WO2005109041A1

WO2005109041A1 - Compositions for use in the manufacture of lenses

Info

Publication number: WO2005109041A1
Application number: PCT/GB2005/001880
Authority: WO
Inventors: Kenneth A. Hodd; Andrew Courtis
Original assignee: Medical Polymers Limited
Priority date: 2004-05-12
Filing date: 2005-05-12
Publication date: 2005-11-17
Also published as: GB0410582D0

Abstract

The invention relates to a polymeric ophthalmic lens composition suitable for foldable intraocular lens manufacture having a Tg <37 °C derived from one or more monomers of the formula: CH2=C(R)-C(O)-O-(Y)p-(Z)q-Ar wherein: R is selected form H, CH3 or phenyl; Y is an optionally hydroxy-substituted n-alkyl group having (3) or more carbon atoms; p is 0 or 1; Z is an ester or ether linkage; q is 0 or 1; with the proviso that when q is 1, p is also 1 and that when p is 0, q is also 0; and Ar is benzyl, phenyl, or other mono- or polycyclic-aromatic or heteroaromatic group substituted with one or two iodine groups.

Description

DESCRIPTION COMPOSITIONS FOR USE IN THE MANUFACTURE OF LENSES

The present invention relates to compositions for use in the manufacture of ocular lenses. The invention also relates to the design, selection and synthesis of novel polymeric materials, suitable for the manufacture of ophthalmic devices, especially lenses and most especially intraocular lenses for small-incision implantation following cataract surgery, such lenses being of a one- or three-part construction.

Foldable intraocular lenses (lOLs) are frequently manufactured from acrylic copolymer elastomers, for example, US 4834750 refers to the use of acrylic materials for foldable lOLs. The attributes of clarity, transparency, dimensional stability and ease of working are believed to be important reasons for preferring foldable acrylics to silicone or hydrogel materials for IOL manufacture ("Foldable Intraocular Lenses" (1993), Ed. Martin et al., Slack Incorporated, Thorofare, N.J.). Many acrylic elastomer compositions used in IOL manufacture are copolymers of aryl(meth)acrylate esters, or silicones. Table 1 below lists the refractive indices (Rls) and glass transition temperatures (Tgs) of examples of the polymeric materials commonly used commercially. Table 1 Properties of Some IOL Materials

When selecting an acrylic copolymer for IOL manufacture research tends to follow the teaching of US 48347501 so as to combine glass-forming monomer(s) with elastomer-forming monomer(s), the molar ratio of each type of monomer being adjusted to meet the requirements of the IOL material.

More recent disclosures cite (meth)acrylic copolymers for IOL manufacture (US 52908923, EP 4851974, US 53590215 and WO 94117646), and outline the advantages of including acrylic monomers with higher refractive indices in lens material formulations. These monomers are, usually, aryl bearing (meth)acrylics that confer high refractive indices on resultant copolymers which allows lenses of thinner cross-section for a given lens power to be manufactured, which improves the unfolding characteristics of the lens and reduces cracking, when implanting through smaller incisions (<3.0mm).

In intraocular lenses made from the copolymers arising from such combinations, the handling characteristics are improved whereas the glass-forming methacrylate monomer also reduces the "tackiness" of the elastomer. Alternatively, because some arylalkylacrylat.es are recognized as tackifiers for, e.g., hot melt adhesives (Simmons, H.E. et al., (1994) J. Appl. Polym. Sci. 52, 727-735) it is necessary to add a third monomer to the elastomer formulation to perform the detackifying role. A number of documents disclose attempts to tackle the problem of tackiness of the lens surface, which interferes with the handling and the unfolding of the lens following implantation. US 4834750 for example, proposes the inclusion of a fluorinated monomer, trifluoroethylmethacrylate as a way of reducing the surface energy of the lens. WO 9411764 discloses the inclusion of a third comonomer in copolymers of phenoxyethylacrylate to reduce tackiness, combining 2-phenoxyethylacrylate for example with alkylacrylate monomer(s), a cross-linker, a vinyl-UV-absorber, and tackiness reducer, such as NVP or a fluorinated alkylacrylate, to yield foldable IOL materials having Rl at least (or at least about) 1.50, and a low Tg (<22°C). WO 9625962 discloses IOL material formulations incorporating fluorinated acrylates, and US 5882421 discusses the use of plasma treatment for the surface of the lens to reduce tack. WO 0060383 proposes the use of copolymers based on 3- phenylpropyl(meth)acrylate to generate materials of low tack. US 5433746 proposes a similar copolymer and refers to isopropylphenyl-(meth)acrylate combinations. WO 0057213 has also drawn attention to the tackiness of acrylic formulations and discloses a solution to replace acrylate with methacrylate monomers. This document also discusses the use of C1-20 alkyl side chains and the examples provided mostly include dodecyl-(lauryl, C12)methacrylate copolymers. There is also a discussion of elastomeric copolymers containing only methacrylates, e.g., copolymers of MMA and laurylmethacrylate that have a reduced tackiness. Combinations of alkyl methacrylate monomers, a cross-linker and a vinyl-UV-absorber to yield foldable PMMA-like IOL materials having Rl 1.47-1.49 and a low Tg <37°C.

