RU2800871C2 - Light-resistant imitation of macular pigment - Google Patents

Abstract

FIELD: ophthalmology.

SUBSTANCE: invention relates to a compound of formula II, where EWG in each case represents cyano; n is either 1, 2 or 3; a R¹ is independently H, C₁-C ₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ thioalkyl, C₃-C₇ cycloalkyl, phenyl, halogen, hydroxy, amino, NR³R⁴, benzyl, SO₃H or SO₃M (M is a monovalent cation such as sodium or potassium) or -Y-P_g where R³ and R⁴ are independently H or C₁-C ₆ alkyl, Y in each occurrence independently represents either C₁-C₈ alkylene or C₁-C₈ oxaalkylene; and P_g at each occurrence is independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinylamide, or styryl; wherein the compound contains 1 or 2 -Y-P_g groups, which may or may not be the same. The invention relates to an ophthalmic device, which is a contact lens containing a compound of formula II according to the invention. The invention also relates to a contact lens based on the compound of formula II according to the invention.

EFFECT: compound having maximum absorption of visible light in the range of 430–480 nm and full width at half height (FWHM) at maximum absorption of visible light of at least 35 nm and up to 100 nm, moreover, the connection is light stable when measured in accordance with ICH Q1B guidance.

13 cl, 2 dwg, 3 tbl, 4 ex

Description

Related Applications

This application claims priority over U.S. Patent Application No. 16/898,638, filed June 11, 2020, and U.S. Provisional Application No. 62/867,968, filed June 28, 2019, which is incorporated herein by reference in its entirety.

Scope of the invention

The present invention relates to visible light absorbers. In particular, the present invention relates to compounds that substantially mimic the visible light absorption characteristics of macular pigment while remaining light stable. These compounds can be used in various products, including ophthalmic devices.

Prerequisites for the creation of the invention

Human eye tissues contain dietary kartinoid lutein (L) and zeaxanthin (Z), collectively referred to as macular pigment (MP; macular pigment). Several conclusions describe the benefits of MP, for example, as a short wavelength filter (blue part of the visible light spectrum) and an effective antioxidant. It is also believed that MP plays a protective role in countering age related macular degeneration (AMD; age related macular degeneration) (Bernstein, P. S., Li, B., Vachali, P. P., Gorusupudi, A., Shyam, R., Henriksen, B. S., Nolan , J. M. Prog. Retin. Eye Res. 2016, 50, 34-66; Beatty, S., Boulton, M., Koh, H-H., Murray, I, J.Br. J. Opthalmol 1999,83, 867-877). In addition, macular pigment has been found to be highly correlated with photovoltage recovery periods, reduced discomfort glare contrast thresholds, and reduced visual discomfort (Stringham, J. M., Garcia., P. V., Smith, P. A., McLin, L, N., Foutch , B.K.IOVS,2011,52(10) 7406-7415).

The chemical building blocks associated with macular pigment are carotenoid derivatives that are highly unsaturated and highly reactive with respect to isomerization and olefin oxidation upon light excitation. The antioxidant defense mechanism provided by carotenoids is essentially "protective" when excitation of the pi system causes it to react in an excited state with triplet oxygen, thus protecting/limiting the excitation and responses of other photosensitive compounds in the eye environment. See, for example, Ribeiro, et al., Food and Chemical Toxicology, Vol. 120, pp. 681-699 (2018); Burton, et al., Can. J. Chem., Vol. 92, pp. 305-316 (2014); Ty, et al., Journal of Oil Palm Research Vol. II no. 1, pp. 62-78 (June 1999); Johnston, et al., Plos One, Vol. 9(10), pp. 1-10 (2014); and Boon, et al., Critical Reviews in Food Science and Nutrition, Vol. 50, pp. 515-532 (2010).

While it is desirable to include macular pigment in products to provide eye protection, the general lack of stability (thermal, oxidative and photochemical) of carotenoids poses a rather powerful barrier to the development of such products. Thus, a significant improvement would be to develop new stable materials that mimic the light-absorbing properties of macular pigment.

Statement of the Invention

The present invention relates to compounds whose absorption spectra of visible light are in the wavelength range from 400 nm to 500 nm, which essentially mimic the spectrum of macular pigment. Such compounds are also light stable, for example, when measuring changes/losses in absorption characteristics when exposed to conditions similar to those described in ICH Q1B. In addition, the compounds can have a high extinction coefficient at desired wavelengths from 400 nm to 500 nm and can therefore be used at low concentrations to provide their light absorbing effect. The compounds described herein can be used, for example, in ophthalmic devices to supplement, for example, macular optical pigment density (MPOD) in users.

Accordingly, in one aspect, the present invention provides a compound having a maximum visible light absorption in the range of 430 nm to 480 nm and a full width at half maximum (FWHM; full width half maximum) of which at maximum visible light absorption is at least 35 nm and up to 100 nm, and the connection is light-resistant.

In another aspect, the present invention provides a compound having a maximum visible light absorption in the range of 430 nm to 480 nm and a full width at half maximum (FWHM) at maximum visible light absorption of at least 35 nm and up to 100 nm, wherein the compound is more lightfast than macular pigment.

In a further aspect, the present invention provides a compound containing a chromophore having the formula I substructure:

where EWG is in each case independently an electron withdrawing group.

In yet another additional aspect, the present invention provides an ophthalmic device containing a compound described herein.

Brief description of graphic materials

In FIG. 1 shows the UV-VIS transmission spectrum of a 0.2 mmol/L solution of Compound A in methanol according to the present invention.

In FIG. 2 shows the UV-VIS absorption spectrum of a 0.2 mmol/L solution of compound A in methanol according to the present invention superimposed on the reference spectra of macular pigment.

In FIG. 3 shows the absorption spectra of contact lenses prepared from Compound A after exposure to light for up to 40 hours.

Detailed description of the invention

It should be understood that the invention is not limited to the details of construction or method steps set forth in the following description. The invention is capable of other embodiments of the invention and may be or is carried out in various ways using the teachings set forth herein.

With regard to the terms used in the present description, the following definitions are provided.

Unless otherwise indicated, all technical and scientific terms used in this document have a generally accepted meaning, understandable to any person skilled in the field to which the invention pertains. Definitions for polymers are consistent with those described in the Compendium of Polymer Terminology and Nomenclature, IUPAC Recommendations 2008 edited by: Richard G. Jones, Jaroslav Kahovec, Robert Stepto, Edward S. Wilks, Michael Hess, Tatsuki Kitayama and W. Val Metanomski. All publications, patent applications, patents and other references mentioned in this document are incorporated herein by reference.

As used herein, the term "(meth)" refers to the possible presence of an optional methyl substituent. Thus, the term "(meth)acrylates" refers to both methacrylates and acrylates.

It should be appreciated that wherever chemical structures are given, variants presented as substituents in the structure may be combined in any combination. Thus, if the structure contains substituents R* and R**, each of which has three lists of potential groups, 9 combinations are possible. The same applies to the combination of properties.

When using a subscript, such as "n" in the standard formula [***] _n , to indicate the number of repeating units in the chemical formula of a polymer, such a formula should be understood as representing the number average molecular weight of the macromolecule.

As used herein, the term "subject" includes humans and vertebrates.

"Biomedical device" means any article capable of being used in or on mammalian tissues or body fluids, and preferably in or on human tissues or body fluids. Examples of such devices include, but are not limited to, wound dressings, bioadhesives, tissue fillers, drug delivery systems, coatings, adhesion barriers, catheters, implants, stents, and ophthalmic devices such as intraocular lenses and contact lenses. Biomedical devices can be ophthalmic devices, specifically contact lenses, more specifically contact lenses made from silicone hydrogels or traditional hydrogels.

"Surface of the eye" includes the superficial and glandular epithelium of the cornea, conjunctiva, lacrimal glands, accessory lacrimal glands, nasolacrimal duct, and meibomian glands, and their apical and basal matrices, punctures, and adjacent or associated structures, including the eyelids, connected as a functional system by continuity. epithelium, innervation and endocrine and immune systems.

The term "ophthalmic device" refers to any optical device relating to the eye and includes devices that are placed in or on the eye, or on any part of the eye, including the surface of the eye. Such devices may provide optical correction, cosmetic enhancement, vision enhancement, therapeutic effect (eg as a dressing), or delivery of active ingredients such as pharmaceutical and nutraceutical ingredients, or any combination of the above. Examples of ophthalmic devices include, but are not limited to, lenses and optic and ophthalmic inserts, including but not limited to punctal obturators, and the like. The term "lenses" includes spectacle lenses, sun lenses, soft contact lenses, hard contact lenses, hybrid contact lenses, intraocular lenses and masking lenses. The ophthalmic device may include a contact lens.

The term "contact lens" means an ophthalmic device that can be placed on the cornea of a patient's eye. A contact lens may provide corrective, cosmetic, or therapeutic benefits, including wound healing, drug or nutraceutical delivery, diagnostic evaluation or monitoring, ultraviolet light absorption, visible or glare reduction, or any combination thereof. A contact lens may be made from any suitable material known in the art and may be a soft lens, a hard lens, or a hybrid lens containing at least two distinct parts with different physical, mechanical, or optical properties such as modulus, water content, light transmission, or combinations thereof.

Spectacle lenses or sun lenses may be composed of a mineral material such as a silicic acid salt or made of an organic material such as polycarbonate; polyamide; polyimide; polysulfones; polyethylene terephthalate/polycarbonate copolymers; and various other materials known in the art.

The biomedical devices, ophthalmic devices and lenses of the present invention may be made from silicone hydrogels or conventional hydrogels. Silicone hydrogels typically contain at least one hydrophilic monomer and at least one silicone-containing component that are covalently bonded to each other in a polymerized device.

The term "target macromolecule" is a macromolecule synthesized from a reactive monomer mixture containing monomers, macromers, prepolymers, crosslinkers, initiators, additives, diluents, etc.

The term "polymerizable compound" means a compound containing one or more polymerizable groups. The term includes, for example, monomers, macromers, oligomers, prepolymers, crosslinkers, and the like.

"Polymerizable groups" are groups that can undergo chain growth polymerization, such as free radical and/or cationic polymerization, eg a carbon double bond group, that can polymerize when exposed to radical polymerization initiation conditions. Non-limiting examples of free radical polymerizable groups include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N -vinyl lactams, N -vinyl amides, O-vinyl carbamates, O-vinyl carbonates, and other vinyl groups. Free radical polymerizable groups preferably contain (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinylamide, styryl functional groups, or mixtures of any of the above. Free radical polymerizable groups more preferably comprise (meth)acrylates, (meth)acrylamides and mixtures thereof. The polymerizable group may be substituted or unsubstituted. For example, the nitrogen atom in (meth)acrylamide may be bonded to a hydrogen, or the hydrogen may be substituted with alkyl or cycloalkyl (which may themselves be further substituted).

Any type of free radical polymerization can be used, including, but not limited to, mass, solution, suspension, and emulsion, as well as any controlled radical polymerization methods such as stable free radical initiated polymerization, nitroxide-mediated living polymerization, atom transfer radical polymerization, polymerization by reversible addition and fragmentation, organotellurium mediated living radical polymerization, etc.

A "monomer" is a monofunctional molecule that can undergo chain-growth polymerization, and in particular free radical polymerization, thus creating a repeating unit in the chemical structure of the target macromolecule. Some monomers have bifunctional impurities that can act as crosslinkers. "Hydrophilic monomer" is also a monomer that gives a clear, single-phase solution when mixed with deionized water at 25°C at a concentration of 5% by weight. A “hydrophilic component” is a monomer, macromer, prepolymer, initiator, crosslinker, additive, or polymer that gives a clear, single phase solution when mixed with deionized water at 25°C at a concentration of 5% by weight. A "hydrophobic component" is a monomer, macromer, prepolymer, initiator, crosslinker, additive, or polymer that is slightly soluble or insoluble in deionized water at 25°C.

A "macromolecule" is an organic compound having a number average molecular weight greater than 1500 and may or may not be reactive.

