GB2561816A

GB2561816A - A silicone hydrogel contact lens

Info

Publication number: GB2561816A
Application number: GB1704187.2A
Authority: GB
Inventors: Tanda Raj
Original assignee: Individual
Current assignee: Individual
Priority date: 2017-03-16
Filing date: 2017-03-16
Publication date: 2018-10-31
Also published as: GB201704187D0

Abstract

A coloured contact lens comprises (a) a lens substrate comprising a silicone hydrogel, (b) a colour coating comprising a metal oxide colorant, and (c) a binding polymer, wherein the colour coating is bonded to the lens substrate by crosslinking carboxyl, hydroxyl and/or amino functionalities present in the lens substrate and the binding polymer with a diisocyanate in the presence of an oxime. Typically, the diisocyanate is toluene diisocyanate (TDI) or hexamethylene diisocyanate (HMDI) and the oxide is butanone oxime. The colorant may be iron oxide or titanium oxide and the binding polymer may be derived from a hydroxyalkylalkacrylate. The concentration of disisocyanate relative to the binding polymer may be 1-50 wt.%. The molar ratio of diisocyanate to oxime is preferably 1:1 to 1:20, especially 1:2. A method of staining a silicone hydrogel contact lens using a diisocyanate crosslinker in the presence of an oxime is also disclosed.

Description

(54) Title of the Invention: A silicone hydrogel contact lens Abstract Title: Coloured contact lens (57) A coloured contact lens comprises (a) a lens substrate comprising a silicone hydrogel, (b) a colour coating comprising a metal oxide colorant, and (c) a binding polymer, wherein the colour coating is bonded to the lens substrate by crosslinking carboxyl, hydroxyl and/or amino functionalities present in the lens substrate and the binding polymer with a diisocyanate in the presence of an oxime. Typically, the diisocyanate is toluene diisocyanate (TDI) or hexamethylene diisocyanate (HMDI) and the oxide is butanone oxime. The colorant may be iron oxide or titanium oxide and the binding polymer may be derived from a hydroxyalkylalkacrylate. The concentration of disisocyanate relative to the binding polymer may be 1-50 wt.%. The molar ratio of diisocyanate to oxime is preferably 1:1 to 1:20, especially 1:2. A method of staining a silicone hydrogel contact lens using a diisocyanate crosslinker in the presence of an oxime is also disclosed.

A Silicone Hydrogel Contact Lens

The present invention relates to a silicone hydrogel contact lens having a colour coating thereon, and to a method of affixing said colour coating thereto.

Contact lenses comprise a colourless lens base manufactured out of a plastics material, and tend to be worn with the sole purpose of correcting the defective eyesight of the wearer. However, contact lenses are also available which have been stained with low concentrations of a specific coloured coating which is added to aid the fitting and removal of the lenses from the eyes. Furthermore, contact lenses are available in which the coloured coating has been added to the lens in higher concentrations and as well as, or instead of, correcting defective eyesight, alter the appearance of the wearer's eye colour, for example, changing the appearance of the colour of the iris from blue to brown.

More recently, contact lenses are now being manufactured in which the colourless lens base is stained with a coloured coating in such a way so as to produce a specific design effect across the surface of the lens.

Staining contact lenses is well known in the art and involves affixing a colour coating, comprising a coloured mix and an associated binding polymer, onto the surface of the contact lens base polymer. The affixing process is brought about by a cross-linking agent which causes the formation of cross-link bonds between hydroxyl, carboxyl and/or amino functional groups which are present on the colour coating binding polymer and on the lens polymer.

In known staining procedures, the colour coating has been shown to have a relatively limited life-span and is worn off the surface of the lens base through repeated use.

It is known to use isocyanate cross-linking agents in staining procedures. However, isocyanates are toxic and so present a health risk. In addition, in these procedures, the colour coating has been shown to have a relatively limited life-span and is worn off the surface of the lens base through repeated use.

It is one of the aims of embodiments of the present invention to address the above problems and to provide a silicone hydrogel contact lens stained with a colour coating, in which the stain of the lens is non-toxic and in which the stain has an improved life-span on the surface of the lens.

According to a first aspect of the present invention, there is provided a coloured contact lens comprising:a) a lens substrate comprising a silicone hydrogel material;

b) a colour coating comprising a colouring substance; and

c) a binding polymer;

wherein the colouring substance comprises a metal oxide; and wherein colour coating is bonded to at least part of the surface of the lens substrate by cross-linking functional groups independently selected from carboxyl, hydroxyl and/or amino groups present in the lens substrateand in the binding polymer, the cross-linking being effected by a diisocyanate in the presence of an oxime .

Advantageously, the use of an oxime with the diisocyante results in a system that is less toxic than those of the prior art.

Preferably, the lens substrate may be a soft contact lens.

By the term silicone hydrogel material, and like terms as used herein unless specified otherwise, is meant a network of silicone-containing polymer chains which are dispersed in an aqueous medium. Preferably, the siliconepolymer chains may be cured, such as, for example, thermally, actinically and/or chemically to obtain a crosslinked silicone-containing polymer.

Preferably, therefore, the silicone hydrogel material comprises silicone-containing polymers. The siliconecontaining polymers may be formed from at least one dimer and/or or oligomer, silicone-containing monomer The silicone-containing monomer, dimer silicon-containing monomer, preferably, at least one and/or dimer.

and/or oligomer may contain one or more silicon atoms.

The silicone-containing polymer may comprise a homopolymer or a (co)polymer. The silicone hydrogel material may comprise a silicone-containing polymer or a combination of different silicone-containing polymers.

Exemplary silicone-containing monomers include, without limitation, methacryloxyalkylsiloxane, 3-methacryloxy propylpentamethyldisiloxane, monomethacrylate dimethylsiloxane, bis(methacryloxypropyl) tetramethyldisiloxane, N[tris(trimethylsiloxy)silylpropyl]acrylamide, N[tris(trimethylsiloxy)silylpropyl]methacrylamide, tris(pentamethyldisiloxyanyl)-3-methacrylatopropylsilane, tris(pentamethyldisiloxyanyl)-3-methacrylatopropylsilane, tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS) and dimers of tris (trimethylsilyloxy)silylpropyl methacrylate (TRIS) .

Preferably, the silicone-containing monomer comprises tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS) and/or dimers of tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS).

In some embodiments, the silicone-containing polymers may be mercapto-terminated, such as, for example, mercaptoterminated polydimethylsiloxane.

The silicone hydrogel material may be formed from and/or comprise further components. Exemplary further components include without limitation an initiator, such as, for example, a photoinitiator or a thermal initiator, a visibility tinting agent, UV-blocking agent, photosensitizers and the like.

The lens substrate comprising a silicone hydrogel material may be commercially available. Exemplary lens substrates comprising a silicone hydrogel material include without limitation lotrafilcon A, lotrafilcon B, etafilcon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon, senofilcon A, and the like.

Preferably, the diisocyanate is used directly as a cross linking agent. Preferably, the diisocyanate has a structure O=C=N-X-N-C=O;

wherein X is a divalent organic bridging group.