Iodine-substituted polymer glasses have long been proposed for use as radio- opaque implants in dentistry and for, e.g., bone-cements. There are reports in the literature of the synthesis and (co)polymerisation of a variety of iodine- bearing methacrylate monomers in the field of dentistry.

A number of structures of iodine-bearing monomers of methacrylate origin have been proposed (Lakshmi, S. et al., (2003) J. Appl. Polym. Sci. 88, (11), 2580- 2584; Jayakrishnan A. and Chithambara Thanoo, B. ibid (1992), 44, 743-748; Davy, K.W.M. et al., (1997) Polym. Int. 43, 143-154; Davy, K.W.M. (1997) J. Dentistry 25, (6), 499-505; Benzina, A. (1996) J. Biomed. Mater. Res. 32, (17), 459-466; and Artola, A. (2003) Biomaterials (10), 4071-80), the compounds largely being triiodobenzoyloxyethylmethacrylat.es for use as radio-opaque (co)polymers resulting from their combination with other common monomers such as MMA and/or HEMA. Other iodine-bearing methacrylates such as 2-(2'- iodobenzoyl)ethyl methacrylate have also been reported in addition to their iodophenylmethacrylates and their (co)polymers (Kruft, M-A. B. et al., (1996) Biomater. 17, (18), 1803-1812 and Kruft, M-A. B. et al., (1994) J. Biomed. Mater. Res. 28, (11), 1259-1266). The preparation, copolymerisation and biomedical applications of 2,5-diiodo-8-quinolinyImethacrylate polymers has also been disclosed (Ginebra, M.P. et al., (1999) J. Mater. Sci. Mater. Med. (10) 733-737 and Vazquez, B. et al., (1999) J. Biomater. (20), 2047-2053).

Synthesis and properties of radio opaque polymer hydrogels which are copolymers of 2,4,6-triiodophenyl- or N-(3-carboxy-2,4,6- triiodophenyl)acrylamide and p-styrene sulphonate have also been reported (Okamura, M. (2002) J. Mol. Struct. 602, (1-2), 17 - 28). WO 02/077044 discloses (meth)acrylate copolymers which include iodine substitution

Whilst a number of compositions have been proposed for use as lOLs and indeed other types of ophthalmic lenses (such as soft contact lenses), there is still a requirement for new materials to be developed that have a high refractive index and that are substantially inert in or on the human eye which are also more easily introduced to the subject. It is therefore an object of the present invention to provide for a composition with a reduced copolymer tack, and increased refractive index.

Cataract surgery involves implantation of an IOL through a small incision made in the eye. When the incision is small enough, it should be self-healing, but may cause trauma. Ophthalmologists seek improvements on the behalf of their patients and implantation becomes easier and less hazardous as the lens thickness is reduced. The size of surgical incisions for the implantation of current foldable lOLs is in the range 3.0 to 2.5mm, but it would be advantageous to produce lOLs manufactured from a material which could be inserted through even smaller incision size, to about 2.0mm or less. Such developments may be realised by a combination of factors, including lens design, lens power, surgical skill, etc., but distinct advantages accrue from the manufacture of lOLs from elastomeric materials of low tack, which have a high refractive index, preferably more than 1.55.

