Ophthalmic devices comprising light stable mimetics of macular pigments and other visible light filters

Abstract

An ophthalmic device comprising a visible light filter is described. The ophthalmic device is a free radical reaction product of a reactive mixture comprising: one or more monomers suitable for making the ophthalmic device; a first visible light filtering compound having a visible light absorption maximum between 430 nm and 480 nm and having a full width at half maximum (FWHM) of at least 35 nm and at most 150 nm at the visible light absorption maximum, where the compound is light stable, and where the compound has a molar extinction coefficient of at least 7740 L.mol <-1 >. Cm <-1 >; and a second visible light filtering compound. The device may provide one or more benefits to the wearer, including enhanced macular pigment optical density (MPOD) as well as improved color perception and color enhancement.

Description

[0001] Related Applications

[0002] This application claims priority to U.S. patent application serial number 63 / 366,471 filed on June 16, 2022, which is incorporated herein by reference in its entirety. Technical Field

[0003] The present invention relates to ophthalmic devices comprising visible light filters. More specifically, the present invention relates to ophthalmic devices containing visible light filter compounds that substantially mimic the absorption properties of macular pigment while remaining photostable. The ophthalmic devices also comprise a secondary visible light filter. Background Art

[0004] Human ocular tissue contains dietary carotenoids lutein (L) and zeaxanthin (Z), collectively referred to as macular pigment (MP). Several reports describe the benefits of MP, such as short-wavelength (blue light) filters and potent antioxidants that have been made. MP is also believed to play a protective role against age-related macular degeneration (AMD) (Bernstein, PS, Li, B., Vachali, PP, Gorusupudi, A., Shyam, R., Henriksen, BS, Nolan, JM, "Prog. Retin. Eye Res. 2016, 50, pp. 34-66; Beatty, S., Boulton, M., Koh, HH., Murray, I, J., "Br. J. Ophthalmol", 1999, 83, pp. 867-877). It was further found that macular pigment was significantly associated with light stress recovery time, reduced disabling glare contrast threshold, and reduced visual discomfort (Stringham, JM, Garcia., PV, Smith, PA, McLin, L, N., Fouch, BK, IOVS, 2011, 52(10), pp. 7406-7415).

[0005] Chemical entities associated with macular pigments are carotenoid derivatives that have extensive unsaturation and are highly reactive toward olefin isomerization and oxidation upon photoexcitation. The mechanism of antioxidant protection provided by carotenoids is essentially sacrificial, where excitation of the pi system results in reaction of its excited state with triplet oxygen, thereby protecting / limiting excitation and reaction of other photosensitive compounds in the ocular environment. See, e.g., Ribeiro et al., Food and Chemical Toxicology, Vol. 120, pp. 681-699 (2018); Burton et al., 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, No. 10, pp. 1-10 (2014); and Boon et al., Critical Reviews in Food Science and Nutrition, Vol. 50, pp. 515–532 (2010).

[0006] Although it is desirable to incorporate macular pigments into products for the purpose of providing eye protection, the lack of overall stability (thermal stability, oxidative stability and photochemical stability) of carotenoids creates a very high barrier to the development of such products. Therefore, it would be a major breakthrough if new stable materials were developed that mimic the light absorption properties of macular pigments. Materials that provide additional visual benefits would also be highly desirable. Summary of the invention

[0007] The present invention relates to an ophthalmic device incorporating a first filter compound that absorbs light in the wavelength range of 400nm to 500nm and has an absorption spectrum that substantially simulates the absorption characteristics of the macular pigment. Such compounds are also photostable, 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 exhibit high extinction coefficients at desired wavelengths in the range of 400nm to 500nm, and can therefore be used in low concentrations to provide their light absorption benefits. In addition, these compounds are thermally stable. Ophthalmic devices incorporating compounds as described herein can enhance the wearer's macular pigment optical density (MPOD). In addition, the device can simulate other visual benefits of the macular pigment, such as improving light stimulus recovery time and disabling glare contrast thresholds, and reducing visual discomfort.

[0008] In addition to the compound that mimics the light absorbing properties of the macular pigment, the ophthalmic devices described herein also contain a second filter compound that filters other wavelengths in the visible spectrum, thereby providing additional visual benefits to the lens wearer.