Preferably, X is a linear or branched C1-C20 alkyl, C2-C18 alkenyl or C2-C18 alkynyl, C3-C10 cycloalkyl or cycloalkenyl, heterocycloalkyl or heterocycloalkenyl which has 3 to 10 ring atoms and is bonded via a carbon atom, a polycyclic hydrocarbon radical with 6 to 10 carbon atoms, C6-C14 aryl, C7-C20 aralkyl, heteroaryl with 5 or 6 ring atoms or heteroaralkyl with 5 or 6 ring atoms and 1 to 6 carbon atoms in the alkyl group, which are unsubstituted or substituted by C1-C12 alkyl, -alkoxy or -alkylthio, C₃Cg cycloalkyl, -cycloalkoxy or -cycloalkylthio, Οβ-Οιο aryl, -aryloxy or -arylthio, C7-C16 aralkyl, -aralkoxy or aralkylthio, heteroaryl or heteroaryloxy with 5 or 6 ring atoms, cyano, halogen, C2-C24 secondary amino, --C(O)OR², -0(0) CR⁴, —NR² (O)CR⁴, —C(O)NR² R³, in which R² is C1-C12 alkyl phenyl or benzyl, R³ is H or is as defined for R² and R⁴ is as defined for R², it being possible for the substituents alkyl, alkoxy and alkylthio in turn to be substituted by C1-C12 alkoxy, halogen, cyano, C2-C24 secondary amino, --C(O)OR², --O(O)CR⁴, --NR² (O)CR⁴, -C(O)NR² R³, cycloalkyl or heterocycloalkyl with 4-8 ring carbon atoms or 5 or 6 ring atoms, and for the substituents cycloalkyl, cycloalkoxy, cycloalkylthio, aryl, aryloxy, arylthio, aralkyl, aralkoxy, aralkylthio, heteroaryl or heteroaryloxy to be substituted by C1-C12 alkyl, -alkoxy or -alkylthio, halogen, cyano, C2-C24 secondary amino, --C(O)OR², --O(O)CR⁴, --NR² (O)CR⁴ or -C(O)NR² R³.

X may be a linear or branched alkyl with, preferably, 1 to 12 carbon atoms, more preferably, 4 to 8 carbon atoms, and, most preferably, 6 carbon atoms. Examples are methyl, ethyl, n- or i-propyl, η-, i- or t-butyl, 1-, 2- or 3pentyl, 1-, 2- or 3-hexyl, 1-, 2-, 3- or 4-heptyl, 1-, 2-, 3- or 4-octyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, hexadecyl, octadecyl and eicosyl. Preferably, X may be a linear hexyl group.

X may be a linear or branched alkenyl with, preferably, 2 to 14 carbon atoms, in particular 2 to 8, carbon atoms. Examples are: allyl, but-l-en-3-yl, but-l-en-4-yl, but-2en-4-yl, pent-l-en-5-yl, pent-l-en-4-yl, pent-l-en-3-yl, pent-2-en-4-yl, pent-3-en-5-yl, hex-l-en-6-yl, hex-2-en-6yl, hex-3-en-6-yl, hex-3-en-2-yl, hex-3-en-5-yl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tetradecenyl, hexadecenyl and octadecenyl.

X may be a linear or branched alkynylalkyl with, preferably, 1 to 12 carbon atoms, more preferably, 4 to 8 carbon atoms, and, most preferably 6 carbon atoms. Examples are propargyl, but-l-in-3-yl, but-2-in-4-yl, pent-3-inl-yl, pent-l-in-3-yl, pent-l-in-4-yl, pent-l-in5-yl, pent-2-in-4-yl, pent-2-in-5-yl, hex-l-in-3-yl or -4yl or -5-yl or -6-yl, hex-2-in-4-yl or -5-yl, or -6-yl, hex-3-in-5-yl or -6-yl, heptinyl, octinyl, noninyl, decinyl, undecinyl, dodecinyl, tetradecinyl, hexadecinyl and octadecinyl.

X may be a cycloalkyl or cycloalkenyl which preferably has 4 to 8 ring carbon atoms and, more preferably, 5 or 6, ring carbon atoms and is unfused or fused with C6-C14 aryl, preferably, benzene, or with heteroaryl with 5 or 6 ring atoms. Examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cycloprop-l-en-3-yl, cyclobut-l-en-3-yl, cyclopent-l-en-3yl, cyclopent-l-en-4-yl, cyclohex-l-en-3-yl, cyclohex-1en-4yl, cyclopentenyl, cyclooctenyl and cyclodecenyl.

X may be a heterocycloalkyl or heterocycloalkenyl which is unfused or fused with C6-C14 aryl, more preferably, benzene, or with heteroaryl with 5 or 6 ring atoms, or heteroaryl, it being possible for these radicals to contain, for example, heteroatoms from the group comprising oxygen, sulphur, and nitrogen. The nitrogen atom is a tertiary nitrogen atom. If the nitrogen atom is present in the ring as a secondary amine group, this nitrogen atom is, for example, C1-C12, and, preferably, CiC4 alkylated, phenylated or benzylated. It may also contain protective groups, for example, C1-C4 alkoxymethyl or R₃ ⁵ Si groups, in which R⁵ is C1-C12 alkyl. These heterocyclic radicals, preferably, contain 1 to 3, in particular 1 or 2, identical or different heteroatoms. The heterocycloalkyl or -alkenyl preferably contains 5 or 6 ring members. Examples of heterocyclic radicals from which R and R¹ may be derived are (protective groups for secondary nitrogen groups are not mentioned): pyrrolidine, tetrahydrofuran, tetrahydrothiophene, pyrroline, dihydrofuran, dihydrothiophene, indane, dihydrocoumaron, dihydrobenzothiophene, carbazole, dibenzofuran, dibenzothiophene, pyrazolidine, imidazolidine, pyrazoline, imidazoline, benzimidazolidine, oxazolidine, oxazoline, thiazolidine, isooxazolidine, isooxazoline, isothiazolidine, isothiazoline, benzoxazolidine, benzisooxazolidine, benzthiazolidine, 1,2,3- or 1,2,4triazolidine, 1,2,3- or 1,2,4-triazoline, 1,2,3,- or 1,2,4-oxazolidine or -oxazoline, piperidine, di- and tetrahydropyridine, dihydro- and tetrahydropyran, di- and tetrahydrothiopyran, piperazine, dehydropiperazine, morpholine, thiomorpholine, 1,3- and 1,4-dioxane, 1,4dithiane, azepan, 1,3-dioxolane, 1,3-dithiolane, pyrrole, indole, imidazole, benzimidazole, furan, thiophene, benzofuran, benzothiophene, carbazole, dibenzofuran, dibenzothiophene, oxazole, isooxazole, thiazole, isothiazole, benzoxazole, benzothiazole, pyridine, pyrimidine, pyrazine, pyridazine, quinoline, isoquinoline, acridine, chromene, chromane, pyran, thiapyran, phenazine, phenoxazine, phenolthiazine and purine. Heterocyclic radicals R and R¹ are bonded to the N atoms in formula I via a carbon atom.

X may be a polycyclic hydrocarbon radical with 6 to 10 carbon atoms. Examples of such hydrocarbons from which R and R¹ may be derived are: bicyclo-[0,0,3]-hexane, bicyclo-[1,0,3]-hexane, bicyclo-[2,2,1]-heptane, bicyclo[2.2.1] -heptene, bicyclo-[2,2,2]-octane and bicyclo[2.2.2] -octene.

X may be a C6-C14 aryl. Examples are phenyl, naphthyl, anthracyl, indenyl, indanyl, fluorenyl and phenanthryl. Phenyl, naphthyl and anthracyl are preferred. Phenyl is most preferred.