In addition, a recent development in lOLs, the intraocular contact lens (ICL) also has a special need for elastomeric materials of higher refractive index. The ICL is designed to correct severe myopia but unlike cataract surgery it is neither necessary, nor desirable as the patients are younger, to remove the natural lens. Myopia is, generally, correctable by laser surgery, provided that the condition is not too extreme. Severe conditions of myopia are not fully correctable by laser surgery, but may be corrected by the insertion of an ICL. The ICL is then an intraocular lens which is implanted in the eye, either anteriorly , or preferably, posteriorly, that is in the sulcus, between the iris and the natural lens (Barraquer, Am J Ophthalmol, (1999), 128, (2), 232; Assetto, Benedetti, Pesando, J Cataract Refract Surg, (1996), 22, (5), 551).

The space between the iris and the natural lens is very restricted, and contact between the implanted lens and the natural lens may cause a cataract. For this reason a very thin lens is essential, and so materials of higher refractive index, which facilitate the manufacture of foldable thin lOLs, are preferred.

According to the present invention there is provided a polymeric ophthalmic lens composition suitable for foldable intraocular lens manufacture having a Tg <37°C derived from one or more monomers of the formula: CH₂=C(R)-C(0)-0-(Y)_p-(Z)_q-Ar wherein:

R is selected from H, CH₃ or phenyl;

Y is an optionally hydroxy-substituted n-alkyl group having 3 or more carbon atoms; p is 0 or 1 ;

Z is an ester or ether linkage; q is 0 or 1 ; with the proviso that when q is 1 , p is also 1 and that when p is 0, q is also 0; and Ar is benzyl, phenyl, or other mono- or polycyclic-aromatic or heteroaromatic group substituted with one or two iodine groups.

Many suitable aromatic groups may be used in the compositions of the invention. However, preferred Ar groups include phenyl, benzyl, quinolinyl, isoquinolinyl and naphthyl.

The lens material preferably has a refractive index of at least about 1.49, preferably at least about 1.51 , more preferably at least about 1.55 and most preferably at least about 1.60.

Ar may have more than one iodine substituent and may have one or more further substituent groups selected from alkyl, aryl, alkenyl, aralkyl, alkaryl, alkenaryl, aralkenyl, cycloalkyl and heteroalkyl groups.

Also provided in accordance with the invention are 2-iodophenylacrylate, 4- iodophenylacrylate, 2-iodobenzylmethacrylate, 2-iodobenzylacrylate, 5,7- diiodoquinolinylmethacrylate and 5,7-diodoquinolinylacrylate which have been found to be useful monomers in the preparation of polymeric materials suitable for use in lens applications. In accordance with yet another aspect of the present invention, there are provided novel monomers capable of being polymerised with themselves or with other monomers or polymers, the novel monomers comprising 4-lodophenylacrylate or or derivatives thereof. In accordance with the present invention there is provided a composition for use in the production of ocular lenses comprising an acrylate or methacrylate monomer with at least one aromatic ring, said aromatic ring being substituted with one or more iodine group.