[0009] Thus, an ophthalmic device as described herein may provide one or more benefits to the wearer, including, but not limited to: improved MPOD, which may help prevent age-related macular degeneration; improved light stimulus recovery time; improved disabling glare contrast threshold; reduced visual discomfort; improved color enhancement; and / or improved color perception.

[0010] Thus, in one aspect, the present invention provides an ophthalmic device that is a free radical reaction product of a reactive mixture comprising, consisting essentially of, or consisting of: one or more monomers suitable for making an ophthalmic device; a first visible light filter compound having a visible light absorption maximum between 430 nm and 480 nm and having a full width at half maximum (FWHM) of at least 35 nm and at most 150 nanometers at the visible light absorption maximum, wherein the compound is photostable, and wherein the compound has at least 7740 L.mol -1 .cm -1 A molar extinction coefficient of; and a second visible light filtering compound.

[0011] In another aspect, the present invention provides an ophthalmic device that is a free radical reaction product of a reactive mixture comprising, consisting essentially of, or consisting of: one or more monomers suitable for making an ophthalmic device; a first visible light filter compound having a visible light absorption maximum between 430 nm and 480 nm and having a full width at half maximum (FWHM) of at least 35 nm and at most 150 nanometers at the visible light absorption maximum, wherein the compound is photostable, and wherein the compound has at least 7740 L.mol -1 .cm -1 and a second visible light filter compound comprising, consisting essentially of, or consisting of: a medium energy visible light filter having one or more visible light absorption maxima between 550 nm and 660 nm.

[0012] In another aspect, the present invention provides an ophthalmic device that is a free radical reaction product of a reactive mixture comprising, consisting essentially of, or consisting of: one or more monomers suitable for making an ophthalmic device; a first visible light filter compound having a visible light absorption maximum between 430 nm and 480 nm and having a full width at half maximum (FWHM) of at least 35 nm and at most 150 nanometers at the visible light absorption maximum, wherein the compound is photostable, and wherein the compound has at least 7740 L.mol -1 .cm -1 and a second visible light filter compound comprising, consisting essentially of, or consisting of a high energy visible light filter that limits the transmittance of the device in the wavelength range of 400 nm to 409 nm to between 0% and 70%, preferably between 0.2% and 40%.

[0013] In another aspect, the present invention provides an ophthalmic device that is a free radical reaction product of a reactive mixture comprising, consisting essentially of, or consisting of: one or more monomers suitable for making an ophthalmic device; a first visible light filter compound having a visible light absorption maximum between 430 nm and 480 nm, and a full width at half maximum (FWHM) of at least 35 nm and at most 150 nanometers at the visible light absorption maximum, wherein the compound is photostable, and wherein the compound has at least 7740 L.mol -1 .cm -1 and a second visible light filter compound comprising, consisting essentially of, or consisting of a mixture of: (a) a mid-energy visible light filter having one or more visible light absorption maxima between 550 nm and 660 nm; and (b) a high-energy visible light filter that limits the transmittance of the device to between 0% and 70% in the wavelength range of 400 nm to 409 nm. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 Shown are the UV-VIS absorption spectra of 0.1 mM methanol solutions of Compound A and Compound B of the present invention superimposed on the literature spectrum of macular pigment.

[0015] Figure 2 The UV-VIS transmission spectrum of a contact lens prepared from Compound B is shown.

[0016] Figure 3Shown are the UV-VIS transmission spectra of contact lenses prepared from Compound B before and after thermal or light stress treatment.

[0017] Figure 4 The UV-VIS transmission spectra of the contact lenses from Example 5, Example 6 and Example 7 are shown.

[0018] Figure 5 The UV-VIS transmission spectrum of the contact lens from Example 8 is shown.

[0019] Figure 6 The UV-VIS transmission spectrum of the contact lens from Example 9C is shown.

[0020] Figure 7 The UV-VIS absorption spectra of compounds C and D are shown.

[0021] Figure 8 The UV-VIS absorption spectrum of the compound of Example 11 is shown. DETAILED DESCRIPTION

[0022] It should be understood that the invention is not limited to the details of construction or process steps set forth in the following description. Using the teachings herein, the invention is capable of other embodiments and can be practiced or carried out in various ways.