A "macromonomer" or "macromer" is a macromolecule that has a single group that can undergo chain propagation polymerization and, in particular, free radical polymerization, thereby creating a repeating unit in the chemical structure of the target macromolecule. As a rule, the chemical structure of the macromer differs from the chemical structure of the target macromolecule, that is, the repeating unit of the side group of the macromer differs from the repeating unit of the target macromolecule or its main chain. The difference between a monomer and a macromer is only in the chemical structure, molecular weight, and molecular weight distribution of the side group. As a result, and in the context of this document, monomers are sometimes defined in the patent literature as polymerizable compounds having a relatively low molecular weight of about 1500 daltons or less, which is known to include some macromers. In particular, monomers and macromers may include mono-n-butyl and monomethacryloxypropyl-terminated polydimethylsiloxane (molecular weight=500-1500 g/mol) (mPDMS) and mono-(2-hydroxy-3-methacryloxypropyl)-propylether-terminated polydimethylsiloxane group and mono-n-butyl (molecular weight=500-1500 g/mol) (OH-mPDMS). In addition, in the patent literature, macromers are sometimes defined as having one or more polymerizable groups, essentially extending the general definition of a macromer to include prepolymers. As a result, and as used herein, difunctional and multifunctional macromers, prepolymers, and crosslinkers can be used interchangeably.

A "silicone-containing component" is a monomer, macromer, prepolymer, crosslinker, initiator, additive, or polymer in a reactive composition with at least one silicon-oxygen bond, typically in the form of siloxy groups, siloxane groups, carbosiloxane groups, and mixtures thereof.

Examples of silicone-containing components that are used in the present invention can be found in U.S. Patent Nos. 3,808,178, 4,120,570, 4,136,250, 4,153,641, 4,740,533, 5,331,067 5,371,147, 5,760,100, 5,849,811, 5,962,548, 5,965,631, 5,998,498, 7,247,692, 7,396,890, 7,461,937, 7,468,398, 7,538,146, 7,553,880, 7,572,841, 7.666.921 420.711, 8.450.387, 8.487.058, 8.568.626, 8.937.110, 8.937.111, 8.940.812, 8.980.972, 9.056.878 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,929;

"Polymer" is a target macromolecule consisting of repeating units of monomers used during polymerization.

"Homopolymer" is a polymer derived from a single monomer; "copolymer" is a polymer derived from two or more monomers; "terpolymer" is a polymer derived from three monomers. "Block copolymer" consists of blocks or segments of different composition. Diblock copolymers have two blocks. Triblock copolymers have three blocks. "Comb copolymers" or "graft copolymers" consist of at least one macromer.

A "repeating unit" is the smallest group of atoms in a polymer that corresponds to the polymerization of a particular monomer or macromer.

An "initiator" is a molecule that can decompose into radicals that can sequentially react with a monomer to initiate a free radical polymerization reaction. The thermal initiator decomposes at a certain rate depending on the temperature; typical examples are azo compounds such as 1,1'-azobisisobutyronitrile and 4,4'-azobis(4-cyanovaleric acid), peroxides such as benzoyl peroxide, t-butyl peroxide, t-butyl hydroperoxide, t-butyl peroxybenzoate, dicumyl peroxide and lauroyl peroxide, peroxyacids such as peracetic acid and potassium persulfate, as well as a variety of redox systems. The photoinitiator is degraded by a photochemical process; typical examples are derivatives of benzyl, benzoin, acetophenone, benzophenone, camphorquinone and mixtures thereof, as well as various monoacyl and bisacyl phosphine oxides and combinations thereof.

A "crosslinker" is a difunctional or multifunctional monomer or macromer that can participate in free radical polymerization at two or more sites in a molecule, thereby creating branch points and forming a polymer network. Common examples include ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, trimethylol propane trimethacrylate, methylene bisacrylamide, triallyl cyanurate, and the like.

A "prepolymer" is a monomer reaction product that contains remaining polymerizable groups capable of further reaction to form a polymer.

"Polymer network" is a cross-linked macromolecule that can swell but cannot dissolve in solvents. "Hydrogels" are polymer networks that swell in water or aqueous solutions, typically absorbing at least 10% by weight of water. "Silicone hydrogels" are hydrogels that are made from at least one silicone-containing component with at least one hydrophilic component. Hydrophilic components may also include non-reactive polymers.

"Conventional hydrogels" refers to polymer networks made from monomers without any siloxy, siloxane, or carbosiloxane groups. Traditional hydrogels are obtained from reaction mixtures containing hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate (HEMA), N-vinylpyrrolidone (NVP), N,N-dimethylacrylamide (DMA), or vinyl acetate. U.S. Patent Nos. 4,436,887, 4,495,313, 4,889,664, 5,006,622, 5,039,459, 5,236,969, 5,270,418, 5,298,533, 5,824,719, 6,420,453, 6,423 ,761, 6,767,979, 7,934,830, 8,138,290 and 8,389,597 describe the preparation of traditional hydrogels. Commercially available traditional hydrogels include, without limitation, etafilcon, genfilcon, gilafilcon, lenefilcon, nesofilcon, omafilcon, polymacon, and vifilcon, including all variants thereof.

The term "silicone hydrogels" refers to polymer networks made from at least one hydrophilic component and at least one silicone-containing component. Examples of commercially available silicone hydrogels include aquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, enfilcon, fanfilcon, formofilcon, halifilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon, including all variants thereof, as well as silicone hydrogels manufactured US Patent Nos. 4,659,782; 4,659,783; 5,244,981; 5,314,960; 5,331,067; 5,371,147; 5,998,498; 6,087,415; 89.461, 5.849.811, 5.965.631, 6.367.929, 6.822.016, 6.867.245 .185 . 9,125,808 .297.928, 9.297.929 , as well as WO 03/22321, WO 2008/061992 and US 2010/0048847. These patents are incorporated herein by reference in their entirety.

An "interpenetrating polymer network" comprises two or more polymer networks that are at least partially intertwined at the molecular level, but are not covalently bonded to each other and cannot be separated without breaking chemical bonds. A "semi-interpenetrating polymer network" comprises one or more networks and one or more polymers characterized by some mixing at the molecular level between at least one network and at least one polymer. A mixture of different polymers is a "polymer blend". A semi-interpenetrating network is technically a polymer blend, but in some cases the polymers are so tightly intertwined that they cannot be easily removed.

"Reactive Components" are the polymerizable compounds (such as monomers, macromers, oligomers, prepolymers, and crosslinkers) in a reaction mixture (defined below), as well as any other reaction mixture components that are intended to substantially remain in the resulting polymer. mesh after completion of polymerization and all processing steps (such as extraction steps) and packaging. The reactive components may be retained in the polymer network by covalent bonding, hydrogen bonding, electrostatic interactions, formation of interpenetrating polymer networks, or any other means. Components intended to be released from the polymer network once it is used are still considered "reactive components". For example, pharmaceutical or nutraceutical components in a contact lens that are intended to be released during wear are considered "reactive components". Components that are intended to be removed from the polymer network during the manufacturing process (eg by extraction), such as diluents, are not "reactive components".

The terms “reaction mixture” and “reaction monomer mixture” refer to a mixture of components that are mixed together and, when subjected to polymerization conditions, result in the formation of a polymer network (such as conventional or silicone hydrogels) as well as biomedical devices, ophthalmic devices, and contact lenses made from them. The reaction mixture may contain reactive components such as monomers, macromers, prepolymers, crosslinkers, initiators, additives such as wetting agents, polymers, dyes, light absorbing compounds such as UV absorbers, pigments, photochromic compounds, pharmaceutical compounds and/or nutraceutical compounds, any of which may be polymerizable or non-polymerizable, but they are able to be retained in the resulting biomedical device (for example, a contact lens). The reaction mixture may also contain other components that are intended to be removed from the device prior to use, such as diluents. It should be understood that a wide variety of additives may be added depending on the type of lens being manufactured and its intended application. The concentrations of the components of the reaction mixture are expressed as mass fractions of all reactive components in the reaction mixture, with the exception of diluents. When diluents are used, their concentrations are expressed as mass fractions of the total amount of all components in the reaction mixture (including the diluent).

The term "silicone hydrogel contact lens" refers to a hydrogel contact lens made from at least one silicone-containing compound. Silicone hydrogel contact lenses essentially have increased oxygen permeability compared to conventional hydrogels. To transfer oxygen to the eye, silicone hydrogel contact lenses use both their water and polymer components.

The term "multifunctional" refers to a component having two or more polymerizable groups. The term "monofunctional" refers to a component having a single polymerizable group.

The terms "halogen" or "halo" refer to fluorine, chlorine, bromine and iodine.

"Alkyl" refers to an optionally substituted straight or branched chain alkyl group containing the specified number of carbon atoms. If the number is not specified, then alkyl (optionally including any substituents on alkyl) may contain from 1 to 16 carbon atoms. The alkyl group preferably has 1 to 10 carbon atoms, alternatively 1 to 8 carbon atoms, alternatively 1 to 6 carbon atoms, or alternatively 1 to 4 carbon atoms. Examples of alkyl include methyl, ethyl, propyl, isopropyl, butyl, iso-, sec-, and tert-butyl, pentyl, hexyl, heptyl, 3-ethylbutyl, and the like. Examples of substituents on an alkyl group include 1, 2, or 3 groups independently selected from hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, thioalkyl, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Alkylene" means a divalent alkyl group such as -CH ₂ -, -CH ₂ CH ₂ -, -CH ₂ CH ₂ CH ₂ -, -CH ₂ CH(CH ₃ )CH ₂ - and -CH ₂ CH ₂ CH _{2 CH2-} .

The term "haloalkyl" refers to an alkyl group as defined above which is substituted by one or more halogen atoms, where each halogen is independently F, Cl, Br, or I. Preferred halogen is F. Preferred haloalkyl groups contain 1-6 carbon atoms , more preferably 1-4 carbon atoms and even more preferably 1-2 carbon atoms. The term "haloalkyl" includes perhaloalkyl groups such as -CF ₃ - or -CF ₂ CF ₃ -. The term "haloalkylene" means a divalent haloalkyl group such as -CH ₂ CF ₂ -.

"Cycloalkyl" refers to an optionally substituted cyclic hydrocarbon containing the specified number of carbon atoms in the ring. If the number is not specified, then cycloalkyl may contain from 3 to 12 carbon atoms in the ring. Preferred are C ₃ -C ₈ cycloalkyl groups, C ₃ -C ₇ cycloalkyl, more preferably C ₄ -C ₇ cycloalkyl and even more preferably C ₅ -C ₆ cycloalkyl. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of substituents on the cycloalkyl group include 1, 2 or 3 groups independently selected from alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, thioalkyl, amido, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. The term "cycloalkylene" means a divalent cycloalkyl group such as 1,2-cyclohexylene, 1,3-cyclohexylene or 1,4-cyclohexylene.

The term "heterocycloalkyl" refers to a cycloalkyl ring or ring system as defined above in which at least one carbon in the ring is replaced by a heteroatom selected from nitrogen, oxygen and sulfur. The heterocycloalkyl ring is optionally fused or otherwise connected to other heterocycloalkyl rings and/or non-aromatic hydrocarbon rings and/or phenyl rings. Preferred heterocycloalkyl groups have 5 to 7 members. More preferred heterocycloalkyl groups have 5 to 6 members. The term "heterocycloalkyl" means a divalent heterocycloalkyl group.

"Aryl" refers to an optionally substituted aromatic hydrocarbon ring system containing at least one aromatic ring. The aryl group contains the indicated number of carbon atoms in the ring. If the number is not specified, aryl may contain from 6 to 14 carbon atoms in the ring. The aromatic ring may optionally be fused or otherwise attached to other aromatic hydrocarbon rings or non-aromatic hydrocarbon rings. Examples of aryl groups include phenyl, naphthyl and biphenyl. Preferred examples of aryl groups include phenyl. Examples of substituents on the aryl group include 1, 2 or 3 groups independently selected from alkyl, hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, thioalkyl, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. The term "arylene" means a divalent aryl group, such as 1,2-phenylene, 1,3-phenylene or 1,4-phenylene.

The term "heteroaryl" refers to an aryl ring or ring system as defined above in which at least one carbon atom in the ring is replaced by a heteroatom selected from nitrogen, oxygen and sulfur. The heteroaryl ring may be fused or otherwise attached to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings, or heterocycloalkyl rings. Examples of heteroaryl groups include pyridyl, furyl, and thienyl. The term "heteroarylene" means a divalent heteroaryl group.