Preferred monomers for use in making the polymeric compositions of the invention include, but are not limited to, 2-iodophenylacrylate, 2- iodophenylmethacrylate, 4-iodophenylacrylate, 4-iodo-phenylmethacrylate, 2- iodobenzylmethacrylate, 2-iodobenzylacrylate, 2,5-diodoquinylacryIate, 2,5- diodoquinylmethacrylate, 5,7-diodoquinylacrylate, 5,7-diodoquinylmethacrylate, 2,5-diiodoisquinoIinylmethacrylate, 5,7-diiodoisoquinolinylmethacrylate, 2,5- diiodoisoquinolinylacrylate, 5,7-diiodoisoquinolinylacrylate, 2,5- diiodoquinolinylmethacrylate, 5,7-diiodoquinolinylmethacrylate, esters of e.g., iodobenzoic acids, such as 2'-iodobenzoyl-2-oxypropylacrylate, 2'-iodobenzoyI-2- oxypropylmethacrylate, 4'-iodobenzoyl-2-oxypropylacrylate, 4'-iodobenzoyl-2- oxypropylmethacrylate, 2'-iodo-benzoyl-3-oxypropylacrylate, 2'-iodobenzoyl-3- oxypropylmethacrylate, 2'-iodobenzoyl-2-hydroxy-3-oxypropylacrylate, 2'- iodobenzoyI-2-hydroxy-3-oxypropylmethacrylate, 2'-iodobenzoyl-4- oxybutylacrylate, 2'-iodobenzoyl-4-oxybutylmethacrylate, 2'-iodo-benzoyl-5- oxypentylacrylate, 2'-iodobenzoyl~5-oxypentylmethacrylate, 2'-iodobenzoyl-6~ oxyhexylacrylate, 2'-iodobenzoyl-6-oxyhexylmethacrylate, 4'-iodo-benzoyl-3- oxypropylacrylate, 4'-iodobenzoyl-3-oxypropylmethacrylate, 4'-iodobenzoyl-2- hydroxy-3-oxypropyIacryIate, 4'-iodobenzoyl-2-hydroxy-3-oxypropylmethacrylate, 4'-iodobenzoyl-4-oxybutylacrylate, 4'-iodobenzoyl-4-oxybutylmethacrylate, 4'- iodo-benzoyl-5-oxypentylacrylate, 4'-iodobenzoyl-5-oxypentylmethacrylate, 4'- iodobenzoyl-6-oxyhexylacrylate, 4'-iodobenzoyl-6-oxyhexylmethacrylate; 2'- iodophenylacetoyl-3-oxypropylacrylate, 3'-iodophenylacetoyl-3-oxypropylacrylate, 4'-iodophenylacetoyl-3-oxypropylacrylate, 2'-iodopheηylacetoyl-3- oxypropylmethacrylate, 3'-iodophenylacetoyl-3-oxypropylmethacrylate, 4'-iodo- phenylacetoyl-3-oxypropylmethacrylate; 4'-iodonaphthoyl-3-oxypropyIacrylate, and 4'-iodonaphthoyl-3-oxypropylmethacrylate.

It will be understood that the acrylate or methacrylate monomer may encompass a range of polymeric materials that contain acrylate or methacrylate such as ethyl acrylate or methyl methacrylate for example.

Also preferably, the monomers of the compositions are polymerised to form a polymeric composition and this may be in conjunction with or independently of a further group of standard monomers that do not contain an iodinated aromatic ring(s) so as to form a lens. The further group of standard monomers may simply be similar monomers without an aromatic ring or a similar monomer without an iodinated aromatic ring. Alternatively, the further group of monomers may be different monomers with or without iodinated aromatic rings. Preferably, the choice of monomer will be dictated by whether or not the monomer is substantially inert and non-toxic in the mammalian body so that it can be used for intraocular applications, such as, lOLs. The monomers in the polymeric compositions in accordance with the present invention may be used in a different quantities to the further group of monomers so as to alter the characteristics of a lens. Preferably, the ratio of the composition to the standard composition may be varied depending on the refractive index of the lens required.

It has therefore been found that the introduction acrylate and/or methacrylate monomers bearing iodinated phenyl (or other aromatic) rings, substituted with one or more iodine atoms per ring, into hydrophobic intraocular lens formulations derived from combinations of acrylate and methacrylate monomers such as 2- phenylacrylate, methyl(meth)acrylate, dodecylmethacrylate, tridecylmethacrylate, benzylacrylate or benzylmethacrylate has a number of unexpected benefits. These benefits include elastomeric copolymer compositions with reduced tack and higher refractive index. These properties are of particular advantage in compositions used for foldable intraocular lenses, and may be beneficially exploited in contact lenses and spectacle lenses.