[0023] With respect to terms used in this disclosure, the following definitions are provided.

[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the invention belongs. Polymer definitions conform to the definitions disclosed in the Compendium of Polymer Terminology and Nomenclature (IUPAC Recommendations 2008) recommended by IUPAC in 2008, which was 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 herein are incorporated herein by reference.

[0025] As used herein, the term "(meth)" refers to optional methyl substitution. Thus, a term such as "(meth)acrylate" refers to both methacrylate and acrylate.

[0026] Wherever a chemical structure is provided, it is understood that the alternatives disclosed for substituents on the structure can be combined in any combination. Thus, if a structure contains substituents R* and R**, each of which contains three lists of possible groups, then nine combinations are disclosed. The same applies to combinations of properties.

[0027] When a subscript (such as the general formula [***] n When "n" in the formula is used to describe the number of repeating units in a polymer formula, the formula should be interpreted as indicating the number average molecular weight of the macromolecule.

[0028] The term "subject" includes humans and vertebrates.

[0029] The term "biomedical device" refers to any article designed to be used in or on mammalian tissue or body fluids, and preferably in or on human tissue or body fluids. Examples of these devices include, but are not limited to, wound dressings, sealants, tissue fillers, drug delivery systems, coatings, anti-adhesive barriers, catheters, implants, stents, and ophthalmic devices (such as intraocular lenses and contact lenses). The biomedical device may be an ophthalmic device, specifically a contact lens, most specifically a contact lens made of a silicone hydrogel or a conventional hydrogel.

[0030] The term "ocular surface" includes the surface and glandular epithelial cells of the cornea, conjunctiva, lacrimal glands, accessory lacrimal glands, nasolacrimal ducts, and meibomian glands and their apical and basal stroma, puncta, and adjacent or related structures, including the eyelids connected as a functional system by epithelial continuity, innervation, and endocrine and immune systems.

[0031] The term "ophthalmic device" refers to any optical device associated with the eye, and includes devices located in or on the eye or any part of the eye (including the ocular surface). These devices can provide optical correction, cosmetic enhancement, improved vision, therapeutic benefits (e.g., as a bandage), or delivery of active components, such as pharmaceutical and nutraceutical components, or a combination of any of the foregoing functions. Examples of ophthalmic devices include, but are not limited to, lenses, optical and ocular inserts (including, but not limited to, punctal plugs, etc.). "Lens" includes spectacle lenses, sunglass lenses, soft contact lenses, hard contact lenses, hybrid contact lenses, intraocular lenses, and overlay lenses. Ophthalmic devices may include contact lenses.

[0032] The term "contact lens" refers to an ophthalmic device that can be placed on the cornea of ​​an individual's eye. Contact lenses can provide corrective, cosmetic, or therapeutic benefits, including wound healing, drug or nutraceutical delivery, diagnostic assessment or monitoring, ultraviolet light absorption, visible light or glare reduction, or any combination thereof. Contact lenses can be any suitable material known in the art, and can be soft lenses, hard lenses, or hybrid lenses comprising at least two different parts having different physical, mechanical or optical properties such as modulus, water content, light transmission, or a combination thereof.

[0033] Eyeglass lenses or sunglass lenses may be composed of mineral materials (e.g., based on silicates), or made of organic materials such as polycarbonate; polyamide; polyimide; polysulfone; polyethylene terephthalate / polycarbonate copolymers; and various other materials known in the art.

[0034] As used herein, the term "central area" refers to the central portion of the contact lens and may include the pupil area of ​​the lens. The central area may, for example, have a diameter ranging from about 3 mm to about 12 mm, preferably from about 5 mm to about 11 mm, and more preferably from about 7 mm to about 10 mm. The so-called "peripheral area" refers to the area of ​​the contact lens that surrounds the central area of ​​the lens at the periphery. The peripheral area may extend to the edge of the lens.

[0035] The biomedical devices, ophthalmic devices and lenses of the present invention may be composed of silicone hydrogels or conventional hydrogels. Silicone hydrogels generally contain at least one hydrophilic monomer and at least one silicone-containing component, which are covalently bonded to each other in the cured device.