The term "alkoxy" means an alkyl group attached to the original fragment of the molecule through an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy and isopropoxy. "Thioalkyl" means an alkyl group attached to the parent molecule through a sulfur-containing bridge. Examples of thioalkyl groups include, for example, methylthio, ethylthio, n-propylthio and isopropylthio. The term "aryloxy" means an aryl group attached to the original fragment of the molecule through an oxygen bridge. Examples include phenoxy. The term "cyclic alkoxy group" means a cycloalkyl group attached to the original fragment through an oxygen bridge.

The term "alkylamine" refers to an alkyl group attached to the original fragment of the molecule through the bridge -NH. The term "alkyleneamine" means a divalent alkylamine group such as -CH ₂ CH ₂ NH-.

The term "siloxanil" refers to a structure having at least one Si-O-Si bond. Thus, for example, a siloxanyl group means a group having at least one Si-O-Si group (ie, a siloxane group), and a siloxanyl compound means a compound having at least one Si-O-Si group. The term "siloxanil" embraces monomeric (eg Si-O-Si) as well as oligomeric/polymeric structures (eg -[Si-O] _n - where n is 2 or more). Each silicon atom in the siloxanyl group is substituted with independently selected groups R ^A (where R ^A is defined as indicated in (b)-(i) of formula A) to fill the valency.

The term "silyl" refers to a structure of formula R ₃ Si-, and "siloxy" refers to a structure of formula R ₃ Si-O-, where each R in silyl or siloxy is independently selected from trimethylsiloxy, C ₁ -C ₈ alkyl (preferably C ₁ -C ₃ alkyl, more preferably alkyl or methyl) and C ₃ -C ₈ cycloalkyl.

The term "alkyleneoxy" refers to groups of the general formula -(alkylene-O) _p - or -(O-alkylene) _p -, where alkylene is defined as above and p is from 1 to 200, or from 1 to 100, or 1 to 50, or 1 to 25, or 1 to 20, or 1 to 10, each alkylene being independently optionally substituted with one or more groups independently selected from hydroxyl, halogen (e.g. fluorine), amino, amido, ether, carbonyl, carboxyl, and combinations thereof. If p is greater than 1, then all alkylenes may be the same or different, and alkyleneoxy may have a block or random configuration. If the alkyleneoxy forms an end group in the molecule, the alkyleneoxy end may, for example, be hydroxy or alkoxy (eg HO-[CH ₂ CH ₂ O] _p - or CH ₃ O-[CH ₂ CH ₂ O] _p -). Examples of alkyleneoxy include polyethyleneoxy, polypropyleneoxy, polybutyleneoxy, and poly(ethyleneoxy-co-propyleneoxy).

The term "oxaalkylene" refers to an alkylene group, as defined above, in which one or more non-adjacent CH ₂ groups have been replaced by an oxygen atom, eg -CH ₂ CH ₂ OCH(CH ₃ )CH ₂ -. The term "thiaalkylene" refers to an alkylene group, as defined above, in which one or more non-adjacent CH ₂ groups have been replaced by a sulfur atom, eg -CH ₂ CH ₂ SCH(CH ₃ )CH ₂ -.

The term "linking group" refers to a functional group that links the polymerizable group to the original molecule. The linking group may be any functional group that is compatible with the compound of which it is a part, that does not adversely affect the polymerization of the compound, is stable under polymerization conditions, as well as under the conditions of processing and storage of the finished product. For example, the linking group may be a bond or may be one or more of alkylene, haloalkylene, amide, amine, alkyleneamine, carbamate, ester (-CO ₂ -), arylene, heteroarylene, cycloalkylene, heterocycloalkylene, alkyleneoxy, oxaalkylene, thiaalkylene , haloalkyleneoxy (alkyleneoxy substituted with one or more halogen groups, for example -OCF ₂ -, -OCF ₂ CF ₂ -, -OCF ₂ CH ₂ -), siloxanyl, alkylenesiloxanyl, or combinations thereof. The linking group may optionally be substituted with 1 or more groups. Acceptable substituents may include groups independently selected from alkyl, halogen (e.g., fluoro), hydroxyl, HO-alkyleneoxy, MeO-alkyleneoxy, siloxanyl, siloxy, siloxy-alkyleneoxy-, siloxy-alkylene-alkyleneoxy- (in which may be present more than one alkyleneoxy group, and in which each methylene in the alkylene or alkyleneoxy is independently optionally substituted with hydroxyl), an ether, an amine, a carbonyl, a carbamate, and combinations thereof. The linking group may also be substituted with a polymerizable group such as (meth)acrylate (in addition to the polymerizable group to which the linking group is attached).

Preferred linking groups include C ₁ -C ₈ alkylene (preferably C ₂ -C ₆ alkylene) and C ₁ -C ₈ oxaalkylene (preferably C ₂ -C ₆ oxaalkylene), each of which is optionally substituted with 1 or 2 groups, independently selected from hydroxyl and siloxy. Preferred linking groups also include carboxylate, amide, C ₁ -C ₈ alkylene carboxylate-C ₁ -C ₈ alkylene or C ₁ -C ₈ alkylene amide-C ₁ -C ₈ alkylene.

If the linking group consists of combinations of the functional groups described above (eg, alkylene and cycloalkylene), then these functional groups may be present in any order. For example, if in formula A below L is indicated as -alkylene-cycloalkylene-, then Rg-L can be either Rg-alkylene-cycloalkylene- or Rg-cycloalkylene-alkylene-. Despite this, the order of enumeration is the preferred order in which the functional groups appear in the compound, starting with the terminal polymerizable group (Rg or Pg) to which the linking group is attached. For example, if in formula A below L is indicated as -alkylene-cycloalkylene-, then Rg-L is preferably Rg-alkylene-cycloalkylene-.

The term "electron withdrawing group" (EWG) refers to a chemical group that draws electron density away from the atom or group of atoms to which the electron withdrawing group is attached. Examples of EWG include, but are not limited to, cyano, amide, ester, keto, or aldehyde. The preferred EWG is cyano (CN).

The term "light-absorbing compound" refers to a chemical material that absorbs light in the visible region of the spectrum (for example, in the range from 380 nm to 780 nm). The terms "high energy absorber", "UV/HEV absorber", or "high energy absorbent compound" refer to a chemical material that absorbs radiation at various wavelengths in the ultraviolet region, the high energy region of the visible spectrum, or both. areas. The ability of a material to absorb certain wavelengths of light can be determined by measuring its range of UV/visible light transmission or absorption.

If the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless otherwise indicated, these compounds are assumed to include the cis, trans, Z, and E configurations. Likewise, all tautomeric forms and salt forms are intended to be included.

The term "optional substituent" means that a hydrogen atom in the underlying functional group is optionally substituted with a substituent. Any substituent may be used in the substitution site which may be sterically desirable and synthetically achievable. The definition of a suitable optional substituent is well known to the person skilled in the art. Examples of "optional substituent" include, without limitation, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ thioalkyl, C ₃ -C ₇ cycloalkyl, aryl, halogen, hydroxy, amino, NR ⁴ R ⁵ , benzyl, SO ₃ H, SO ₃ Na or -YP _g , where R ⁴ and R ⁵ are independently H or C ₁ -C ₆ alkyl, Y is a linking group; and P _g is a polymerizable group. The above substituents may optionally be substituted with an optional substituent (which, unless otherwise indicated, is preferably no longer substituted). For example, alkyl may be substituted with halogen (which gives, for example, CF ₃ ).

The term "substructure" means the chemical structure of a compound and any compounds derived from that chemical structure by replacing one or more hydrogen atoms with any other atom (this atom may be bonded to other atoms or groups). The substitution, for example, may be the replacement of one or more, preferably 1 or 2 hydrogen atoms, more preferably 1 hydrogen atom, with an independently selected optional substituent. The term "substructure" encompasses materials in which the substructure forms a fragment of a larger compound, such as a monomer (eg, containing one or more polymerizable groups), a polymer, or a macromolecule.

The term "maximum visible light absorption" means a wavelength in the visible light wavelength range (380 nm to 760 nm) at which light absorption is maximum. This definition covers materials that have maximum absorption values outside the visible light range, such as the UV region.

The terms "lightfastness", "lightfastness" or similar expressions mean that the compound (which, when measured, may optionally be embedded in an ophthalmic device such as a hydrogel contact lens, and optionally measured either inside or outside the blister pack or vial) has an absorption loss at a maximum absorption of visible light of not more than 20 percent after exposure to light under conditions such as those indicated in the International Conference on Harmonization (ICH; International Conference on Harmonization) guidelines for the technical requirements for registration of medicinal products for medical use "Photostability test Q1B new drug substances and products" (Q1B Photostability Testing of New Drug Substances and Products), published in November 1996. Preferably, the exposure is carried out in accordance with the ICH guidelines for the study of photostability using the light source from option 2 with a calculated illumination of 1.5192 × 10 ⁶ lux/h (168.8 h exposure time) and a calculated UV irradiance of 259.4 Wh/m ² (16.2 h exposure time), preferably in a photostability test chamber stabilized at 25°C and relative humidity of the environment. After exposure, the UV/VIS spectrum of the sample is recorded and compared with the spectrum of the sample before exposure. As an example, if the absorption at the maximum absorption of visible light is 4 optical units before exposure and 2 optical units after exposure, then the absorption loss is 50 percent. In the present invention, the absorption loss after exposure is preferably no more than 15 percent, or no more than 10 percent, or no more than 5 percent, or no more than 4 percent, or no more than 3 percent, or no more than 2 percent, or no more than 1 percent, or not more than 0.5 percent, or not more than 0.1 percent.

The expression "more lightfast than macular pigment" or a similar expression means that the compound (which, when tested, may optionally be embedded in an ophthalmic device such as a hydrogel contact lens, and optionally measured inside or outside the blister pack) has less absorption loss at maximum absorbance of visible light than that observed in macular pigment after exposure to light, for example, in accordance with the ICH Guidelines for the study of light fastness, as described above.

The term "full width at half maximum" (FWHM) means the width of an absorption peak at half its maximum intensity.

Unless otherwise indicated, ratios, percentages, fractions, etc. are by weight.

Unless otherwise noted, numeric ranges, such as "from 2 to 10" or "between 2 and 10", include the numbers that define the range (eg, 2 and 10).

As noted above, in one aspect, the present invention provides compounds that substantially mimic the visible light absorption characteristics of a macular pigment. These compounds are more light stable than macular pigment and can therefore be used in the manufacture of products. For example, these compounds can be used in ophthalmic devices.

Thus, the compound of the present invention can have a maximum visible light absorption in the range of 430 nm to 480 nm and a full width at half maximum (FWHM) with a maximum visible light absorption of at least 35 nm and up to 100 nm. The compound may be lightfast (eg when measured according to ICH Q1B). The compound may be more light stable than the macular pigment.

The compound may have a maximum visible light absorption in the range of 440 nm to 470 nm, or 445 nm to 465 nm, or 450 nm to 460 nm, or 455 nm to 460 nm.

The compound may have a FWHM with a visible light absorption maximum of at least 35 nm, or at least 40 nm, or at least 45 nm, or at least 55 nm, or at least 60 nm, or at least 65 nm. The compound may have FWHM at a maximum absorption of visible light up to 95 nm, or up to 90 nm, or up to 85 nm, or up to 80 nm, or up to 75 nm, or up to 70 nm. FWHM at maximum absorption of visible light can be in the range of 35 nm to 100 nm, or 45 nm to 90 nm, or 55 nm to 80 nm, or 60 nm to 75 nm, or 65 nm to 70 nm.

The compound of the present invention may have a molar extinction coefficient at maximum absorption of visible light of at least 5000, or at least 5500, or at least 6000, or at least 6500, or at least 7000, or at least 7500 .

The compound of the present invention may contain a chromophore having the substructure of formula I:

where EWG in each case independently represents an electron withdrawing group, and where the peak absorption of visible light of the compound is in the range from 440 nm to 480 nm.

EWG can independently in each occurrence be cyano, amide, ester, keto, or aldehyde. Preferably, EWG is cyano in each case.