Preferable hydrophobic, elastomeric, compositions suitable for the manufacture of intraocular lenses, comprises the copolymer formed by a combination of 4- iodo-phenylmethacrylate (0.1 to 30.0 mole%), 2-phenylethylmethacrylate and/or methylmethacrylate (0.0 to 20 mole%) and 2-phenylethylacrylate (99.9 to 50 mole%), together with 1 ,6-hexanedioldiacryIate as a crosslinker (2.9 weight% of the combined monomer weight); more preferable compositions, suitable for the manufacture of foldable intraocular lenses comprises the copolymer formed by a combination of 4-iodophenylmethacrylate (1.0 to 12.0 mole%), 2- phenylethylmethacrylate and/or methylmethacrylate (0.0 to 9.0 mole%) and 2- phenylethylacrylate (99 to 88 mole%), together with 1 ,6-hexanedioldiacrylate as a crosslinker (2.9 weight% of the combined monomer weight); and most preferably the copolymer formed by a combination of 4-iodophenylmethacrylate (1.0 to 10 .0 mole%), 2-phenylethylmethacrylate (0.0 to 5.0 mole%) and 2- phenylethylacrylate (99 to 90 mole%), together with 1 ,6-hexanedioI-diacrylate as a crosslinker (2.9 weight% of the combined monomer weight). Those skilled in the art will know other crosslinkers that may be substituted for 1 ,6-hexanediol- diacrylate in the preferred compositions cited, these include, 1 ,3-propanediol di(meth)acrylate 1 ,4-butanediol di(meth)acrylate, 1,5-pentanediol di(meth)acrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, allyl(meth)acrylate, and similar compounds used singly or in combination. Preferred crosslinkers are 1 ,4-butanediol di(meth)acry!ate, 1 ,6- hexanediol di(meth)acrylate, added to the elastomeric formulation in concentration of at least 0.1 weight %.

Another combination of iodinated and non-iodinated (meth)acrylate monomers forming a preferred composition is 4-iodophenylmethacrylate (1 to 20 mole%), 2- phenylethylmethacrylate (5 to 25 mole%), butylacrylate (50 to 80 mole%), and hexafluoropropylmethacrylate (2 to 5 mole%), together with 1 ,6-hexanediol- diacrylate as a crosslinker (1.0-3.5 weight% of the combined monomer weight), or another of the crosslinkers referred to above.

Yet another preferred combination comprises 2-iodobenzylmethacrylate (1 to 10 mole%), benzylacrylate (89 to 98 mole%) and tetrafluoropropylmethacrylate (1 to 5 mole%), together with 1 ,6-hexanediol-diacrylate as a crosslinker (1.0-3.5 weight% of the combined monomer weight), or another of the crosslinkers referred to above.

In cataract surgery, it is recognised that trauma minimised as the incision size is reduced. In a foldable intraocular lens the ultimate incision size for a lens, of a given power and design, is controlled by the refractive index of the lens material; the higher the refractive index the smaller the incision..

Preferably the refractive index of the lens, manufactured from a preferred hydrophobic composition will be greater than 1.5, and in the range 1.55 to 1.63. Preferably, a IOL manufactured from the preferred material containing the composition is capable of being inserted through an incision in the eye of a size of about 3.0mm or less; particularly the more preferred less than 3.0mm, and more particularly the most preferred in the range 2.5-2.0mm.

It will be evident to one skilled in the art that the lens may be formed from a blank by standard milling and lathe cutting equipment or by moulding as intraocular lenses are formed, generally.

A number of examples of iodine bearing (meth)acrylate monomers have been produced in accordance with the present invention, examples of which are outlined in Table 2 below

EXAMPLE 1

An experiment was conducted to produce a monomer in accordance with the present invention. The monomer produced was 4-iodophenyl methacrylate (denoted as IBM 1)

A solution of methacryloyl chloride (8.55 g, 81.8 mmol) in 75 ml of dry dichloromethane was added dropwise over 60 min to a magnetically stirred and cooled (-5°C) solution of 4-iodophenol ( 5.05 g, 68.4 mmol) and dry triethylamine (13.80 g, 136.4 mmol) in dry dichloromethane (200 ml). During the addition the reaction mixture changed from dark to light brown. Upon completion of the addition, the cooling bath was removed and stirring was continued for one hour. The reaction mixture was cooled to -5°C, distilled water (250 ml) added and the organic layer was separated and washed with saturated NaHCθ₃ (200 ml) and brine (200 ml).