X may be an aralkyl with, preferably, 7 to 14 carbon atoms. The aryl is, preferably, naphthalene and, more preferably, benzene. The alkyl group, preferably, contains 1 to 3 carbon atoms. Examples of aralkyl are benzyl, 1phenyleth-l-yl, l-phenyleth-2-yl, 1-phenylprop-l-yl, -2-yl or -3-yl and 2-phenylprop-2-yl or -1-yl.

X may be a heteroaralkyl. Heteroaryl radicals and preferred radicals have been mentioned above. The alkyl group of the heteroaralkyl preferably contains 1-3 carbon atoms and is, for example, methyl, 1,1- or 1,2-ethyl or 1,1-, 2,2-, 1,2- or 1,3-propyl.

X may be substituted in any desired positions by identical or different radicals, for example, by 1 to 5, preferably, 1 to 3, substituents.

Suitable substituents for X are: C1-C12, preferably, C1-C6 and, more preferably, C1-C4 alkyl, -alkoxy or -alkylthio, for example, methyl, ethyl, propyl, η-, i- and t-butyl and the isomers of pentyl, hexyl, octyl, nonyl, decyl, undecyl and dodecyl, and corresponding alkoxy and alkylthio radicals; C3-C6, in particular, C5- or C6 cycloalkyl, cycloalkoxy or -cycloalkylthio, for example cyclopentyl, cyclohexyl, cyclohexyloxy and cyclohexylthio; halogen, preferably fluorine and Chlorine; CN; C6-C12 aryl, -aryloxy or -arylthio, in which aryl is, preferably, naphthyl and, more preferably, phenyl, C7-C16 aralkyl, -aralkoxy and aralkylthio, in which the aryl radical is, preferably, naphthyl and, more preferably, phenyl and the alkylene radical is linear or branched and contains 1 to 10 carbon atoms, preferably, 1 to 6 carbon atoms, and, more preferably, 1-3 carbon atoms, for example benzyl, naphthylmethyl, 1- or 2-phenyleth-l-yl or -eth-2-yl or 1-,

2- or 3-phenyl-prop-l-yl, -prop-2-yl or -prop-3-yl, benzyl being particularly preferred;

heteroaryl or heteroaryloxy with 5 or 6 ring atoms and preferably heteroatoms from the group comprising oxygen, sulphur and nitrogen, the nitrogen atom being tertiary as defined above. Examples are: pyridyl, pyrimidyl, pyrryl, furyl, thienyl and pyridyloxy;

secondary amino with 2 to 24 carbon atoms, preferably, 2 to 12 carbon atoms, and, more preferably, 2 to 6 carbon atoms, the secondary amino, preferably, containing 2 alkyl groups, for example, dimethyl-, methylethyl-, diethyl-, methyl-n-propyl-, methyl-n-butyl-, di-n-propyl-, di-n11 butyl- and di-n-hexylamino; --CONR² R³ or --NR² (O)CR⁴, in which R³ is H, R², R³ and R⁴ independently of one another are C1-C12, preferably, C1-C6 and, more preferably, C1-C4 alkyl, phenyl or benzyl, it being possible for the alkyl to be linear or branched, for example, dimethyl-, methylethyl-, diethyl-, methyl-n-propyl-, ethyl-n-propyl-, di-n-propyl-, methyl-n-butyl-, ethyl-n-butyl-, n-propyl-nbutyl- and di-n-butylcarbamoyl, and in which R⁴ is, preferably, C1-C4 -alkyl, phenyl or benzyl;

--COOR² or --O(O)CR⁴, in which R² and R⁴ independently of one another are C1-C12, preferably, C1-C6 alkyl, phenyl or benzyl, wherein the alkyl can be linear or branched, for example, methyl, ethyl, n- and i-propyl, η-, i- and tbutyl, and the isomers of pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl, and in which R⁴ is, preferably, C1-C4 alkyl, phenyl or benzyl.

The substituents alkyl, alkoxy and alkylthio may in turn be mono- or poly-substituted, in particular, mono-, di- or trisubstituted, by halogen, cyano, C2-C24 secondary amino, --C(O)OR², --O(O)CR⁴, --NR² (O)CR⁴, --C(O)NR² R³, cycloalkyl or heterocycloalkyl with 4-8 ring carbon atoms or 5 or 6 ring atoms. The preferred meanings described above apply to R², R³ and R⁴. If the alkyl, alkoxy or alkylthio is substituted by a halogen, preferably, chlorine, the radical may be, for preferably, C1-C4 haloalkyl, for example, trifluoro- or trichloromethyl, difluorochloromethyl, fluorodichloromethyl, 1,1-difluoroeth-l-yl, 1,1fluoride and/or example, C1-C6, dichloroeth-l-yl, 1,1,1-trichloro- or -trifluoroeth-2-yl, pentachloroethyl, pentafluoroethyl, 1,1,1-trifluoro-2,2dichloroethyl, n-perfluoropropyl, i-perfluoropropyl, nperfluorobutyl, fluoro- or chloromethyl, difluoro- or dichloromethyl, 1-fluoro- or -chloroeth-2-yl or -eth-l-yl,

1- , 2- or 3-fluoro- or -chloro-prop-l-yl or -prop-2-yl or

-prop-3-yl, 1-fluoro- or -chloro-but-1 -yl, -but-2-yl, but-3-yl, or -but-4-yl, 2,3-dichloro-prop-l-yl, 1-chloro2- fluoro-prop-3-yl or 2,3-dichlorobut-l-yl.

Examples of alkyl, alkoxy or alkylthio substituted by cyano are cyanomethyl, 1- or 2-cyanoethyl, 1- or 2cyanopropyl and 2-cyanoethyloxy. If the alkyl, alkoxy or alkylthio is substituted by --C(O)OR², --O(O)CR⁴, --NR² (O)CR⁴ or --C(O)NR² R³, it, preferably, contains 1 to 3 carbon atoms. Examples are methoxy- or ethoxycarbonylmethyl, ethoxycarbonylethyl, ethoxycarbonylpropyl, acetyloxymethyl, 1- or 2Examples are

1- or 2-methoxy1-, 2- or 3-methoxy acetyloxymethyl, 1methoxyor or or acetyloxyethyl, dimethylaminocarbonylmethyl or -ethyl, Nmethylacetylamino, methoxycarbonylmethoxy or 1(methoxycarbonyl)eth-2-oxy.

If the alkyl, alkoxy and alkylthio are substituted by cycloalkyl or heterocycloalkyl, the cycloalkyl preferably contains 5 or 6 ring carbon atoms and the heterocycloalkyl 5 or 6 ring atoms and, preferably, heteroatoms from the group comprising oxygen, nitrogen and sulphur, in particular oxygen, the nitrogen atom being tertiary. Examples are cyclohexylmethyl or -methoxy or -methylthio, cyclopentylethyl, tetrahydrofurylmethyl and pyridylmethyl.