The compounds of the present invention may have the formula II:

where EWG in each case independently represents an electron withdrawing group; n is 1, 2 or 3; and R ¹ is independently H, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ thioalkyl, C ₃ -C ₇ cycloalkyl, aryl, halogen, hydroxy, amino, NR ³ R ⁴ benzyl, SO ₃ H or SO ₃ M (M is a monovalent cation such as sodium or potassium) or -YP _g where R ³ and R ⁴ are independently H or C ₁ -C ₆ alkyl, Y is linking group; and P _g is a polymerizable group. Preferably, the compound contains 0 groups, 1 group, or 2 -YP _g groups (which may or may not be the same). If n in formula II is 2 or 3, the R ¹ groups may be located in any substitutable position in the ring.

The compounds of formula II may include compounds of formula II-1, which are compounds of formula II, where R ¹ in each case independently represents H or C ₁ -C ₆ alkyl (preferably ethyl or methyl).

Chromophores of formula II may include compounds of formula II-2, which are compounds of formula II, where n is 1 and R ¹ represents YP _g .

Compounds of formulas II and II-2 may include compounds of formula II-3 which are compounds of formula II or II-2 wherein P _g (polymerizable group) each independently contains styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N -vinyl lactam, N-vinylamide, (meth)acrylate or (meth)acrylamide. Preferred polymerizable groups include (meth)acrylate or (meth)acrylamide. A more preferred polymerizable group is methacrylate.

Compounds of formulas II, II-2 and II-3 may include compounds of formula II-4 which are compounds of formula II, II-2 or II-3, where Y (linking group) in each occurrence is independently alkylene, cycloalkylene, heterocycloalkylene, arylene (eg phenylene), heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene or combinations of any of the above groups. Preferred linking groups include C ₁ -C ₈ alkylene (eg ethylene or propylene), C ₁ -C ₈ oxaalkylene, C ₁ -C ₈ alkylene amide-C ₁ -C ₈ alkylene and C ₁ -C ₈ alkylene amine -C ₁ -C ₈ alkylene. Especially preferred is C ₁ -C ₈ oxaalkylene, or C ₂ -C ₄ oxaalkylene, or oxaethylene (-O-CH ₂ CH ₂ -).

Compounds of formula II, II-1, II-2, II-3 and II-4 may include compounds of formula II-5 which are compounds of formula II, II-1, II-2, II-3 or II- 4, where EWG is independently at each occurrence cyano, amide, ester, keto, or aldehyde. EWG in each case may be cyano.

Compounds of formula II, II-1, II-2, II-3, II-4 and II-5 may include compounds of formula II-6 which are compounds of formula II, II-1, II-2, II-3 , II-4 or II-5, where n is 1 or 2, preferably n is 1.

The compounds of the present invention may have the formula III:

where EWG in each case independently represents an electron withdrawing group; and R ¹ is H, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ thioalkyl, C ₃ -C ₇ cycloalkyl, aryl, halogen, hydroxy, amino, NR ³ R ⁴ , benzyl, SO ₃ H or SO ₃ M (M is a monovalent cation, eg sodium or potassium) or YP _g where R ³ and R ⁴ are independently H or C ₁ -C ₆ alkyl, Y is a linking group; and P _g is a polymerizable group.

The compounds of formula III may include compounds of formula III-1, which are compounds of formula III, where R ¹ represents H or C ₁ -C ₆ alkyl (preferably ethyl or methyl).

Compounds of formula III may include compounds of formula III-2, which are compounds of formula III, where R ¹ represents YP _g .

Compounds of formulas III and III-2 may include compounds of formula III-3, which are compounds of formula III or III-2, where P _g (polymerizable group) contains styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N- vinylamide, (meth)acrylate or (meth)acrylamide. Preferred polymerizable groups include (meth)acrylate or (meth)acrylamide. A more preferred polymerizable group is methacrylate.

Compounds of formula III, III-2 and III-3 may include compounds of formula III-4 which are compounds of formula III, III-2 or III-3 where Y (linking group) is alkylene, cycloalkylene, heterocycloalkylene, arylene (eg phenylene), heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene or combinations of any of the above groups. Preferred linking groups include C ₁ -C ₈ alkylene (eg ethylene or propylene), C ₁ -C ₈ oxaalkylene, C ₁ -C ₈ alkylene amide-C ₁ -C ₈ alkylene and C ₁ -C ₈ alkylene amine -C ₁ -C ₈ alkylene. Especially preferred is C ₁ -C ₈ oxaalkylene, or C ₂ -C ₄ oxaalkylene, or oxaethylene (-O-CH ₂ CH ₂ -).

Compounds of formula III, III-1, III-2, III-3 and III-4 may include compounds of formula III-5 which are compounds of formula III, III-1, III-2, III-3 or III-4 where EWG is independently at each occurrence cyano, amide, ester, keto, or aldehyde. EWG in each case may be cyano.

Specific examples of the compounds of the present invention are shown in Table A.

Table A

2-(9H-thioxanthene-9-ylidene)malonitrile
2-((9-(dicyanomethylene)-9H-thioxanthen-2-yl)oxy)ethyl methacrylate

The compounds of the present invention can be used in combination with other light absorbing compounds to provide the desired absorption characteristics. For example, preferred compositions may contain a compound described above together with a UV absorbing compound. Suitable UV absorbing compounds are known in the art and fall into several classes including, but not limited to, benzophenones, benzotriazoles, triazines, substituted acrylonitriles, salicyclic acid derivatives, benzoic acid derivatives, cinnamic acid derivatives, chalcone derivatives, dipnon derivatives , derivatives of crotonic acid or any mixture thereof. A preferred class of UV absorbing compounds are benzotriazoles such as Norbloc (2-(2'-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole).

The compounds of the present invention can be included in reaction mixtures to form various products, including biomedical devices and ophthalmic devices. These compounds may, for example, be included in the device and/or applied to the surface of the device. When included in a device, these compounds can essentially be added to the reaction mixture from which the device is made, and can be present in any amount up to the limit value of their solubility. For example, the concentration of these compounds may be in the range of at least 0.1 percent or at least 2 percent; and up to 10 percent or up to 5 percent, based on the mass fraction of all components in the reaction mixture, with the exception of the diluent. A typical concentration may be in the range of 1 to 5 percent. The upper limit is generally determined by the solubility of the compound with other comonomers and/or diluents in the reaction monomer mixture.

The compounds of the present invention are preferably formulated into ophthalmic devices. A variety of ophthalmic devices can be made, including spectacle lenses, sun lenses, hard contact lenses, soft contact lenses, corneal patches, corneal implants, intraocular lenses, or masking lenses. The ophthalmic device is preferably an intraocular lens or a soft contact lens. A soft contact lens can be made from conventional (non-silicone) hydrogel or silicone hydrogel.

The ophthalmic devices of the present invention may comprise a free radical reaction product of a reaction mixture containing one or more monomers suitable for making the desired ophthalmic device (also referred to herein as device-forming monomers or hydrogel-forming monomers), and optional components. Upon polymerization, the reaction mixture results in the formation of a polymeric network that can be used to form an ophthalmic device. The polymeric network may be, for example, a hydrogel (eg a conventional hydrogel or a silicone hydrogel).

The compound of the present invention may be copolymerized with other components of the reaction mixture, in which case the reaction mixture may, in addition to one or more monomers suitable for making the desired ophthalmic device (and any optional components), also contain one or more compounds of the present invention .

Non-limiting examples of polymeric networks into which a compound of the present invention may be incorporated (e.g., as a monomer) are described above and include, for example, etafilcon, genfilcon, gilafilcon, lenefilcon, nesofilcon, omafilcon, polymacon, vifilcon, aquafilcon, asmophilcon, balafilcon, comfilcon, defilcon, enfilcon, fanfilcon, formofilcon, halifilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon and stenfilcon, including all variants thereof.

As a further example, a polymer network can be made from a reaction mixture containing one or more of: hydrophilic components, hydrophobic components, silicone-containing components, wetting agents such as polyamides, cross-linking agents, and additional components such as diluents and initiators. As described above, the reaction mixture may also contain one or more compounds of the present invention.

Hydrophilic components

Examples of suitable families of hydrophilic monomers that may be present in the reaction mixture include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinylamides, N-vinylimides, N-vinylureas, O-vinylcarbamates. , O-vinyl carbonates, other hydrophilic vinyl compounds and mixtures thereof.

Non-limiting examples of hydrophilic (meth)acrylate and (meth)acrylamide monomers include: acrylamide, N-isopropylacrylamide, N,N-dimethylaminopropyl(meth)acrylamide, N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl(meth)acrylate, 3-hydroxypropyl(meth)acrylate, 2,3-dihydroxypropyl(meth)acrylate, 2-hydroxybutyl(meth)acrylate, 3-hydroxybutyl(meth)acrylate, 4-hydroxybutyl(meth)acrylate, N-(2-hydroxyethyl)(meth)acrylamide, N,N-bis(2-hydroxyethyl)(meth)acrylamide, N-(2-hydroxypropyl)(meth)acrylamide, N,N-bis(2-hydroxypropyl)( meth)acrylamide, N-(3-hydroxypropyl)(meth)acrylamide, N-(2-hydroxybutyl)(meth)acrylamide, N-(3-hydroxybutyl)(meth)acrylamide, N-(4-hydroxybutyl)(meth) acrylamide, 2-aminoethyl(meth)acrylate, 3-aminopropyl(meth)acrylate, 2-aminopropyl(meth)acrylate, N-2-aminoethyl(meth)acrylamides), N-3-aminopropyl(meth)acrylamide, N-2 -aminopropyl(meth)acrylamide, N,N-bis-2-aminoethyl(meth)acrylamides, N,N-bis-3-aminopropyl(meth)acrylamide), N,N-bis-2-aminopropyl(meth)acrylamide, glycerol methacrylate, polyethylene glycol monomethacrylate, (meth)acrylic acid, vinyl acetate, acrylonitrile, and mixtures thereof.

Hydrophilic monomers can also be ionic, including anionic, cationic, zwitterion, betaines, and mixtures thereof. Non-limiting examples of such charged monomers include (meth)acrylic acid, N-[(ethenyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropanoic acid (ACA1), 5-acrylamidopentanoic acid (ACA2), 3-acrylamido -3-methylbutanoic acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q-salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)-N, N -dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, internal salt (CBT), 1-propanaminium, N,N-dimethyl-N-[3-[(1-oxo- 2-propen-1-yl) amino]propyl]-3-sulfo-, internal salt (SBT), 3,5-dioxa-8-aza-4-phosphonoundec-10-ene-1-aminium, 4-hydroxy- N,N,N-trimethyl-9-oxo-, internal salt, 4-oxide (9CI) (PBT), 2-methacryloyloxyethylphosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio )propane-1-sulfonate (APDAPS); and methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

Non-limiting examples of hydrophilic N-vinyl lactam and N-vinylamide monomers include: N-vinylpyrrolidone (NVP), N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2 -caprolactam, N-vinyl-3-methyl-2-piperidone, N-vinyl-4-methyl-2-piperidone, N-vinyl-4-methyl-2-caprolactam, N-vinyl-3-ethyl-2-pyrrolidone , N-vinyl-4,5-dimethyl-2-pyrrolidone, N-vinylacetamide (NVA), N-vinyl-N-methylacetamide (VMA), N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N -vinylformamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N-vinyl-2-methylpropionamide, N-vinyl-N, N'-dimethylurea, 1-methyl-3-methylene- 2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone; 1-ethyl-5-methylene-2-pyrrolidone, N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-N-propyl-3-methylene-2-pyrrolidone, 1-N-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-ethylacetamide, N-vinyl- N-ethylformamide, N-vinylformamide, N-vinylisopropylamide, N-vinylcaprolactam, N-vinylimidazole and mixtures thereof.

Non-limiting examples of hydrophilic monomers of O-vinyl carbamates and O-vinyl carbonates include N-2-hydroxyethyl vinyl carbamate and N-carboxy-β-alanine N-vinyl ester. Additional examples of hydrophilic vinyl carbonate or vinyl carbamate monomers are described in US Pat. No. 5,070,215. Hydrophilic oxazolone monomers are described in US Pat. No. 4,910,277.

Other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, 2-ethyloxazoline.

The hydrophilic monomers may also be macromers or prepolymers of straight or branched poly(ethylene glycol), poly(propylene glycol), or random or block copolymers of ethylene oxide and propylene oxide having polymerizable moieties such as (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinylamides, and the like. The macromer of such polyethers has one polymerizable group; prepolymers may have two or more polymerizable groups.