The organic phase was then dried over MgS0₄, filtered and concentrated to 75- 100 ml. The residue was chromatographed in a 150 ml volume silica gel gravity column, using petroleum ether 40-65 and 2-butanone (95:5 volume, 150 ml) as eluent. From the fractions collected colourless IBM1 crystallised on standing (T_m

"29°C"). Yield was 14.6 g (71.3 %), purity 96.4% (by GC). IBM1 IR spectrum

showed absorption at 1720 cm^"1 (carbonyl stretching in the methacrylate group: R-0-CO-C(CH3)=C); 1640 cm^"1 (alkenyl C=C stretching); 1480 and 1580 cm^"1 (C=C aromatic) and 2900-3000 cm^"1 (C-H, methyl group). The compound showed a strong absorption peak at 237 nm and also absorbs strongly in the range 270-320 nm.

EXAMPLE 2

An experiment was conducted to produce another monomer in accordance with the present invention, the monomer produced was 5,7-diiodo-8- quinoylmethacrylate (denoted as 1BM2).

5,7-Diiodo-8-hydroxyquinoline (27.15 g, 68.4 mmol) and methacryloyl chloride (14.29 g, 136.8 mmol) were dissolved in dichloromethane (700 ml) and cooled to 0°C. Triethylamine (20.57 g, mmol) dissolved in dichloromethane (50 ml) was added dropwise over 1 h to the stirred solution. The reacting solution, which was an olive green with a dark green precipitate was stirred at RT for 18 h, then R.O. water (800 ml) was added to the suspension. The organic phase was collected and washed in sequence with aq. HCI (0.5 M, 750 ml) to pH< 7, saturated NaHC0₃ solution (750 ml), and saturated brine (750 ml).

The organic phase was dried over MgS0₄ filtered, 50 ppm of methylhydroquinine (MEHQ inhibitor) were added and the solution's volume reduced to 50 ml in the rotary evaporator. The concentrated solution was chromatographed in a silica gel gravity column using petroleum-ether (40-65)/ butanone mixtures to develop the chromatogram. Eluated fractions were combined and further purified by dissolving in dichloromethane and washing with aq. NaOH (0.34M, 300 ml).

Green IBM2 crystallised (T_m 100-104 °C). IBM2 IR spectrum showed absorption at 1720 cm^"1 (carbonyl stretching in the methacrylate group: R-0-CO-C(CH3)=C); 1640 cm^"1 (alkenyl C=C stretching) and 1580 cm^"1 (C=C aromatic)). The yield was 14.0 g (44.02%) purity 88.43 % ( by GC).

EXAMPLE 3

An experiment was conducted to produce a monomer in accordance with the present invention, the monomer produced was 4-lodophenylacrylate (denoted as IBM3).

IBM3 was prepared by the method described for the preparation of IBM1 substiuting acryloyl chloride (7.40 g, 81.8 mmol) for methacryloyl chloride. IBM3 was found to be an oil at RT, and showed absorption at 1720 cm^"1 (carbonyl stretching in the methacrylate group: R-0-CO-C(CH3)=C); 1640 cm^"1 (alkenyl C=C stretching); 1480 (strong) and 1580 (weak) cm^"1 (C=C aromatic) The yield was 11.93 g (63.68 %), purity 99.1% (by GC).

EXAMPLE 4

An experiment was conducted in an analogous manner to EXAMPLES 1 to 3, combining 4-iodobenzylalcohol and methacryloyl chloride, to produce a monomer in accordance with the present invention, the monomer produced was 2- iodobenzylmethacr late (IBM8).

IBM8 was found to be a mobile yellow oil, which showed absorption at 1750 cm^"1 (carbonyl stretching in the methacrylate group: R-0-CO-C(CH3)=C); 1650 cm^"1 (alkenyl C=C stretching); 1480 (strong) and 1580 (weak) cm^"1 (C=C aromatic); its purity was >98%(GC).

EXAMPLE 5

An experiment was conducted in an analogous manner to EXAMPLES 1 to 4, combining 2-iodobenzylalcohol and acryloyl chloride, to produce a monomer in accordance with the present invention, the monomer produced was 4- iodobenzylacrylate (IBM9). IBM9 was found to be a mobile yellow oil, which was purified, by recrystallisation from petroleum ether, as fine pale yellow needles, m.p.> -5°C and showed absorption at 1750 cm^"1 (carbonyl stretching in the acrylate group: R-O-CO- CH=C); 1650 cm^"1 (alkenyl C=C stretching); 1480 (strong) and 1580 (weak) cm^"1 (C=C aromatic); its purity was >96.5%(GC).