The substituents cycloalkyl, cycloalkoxy, cycloalkylthio, aryl, aryloxy, arylthio, aralkyl, aralkoxy, aralkylthio, heteroaryl and heteroaryloxy may in turn be substituted as defined for alkyl, alkoxy and alkylthio and may additionally be mono- or polysubstituted, preferably, mono-, di- or trisubstituted, by C1-C12, in particular CiCg alkyl or -alkylthio. Examples are methylcyclohexyl, hexoxy and -hexylthio, methylphenyl, dimethylphenyl, methylchlorophenyl, cyanophenyl, dichlorophenoxy, trifluoromethylphenyl methoxyphenyl or -phenoxy, fluoro- or difluorophenyl or phenoxy, chlorobenzyl or -benzyloxy, methyl- or dimethylbenzyl, carbomethoxyphenyl, methoxybenzyl, chloroor dichloropyrridyl, methylpyrridyl, methylpyrridyloxy, and chloro- or dichloropyrridyloxy.

chlorophenoxy, or -phenoxy,

A preferred group of substituents for X is C1-C6 alkyl, halogenalkyl and -alkoxy, C1-C6 alkoxy-Ci-C3 alkyl and alkoxy, C1-C6 cyanoalkyl, C1-C4 alkyl O(O)Ci-C6 alkyl, C6-C12 -aryl- and -aryloxy, C7-C16 alkaryl and -alkaryloxy, fluoro- and/or chloroaryl and -aryloxy, trifluoromethylaryl and -aryloxy, C1-C6 alkoxyaryl and aryloxy, Cg-Ci6 alkaralkyl and -alkaralkyloxy, fluoroand/or chloro- and/or trifluoromethyl, C7-C12 -aralkyl and -aralkoxy, C7-C12 aralkyl, pyrridyl, pyrridyloxy and fluoroand/or chloropyrridyl and -pyrridyloxy.

Preferably, X is substituted or unsubstituted C1-C12 alkyl or C6-C14 aryl, more preferably, substituted or unsubstituted C4-C8 alkyl or C6-C14 aryl, most preferably, substituted or unsubstituted C6 alkyl or phenyl. In a preferred embodiment, X is unsubstituted C6 alkyl. In another preferred embodiment, X is unsubstituted phenyl.

Preferably, the cross-linking agent is toluene diisocyanate (TDI) and/or hexamethylene diisocyanate (HMDI).

Preferably, the concentration of diisocyanate used in the preparation of the lens as the cross-linking agent is in the range of 1% to 50% (w/w) of the total weight of the binding polymer, more preferably, in the range of 2% to 30% (w/w), even more preferably, in the range of 3% to 15% (w/w), and most preferably, in the range of 4% to 8% (w/w) of the total weight of the binding polymer.

Preferably, the oxime has a structure R⁵ (R⁶)C=N-0-R⁷;

wherein R⁵ is an organic group; and

R⁶ and R⁷ are each independently hydrogen or an organic group .

Preferably, R⁵ is a linear or branched C1-C20 alkyl, C2-C18 alkenyl or C2-C18 alkynyl, C3-C10 cycloalkyl or cycloalkenyl, heterocycloalkyl or heterocycloalkenyl which has 3 to 10 ring atoms and is bonded via a carbon atom, a polycyclic hydrocarbon radical with 6 to 10 carbon atoms, C6-C14 aryl, C7-C20 aralkyl, heteroaryl with 5 or 6 ring atoms or heteroaralkyl with 5 or 6 ring atoms and 1 to 6 carbon atoms in the alkyl group, which are unsubstituted or substituted by C1-C12 alkyl, -alkoxy or -alkylthio, C₃Cg cycloalkyl, -cycloalkoxy or -cycloalkylthio, Cg-Cio aryl, -aryloxy or -arylthio, C7-C16 aralkyl, -aralkoxy or aralkylthio, heteroaryl or heteroaryloxy with 5 or 6 ring atoms, cyano, halogen, C2-C24 secondary amino, --C(O)OR², -0(0) CR⁴, —NR² (0) CR⁴, —C(O)NR² R³, in which R² is C!-C₁₂alkyl phenyl or benzyl, R³ is H or is as defined for R²and R⁴ is as defined for R², it being possible for the substituents alkyl, alkoxy and alkylthio in turn to be substituted by C1-C12 alkoxy, halogen, cyano, C2-C24 secondary amino, --C(O)OR², --O(O)CR⁴, --NR² (O)CR⁴, -C(0)NR² R³, cycloalkyl or heterocycloalkyl with 4-8 ring carbon atoms or 5 or 6 ring atoms, and for the substituents cycloalkyl, cycloalkoxy, cycloalkylthio, aryl, aryloxy, arylthio, aralkyl, aralkoxy, aralkylthio, heteroaryl or heteroaryloxy to be substituted by C1-C12 alkyl, -alkoxy or -alkylthio, halogen, cyano, C2-C24 secondary amino, --C(O)OR², --O(O)CR⁴, --NR² (0)CR⁴ or -C (0) NR² R³ .

R⁵ may be a linear or branched alkyl with, preferably, 1 to 12 carbon atoms, more preferably, 4 to 8 carbon atoms, and, most preferably, 6 carbon atoms. Examples are methyl, ethyl, n- or i-propyl, η-, i- or t-butyl, 1-, 2- or 3pentyl, 1-, 2- or 3-hexyl, 1-, 2-, 3- or 4-heptyl, 1-, 2-,

3- or 4-octyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, hexadecyl, octadecyl and eicosyl.

R³ may be a linear or branched alkenyl with, preferably, 2 to 14 carbon atoms, in particular 2 to 8, carbon atoms. Examples are: allyl, but-l-en-3-yl, but-l-en-4-yl, but-216 en-4-yl, pent-l-en-5-yl, pent-l-en-4-yl, pent-l-en-3-yl, pent-2-en-4-yl, pent-3-en-5-yl, hex-l-en-6-yl, hex-2-en-6yl, hex-3-en-6-yl, hex-3-en-2-yl, hex-3-en-5-yl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tetradecenyl, hexadecenyl and octadecenyl.

R^b may be a linear or branched alkynylalkyl with, preferably, 1 to 12 carbon atoms, more preferably, 4 to 8 carbon atoms, and, most preferably 6 carbon atoms. Examples are propargyl, but-l-in-3-yl, but-2-in-4-yl, pent-3-inl-yl, pent-l-in-3-yl, pent-l-in-4-yl, pent-l-in5-yl, pent-2-in-4-yl, pent-2-in-5-yl, hex-l-in-3-yl or -4yl or -5-yl or -6-yl, hex-2-in-4-yl or -5-yl, or -6-yl, hex-3-in-5-yl or -6-yl, heptinyl, octinyl, noninyl, decinyl, undecinyl, dodecinyl, tetradecinyl, hexadecinyl and octadecinyl.

R⁵ may be a cycloalkyl or cycloalkenyl which preferably has 4 to 8 ring carbon atoms and, more preferably, 5 or 6, ring carbon atoms and is unfused or fused with C6-C14 aryl, preferably, benzene, or with heteroaryl with 5 or 6 ring atoms. Examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cycloprop-l-en-3-yl, cyclobut-l-en-3-yl, cyclopent-l-en-3yl, cyclopent-l-en-4-yl, cyclohex-l-en-3-yl, cyclohex-1en-4yl, cyclopentenyl, cyclooctenyl and cyclodecenyl.