Preferred hydrophilic monomers of the present invention are DMA, NVP, HEMA, VMA, NVA and mixtures thereof. Preferred hydrophilic monomers include mixtures of DMA and HEMA. Other suitable hydrophilic monomers will be apparent to those skilled in the art.

In general, there are no particular restrictions on the amount of hydrophilic monomer present in the reaction mixture. The amount of hydrophilic monomer can be selected based on the desired characteristics of the resulting hydrogel, including water content, transparency, wettability, protein uptake, and the like. Wettability can be measured using the contact angle. Desirable contact angles are less than about 100˚, less than about 80˚, and less than about 60˚. The hydrophilic monomer may be present in an amount in the range, for example, from about 0.1 wt.% to about 100 wt.%, in another embodiment, in the range from about 1 wt.% to about 80 wt.%, in another embodiment, in the range from about 5 wt.% to about 65 wt.%, in another embodiment in the range from about 40 wt.% to about 60 wt.%, or in another embodiment in the range from about 55 to about 60 wt.% of the total weight of the reactive components in reaction monomer mixture.

Silicone containing components

Silicone-containing components suitable for use in the invention comprise one or more polymerizable compounds, each compound independently containing at least one polymerizable group, at least one siloxane group, and one or more linking groups connecting the polymerizable group(s)(- s) with siloxane(s) group(s). Silicone-containing components may, for example, contain from 1 to 220 siloxane repeating units, such as the groups described below. The silicone-containing component may also contain at least one fluorine atom.

The silicone-containing component may contain: one or more polymerizable groups as defined above; one or more optionally repeating siloxane units; and one or more linking groups linking the polymerizable groups to the siloxane units. The silicone-containing component may contain: one or more polymerizable groups, which are independently (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinylamide, O-vinyl carbamate, O-vinyl carbonate, vinyl group, or mixtures of the above; one or more optionally repeating siloxane units; and one or more linking groups linking the polymerizable groups to the siloxane units.

The silicone-containing component may contain: one or more polymerizable groups which are independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinylamide, styryl, or mixtures of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups linking the polymerizable groups to the siloxane units.

The silicone-containing component may contain: one or more polymerizable groups, which are independently (meth)acrylate, (meth)acrylamide, or mixtures of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups linking the polymerizable groups to the siloxane units.

The silicone-containing component may contain one or more polymerizable groups of formula A:

wherein:

at least one R ^A is a group of formula R _g -L-, where R _g is a polymerizable group and L is a linking group, and each of the remaining R ^A is independently:

(a) _Rg -L-,

(b) C ₁ -C ₁₆ alkyl optionally substituted with one or more of hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halogen, phenyl, benzyl, or combinations thereof,

(c) C ₃ -C ₁₂ cycloalkyl optionally substituted with one or more of alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, amido, carbamate, carbonate, halogen, phenyl, benzyl, or combinations thereof,

(d) C ₆ -C ₁₄ aryl optionally substituted with one or more of alkyl, hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halogen, phenyl, benzyl, or combinations thereof,

(e) halogen,

(f) alkoxy, cyclic alkoxy or aryloxy,

(g) siloxy,

(h) an alkyleneoxyalkyl or alkoxyalkyleneoxyalkyl such as polyethyleneoxyalkyl, polypropyleneoxyalkyl or poly(ethyleneoxysopropyleneoxyalkyl), or

(i) a monovalent siloxane chain containing from 1 to 100 siloxane repeating units optionally substituted with alkyl, alkoxy, hydroxy, amino, oxa, carboxy, alkylcarboxy, alkoxy, amido, carbamate, halogen, or combinations thereof; And

n is from 0 to 500, or from 0 to 200, or from 0 to 100, or from 0 to 20, and it is assumed that if n is different from 0, then n is a distribution having a mode equal to the declared value. If n is 2 or more, the SiO units may have the same or different R ^A substituents, and if different R ^A substituents are present, then the n groups may have a random or block configuration.

In Formula A, each of the three ^RAs may contain a polymerizable group, alternatively, each of the two ^RAs may contain a polymerizable group, or alternatively, one ^RA may contain a polymerizable group.

Examples of silicone-containing components suitable for use in the present invention include, without limitation, the compounds listed in Table B. If the compounds in Table B contain polysiloxane groups, the number of SiO repeating units in such compounds, unless otherwise indicated, is preferably from 3 to 100, more preferably 3 to 40, or even more preferably 3 to 20.

Table B

1 monomethacryloxypropyl and mono-n-butyl terminated polydimethylsiloxanes (mPDMS) (preferably containing 3 to 15 SiO repeating units) 2 polydimethylsiloxane with monoacryloxypropyl and mono-n-butyl end groups 3 polydimethylsiloxane with mono(meth)acryloxypropyl and mono-n-methyl end groups 4 polydiethylsiloxane with mono(meth)acryloxypropyl and mono-n-butyl end groups 5 polydiethylsiloxane with mono(meth)acryloxypropyl and mono-n-methyl end groups 6 mono(meth)acrylamidoalkylpolydialkylsiloxanes 7 monoalkylpolydiarylsiloxanes with mono(meth)acryloxyalkyl end groups 8 3-methacryloxypropyltris(trimethylsiloxy)silane (TRIS) 9 3-Methacryloxypropylbis(trimethylsiloxy)methylsilane 10 3-methacryloxypropylpentamethyldisiloxane eleven mono(meth)acrylamidoalkylpolydialkylsiloxanes 12 mono(meth)acrylamidoalkylpolydimethylsiloxanes 13 N-(2,3-dihydroxypropane)-N'-(propyltetra(dimethylsiloxy)dimethylbutylsilane)acrylamide 14 N-[3-tris(trimethylsiloxy)silyl]propylacrylamide (TRIS-Am) 15 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]propyl methacrylate (SiMAA) 16 2-hydroxy-3-methacryloxypropyloxypropyltris(trimethylsiloxy)silane 17
mono(2-hydroxy-3-methacryloxypropyl)-propylether and mono-n-butyl terminated polydimethylsiloxanes (OH-mPDMS) (containing 4 to 30, or 4 to 20, or 4 to 15 SiO repeating units) 18 19 20 21 22 23 24

Additional non-limiting examples of suitable silicone-containing components are listed in Table C. Unless otherwise indicated, where applicable, j2 is preferably from 1 to 100, more preferably from 3 to 40, or even more preferably from 3 to 15. In compounds containing j1 and j2, the sum of j1 and j2 is preferably 2 to 100, more preferably 3 to 40, or even more preferably 3 to 15.

Table C

25 26
p is between 1 and 10 27
p is between 5 and 10 28 29 thirty 1,3-bis[4-(vinyloxycarbonyloxy)but-1-yl]tetramethyldisiloxane 31 3-(vinyloxycarbonylthio)propyl[tris(trimethylsiloxy)silane] 32 3-[tris(trimethylsiloxy)silyl]propylallyl carbamate 33 3-[tris(trimethylsiloxy)silyl]propylvinylcarbamate 34 tris(trimethylsiloxy)silylstyrene (Styryl-TRIS) 35 36 37 38 39 40 41

It is possible to use mixtures of silicone-containing components. By way of example, suitable mixtures may include, but are not limited to: a mixture of mono-(2-hydroxy-3-methacryloxypropyloxy)-propyl and mono-n-butyl terminated polydimethylsiloxane (OH mPDMS) of various molecular weights, such as a mixture of OH mPDMS, containing 4 and 15 repeating units of SiO; a mixture of OH mPDMS of various molecular weights (eg, containing 4 and 15 SiO repeating units) together with a silicone crosslinker such as bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (ac-PDMS); a mixture of 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA) and monomethacryloxypropyl and mono-n-butyl terminated polydimethylsiloxane (mPDMS), such as mPDMS 1000.

Silicone-containing components for use in the present invention may have an average molecular weight of from about 400 to about 4000 daltons.

The silicone-containing(s) component(s) may be included in the composition in an amount of up to about 95 wt.%, from about 10 wt.% to about 80 wt.%, from about 20 to about 70 wt.% of the total content reactive components in the reaction mixture (excluding diluents).

Polyamides

The reaction mixture may include at least one polyamide. Used in this document, the term "polyamide" refers to polymers and copolymers containing repeating units, which include amide groups. The polyamide may contain cyclic amide groups, acyclic amide groups, and combinations thereof, and may be any polyamide known to those skilled in the art. Acyclic polyamides contain pendant amide groups and are capable of associating with hydroxyl groups. Cyclic polyamides contain cyclic amide groups and are capable of associating with hydroxyl groups.

Examples of suitable acyclic polyamides include polymers and copolymers containing repeating units of formulas G1 and G2:

Formula G1

Formula G2

where X represents a direct connection, -(CO)- or -(CONHR ₄₄ )-, and R ₄₄ represents a C ₁ -C ₃ alkyl group; R ₄₀ is selected from H, substituted or unsubstituted C ₁ -C ₄ straight or branched chain alkyl groups; R ₄₁ is selected from H, substituted or unsubstituted C ₁ -C ₄ straight or branched chain alkyl groups, amino groups containing no more than two carbon atoms, amide groups containing no more than four carbon atoms, and alkoxy groups containing no more than two atoms carbon; R ₄₂ is selected from H, substituted or unsubstituted C ₁ -C ₄ straight or branched chain alkyl groups; or methyl, ethoxy, hydroxyethyl and hydroxymethyl; R ₄₃ is selected from H, substituted or unsubstituted C ₁ -C ₄ straight or branched chain alkyl groups; or methyl, ethoxy, hydroxyethyl and hydroxymethyl; where the number of carbon atoms in R ₄₀ and R ₄₁ taken together is 8 or less, including 7, 6, 5, 4, 3 or less; and where the number of carbon atoms in R ₄₂ and R ₄₃ taken together is 8 or less, including 7, 6, 5, 4, 3 or less. The number of carbon atoms in R ₄₀ and R ₄₁ taken together may be 6 or less, or 4 or less. The number of carbon atoms in R ₄₂ and R ₄₃ taken together may be 6 or less. As used herein, substituted alkyl groups include alkyl groups substituted with amino, amide, ether, hydroxyl, carbonyl, carboxyl groups, or combinations thereof.

R ₄₀ and R ₄₁ may be independently selected from H, substituted or unsubstituted C ₁ -C ₂ alkyl groups. X may be a direct bond, and R ₄₀ and R ₄₁ may be independently selected from H, substituted or unsubstituted C ₁ -C ₂ alkyl groups. R ₄₂ and R ₄₃ may be independently selected from H, substituted or unsubstituted C ₁ -C ₂ alkyl groups, methyl, ethoxy, hydroxyethyl and hydroxymethyl.

The acyclic polyamides of the present invention may contain most of the formula LV or formula LVI repeating units, or the acyclic polyamides may contain at least 50 mole percent of the formula G or formula G1 repeating units, including at least 70 mole percent and at least 80 mole percent. Specific examples of repeating units of formula G and formula G1 include repeating units derived from N-vinyl-N-methylacetamide, N-vinylacetamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N-vinyl -2-methylpropionamide, N-vinyl-N, N'-dimethylurea, N, N-dimethylacrylamide, methacrylamide and acyclic amides of formulas G2 and G3:

Formula G2

Formula G3

Examples of suitable cyclic amides that can be used to prepare the cyclic polyamides of the present invention include α-lactam, β-lactam, γ-lactam, δ-lactam and ε-lactam. Examples of suitable cyclic polyamides include polymers and copolymers containing repeating units of formula G4:

Formula G4

where R ₄₅ represents a hydrogen atom or a methyl group; where f is an integer from 1 to 10; where X represents a direct connection, -(CO)- or -(CONHR ₄₆ )-, where R ₄₆ represents a C ₁ -C ₃ alkyl group. In formula LIX, f may be 8 or less, including 7, 6, 5, 4, 3, 2, or 1. In formula G4, f may be 6 or less, including 5, 4, 3, 2, or 1. In formula G4 f may be 2 to 8, including 2, 3, 4, 5, 6, 7, or 8. In Formula LIX, f may be 2 or 3. If X is a direct bond, f may be 2. In such cases, the cyclic polyamide may be polyvinylpyrrolidone (PVP).

The cyclic polyamides of the present invention may contain 50 mole percent or more of a repeating unit of formula G4, or the cyclic polyamides may include at least 50 mole percent of a repeating unit of formula G4, including at least 70 mole percent, and at least 80 mole percent.