[0036] "Target macromolecule" means a macromolecule synthesized from a reactive monomer mixture including monomers, macromonomers, prepolymers, crosslinking agents, initiators, additives, diluents, and the like.

[0037] The term "polymerizable compound" means a compound containing one or more polymerizable groups. The term encompasses, for example, monomers, macromers, oligomers, prepolymers, crosslinking agents, and the like.

[0038] "Polymerizable group" is a group in which chain growth polymerization (such as free radical and / or cationic polymerization, preferably free radical polymerization) can occur, for example, a carbon-carbon double bond that can be polymerized when subjected to free radical polymerization initiation conditions. Non-limiting examples of polymerizable groups include (meth) acrylate, styryl, (meth) acrylamide and vinyl groups. Preferably, the polymerizable group is selected from (meth) acrylate, (meth) acrylamide, N-vinyl lactam, N-vinyl amide, ethylene carbonate, vinyl ether, vinyl carbamate and styryl functional groups. More preferably, the polymerizable group is selected from (meth) acrylate and (meth) acrylamide. The polymerizable group may be unsubstituted or substituted. For example, the nitrogen atom in (meth) acrylamide may be bonded to hydrogen, or hydrogen may be replaced by an alkyl or cycloalkyl group (which itself may be further substituted).

[0039] Any type of free radical polymerization may be used, including but not limited to bulk, solution, suspension, and emulsion, as well as any of the controlled radical polymerization methods such as stable free radical polymerization, nitroxide-mediated living polymerization, atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization, organotellurium-mediated living radical polymerization, and the like.

[0040] "Monomers" are monofunctional molecules that can undergo chain growth polymerization (and specifically free radical polymerization) to form repeating units in the chemical structure of the target macromolecule. Certain monomers have difunctional impurities that can act as crosslinking agents. "Hydrophilic monomers" are also monomers that produce a clear single-phase solution when mixed with deionized water at a concentration of 5% by weight at 25°C. "Hydrophilic components" are monomers, macromers, prepolymers, initiators, crosslinkers, additives or polymers that produce a clear single-phase solution when mixed with deionized water at a concentration of 5% by weight at 25°C. "Hydrophobic components" are monomers, macromers, prepolymers, initiators, crosslinkers, additives or polymers that are slightly soluble or insoluble in deionized water at 25°C.

[0041] "Macromolecules" are organic compounds having a number average molecular weight greater than 1500, and may be reactive or non-reactive.

[0042] A "macromer" is a macromolecule having a group that can undergo chain growth polymerization (and specifically free radical polymerization) to form a repeating unit in the chemical structure of the target macromolecule. Typically, the chemical structure of the macromonomer is different from the chemical structure of the target macromolecule, in other words, the repeating units of the side groups of the macromonomer are different from the repeating units of the target macromolecule or its main chain. The difference between a monomer and a macromonomer is only one of chemical structure, molecular weight, and molecular weight distribution of the side groups. Therefore, and as used herein, the patent literature occasionally defines a monomer as a relatively low molecular weight polymerizable compound of about 1,500 Daltons or less, which essentially includes some macromonomers. Specifically, mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxane (molecular weight = 500-1500 g / mol) (mPDMS) and mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether-terminated mono-n-butyl-terminated polydimethylsiloxane (molecular weight = 500-1500 g / mol) (OH-mPDMS) may be referred to as monomers or macromers. In addition, patent literature occasionally defines macromers as having one or more polymerizable groups, thereby substantially extending the general definition of macromers to include prepolymers. Therefore, and as used herein, difunctional and multifunctional macromers, prepolymers, and crosslinkers may be used interchangeably.

[0043] A "silicone-containing component" is a monomer, macromer, prepolymer, crosslinker, initiator, additive or polymer in a reactive mixture having at least one silicon-oxygen bond, typically in the form of a siloxy group, a siloxane group, a carbosiloxane group, and mixtures thereof.