R⁵ may be a heterocycloalkyl or heterocycloalkenyl which is unfused or fused with C6-C14 aryl, more preferably, benzene, or with heteroaryl with 5 or 6 ring atoms, or heteroaryl, it being possible for these radicals to contain, for example, heteroatoms from the group comprising oxygen, sulphur, and nitrogen. The nitrogen atom is a tertiary nitrogen atom. If the nitrogen atom is present in the ring as a secondary amine group, this nitrogen atom is, for example, C1-C12, and, preferably, (frC4 alkylated, phenylated or benzylated. It may also contain protective groups, for example, C1-C4 alkoxymethyl or R₃ ⁵ Si groups, in which R⁵ is C1-C12 alkyl. These heterocyclic radicals, preferably, contain 1 to 3, in particular 1 or 2, identical or different heteroatoms. The heterocycloalkyl or -alkenyl preferably contains 5 or 6 ring members. Examples of heterocyclic radicals from which R and R¹ may be derived are (protective groups for secondary nitrogen groups are not mentioned): pyrrolidine, tetrahydrofuran, tetrahydrothiophene, pyrroline, dihydrofuran, dihydrothiophene, indane, dihydrocoumaron, dihydrobenzothiophene, carbazole, dibenzofuran, dibenzothiophene, pyrazolidine, imidazolidine, pyrazoline, imidazoline, benzimidazolidine, oxazolidine, oxazoline, thiazolidine, isooxazolidine, isooxazoline, isothiazolidine, isothiazoline, benzoxazolidine, benzisooxazolidine, benzthiazolidine, 1,2,3- or 1,2,4triazolidine, 1,2,3- or 1,2,4-triazoline, 1,2,3,- or 1,2,4-oxazolidine or -oxazoline, piperidine, di- and tetrahydropyridine, dihydro- and tetrahydropyran, di- and tetrahydrothiopyran, piperazine, dehydropiperazine, morpholine, thiomorpholine, 1,3- and 1,4-dioxane, 1,4dithiane, azepan, 1,3-dioxolane, 1,3-dithiolane, pyrrole, indole, imidazole, benzimidazole, furan, thiophene, benzofuran, benzothiophene, carbazole, dibenzofuran, dibenzothiophene, oxazole, isooxazole, thiazole, isothiazole, benzoxazole, benzothiazole, pyridine, pyrimidine, pyrazine, pyridazine, quinoline, isoquinoline, acridine, chromene, chromane, pyran, thiapyran, phenazine, phenoxazine, phenolthiazine and purine. Heterocyclic radicals R and R¹ are bonded to the N atoms in formula I via a carbon atom.

R⁵ may be a polycyclic hydrocarbon radical with 6 to 10 carbon atoms. Examples of such hydrocarbons from which R and R¹ may be derived are: bicyclo-[0,0,3]-hexane, bicyclo-[1,0,3]-hexane, bicyclo-[2,2,1]-heptane, bicyclo[2.2.1] -heptene, bicyclo-[2,2,2]-octane and bicyclo[2.2.2] -octene.

R⁵ may be a C6-C14 aryl. Examples are phenyl, naphthyl, anthracyl, indenyl, indanyl, fluorenyl and phenanthryl. Phenyl, naphthyl and anthracyl are preferred. Phenyl is most preferred.

R⁵ may be an aralkyl with, preferably, 7 to 14 carbon atoms. The aryl is, preferably, naphthalene and, more preferably, benzene. The alkyl group, preferably, contains 1 to 3 carbon atoms. Examples of aralkyl are benzyl, 1phenyleth-l-yl, l-phenyleth-2-yl, 1-phenylprop-l-yl, -2-yl or -3-yl and 2-phenylprop-2-yl or -1-yl.

R⁵ may be a heteroaralkyl. Heteroaryl radicals and preferred radicals have been mentioned above. The alkyl group of the heteroaralkyl preferably contains 1-3 carbon atoms and is, for example, methyl, 1,1- or 1,2-ethyl or 1,1-, 2,2-, 1,2- or 1,3-propyl.

R⁵ may be substituted in any desired positions by identical or different radicals, for example, by 1 to 5, preferably, 1 to 3, substituents.

Suitable substituents for R⁵ are: C1-C12, preferably, C1-C6 and, more preferably, C1-C4 alkyl, -alkoxy or -alkylthio, for example, methyl, ethyl, propyl, η-, i- and t-butyl and the isomers of pentyl, hexyl, octyl, nonyl, decyl, undecyl and dodecyl, and corresponding alkoxy and alkylthio radicals .

The substituents alkyl, alkoxy and alkylthio may in turn be mono- or poly-substituted, in particular, mono-, di- or trisubstituted, by halogen, cyano, C2-C24 secondary amino, --C(O)OR², --O(O)CR⁴, or heterocycloalkyl with 4-8 ring carbon atoms or 5 or 6 ring atoms. The preferred meanings described above apply to R², R³ and R⁴. If the alkyl, alkoxy or alkylthio is

-NR² (O)CR⁴,

C(O)NR² R³, cycloalkyl fluoride and/or example, C1-C6, substituted by a halogen, preferably, chlorine, the radical may be, for preferably, C1-C4 haloalkyl, for example, trifluoro- or trichloromethyl, difluorochloromethyl, fluorodichloromethyl, 1,1-difluoroeth-l-yl, 1,1dichloroeth-l-yl, 1,1,1-trichloro- or -trifluoroeth-2-yl, pentachloroethyl, pentafluoroethyl, 1,1,1-trifluoro-2,2dichloroethyl, n-perfluoropropyl, i-perfluoropropyl, nperfluorobutyl, fluoro- or chloromethyl, difluoro- or dichloromethyl, 1-fluoro- or -chloroeth-2-yl or -eth-l-yl, 1-, 2- or 3-fluoro- or -chloro-prop-l-yl or -prop-2-yl or

-prop-3-yl, 1-fluoro- or -chloro-but-1 -yl, -but-2-yl, but-3-yl, or -but-4-yl, 2,3-dichloro-prop-l-yl, 1-chloro2-fluoro-prop-3-yl or 2,3-dichlorobut-l-yl.

Examples of alkyl, alkoxy or alkylthio substituted by cyano are cyanomethyl, 1- or 2-cyanoethyl, 1- or 2cyanopropyl and 2-cyanoethyloxy. If the alkyl, alkoxy or alkylthio is substituted by

-C (0) OR²,

-0 (0) CR⁴,

-NR [O)CR⁴ or --C(O)NR² R³, it, preferably, contains 1 to 3 carbon atoms.

ethoxycarbonylmethyl, ethoxycarbonylethyl, ethoxycarbonylpropyl, are methoxyor

2Examples

1- or 2-methoxy- or 1-, 2- or 3-methoxy- or acetyloxymethyl, 1- or acetyloxyethyl, dimethylaminocarbonylmethyl or -ethyl, Nmethylacetylamino, methoxycarbonylmethoxy or 1(methoxycarbonyl)eth-2-oxy.

The substituents cycloalkyl, cycloalkoxy, cycloalkylthio, aryl, aryloxy, arylthio, aralkyl, aralkoxy, aralkylthio, heteroaryl and heteroaryloxy may in turn be substituted as defined for alkyl, alkoxy and alkylthio and may additionally be mono- or polysubstituted, preferably, mono-, di- or trisubstituted, by C1-C12, in particular Ci21 chlorophenoxy, or -phenoxy,

Cg alkyl or -alkylthio. Examples are methylcyclohexyl, hexoxy and -hexylthio, methylphenyl, dimethylphenyl, methylchlorophenyl, cyanophenyl, dichlorophenoxy, trifluoromethylphenyl methoxyphenyl or -phenoxy, fluoro- or difluorophenyl or phenoxy, chlorobenzyl or -benzyloxy, methyl- or dimethylbenzyl, carbomethoxyphenyl, methoxybenzyl, chloroor dichloropyrridyl, methylpyrridyl, methylpyrridyloxy, and chloro- or dichloropyrridyloxy.