Polyamides can also be copolymers containing repeating units of cyclic and acyclic amides. Additional repeating units may be formed from monomers selected from hydroxyalkyl(meth)acrylates, alkyl(meth)acrylates or other hydrophilic monomers, and siloxanes substituted with (meth)acrylates. Any of the monomers listed above as suitable hydrophilic monomers may be used as a comonomer to form further repeating units. Specific examples of additional monomers that can be used to form polyamides include 2-hydroxyethyl (meth)acrylate, vinyl acetate, acrylonitrile, hydroxypropyl (meth)acrylate, methyl (meth)acrylate and hydroxybutyl (meth)acrylate, dihydroxypropyl (meth)acrylate, polyethylene glycol mono (meth)acrylate, etc., and mixtures thereof. Ionic monomers may also be included. Examples of ionic monomers include (meth)acrylic acid, N-[(ethenyloxy)carbonyl]-β-alanine (VINAL, CAS number 148969-96-4), 3-acrylamidopropionic acid (ACA1), 5-acrylamidopentanoic acid (ACA2), 3-acrylamido-3-methylbutanoic acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)- N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, internal salt (CBT, carboxybetaine; CAS 79704-35-1), 1-propanaminium, N,N-dimethyl -N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-, internal salt (SBT, sulfobetaine, CAS 80293-60-3), 3,5-dioxa -8-aza-4-phosphoundec-10-en-1-aminium, 4-hydroxy-N, N,N-trimethyl-9-oxo-, internal salt, 4-oxide (9CI) (PBT, phosphobetaine, CAS 163674 -35-9), 2-methacryloyloxyethylphosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3 -((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS), methacryloyloxy)propyl)dimethylammonio)propane-1- sulfonate (MAPDAPS).

The monomer reaction mixture may contain both acyclic polyamide and cyclic polyamide or their copolymers. The acyclic polyamide can be any of the acyclic polyamides described herein or their copolymers, and the cyclic polyamide can be any of the cyclic polyamides described herein or their copolymers. The polyamide may be selected from the group consisting of polyvinylpyrrolidone (PVP), polyvinylmethacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof. The polyamide may be a mixture of PVP (eg, PVP K90) and PVMA (eg, having an M _w of approximately 570 kDa).

The total amount of polyamides in the reaction mixture can be in the range from 1 wt.% to about 35 wt.%, including in the range from about 1 wt.% to about 15 wt.%, and in the range from about 5 wt.% to about 15 wt. wt.% in all cases, based on the total weight of the reactive components in the reaction monomer mixture.

Without wishing to be bound by theory, when used with silicone hydrogel, the polyamide acts as an internal wetted agent. The polyamides of the present invention may be non-polymerizable, in which case they are incorporated into silicone hydrogels as semi-interpenetrating polymer networks. The polyamides are captured or physically held within the silicone hydrogels. Alternatively, the polyamides of the present invention may be polymerizable, eg polyamide macromers or prepolymers, and in this case, are covalently incorporated into silicone hydrogels. Mixtures of polymerizable and non-polymerizable polyamides can also be used.

When polyamides are incorporated into the reactive monomer mixture, they may have a number average molecular weight of at least 100,000 daltons; more than approximately 150,000; between about 150,000 daltons to about 2,000,000 daltons; between about 300,000 daltons to about 1,800,000 daltons; Higher molecular weight polyamides may be used if they are compatible with the reactive monomer mixture.

Crosslinkers

As such, it is desirable to add one or more crosslinking agents, also referred to as crosslinking monomers, multifunctional macromers, and prepolymers, to the reaction mixture. Crosslinkers can be selected from bifunctional crosslinkers, trifunctional crosslinkers, tetrafunctional crosslinkers, and mixtures thereof, including silicone and non-silicon crosslinkers. Non-silicone crosslinkers include ethylene glycol dimethacrylate (EGDMA), tetraethylene glycol dimethacrylate (TEGDMA), trimethylol propane trimethacrylate (TMPTMA), triallyl cyanurate (TAC), glycerol methacrylate, methacryloxyethyl vinyl carbonate (HEMAVc), allyl methacrylate, methylene bisacrylamide (MBA), and polyethylene glycol dimethacrylate, with polyethylene the glycol has a molecular weight of up to about 5000 daltons. Crosslinkers are used in conventional amounts, for example, from about 0.000415 to about 0.0156 moles per 100 grams of reactive formulas in the reaction mixture. In another embodiment, if the hydrophilic monomers and/or silicone-containing components are multifunctional due to the structure of the molecule or due to the presence of impurities, then additional introduction of a crosslinking agent into the reaction mixture is optional. Examples of hydrophilic monomers and macromers that can act as crosslinkers and do not require additional crosslinkers to be added to the reaction mixture include (meth)acrylate and (meth)acrylamide terminated polyesters. Other crosslinkers are known to those skilled in the art that can be used to prepare the silicone hydrogels of the present invention.

It may be desirable to select crosslinkers with the same reactivity as one or more other reactive components in the formulation. In some cases, it may be desirable to select a mixture of crosslinkers with different reactivity to control some physical, mechanical, or biological property of the resulting silicone hydrogel. The structure and morphology of the silicone hydrogel can also be influenced by the diluent(s) and the polymerization conditions used.

Multifunctional silicone-containing components, including macromers, crosslinkers, prepolymers, can also be used to further increase the elastic modulus while maintaining tensile strength. Silicone-containing crosslinkers may be used alone or in combination with other crosslinkers. An example of a silicone-containing component that acts as a crosslinker, and which does not require additional crosslinkers to be added to the reaction mixture, is α,ω-bismethacryloxypropyl polydimethylsiloxane. Another example is bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (ac PDMS).

Crosslinking agents that have rigid chemical structures and polymerizable groups involved in free radical polymerization can also be used. Non-limiting examples of suitable rigid structures include phenyl and benzyl ring containing crosslinkers such as 1,4-phenylenediacrylate, 1,4-phenylenedimethacrylate, 2,2-bis(4-methacryloxyphenyl)-propane, 2,2-bis [4-(2-acryloxyethoxy)phenyl]propane, 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl]propane and 4-vinylbenzylmethacrylate and combinations thereof. Rigid cross-linking agents can be introduced in amounts between about 0.5 and about 15, or 2-10, 3-7, based on the total weight of all reaction components. The physical and mechanical properties of the silicone hydrogels of the present invention can be optimized for a particular application by adjusting the components of the reaction mixture.

Non-limiting examples of silicone crosslinkers also include the multifunctional silicone-containing components shown in Table D above.

Additional components

The reaction mixture may contain additional components such as, but not limited to, diluents, initiators, UV absorbers, visible light absorbers, photochromic compounds, drugs, nutraceuticals, antimicrobials, dyes, pigments, copolymerizable dyes and non-polymerizable dyes, releasing agents and their combinations.

Classes of suitable diluents for silicone hydrogel reactive mixtures include alcohols having 2 to 20 carbon atoms, amides having 10 to 20 carbon atoms derived from primary amines, and carboxylic acids having 8 to 20 carbon atoms. Diluents can be primary, secondary and tertiary alcohols.

Essentially, the reactive components are mixed with a diluent to form a reaction mixture. Acceptable diluents are known to those skilled in the art. Suitable diluents for silicone hydrogels are described in WO 03/022321 and US 6020445, the description of which is incorporated herein by reference.

Classes of suitable diluents for silicone hydrogel reactive mixtures include alcohols having 2 to 20 carbon atoms, amides having 10 to 20 carbon atoms derived from primary amines, and carboxylic acids having 8 to 20 carbon atoms. Primary and tertiary alcohols may be used. Preferred classes include alcohols having 5 to 20 carbon atoms and carboxylic acids having 10 to 20 carbon atoms.

Specific diluents that may be used include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropanol, 3,7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-octanol, 1-pentanol, 2 -pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, tert-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2- propanol, 1-propanol, ethanol, 2-ethyl-1-butanol, (3-acetoxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane, 1-tert-butoxy-2-propanol, 3,3-dimethyl-2-butanol , t-butoxyethanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, 2-(diisopropylamino)ethanol, mixtures thereof, and the like. Examples of amide diluents include N, N dimethyl propionamide and dimethylacetamide.

Preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol , 2-pentanol, tert-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, mixtures thereof, etc.

More preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 1-dodecanol, 3- methyl 3-pentanol, 1-pentanol, 2-pentanol, tert-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, 3.3 -dimethyl-2-butanol, 2-octyl-1-dodecanol, mixtures thereof, etc.

As such, there is no particular limitation on the amount of diluent present, so long as the diluent is present. If a diluent is used, it may be present in an amount in the range from about 2 wt.% to about 70 wt.%, including in the range from about 5 wt.% to about 50 wt.%, and in the range from about 15 wt.% to about 40 wt.% of the total mass of the reaction mixtures (including reactive and non-reactive formula). Mixtures of diluents may be used.

A polymerization initiator may be used in the reaction mixture. Polymerization initiators may include at least one of lauroyl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, and the like, which generate free radicals at moderately elevated temperatures, and photosensitizing systems such as aromatic alpha-hydroxy ketones, alkoxyoxybenzoins, acetophenones, acrylphosphine oxides, bisacylphosphine oxides, and tertiary amine plus diketone, mixtures thereof, etc. Illustrative examples of photoinitiators are 1-hydroxycyclohexylphenyl ketone, 2-hydroxy-2-methyl-1-phenylpropan-1-one, bis(2,6-dimethoxybenzoyl)-2,4-4 -trimethylpentylphosphine oxide (DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure 819), 2,4,6-trimethylbenzyldiphenylphosphine oxide and 2,4,6-trimethylbenzoyldiphenylphosphine oxide, benzoin methyl ether, and a combination of camphorquinone and ethyl-4-( N,N-dimethylamino)benzoate.

Marketed (by IGM Resins B.V., The Netherlands) visible light sensitive initiator systems include Irgacure® 819, Irgacure® 1700, Irgacure® 1800, Irgacure® 819, Irgacure® 1850 and Lucrin® TPO initiator. Marketed (by IGM Resins B.V.) UV-sensitive photoinitiators include Darocur® 1173 and Darocur® 2959. These and other photoinitiators that may be used are described in Volume III Photoinitiators for Free Radical Cationic & Anionic Photopolymerization, Volume III, 2 th edition by J. V. Crivello and K. Dietliker; edited by G. Bradley; John Wiley and Sons; New York; 1998. The initiator is used in the reaction mixture in effective amounts to initiate photopolymerization of the reaction mixture, for example, from about 0.1 to about 2 parts by weight per 100 parts of the reaction monomer mixture. The polymerization of the reaction mixture can be initiated by properly selected heating, or by exposure to visible or ultraviolet light, or by other means, depending on the polymerization initiator used. Alternatively, the initiation can be carried out using an electron beam without a photoinitiator. However, if a photoinitiator is used, the preferred initiators are bisacylphosphine oxides such as bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure® 819) or a combination of 1-hydroxycyclohexylphenylketone and bis(2,6-dimethoxybenzoyl)-2,4-4 -trimethylphenylphosphine oxide (DMBAPO).

The reaction mixture for the manufacture of ophthalmic devices of the present invention, in addition to the compound of the present invention, may contain any of the polymerizable compounds and additional components described above.

The reaction mixture may contain: a compound of the present invention, such as a compound of formula I, and a hydrophilic component.

The reaction mixture may contain: a compound of the present invention, such as a compound of formula I, and a hydrophilic component selected from DMA, NVP, HEMA, VMA, NVA, methacrylic acid, and mixtures thereof. Mixtures of HEMA and methacrylic acid are preferred.

The reaction mixture may contain: a compound of the present invention such as a compound of formula I, a hydrophilic component and a silicone-containing component.

The reaction mixture may contain: a compound of the present invention, such as a compound of formula I, a hydrophilic component selected from DMA, HEMA, and mixtures thereof; a silicone-containing component selected from 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]propyl methacrylate (SiMAA), monomethacryloxypropyl and mono-n-butyl-terminated polydimethylsiloxane (mPDMS), mono-terminated polydimethylsiloxane -(2-hydroxy-3-methacryloxypropyloxy)-propyl and mono-n-butyl groups (OH-mPDMS) and mixtures thereof; and a wetting agent (preferably PVP or PVMA). For the hydrophilic component, mixtures of DMA and HEMA are preferred. For the silicone-containing component, blends of SiMAA and mPDMS are preferred.