[0044] Examples of silicone-containing components useful in the present invention can be found in U.S. Patents 3,808,178, 4,120,570, 4,136,250, 4,153,641, 4,740,533, 5,034,461, 5,070,215, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,760,100, 5,849,811 、5,962,548、5,965,631、5,998,498、6,367,929、6,822,016、6,943,203、6,951,894、7,052,131、7,247,692、7,396,890、7,461,937、7,468,398、7,538,146、7,553,880、7,572,841、7,66 6,921、7,691,916、7,786,185、7,825,170、7,915,323、7,994,356、8,022,158、8,163,206、8,273,802、8,399,538、8,415,404、8,420,711、8,450,387、8,487,058、8,568,626、8,937,110 , 8,937,111, 8,940,812, 8,980,972, 9,056,878, 9,125,808, 9,140,825, 9,156,934, 9,170,349, 9,217,813, 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,929 and European Patent No. 080539. These patents are hereby incorporated by reference in their entirety.

[0045] A "polymer" is a macromolecule of interest composed of repeating units of the monomers used during polymerization.

[0046] A "homopolymer" is a polymer made from one monomer; a "copolymer" is a polymer made from two or more monomers; a "terpolymer" is a polymer made from three monomers. A "block copolymer" is made up of compositionally distinct blocks or segments. A diblock copolymer has two blocks. A triblock copolymer has three blocks. A "comb or graft copolymer" is made from at least one macromonomer.

[0047] A "repeat unit" is the smallest grouping of atoms in a polymer that corresponds to the polymerization of a particular monomer or macromer.

[0048] An "initiator" is a molecule that decomposes into free radicals that can then react with monomers to initiate free radical polymerization. Thermal initiators decompose at a rate that depends 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, tert-butyl peroxide, tert-butyl hydroperoxide, tert-butyl peroxybenzoate, dicumyl peroxide, and lauroyl peroxide, peracids such as peracetic acid and potassium persulfate, and various redox systems. Photoinitiators decompose photochemically; typical examples are derivatives of benzil, benzoin, acetophenone, benzophenone, camphorquinone, and mixtures thereof and various mono- and bis-acylphosphine oxides, and combinations thereof.

[0049] A "crosslinking agent" is a difunctional or multifunctional monomer or macromer that can undergo free radical polymerization at two or more positions on the molecule to form branching points and a polymer network. Common examples are ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, methylenebisacrylamide, triallyl cyanurate, etc.

[0050] A "prepolymer" is the reaction product of monomers which contains residual polymerizable groups capable of further reaction to form a polymer.

[0051] A "polymer network" is a cross-linked macromolecule that is swellable in a solvent but not soluble. A "hydrogel" is a polymer network that swells in water or an aqueous solution, typically absorbing at least 10% by weight of water. A "silicone hydrogel" is a hydrogel made from at least one silicone-containing component and at least one hydrophilic component. The hydrophilic component may also include a non-reactive polymer.

[0052] "Conventional hydrogel" refers to a polymer network made from components that do not contain any siloxy, siloxane, or carbosiloxane groups. Conventional hydrogels are prepared from a reactive mixture containing hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate ("HEMA"), N-vinyl pyrrolidone ("NVP"), N,N-dimethylacrylamide ("DMA"), or vinyl acetate. U.S. Patent Nos. 4,436,887, 4,495,313, 4,889,664, 5,006,622, 5,039459, 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 disclose the formation of conventional hydrogels. Commercially available conventional hydrogels include, but are not limited to, etafilcon, genfilcon, hilafilcon, linifilcon, nesofilcon, omafilcon, polymacon and vefilcon, including all their variants.

[0053] "Silicone hydrogel" refers to a polymer network made of at least one hydrophilic component and at least one silicone-containing component. Examples of suitable types of hydrophilic components that may be present in the reactive mixture include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl carbamates, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof. Silicone-containing components are well known and have been extensively described in the patent literature. For example, the silicone-containing component may include at least one polymerizable group (e.g., (meth)acrylates, styryls, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, O-vinyl carbamates, O-vinyl carbonates, vinyl groups, or mixtures thereof), at least one siloxane group, and one or more linking groups (which may be bonds) connecting one or more polymerizable groups to one or more siloxane groups. The silicone-containing component may, for example, contain 1 to 220 siloxane repeating units. The silicone-containing component may also include at least one fluorine atom. The silicone hydrogel lens may include a coating, and the coating may be the same or a different material than the substrate.