Preferably, R⁶ and R⁷ are each independently hydrogen or as defined above for R⁵ .

Preferably, R⁵ is Ci-io alkyl, more preferably, C1-4 alkyl most preferably, methyl.

Preferably, R⁶ is hydrogen or C1-10 alkyl, more preferably, C2-6 alkyl most preferably, ethyl.

Preferably, R⁷ is hydrogen or C1-10 alkyl, more preferably, hydrogen or C1-4 alkyl most preferably, hydrogen.

Exemplary oximes include without limitation acetaldoxime, acetone oxime, aldicarb, alprenoxime, asoprisnil, asoxime chloride, aspergillusol, brasofensine, butanone oxime, caproxamine, cefdaloxime, cefepime, cefetamet, cefmatilen, cefmenoxime, cefodizime, cefotaxime, cefovecin, cefozopran, cefpirome, cefpodoxime, cefquinome, cefteram, ceftiofur, ceftiolene, ceftobiprole, cefuroxime, chloro(pyridine)cobaloxime, CI-1017, clovoxamine, CPCCOEt, demexiptiline, dimethylglyoxime, eplivanserin, ethyl cyanohydroxyiminoacetate, FERb 033, fluvoxamine, gemifloxacin, istaroxime, mariptiline, methylethyl ketone oxime, milameline, nisterime, nisterime acetate, NNC-711, norgestimate, noxiptiline, NS-2710, obidoxime, olesoxime, Pl-185, perillartine, phosgene oxime, pralidoxime, sabcomeline, salicylaldoxime, selumetinib, technetium (99mTc) exametazime, tirpate, bromide, and the like.

sibrafiban, trimedoxime

Preferably, the oxime is butanone oxime

Advantageously, the diisocyanate in the presence of the oxime brings about a rapid and permanent reaction between the carboxyl, hydroxyl and/or amino functional groups of the silicone hydrogel material and binding polymer. For example, the diisocyanate functional groups react with the carboxyl, hydroxyl and/or amino functional groups of the silicone hydrogel material and binding polymer to form diurethane linkages. Advantageously, the use of the combination of diisocyanate and oxime result in the formation of a diurethane functional group that is substantially non-toxic.

Preferably, the amount of oxime used in the preparation of the lens is stoichiometric to the amount of diisocyanate. Preferably, the molar ratio of diisocyanate to oxime is from about 1:1 to 1:20, more preferably from about 1:1 to 1:10, even more preferably from about 1:1 to 1:5. Most preferably, the molar ratio of diisocyanate to oxime is about 1:2.

According to a second aspect of the present invention, there is provided a method of staining a contact lens comprising the steps of :a) providing a lens substrate comprising a silicone hydrogel material;

b) providing a colour coating comprising a colouring substance;

a) providing a binding polymer;

b) providing a diisocyanate cross-linking agent and an oxime; and

c) reacting the diisocyanate cross-linking agent, in the presence of the oxime, with functional groups selected independently from carboxyl, hydroxyl, and/or amino present in the lens substrate and binding polymers;

wherein the colouring substance comprises a metal oxide.

Preferably, the binding polymer is prepared by the polymerisation of monomers or pre-polymers in a binding polymer mix, preferably, using a free radical initiator to initiate the polymerisation reaction. Preferably, the binding polymer comprises a pre-polymer which may contain non-reacted monomer and residual free radical initiator.

The binding polymer may be prepared from any monomer or combination of monomers such that the polymer formed comprises side groups independently selected from carboxyl, hydroxyl, and/or amino. Furthermore, the use of various co-monomers may be possible in order to modify the properties of the binding polymer formed.

The binding polymer mix and, hence, binding polymer may contain solvent. Suitable solvents used in the binding polymer mix for the preparation of the binding polymer may include any polar solvent, for example, tetrahydrofuran, alcohol or ketone. Preferably, the solvent used in the preparation of the binding polymer is polycyclohexanone and, more preferably, cyclohexanone.

Preferably, the concentration of the solvent is in the range of 30% to 80% (w/w) of the total weight of the binding polymer mix, more preferably, in the range of 40% to 70% (w/w), even more preferably, in the range of 50% to 60% (w/w), and most preferably, in the range of 53% to 57% (w/w) of the total weight of binding polymer mix.

Preferably, the binding polymer is derived from a suitable monomer, preferably, hydroxyalkylalkacrylate. For example, Ci-Cg alkylalkacrylate, more preferably, Ci-Cg alkylmethacrylate is used.

Preferably, the binding polymer mix comprises hydroxy alkylalkacrylate monomer. Preferably, an ethylmethacrylate monomer is used and, more preferably, hydroxyethylmethacrylate monomer is used.

Preferably, the concentration of monomer is in the range

of 20%	to	70% (w/w) of the	total weight	of	the	binding
polymer	mix	, more preferably,	in the range	of	30%	to 60%
(w/w) ,	even	more preferably,	in the range	of	40%	to 50%
(w/w) ,	and	most preferably,	in the range	of	42%	to 46%

(w/w) of the total weight of the binding polymer mix.

Suitable free radical initiators in the binding polymer mix for the preparation of the binding polymer may be used, for example, 2,2 Azobis (2-methylpropanitrile).

Preferably, the concentration of the initiator is in the range of 0.1% to 10% (w/w) of the total weight of the binding polymer mix, more preferably, in the range of 0.2% to 5% (w/w), even more preferably, in the range of 0.3% to 2% (w/w), and most preferably, in the range of 0.4% to 0.6% (w/w) of the total weight of the binding polymer mix.

Suitable additives in the binding polymer mix for the preparation of the binding polymer may be used, for example, crotonic acid.

Advantageously, the addition of crotonic acid extends the shelf-life of the binding polymer mix. Furthermore and advantageously, crotonic acid ensures that the binding polymer expands at substantially a similar rate to that of the polymers of the silicone hydrogel material as they are added to the cross-linking agent to thereby reduce the likelihood of the lens from cracking.

Preferably, the concentration of additive is in the range of 0.1% to 10% (w/w) of the total weight of the binding polymer mix, more preferably, in the range of 0.2% to 5% (w/w), even more preferably, in the range of 0.3% to 2% (w/w), and most preferably, in the range of 0.4% to 0.6% (w/w) of the total weight of the binding polymer mix.

Suitable chain terminators or agents to control chain length during the polymerisation reaction may be used in the binding polymer mix for the preparation of the binding polymer, for example, mercaptoethanol.

Preferably, the concentration of chain terminator is in the range of 0.1% to 10% (w/w) of the total weight of the binding polymer mix, more preferably, in the range of 0.2% to 5% (w/w), even more preferably, in the range of 0.3% to 2% (w/w), and most preferably, in the range of 0.4% to 0.6% (w/w) of the total weight of the binding polymer mix.

Preferably,	the	binding polymer	mix	is	heated	to a
temperature	in	the range of	-10°C	to	130°C,	more
preferably,	in	the range of 10°	C to	110	°C, and	most

preferably, in the range of 50°C to 90°C.

Preferably, the binding polymer mix is heated at this temperature for between 1 to 300 minutes, more preferably, between 10 to 100 minutes and most preferably, between 30 to 60 minutes.

