 in the amounts there specified.

78. A bioimplantable device comprising a polymer as claimed in any one of Claims 23 to 71,73 or 74.

79. A process of making a hydrogel-forming polymer (copolymer or multi-component polymer) as claimed in Claim 23 or Claim 73 which process comprises heating a mixture ofthe monomers, cross-linking agent and polymerization initiator.

80. A process of making a hydrogel-forming polymer (copolymer or multi-component polymer) as claimed in Claim 23 or Claim 73 which process comprises subjecting a mixture ofthe monomers and cross-linking agents to irradiation.

81. A process as claimed in Claim 79 or Claim 80 and substantially as hereinbefore described with reference to a specific Example contained hereinbefore.

82. A hydrogel forming polymer as claimed in Claim 23 or Claim 73 obtained buy a process as claimed in any one of Claims 79 to 81.