EXAMPLE 6

This example describes the preparation of copolymers of the monomers produced in Examples 1 to 5.

Monomer mixtures as detailed in Table 2, and which had been previously blown through with N₂, were prepared, poured into tubes, capped under N₂ (13 cm x 14 mm i.d.), or cast between glass plates (10x10cm) separated by a flexible polymer gasket (2.0mm thick), and. heated at 65°C (24 h), 80°C (24 h), and then dismoulded and postcured at 120°C (48 h). Properties of interest of the resulting copolymers are also collected in Table 2.

Table 2. IBM Compolvmer compositions & properties

^a 3 g of HDDA (cross-linker) and 0.8 g of TBPEH (initiator) were added to 100 g of combined monomers. ^bDigit in brackets refers to a monomer from examples 1 to 5. ^c PEA = 2-phenylethylacrylate; PEMA= 2-phenylethylmethacryIate; BA= benzylacrylate; MMA= methylmethacrylate; BuA= butylacrylate; HFIPMA= hexafluoroisopropylmethacrylate; TFPMA= tetrafluoropropylmethacrylate ^dThe values of T_g indicate that thelBM coplymers are elastomers at body temperature. ^e The tack of the IBM copolymers is numbered in increasing tackiness, from

0=no tack to polyethylene film to 2=slight tack to polyethylene film.

Claims

1. A polymeric ophthalmic lens composition suitable for foldable intraocular lens manufacture having a Tg <37°C derived from one or more monomers of the formula:

CH₂=C(R)-C(0)-0-(Y)_p-(Z)_q-Ar

wherein:

R is selected from H, CH₃ or phenyl;

Z is an ester or ether linkage; q is 0 or 1 ;

with the proviso that when q is 1 , p is also 1 and that when p is 0, q is also 0;

and Ar is benzyl, phenyl, or other mono- or polycyclic-aromatic or heteroaromatic group substituted with one or two iodine groups.

2. A polymeric composition as claimed in claim 1 wherein the monomer is selected from one or more of the following:

2- or 4-iodophenyl (meth)acrylate;

2,5- or 5,7-diiodoquinolinyl(meth)acrylate;

2,5- or 5,7-diiodo(iso)quinolinyl(meth)acrylate;

2'- or 4'-iodobenzoyl-3-oxypropyl(meth)acrylate;

2'- or 4'-iodobenzoyl-2-hydroxy-3-oxypropyl(meth)acrylate;

2'- or 4'-iodobenzoyl-4-oxybutyl(meth)acrylate;

2'- or 4'-iodobenzoyl-5-oxypentyl(meth)acrylate;

2'- or 4'-iodobenzoyl-6-oxyhexyl(meth)acrylate;

2'- or 4'-iodonaphthoyl-3-oxypropyl(meth)acrylate; 2'- or 4'-iodophenylacetoyl-3-oxypropyl(meth)acrylate;

3. A polymeric ophthalmic lens composition according to claim 1 or claim 2 derived from a copolymerisable crosslinking co-monomer having more than one ethylenically unsaturated group.

4. A polymeric ophthalmic lens composition according to claim 2, wherein the co-monomer is non-iodinated.

5. A polymeric ophthalmic lens composition according to claim 2, wherein the co-monomer is iodinated.

6. A polymeric ophthalmic lens composition as claimed in any one of claims 3 to 5 wherein the co-monomer is selected from one or more of the following:

2-phenylethyl(meth)acrylate; 3-phenylpropyl(meth)acrylate;

4-phenyIbutyl(meth)acrylate;

methyl- or ethyl- or propyl- or butyl- or dodecyl- or pentyl- or hexyl- or heptyl- or octyl- or nonyl- or decyl- or undecyl or tridecyl-(meth)acrylate;

7. A polymeric ophthalmic lens composition as claimed in any one of claims 3 to 6 wherein the ratio of monomer to comonomer is selected to yield a material of refractive index suitable for use in a lens.