[0054] Examples of silicone hydrogels include acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, lehfilcon, serafilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon, including all variations thereof, and as described in U.S. Patents 4,659,782; 4,659,783; 5,244,981; 5,314,960; 5,331,067; 5,371,147; 5,998,498; 6,087,415; 5,760,100; 5,776,999; 5,789,461; 5,849,811; 5,965,631、6,367,929、6,822,016、6,867,245、6,943,203、7,247,692、7,249,848、7,553,880、7,666,921、7,786,185、7,956,131、8,022,158、8,273,802、8,399,538、8,470,906、8,450,387、8,487,058、8 , 507,577, 8,637,621, 8,703,891, 8,937,110, 8,937,111, 8,940,812, 9,056,878, 9,057,821, 9,125,808, 9,140,825, 9156,934, 9,170,349, 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,929 and WO 03 / 22321, WO 2008 / 061992 and US2010 / 0048847. These patents are hereby incorporated by reference in their entirety.

[0055] An "interpenetrating polymer network" includes two or more networks that are at least partially interwoven on a molecular scale but are not covalently bound to each other and cannot be separated without interfering chemical bonds. A "semi-interpenetrating polymer network" includes one or more networks and one or more polymers characterized by some intermixing on a molecular level between at least one network and at least one polymer. A mixture of different polymers is a "polymer blend." Technically, a semi-interpenetrating network is a polymer blend, but in some cases the polymers are entangled so that they cannot be easily removed.

[0056] "Reactive components" are polymerizable compounds (such as monomers, macromers, oligomers, prepolymers, and crosslinkers) in a reactive mixture (defined below), and any other components in the reactive mixture, which are intended to be substantially retained in the resulting polymer network after polymerization and all post-processing steps (such as extraction steps) and packaging steps have been completed. Reactive components may be retained in the polymer network by covalent bonding, hydrogen bonding, electrostatic interactions, formation of an interpenetrating polymer network, or any other means. Components that are intended to be released from the polymer network while in use are still considered "reactive components". For example, a pharmaceutical component or nutritional component in a contact lens that is intended to be released during wear is considered a "reactive component". Components such as diluents that are intended to be removed from the polymer network during the manufacturing process (e.g., by extraction) are not "reactive components".

[0057] The terms "reactive mixture" and "reactive 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 a conventional hydrogel or a silicone hydrogel), as well as biomedical devices, ophthalmic devices, and contact lenses made therefrom. The reactive mixture may include reactive components (such as monomers, macromers, prepolymers, crosslinkers, and initiators), additives (such as wetting agents), polymers, dyes, light absorbing compounds (such as UV absorbers), pigments, photochromic compounds, pharmaceutical compounds, and / or nutritional compounds, any of which may be polymerizable or non-polymerizable, but capable of being retained in the resulting biomedical device (e.g., contact lens). The reactive mixture may also include other components, such as diluents, that are intended to be removed from the device prior to use. It should be understood that a wide range of additives may be added based on the contact lens being produced and its intended use. The concentrations of the components of the reactive mixture are expressed as a weight percentage of all reactive components (thus excluding diluents) in the reactive mixture. When diluents are used, their concentrations are expressed as weight percent based on the amounts of all components (including the diluent) in the reactive mixture.

[0058] The term "residue" used in conjunction with a compound or monomer means the portion from such compound or monomer that has been incorporated into at least a portion of the polymeric network after polymerization of the reactive monomer mixture.

[0059] The term "silicone hydrogel contact lens" refers to a hydrogel contact lens made from at least one silicone-containing compound. Silicone hydrogel contact lenses generally have increased oxygen permeability compared to conventional hydrogels. Silicone hydrogel contact lenses utilize both their water and polymer content to transport oxygen to the eye.

[0060] The term "multifunctional" refers to a component having two or more polymerizable groups. The term "monofunctional" refers to a component having one polymerizable group.

[0061] The term "halogen" or "halo" refers to fluorine, chlorine, bromine and iodine.