Preferably, the concentration of diisocyanate used in the preparation of the lens as the cross-linking agent is in the range of 1% to 50% (w/w) of the total weight of the binding polymer mix, more preferably, in the range of 2% to 30% (w/w), even more preferably, in the range of 3% to 15% (w/w) , and most preferably, in the range of 4% to 8% (w/w) of the total weight of the binding polymer mix.

Preferably, the amount of oxime used in the preparation of the lens is stoichiometric to the amount of diisocyanate. Preferably, the molar ratio of diisocyanate to oxime used in the preparation of the lens is from about 1:1 to 1:20, more preferably from about 1:1 to 1:10, even more preferably from about 1:1 to 1:5. Most preferably, the molar ratio of diisocyanate to oxime used in the

preparation	of the lens is about 1:2
Preferably,	the binding polymer mix is mixed with the
cross-linking agent in a range of 2:1 to 11:1 (w/w), more
preferably,	in a range of 4:1 to 9:1 (w/w), and most
preferably,	in a range of 6:1 to 7:1 (w/w).
Preferably,	the binding polymer mix is mixed with the
colouring substance in a range of 0.5:1 to 4.5:1 (w/w),
more preferably, in a range of 1:1 to 4:1 (w/w), and most

preferably, in a range of 1.5:1 to 2.5:1 (w/w).

Preferably, the colouring substance is mixed with the cross-linking agent in a range of 0.5:1 to 6:1 (w/w), more preferably, in a range of 1:1 to 5:1 (w/w), and most preferably, in a range of 2:1 to 4:1 (w/w).

The colouring substance comprises a metal oxide. The colour compound may comprise iron oxide or titanium oxide.

The lenses may be printed with the colour coating by tampon printing. The diisocyanate cross-linking reaction with the silicone hydrogel material and binding polymers may be performed by heating the coated lens.

Preferably, the lens is heated to a first temperature in the range of -10°C to 130°C, more preferably, in the range of 10°C to 100°C, most preferably, in the range of 30°C to 80°C.

Preferably, the lens is heated at this first temperature for between 1 to 300 minutes, more preferably, between 10 to 100 minutes and, most preferably, between 30 to 60 minutes .

Preferably, the lens is heated to a second temperature in the range of 30°C to 210°C, more preferably, in the range of 60°C to 180°C and, most preferably, in the range of 90°C to 150°C.

Preferably, the lens is heated at this second temperature for between 1 to 300 minutes, more preferably, between 10 to 100 minutes and, most preferably, between 30 to 60 minutes .

Preferably, following the cross-linking reaction, the lens is hydrated, preferably, by immersion in saline, more preferably physiological saline.

Preferably, the lens is boiled in the saline for 1 to 300 minutes, more preferably, between 10 to 100 minutes and, most preferably, between 30 to 60 minutes.

Preferably, following hydration, the lenses are removed from the saline and heated to a temperature in the range of 30°C to 210°C, more preferably, in the range of 60°C to 180°C and, most preferably, in the range of 90°C to 150°C.

All of the features described herein may be combined with any of the above aspects, in any combination.

The following examples describe a procedure for staining contact lenses with a colour coating in accordance with the invention.

Example 1

The procedure uses a pre-hydrated contact lens substrate which has at least part of the surface consisting of a polymer containing hydroxyl, carboxyl and/or amino functional groups. A colour coating containing a colour substance and a binding polymer containing hydroxyl, carboxyl and/or amino functional groups is affixed to the surface of the lens by the action of a cross-linking agent (cross-linker). The example will now describe the procedure in successive stages:30

1. Preparation of a binding polymer

The following reagents are mixed in a suitable receptacle and heated in a water bath at 70°C for 45 minutes until the correct viscosity is achieved. The reagents are constantly stirred to ensure thorough mixing.

Reagent	Weight (g)	% (w/w) total weight of binding polymer mix (%)
Cyclohexanone	81.75	54.5
3- tris(trimethylsilyloxy)silylpropyl methacrylate	66.00	44.0
2,2 azobis(2-methylpropanitrile)	0.75	0.5
Crotonic acid	0.75	0.5
Mercaptoethanol	0.75	0.5

2. Preparation of a cross-linking agent

A cross-linking agent is prepared with the following formulation: -

( cL ! (b;	4.3 g of toluene di-isocyanate (TDl)	J (HD I)
1.2g of hexa:	methylene di-isocyanate
(C)	6.5g of butanone oxime (BO)
(d)	12.5g of tet	rahydrofuran (THE)
3 .	Preparation of a	colour coating
A	colour coating	is prepared with	the following

formulation: 31 (a) 50g of the binding polymer made in part 1.

(b) 8g of the cross-linking agent formed in part 2.

(c) 12g of colour substance, for example, titanium dioxide which gives a white colour, or iron oxide which gives a red colour.

All three components are placed in a suitable vessel and mixed until the correct viscosity is achieved. Viscosity may be adjusted using various known solvents.

4. Printing the colour coating onto the lens

The lenses are coated by imprinting onto the lens surface by the tampon print method which is well known in the art. Fixing the colour coating onto the lens surface is achieved by heating the lens in an oven, firstly at 55°C for 30-45 minutes, and then secondly at 130°C for 30-45 minutes .

5. Hydration of the contact lens

Following fixing, the lens is finally hydrated, by immersing the dry lenses in physiological saline and the lenses are boiled for 45 minutes. Following hydration, the lenses are then removed from the saline solution, placed in suitable vials and then placed in an autoclave at 120°C for a period of 20 minutes.

. Life-span Tests

The permanence (life-span) of the colour coating fixed onto the lens polymer by the procedure described above may be tested by carrying out a rub test and methanol test.

In the rub test, the hydrated lens is folded back upon itself so that the side printed with the colour coating faces inwards and then rubbed between the thumb and forefinger. The methanol test is identical to the rub test except that the lens is first immersed in methanol and buffered saline for 30 seconds prior to rubbing. In both tests, carried out in sets of 5, the degree of adhesion to the surface of the lens may be observed.

Time (days)	Rub Test (Pass=5, Fail =0)	Methanol Test (Pass=5, Fail=0)
0	5	5
2	5	5
4	5	5
7	5	5
9	5	5
11	5	5
14	5	5
16	5	5
18	5	5
21	5	5

The results of both the rub test and the method test clearly illustrate that use of the diurethane as a crosslinking agent results in the colour coating having a considerable life-span on the surface of the contact lens.

Eye Irritation Tests

A study was performed to assess the eye irritation potential of Corrective Contact Lenses to the rabbit. The method followed was based on that described in BS EN ISO 10993-10 (1996) Biological evaluation of medical devices, Part 10. Tests for irritation and sensitization.

Three rabbits were each administered a single ocular dose of 0.1 ml of a saline extract of the test article. A further three rabbits were each administered a single ocular dose of 0.1 ml of a cotton seed oil extract of the test article. Control animals received the extracting media only. All animals were observed for three days after instillation.

There was no evidence of ocular irritation in any test or control animal following a single ocular dose of 0.1 ml of a saline extract of Corrective Contact Lenses.

Transient, very slight conjunctival irritation was seen in the test and control animals following a single ocular dose of 0.1 ml of a cotton seed oil extract of Corrective Contact Lenses. However, as there was no difference in the severity of the reactions seen in test animals compared with the control animals, this was considered to be due to the extract medium, not a result of any irritant fraction extracted from the test article.

In conclusion, Corrective Contact Lenses were not considered to be eye irritants.

The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive.