8. A polymeric ophthalmic lens composition as claimed in any one of the preceding claims wherein the ratio of monomer to comonomer is selected to control the flexibility and/or tackiness of the composition.

9. A polymeric ophthalmic lens composition according to any one of the preceding claims comprising a copolymer of: 4-iodophenylmethacrylate in an amount of 0.1-30.0 mol% of the composition; 2-phenylethylmethacrylate and/or methylmethacrylate in an amount of 0.0-20.0 mol% of the composition and 2- phenylethylacrylate in an amount of 99.9-50.0 mol% of the composition together with 1 ,6-hexanedioldiacrylate as a crosslinker in an amount of 0.5-5.0 wt% of the combined weight of monomers.

10. A polymeric ophthalmic lens composition according to claim 9 comprising a copolymer of 4-iodophenylmethacrylate in an amount of 1.0-12.0 mol% of the composition; 2-phenylethylmethacrylate and/or methylmethacrylate in an amount of 0.0-9.0 mol% of the composition and 2-phenylethylacrylate in an amount of 99.0-79.0 mol% of the composition together with 1 ,6-hexanedioldiacrylate as a crosslinker in an amount of 1.0-4.0 wt% of the combined weight of monomers.

11. A polymeric ophthalmic lens composition according to claim 10 comprising a copolymer of 4-iodophenylmethacrylate in an amount of 1.0-10.0 mol% of the composition; 2-phenylethylmethacrylate in an amount of 0.0-8.0 mol% of the composition and 2-phenylethylacrylate in an amount of 99.0-82.0 mol% of the composition together with 1 ,6-hexanedioldiacrylate as a crosslinker in an amount of 1.0-4.0 wt% of the combined weight of monomers.

12. A polymeric ophthalmic lens composition according to claim 11 comprising a copolymer of 4-iodophenylmethacrylate in an amount of 2.5-10.0 mol% of the composition; 2-phenylethylacrylate in an amount of 97.5.0-90.0 mol% of the composition together with 1 ,6-hexanedioldiacrylate as a crosslinker in an amount of 1.0-4.0 wt% of the combined weight of monomers.

13. A polymeric ophthalmic lens composition according to claim 11 comprising a copolymer of 4-iodophenylmethacrylate in an amount of 1 to 20 mole% of the composition, 2-phenylethylmethacrylate in an amount of 5 to 25 mole% of the composition, butylacrylate in an amount of 50 to 80 mole% of the composition, and hexafluoropropylmethacrylate in an amount of 2 to 5 mole% of the composition, together with 1 ,6-hexanediol-diacrylate as a crosslinker in an amount of 1.0-3.5 weight% of the combined monomer weight.

14. A polymeric ophthalmic lens composition according to claim 11 comprising a copolymer of 2-iodobenzylmethacrylate in a quantity of 1 to 10 mole%, benzylacrylate in an amount of 90 to 97 mole% of the composition and hexafluoropropylmethacrylate in an amount of 2 to 5 mole% of the composition, together with 1 ,6-hexanediol-diacrylate as a crosslinker in an amount of 1.0-3.5 weight% of the combined monomer weight.

15. A polymeric ophthalmic lens composition as claimed in any of the preceding claims wherein the composition additionally comprises light absorbers for selected frequencies.

16. A polymeric ophthalmic lens composition as claimed in any preceding claim, wherein Ar has one or more substituent groups selected from: alkyl, aryl, alkenyl, aralkyl, alkaryl, alkenaryl, aralkenyl, cycloalkyl, heteraryl or aralkenyl.

17. A polymeric ophthalmic lens composition as claimed in any preceding claim wherein Ar is selected from phenyl, benzyl, quinolinyl, isoquinolinyl and naphthyl.

18. A lens manufactured from a composition as claimed in any of the preceding claims, being an intraocular lens, an intraocular contact lens, an extraocular contact lens or a spectacle lens.

19. An intraocular lens according to claim 18 having a refractive index in the range 1.49 and 1.70 and being implantable through a surgical incision in the eye of less than 3 mm.

20. An intraocular lens according to claim 19 having a refractive index greater than 1.55 and being implantable through an incision of less than 2.5mm.