The reaction mixture may contain: a compound of the present invention, such as a compound of formula I, a hydrophilic component containing a mixture of DMA and HEMA; a silicone-containing component containing an OH-mPDMS mixture having 2 to 20 repeat units (preferably a mixture having 4 to 15 repeat units). The reaction mixture preferably further contains a silicone-containing cross-linking agent such as ac-PDMS. It is also preferred that the reaction mixture contains a wetting agent (preferably DMA, PVP, PVMA or mixtures thereof).

The reaction mixture may contain: a compound of the present invention, such as a compound of formula I; from about 1 wt.% to about 15 wt.% at least one polyamide (eg, acyclic polyamide, cyclic polyamide, or mixtures thereof); at least one first monofunctional hydroxyl-substituted poly(disubstituted siloxane) containing 4 to 8 siloxane repeating units (eg OH-mPDMS where n is 4 to 8, preferably n is 4); at least one second hydroxyl-substituted poly(disubstituted siloxane) which is a monofunctional hydroxyl-substituted poly(disubstituted siloxane) having 10 to 200 or 10-100 or 10-50 or 10-20 siloxane repeating units (e.g. OH-mPDMS, where n is from 10 to 200, or 10-100, or 10-50, or 10-20, or preferably n is 15); from about 5 wt.% to about 35 wt.% at least one hydrophilic monomer; and in some cases, a multifunctional hydroxyl-substituted poly(disubstituted siloxane) having 10 to 200 or 10 to 100 siloxane repeat units (eg, ac-PDMS). The first monofunctional hydroxyl-substituted poly(disubstituted siloxane) and the second hydroxyl-substituted poly(disubstituted siloxane) are preferably present in concentrations that provide the ratio of the mass fraction of the first monofunctional hydroxyl-substituted poly(disubstituted siloxane) to the mass fraction of the second hydroxyl-substituted poly(disubstituted siloxane) equal to 0.4-1 .3 or 0.4-1.0.

The above reaction mixtures may contain optional ingredients such as but not limited to one or more initiators, internal wetting agents, crosslinking agents, other UV/HEV absorbers and diluents.

Hydrogel curing and lens fabrication

The reaction mixtures can be formed by any method known in the art, such as agitation or agitation, and used to form polymer articles or devices by known methods. The reactive components are mixed with or without a diluent to form a reaction mixture.

For example, ophthalmic devices can be made by mixing reactive components and optionally diluent(s) with a polymerization initiator and curing under the proper conditions to form a product that can subsequently be shaped by turning, milling, or the like. Alternatively, the reaction mixture may be placed in a mold and subsequently polymerized into a suitable product.

A method for manufacturing a molded ophthalmic device such as a silicone hydrogel contact lens may include: preparing a reactive monomer mixture; transferring the reaction monomer mixture to the first mold; placing the second mold on top of the first mold filled with the reactive monomer mixture; and curing the reactive monomer mixture by free radical copolymerization to form a silicone hydrogel in the form of a contact lens.

The reaction mixture can be cured by any known method of molding the reaction mixture in the manufacture of contact lenses, including spin casting and static casting. Centrifugal casting methods are described in US Pat. Nos. 3,408,429 and 3,660,545, and static casting methods are described in US Pat. Using this method, the reaction mixture is placed in a mold having the shape of the finished silicone hydrogel, and the reaction mixture is subjected to conditions under which the monomers are polymerized, thereby obtaining a polymer whose shape approximately corresponds to the desired shape of the finished product.

After polymerization, the lens may be subjected to extraction to remove unreacted components, after which the lens is removed from the mold. The extraction may be carried out using conventional extractants such as organic solvents, for example alcohols, or may be carried out using aqueous solutions.

Aqueous solutions are solutions containing water. Aqueous solutions of the present invention may contain at least about 20 wt.% water, or at least about 50 wt.% water, or at least about 70 wt.% water, or at least about 95 wt.% water. Aqueous solutions may also include additional water-soluble formulas such as inorganic salts or release agents, wetting agents, anti-friction additives, drug and nutraceutical formulas, combinations thereof, and the like. Release agents are compounds or mixtures of compounds that, when combined with water, reduce the time required to remove the contact lens from the mold, compared with the time required to remove such a lens using an aqueous solution that does not contain a release agent. Aqueous solutions may not require special handling, such as cleaning, recycling, or special disposal procedures.

Extraction can be performed, for example, by immersing the lens in an aqueous solution or by exposing the lens to a stream of an aqueous solution. The extraction may also include, for example, one or more of: heating the aqueous solution; stirring the aqueous solution; increasing the level of the auxiliary release agent in the aqueous solution to a level sufficient to remove the lens; mechanical or ultrasonic agitation of the lens; and introducing into the aqueous solution at least one leaching or extraction aid to a level sufficient to facilitate adequate removal of unreacted components from the lens. The above processes can be carried out sequentially or continuously with or without additional exposure to heating, stirring, or both.

Physical agitation may be required to facilitate leaching and recovery. For example, the portion of the mold to which the finished lens is attached may be subjected to vibration or back and forth movement within an aqueous solution. Other methods may include passing ultrasonic waves through an aqueous solution.

The lenses may be sterilized by known methods such as, but not limited to, autoclaving.

As stated above, the preferred ophthalmic devices are contact lenses, more preferably soft hydrogel contact lenses. The wavelengths and percentage transmittances described herein can be measured at various lens thicknesses using, for example, the techniques described in the examples. As an example, the preferred thickness of the central part for measuring transmission spectra in a soft contact lens may be from 80 to 100 microns, or from 90 to 100 microns, or from 90 to 95 microns. Typically, the measurement can be made at the center of the lens using, for example, an instrument with a 4 nm slot.

Silicone hydrogel ophthalmic devices (eg contact lenses) according to the invention preferably have the following properties. All listed values are preceded by the "approximately" modifier, and devices can have any combination of the listed properties. Properties can be determined by methods known to those skilled in the art, for example, as described in US patent application US20180037690, the contents of which are incorporated herein by reference.

Water concentration, %: at least 20% or at least 25%, and up to 80% or up to 70%

Haze: 30% or less or 10% or less

Dynamic weep angle (Wilhelmy plate method): 100° or less or 80° or less; or 50° or less

Tensile modulus (psi): 120 or less, or 80 to 120

Oxygen permeability (Dk, barrers): at least 80 or at least 100 or at least 150 or at least 200

Elongation at break: at least 100

For ionic silicone hydrogels, the following properties may also be preferred (in addition to those listed above):

Lysozyme uptake (µg/lens): at least 100 or at least 150 or at least 500 or at least 700

Polyquaternium 1 (PQ1) absorption (%): 15 or less, or 10 or less, or 5 or less

The compounds of the present invention can be used with products other than ophthalmic devices. For example, these connections can be used in windows (eg, windows of vehicles or buildings) or optical equipment such as binoculars and cameras, etc. In such an application, the connections, for example, can be applied to the surface of the device. To facilitate coating, the compound can be dissolved in a solvent.

Some embodiments of the invention will be described in detail in the following examples.

EXAMPLES

Testing Methods

UV-visible spectra of compounds in solution were measured using a Perkin Elmer Lambda 45, Agilent Cary 6000i, or Ocean Optics QE65 PRO scanning spectrometer (DH-2000-BAL light source). Before use, the instrument was thermally equilibrated for at least thirty minutes. For the Perkin Elmer instrument, the scan range was 200-800 nm; the scanning speed was 960 nm per minute; the slot width was 4 nm; the mode was set to transmit or absorb; and baseline correction selected. For the Cary instrument, the scanning range was 200-800 nm; the scanning speed was 600 nm/min; the slot width was 2 nm; the mode was for transmission or absorption; and baseline correction selected. For the Ocean Optics instrument, the scanning range was 200–800 nm; the slot width was 10 μm; the mode was for transmission or absorption; and baseline correction selected. Before analyzing the samples using the auto-zero function, a baseline correction was performed.

Spectra of contact lenses formed in part from the claimed compositions in the UV and visible region were measured using a scanning spectrometer Perkin Elmer Lambda 45 UV/VIS, Agilent Cary 6000i UV/VIS or Ocean Optics UV/VIS. Before use, the instrument was thermally equilibrated for at least thirty minutes. Baseline correction was performed using cuvettes containing two-cavity plastic lens holders and identical solvents. These two two-socket contact lens holders were configured to hold the sample in the quartz cuvette at the location through which the incident light passes. The control cuvette also contained a two-slot holder. To ensure consistent specimen thickness, all lenses were manufactured using identical molds. The thickness of the center of the contact lens was measured using an electronic thickness gauge. The given thicknesses of the central part and the transmission spectra are obtained by averaging the data for three separate lenses.

It is important to ensure that the external surfaces of the cuvette are completely clean and dry and free from air bubbles. The reproducibility of measurement results is improved when the reference cuvette and its lens holder are not interchanged, and when the same test cell and its lens holder are used in all samples, making sure that both cuvettes are properly inserted into the instrument.

In the examples and figures, the following abbreviations will be used, the meanings of which are given below:

l: liter(s)

ml: milliliter(s)

Equiv. or equivalent: equivalent

kg: kilogram(s)

g: grams(s)

mg: milligram(s)

mol: mol(s)

mmol: millimol(s)

Yes: dalton or g/mol

kDa: kilodalton or atomic mass unit equal to 1000 daltons

min: minute(s)

µm: micrometer(s)

nm: nanometer(s)

¹ H NMR: nuclear magnetic resonance spectroscopy

UV-VIS: spectroscopy in the visible and ultraviolet regions of the spectrum

TLC: thin layer chromatography

BC: back or main curve plastic mold

FC: front curve plastic mold

PP: polypropylene, which is a propylene homopolymer

TT: Tuftec which is a hydrogenated styrene-butadiene block copolymer (Asahi Kasei Chemicals)

Z: Zeonor which is a polycycloolefin thermoplastic polymer (Nippon Zeon Co Ltd)

DMA: N,N-dimethylacrylamide (Jarchem)

HEMA: 2-hydroxyethyl methacrylate (Bimax)

PVP K90: poly(N-vinylpyrrolidone) (ISP Ashland)

EGDMA: ethylene glycol dimethacrylate (Esstech)

TEGDMA: tetraethylene glycol dimethacrylate (Esstech)

Irgacure or Omnirad 1870: mixture of bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide and 1-hydroxycyclohexylphenylketone (IGM Resins or BASF or Ciba Specialty Chemicals)

mPDMS: mono-n-butyl and monomethacryloxypropyl terminated polydimethylsiloxane (M _n =800-1500 daltons) (Gelest)

HO-mPDMS: mono-n-butyl and mono-(2-hydroxy-3-methacryloxypropyl)propyl ether terminated polydimethylsiloxane (M _n =400-1500 g/mol) (Ortec or DSM-Polymer Technology Group)

HO-mPDMS (n=4):

HO-mPDMS (n=15):

nBu: n-butyl

XLMA: bis-3-methacryloxy-2-hydroxypropyloxypropylpolydimethylsiloxane (Mn=2000 daltons, mean n=23 at H ¹ NMR (CDCl ₃ , 500 MHz) (Shin Etsu)

SiMAA: 2-propenoic acid, 2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl ester (Toray) or 3 -(3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy)-2-hydroxypropyl methacrylate

Norbloc: 2-(2'-hydroxy-5-methacryloxyethylphenyl)-2H-benzotriazole (Janssen)

RB247: 1,4-Bis[2-methacryloxyethylamino]-9,10-anthraquinone

TL03 light sources: Phillips TLK 40W/03 lamps

LED: LED

D3O: 3,7-dimethyl-3-octanol (Vigon)

3M3P: 3-ethyl 3-pentanol

DIW: deionized water

MeOH: methanol

IPA: isopropyl alcohol

DMF: N,N-dimethylformamide

DMSO: dimethyl sulfoxide

DCM or CH ₂ Cl ₂ : dichloromethane or methylene chloride

DCE: 1,2-dichloroethane

CDCl ₃ : deutrochloroform

PhOH: phenol

H ₂ SO ₄ : sulfuric acid

HCl: hydrochloric acid

pTsOH: p-toluenesulfonic acid

Ac ₂ O: acetic anhydride

Cs ₂ CO ₃ : cesium carbonate

SOCl ₂ : thionyl chloride

NaH: sodium hydride

CPTP: 2-(3-chloropropoxy)tetrahydro-2H-pyran

NaI: sodium iodide

borate buffered storage solution: 18.52 grams (300 mmol) boric acid, 3.7 grams (9.7 mmol) sodium borate decahydrate and 28 grams (197 mmol) sodium sulfate were dissolved in enough deionized water to fill 2- liter measuring flask.