[0062] "Alkyl" refers to an optionally substituted straight or branched chain alkyl group containing a specified number of carbon atoms. If no number is specified, the alkyl group (including any optional substituents on the alkyl group) may contain 1 to 16 carbon atoms. Preferably, the alkyl group contains 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 groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl, amyl, hexyl, heptyl, 3-ethylbutyl, etc. Examples of substituents on the alkyl group include 1, 2 or 3 groups independently selected from the following items: hydroxyl, amino, amide, oxa, carboxyl, alkylcarboxyl, carbonyl, alkoxy, alkylthio, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Alkylene" means a divalent alkyl group such as -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH(CH)3CH2-, and -CH2CH2CH2CH2-.

[0063] "Haloalkyl" refers to an alkyl group as defined above substituted with one or more halogen atoms, wherein each halogen is independently F, Cl, Br or I. Preferred halogens are F. Preferred haloalkyl groups contain 1 to 6 carbons, more preferably 1 to 4 carbons, and still more preferably 1 to 2 carbons. "Haloalkyl" includes perhaloalkyl groups, such as -CF3- or -CF2CF3-. "Haloalkylene" means a divalent haloalkyl group, such as -CH2CF2-.

[0064] "Cycloalkyl" refers to an optionally substituted cyclic hydrocarbon containing a specified number of ring carbon atoms. If the number is not indicated, the cycloalkyl may contain 3 to 12 ring carbon atoms. Preferably, a C3-C8 cycloalkyl group, a C3-C7 cycloalkyl, more preferably a C4-C7 cycloalkyl, and still more preferably a C5-C6 cycloalkyl. Examples of cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of substituents on the cycloalkyl include 1, 2, or 3 groups independently selected from the following: alkyl, hydroxyl, amino, amide, oxa, carbonyl, alkoxy, alkylthio, amide, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Cycloalkylene" means a divalent cycloalkyl group, such as 1,2-cyclohexylene, 1,3-cyclohexylene, or 1,4-cyclohexylene.

[0065] "Heterocycloalkyl" refers to a cycloalkyl ring or ring system as defined above in which at least one ring carbon has been replaced by a heteroatom selected from nitrogen, oxygen and sulfur. The heterocycloalkyl ring is optionally fused to or otherwise connected to other heterocycloalkyl rings and / or non-aromatic hydrocarbon rings and / or benzene rings. Preferred heterocycloalkyl groups have 5 to 7 members. More preferred heterocycloalkyl groups have 5 or 6 members. Heterocycloalkylene means a divalent heterocycloalkyl group.

[0066] "Aryl" refers to an optionally substituted aromatic hydrocarbon ring system containing at least one aromatic ring. The aryl group contains a specified number of ring carbon atoms. If the number is not indicated, the aryl group may contain 6 to 14 ring carbon atoms. The aromatic ring may be optionally fused or otherwise connected 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 the following items: alkyl, hydroxyl, amino, amide, oxa, carboxyl, alkylcarboxyl, carbonyl, alkoxy, alkylthio, carbamate, carbonate, halo, phenyl, benzyl, and combinations thereof. "Arylene" means a divalent aryl group, such as 1,2-phenylene, 1,3-phenylene or 1,4-phenylene.

[0067] "Heteroaryl" means an aryl ring or ring system as defined above in which at least one ring carbon atom has been 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, furanyl and thienyl. "Heteroarylene" means a divalent heteroaryl group.

[0068] "Alkoxy" means an alkyl group attached to the parent molecular moiety through an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy, and isopropoxy. "Alkylthio" means an alkyl group attached to the parent molecular moiety through a sulfur bridge. Examples of alkylthio groups include, for example, methylthio, ethylthio, n-propylthio, and isopropylthio. "Aryloxy" means an aryl group attached to the parent molecular moiety through an oxygen bridge. Examples include phenoxy. "Cycloalkoxy" means a cycloalkyl group attached to the parent moiety through an oxygen bridge.

[0069] "Alkylamine" refers to an alkyl group attached to the parent molecular moiety through an -NH bridge. Alkyleneamine means a divalent alkylamine group, such as -CH2CH2NH-.

[0070] "Siloxane" refers to a structure having at least one Si-O-Si bond. Thus, for example, a siloxane group means a group having at least one Si-O-Si group (i.e., a siloxane group), and a siloxane compound means a compound having at least one Si-O-Si group. "Siloxane" encompasses monomers (e.g., Si-O-Si) as well as oligomeric / polymeric structures (e.g., -[Si-O] n -, wherein n is 2 or greater). Each silicon atom in the siloxane group is independently selected by R A Group substitution (where R A As defined in Formula A options (b) to (i)) to complete its valency.