Each feature disclosed in this specification (including any accompanying claims, abstract and drawings), may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

The invention is not restricted to the details of the foregoing embodiment (s) . The invention extend to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings) , or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

Claims

1. A coloured contact lens comprising:-

a) a lens substrate hydrogel material; comprising a silicone b) a colour coating substance; and comprising a colouring c) a binding polymer; wherein oxide; the colouring sub: and wherein colour stance comprises a metal coating is bonded to at

least part of the surface of the lens substrate by cross-linking functional groups independently selected from carboxyl, hydroxyl and/or amino groups present in the lens substrateand in the binding polymer, the cross-linking being effected by a diisocyanate in the presence of an oxime.

2. A coloured contact lens as claimed in claim 1, wherein the diisocyanate is used directly as a cross-linking agent.

3. A coloured contact lens as claimed in either claim 1 or claim 2, wherein the diisocyanate has a structure O=C=N-X-N-C=O, wherein X is a divalent organic bridging group.

4. A coloured contact lens according to claim 3, wherein the diisocyanate is toluene diisocyanate (TDI) and/or hexamethylene diisocyanate (HMDI).

5. A coloured contact lens according to any preceding claim, wherein the oxime is selected from acetaldoxime, acetone oxime, aldicarb, alprenoxime, asoprisnil, brasofensine, cefdaloxime, cefmenoxime, cefozopran, cefteram, cefuroxime, asoxime chloride, butanone oxime, cefepime, cefodizime, cefpirome, ceftiofur, cefetamet, cefotaxime, cefpodoxime, ceftiolene, chloro(pyridine)cobaloxime, aspergillusol, caproxamine, cefmatilen, cefovecin, cefquinome, ceftobiprole,

CI-1017, clovoxamine, CPCCOEt, demexiptiline, dimethylglyoxime, eplivanserin, ethyl 033, fluvoxamine, cyanohydroxyiminoacetate, FERb gemifloxacin, istaroxime, mariptiline, methylethyl ketone oxime, milameline, nisterime, nisterime acetate, NNC-711, norgestimate, noxiptiline, NS-2710, obidoxime, olesoxime, Pl-185, perillartine, phosgene oxime, pralidoxime, sabcomeline, salicylaldoxime, selumetinib, sibrafiban, technetium (99mTc) exametazime, tirpate or trimedoxime bromide .

6. A coloured contact lens according to claim 5, wherein the oxime is butanone oxime.

7. A coloured contact lens according to any preceding claim, wherein the concentration of diisocyanate used in the preparation of the lens is in the range of 1% to 50% (w/w) of the total weight of the binding polymer .

8. A coloured contact lens according to any preceding claim, wherein the molar ratio of diisocyanate to oxime is from 1:1 to 1:20.

9. A coloured contact lens according to claim 8, wherein molar ratio of diisocyanate to oxime is 1:2.

10. A coloured contact lens according to any preceding claim, wherein the colouring substance comprises iron oxide or titanium oxide.

11. A method of staining a contact lens comprising the steps of :a) providing a lens substrate comprising a silicone hydrogel material;

b) providing a colour coating comprising a colouring substance;

c) providing a binding polymer;

d) providing a diisocyanate cross-linking agent and an oxime; and

e) reacting the diisocyanate cross-linking agent, in the presence of the oxime, with functional groups selected independently from carboxyl, hydroxyl, and/or amino present in the lens substrate and binding polymers;

wherein the colouring substance comprises a metal oxide .

12. A method as claimed in claim 11, wherein the binding polymer is prepared by the polymerisation of monomers or pre-polymers in a binding polymer mix.

13. A method as claimed in either claim 11 or claim 12, wherein the binding polymer contains solvent.

14. A method as claimed in claim 13, wherein the concentration of the solvent is in the range of 30% to 80% (w/w) of the total weight of the binding polymer mix .

15. A method as claimed in any one of claims 11 to 14, wherein the binding polymer is derived from a suitable hydroxyalkylalkacrylate.

16. A method as claimed in any one of claims 11 to 15, wherein the concentration of monomer is in the range of 20% to 70% (w/w) of the total weight of the binding polymer mix.

17. A method as claimed in any one of claims 12 to 16, wherein suitable free radical initiators in the binding polymer mix for the preparation of the binding polymer are used.

18. A method as claimed in claim 17, wherein the

concentration to 10% (w/w) polymer mix. of the initiator is in the range of 0.1% of the total weight of the binding

19. A method as claimed in any one of claims 11 to 17,

wherein suitable additives in the binding polymer mix for the preparation of the binding polymer may be used, for example, crotonic acid.

20. A method as claimed in claim 19, wherein the concentration of additive is in the range of 0.1% to 10% (w/w) of the total weight of the binding polymer mix .

21. A method as claimed in any one of claims 12 to 20, wherein suitable chain terminators or agents to control chain length during the polymerisation reaction are used in the binding polymer mix for the preparation of the binding polymer.

22. A method as claimed in claim 21, wherein the concentration of chain terminator is in the range of

0.1% to 10% polymer mix. (w/w) of the total weight of the binding

23. A method as claimed in any one of claims 12 to 22, wherein the binding polymer mix is heated to a temperature in the range of -10° C to 130°C.

24. A method as claimed in claim 23, wherein the binding polymer mix is heated at this temperature for between 1 to 300 minutes.

25. A method as claimed in any one of claims 11 to 24, wherein the concentration of diisocyante used in the preparation of the lens as the cross-linking agent is in the range of 1% to 50% (w/w) of the total weight of the binding polymer mix.

26. A method as claimed in any one of claims 11 to 25, wherein the molar ratio of diisocyanate to oxime used in the preparation of the lens is from 1:1 to 1:20.

27. A coloured contact lens according to claim 26, wherein molar ratio of diisocyanate to oxime used in the

preparation of the lens is 1:2.

28 . A method as claimed in any one of claims 11 to 27, wherein the binding polymer mix is mixed with the cross-linking agent in a range of 2:1 to 11:1 (w/w).

29. A method as claimed in any one of claims 11 to 28, wherein the binding polymer mix is mixed with the colouring substance in (w/w). a range of 0.5:1 to 4.5:1

30 . A method as claimed in any one of claims 11 to 29, wherein the colouring substance is mixed with the cross-linking agent in a range of 0.5:1 to 6:1 (w/w).

31 . A method as claimed in any one of to claims 11 to 30, wherein the colouring substance comprises a metal oxide .

32 . A method as claimed in any one of claims 11 to 31,

wherein the lens is heated to a first temperature in the range of -10°C to 130°C.

33. A method as claimed in claim 32, wherein the lens is heated at this first temperature for between 1 to 300 minutes .

34. A method as claimed in any one of claims 11 to 33, wherein the lens is heated to a second temperature in the range of 30°C to 210°C.

35. A method as claimed in claim 34, wherein the lens is heated at this second temperature for between 1 to 300 minutes .

36. A method as claimed in any one of claims 11 to 35, following the cross-linking reaction, the lens is hydrated.

37. A method as claimed in any one of claims 7 to 36, wherein the lens is boiled in the saline for 1 to 300 minutes .

38. A method as claimed in claim 37, wherein the lenses are removed from the saline and heated to a

temperature in the range of 30°C to 210°C.

39.

A method as claims in any one of claims 11 to 38, wherein the colouring substance comprises iron oxide or titanium oxide.

Intellectual

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Application No: GB1704187.2 Examiner: Dr Paul Minton