Example 1 Synthesis of 2-((9-(dicyanomethylene)-9H-thioxanthen-2-yl)oxy)ethyl methacrylate (Compound A) as shown in Scheme 1

Scheme 1

Thiosalicylic acid (6.3 g, ~0.041 mol) was added over 5 min to 60 ml of concentrated sulfuric acid with constant stirring of the system. Phenol (18.8 g, ~5 equiv.) was added to the reaction mixture in portions over 30 minutes, during which the temperature was raised to 60 °C. After the termination of the exothermic reaction, the mixture was heated to 80°C and then kept at this temperature for 2.5 h with constant stirring. The reaction mixture was slowly added to 600 ml of boiling water while stirring the solution. Upon dilution, a bright yellow precipitate formed, the suspension was heated for another 10 min, after which it was cooled to room temperature. The solids were filtered through a fritted glass funnel. The yellow solids were washed 3 times with 300 ml of water, dried in a vacuum oven at 50°C and used as is in the next step.

A suspension of 2-hydroxy-9H-thioxanthen-9-one (2.28 g, 0.01 mol), 2.0 g of 2-chloroethyl methacrylate (0.0135 mol) and 5.0 g of cesium carbonate (0.015 mol) in 25 ml of anhydrous DMSO was stirred under nitrogen at 60°C overnight. The mixture was cooled to room temperature and poured into 300 ml of ethyl acetate. The organic layers were extracted 3 times with 200 ml of 1% sodium chloride aqueous solution, after which the volatiles were evaporated under reduced pressure. The remaining solids were washed with fritted glass funnel with hexanes, dried in a vacuum oven at 50°C, and used as is in the next step.

2.4 g of crude 2-(2-methacryloxyethoxy)-9H-thioxanthen-9-one (0.007 mol) was charged into a round bottom flask equipped with a magnetic stirrer and reflux condenser. The system was placed under a nitrogen atmosphere and thionyl chloride (8 mL, 13.12 g, 0.111 mol) was added to the flask. The mixture was gently heated under reflux for one hour, after which the thionyl chloride was evaporated under reduced pressure. The flask was placed under a nitrogen atmosphere, a solution of 1.39 g of malonitrile (~3 eq.) and 5 g of pyridine in 20 ml of dichloromethane was added and the mixture was stirred at gentle reflux for another two hours.

After completion of the reaction, the mixture was diluted with 300 ml of ethyl acetate, and the organic layers were extracted with 0.2 N hydrochloric acid, followed by washing twice with 300 ml of water. The product was isolated as an orange solid after silica gel chromatography using methylene chloride and acetone. Compound A: ¹ H NMR (500 MHz, CDCl ₃ ) δ 1.92 (3H, bs, CH ₃ ), 4.31 (1H, t, J=4.0 Hz), 4.51 (1H, t, 4.5 Hz), 5.56 (1H, bs, vinyl), 6.12 (1H, bs, vinyl), 7.13-8.11 (6H, ArH).

The UV-VIS transmission spectrum of a 0.2 mmol/L solution of Compound A in methanol is shown in FIG. 1. The UV-VIS absorption spectrum of a 0.2 mmol/L methanol solution of Compound A superimposed on the reference spectra of macular pigment is shown in FIG. 2.

Example 2

Monomer reaction mixtures were prepared containing 77 weight percent of the compositions listed in Table 1 and 23 weight percent of D3O diluent. The monomer reaction mixtures are filtered through a 3 μm filter using a pressurized stainless steel syringe.

Table 1

Component
(wt%) Example 2 mPDMS: 30-32 SiMAA 28-30 DMA 24-25 HEMA 5.5-6.5 TEGDMA 1-2 PVP K90 6-8 Omnirad 1870 0.2-0.4 RB247 0.01-0.03 Connection A 0.05-1

Said monomer reaction mixture is degassed at ambient temperature by applying a vacuum (40 torr) for at least 20 minutes. In a glove box under nitrogen gas atmosphere and about 0.1-0.2 percent oxygen gas, about 75 µl of the reaction mixture is pipetted with an Eppendorf pipette at room temperature into FC made from a Zeonor/TT mixture in a ratio of 90:10 (according to mass). Then BC, made from a mixture of Z:TT in a ratio of 90:10 (by weight) is placed in FC. The molds are kept in the glove box for at least twelve hours before application. The trays, each containing eight injection molds, are transferred to an adjacent glove box kept at 65°C and the lenses are polymerized top and bottom using LED lamps at 435 nm wavelength and about 1.5 mW/ cm² for 3 minutes and then about 2.5 mW/cm² for 7 minutes.

The lenses are manually demolded and liberated by suspending the lenses in approximately one liter of 70% IPA for about one hour, followed by soaking twice in 70% IPA for 30 minutes; then twice in fresh DIW for 15 minutes; then twice in with the packaging solution for 30 minutes. The lenses are balanced and stored in a borate buffered packaging solution. One of ordinary skill in the art will appreciate that this lens extraction process can be modified depending on the lens composition and mold materials, taking into account the concentration of isopropanol aqueous solutions, the number of washes with each solvent, and the duration of each step. The goal of the lens retrieval process is to remove all lenses without causing damage and transition from swollen diluent meshes to swollen storage solution meshes.

Example 3

A monomer reaction mixture was obtained containing 77 weight percent of the composition shown in Table 2 and 23 weight percent of the 3M3P diluent. Compound A was first dissolved in DMA; then the resulting solution was added to another solution containing all other components and diluent. The monomer reaction mixture was filtered through a 3 μm filter using a pressurized stainless steel syringe. The monomer reaction mixture was degassed at ambient temperature by applying a vacuum (40 torr) for at least 20 minutes. In a glove box with nitrogen gas atmosphere and about 0.1-0.2 percent oxygen gas, about 75 µl of the reaction mixture was dosed using an Eppendorf pipette at room temperature in FC made from a Zeonor/TT mixture in a ratio of 90:10 (according to mass). Then BC, made from a mixture of Z:PP in a ratio of 90:10 (by weight) was placed in FC. The molds are kept in the glove box for at least twelve hours before application. The trays, each containing eight molds, were transferred to an adjacent glovebox, which was kept at 65°C, and the lenses were polymerized top and bottom using 420 nm LED lamps with an intensity of about 1.5 mW/ cm² for 3 minutes and then about 5 mW/cm² for 5 minutes.

The lenses are manually demoulded and released by suspending the lenses in approximately one liter of 70% IPA for about one hour, followed by soaking twice in 70% IPA for 30 minutes; then twice in fresh DIW for 15 minutes; then twice in with the packaging solution for 30 minutes. The lenses are balanced and stored in a borate buffered packaging solution. One of ordinary skill in the art will appreciate that this lens extraction process can be modified depending on the lens composition and mold materials, taking into account the concentration of isopropanol aqueous solutions, the number of washes with each solvent, and the duration of each step. The goal of the lens retrieval process is to remove all lenses without causing damage and transition from swollen diluent meshes to swollen storage solution meshes. The lenses were stored in vials. After one day of equilibration, the lenses were examined and sterilized in an autoclave at 122°C for 30 minutes.

table 2

Component Example 3
(wt%) HO-mPDMS (n=15) 28 HO-mPDMS (n=4) 25 XLMA 4 DMA 21 HEMA 11.33 EGDMA 0.25 PVP K90 9 Omnirad 1870 0.25 RB247 0.02 Connection A 0.15

Example 4 Exposure to Light

Lenses made essentially as described in Example 3 were sealed in vials (containing packaging solution) by known methods and exposed to light in a glovebox. The lighting conditions applied are considered to be at least as stringent as those specified in the ICH Q1B guideline described above (thus, according to the ICH Q1B guideline, equivalent or less photodecomposition can be expected than observed in this example). The following conditions were created: 10 vials, each containing 1 lens, were centered on the stage, approximately 10 cm (4 inches) above the 435 ± 5 nm LED panel, and exposed to radiation at a surface density of 20 mW/cm ² for 40 hours at room temperature.

The absorption spectra of the UV/VIS lenses obtained at time zero (control) and after 40 hours are shown in FIG. 3. The absorbance values in the range from 445 nm to 455 nm, as well as the percentage change in absorbance after exposure for 40 hours relative to the control, are shown in Table 3. As seen in FIG. 3 and Table 3, the test compound, which has an absorption at a wavelength of about 450 nm, similar to natural macular pigment, has the additional advantage that it has good light fastness.

Table 3

Wavelength (nm) Absorption coefficient
(Control) Absorption coefficient
(40 hours) % change
(40 hours) 455 0.14782 0.13311 9.9 454 0.14820 0.13344 10.0 453 0.14845 0.13365 10.0 452 0.14853 0.13369 10.0 451 0.14846 0.13358 10.0 450 0.14830 0.13338 10.1 449 0.14796 0.13303 10.1 448 0.14749 0.13258 10.1 447 0.14681 0.13190 10.2 446 0.14610 0.13119 10.2 445 0.14526 0.13034 10.3

Claims (19)

1. Compound of formula II: , where EWG in each case is cyano; n is 1, 2 or 3; a R ¹ is independently H, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ thioalkyl, C ₃ -C ₇ cycloalkyl, phenyl, halogen, hydroxy, amino, NR ³ R ⁴ , benzyl, SO ₃ H or SO ₃ M (M is a monovalent cation such as sodium or potassium) or -YP _g where R ³ and R ⁴ are independently H or C ₁ -C ₆ alkyl, Y in each occurrence independently represents C ₁ -C ₈ alkylene or C ₁ -C ₈ oxaalkylene; and P _g at each occurrence is independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinylamide, or styryl; wherein the compound contains 1 or 2 -YP _g groups, which may or may not be the same. 2. The connection according to claim 1, in which Y (i) is ethylene or propylene, or (ii) is C ₂ -C ₄ oxaalkylene, or oxaethylene (-O-CH ₂ CH ₂ -). 3. A compound according to claim 1 or 2, wherein P _g each independently contains styryl, N-vinyl lactam, (meth)acrylate, or (meth)acrylamide. 4. The connection according to any one of paragraphs. 1-3, in which P _g (i) is (meth)acrylate or (meth)acrylamide or (ii) is methacrylate. 5. Connection according to any one of paragraphs. 1-4, in which R ¹ in each case independently represents H, C ₁ -C ₆ alkyl or -YP _g . 6. The connection according to any one of paragraphs. 1-5, in which R ¹ is -YP _g . 7. The compound according to claim 1, which is 2-((9-(dicyanomethylene)-9H-thioxanthen-2-yl)oxy)ethyl methacrylate. 8. Connection according to any one of paragraphs. 1-7, whose maximum visible light absorption occurs in the range of 430 nm to 480 nm, optionally in the range of 440 nm to 470 nm, and whose full width at half maximum (FWHM) at the maximum absorption of visible light is at least 35 nm and up to 100 nm, the compound being lightfast when measured according to ICH Q1B, where lightfastness includes loss of absorbency at a maximum visible light absorption of no more than 20 percent. 9. The compound according to claim 8, wherein the FWHM at the maximum absorption of visible light is at least 40 nm and up to 95 nm. 10. Connection according to any one of paragraphs. 1-9, in which the maximum absorption of visible light is observed in the range from 430 nm to 480 nm and the full width at half height (FWHM) of which at the maximum absorption of visible light is at least 35 nm and up to 100 nm, and the connection is more light stable than macular pigment when measured according to ICH Q1B. 11. Ophthalmic product, which is a contact lens containing a compound according to any one of paragraphs. 1-10. 12. Contact lens, which is a polymerization reaction product of the reaction mixture, containing: a monomer suitable for the manufacture of an ophthalmic device; and (b) a compound according to any one of paragraphs. 1-10. 13. A contact lens containing (a) a mineral material or an organic material, or a combination thereof, and (b) a compound according to any one of paragraphs. 1-10.