[0071] "Silyl" refers to a structure of the formula R3Si-, and "siloxy" refers to a structure of the formula R3Si-O-, wherein each R in the silyl or siloxy group is independently selected from trimethylsiloxy, C1-C8 alkyl (preferably C1-C3 alkyl, more preferably ethyl or methyl) and C3-C8 cycloalkyl.

[0072] "Alkyleneoxy" refers to a group having the general formula -(alkylene-O-) p -or-(O-alkylene) p -, wherein alkylene is as defined above, and p is 1 to 200, or 1 to 100, or 1 to 50, or 1 to 25, or 1 to 20, or 1 to 10, wherein each alkylene is independently optionally substituted by one or more groups, and the one or more groups are independently selected from hydroxyl, halo (e.g., fluorine), amino, amide, ether, carbonyl, carboxyl, and combinations thereof. If p is greater than 1, each alkylene may be the same or different, and the alkyleneoxy may be a block or random configuration. When the alkyleneoxy forms an end group in the molecule, the end of the alkyleneoxy may be, for example, a hydroxyl or alkoxy (e.g., HO-[CH2CH2O] p - or CH3O-[CH2CH2O] p -). Examples of the alkyleneoxy group include polyethyleneoxy, polypropyleneoxy, polybutyleneoxy and poly(ethyleneoxy-co-propyleneoxy).

[0073] "Oxaalkylene" refers to an alkylene group as defined above, wherein one or more non-adjacent CH2 groups have been replaced by oxygen atoms, such as -CH2CH2OCH(CH3)CH2-. "Thiaalkylene" refers to an alkylene group as defined above, wherein one or more non-adjacent CH2 groups have been replaced by sulfur atoms, such as -CH2CH2SCH(CH3)CH2-.

[0074] The term "linking group" refers to the part by which a polymerizable group is connected to a parent molecule. A linking group can be any part compatible with a compound, which is a part of a compound and does not undesirably interfere with the polymerization of the compound, and is stable under polymerization conditions and under conditions for processing and storing the final product. For example, the linking group can be a key, or it can include one or more alkylene groups, halogenated alkylene groups, amides, amines, alkyleneamines, carbamates, esters (-CO2-), arylidenes, heteroarylidenes, cycloalkylene groups, heterocycloalkylene groups, alkyleneoxy groups, oxaalkylene groups, thioalkylene groups, halogenated alkyleneoxy groups (alkyleneoxy groups substituted with one or more halo groups, such as-OCF2-,-OCF2CF2-,-OCF2CH2-), siloxane groups, siloxyalkylene groups or combinations thereof. A linking group can be optionally substituted with one or more substituent groups. Suitable substituent groups may include those independently selected from alkyl, halo (e.g., fluorine), hydroxy, HO-alkyleneoxy, MeO-alkyleneoxy, siloxane, siloxy, siloxy-alkyleneoxy-, siloxy-alkylene-alkyleneoxy- (wherein there may be more than one alkyleneoxy group, and wherein each methylene group in the alkylene and alkyleneoxy groups is independently optionally substituted with hydroxy), ether, amine, carbonyl, 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).

[0075] Preferred linking groups include C1-C8 alkylene (preferably C2-C6 alkylene), C1-C8 oxoalkylene (preferably C2-C6 oxoalkylene), C1-C8 thioalkylene, C1-C8 alkylene-carboxylate-C1-C8 alkylene, C1-C8 alkylene-amide-C1-C8 alkylene and C1-C8 alkylene-amine-C1-C8 alkylene, each of which is optionally substituted by 1 or 2 groups independently selected from hydroxyl and siloxy.

[0076] When the linking group is composed of a combination of parts (e.g., alkylene and cycloalkylene) as described above, the parts can exist in any order. For example, if in the following formula A, L is indicated as -alkylene-cycloalkylene-, then Rg-L can be Rg-alkylene-cycloalkylene-or Rg-cycloalkylene-alkylene-. Nevertheless, the order of listing represents the preferred order of the parts that appear in the compound starting from the terminal polymerizable group (Rg or Pg) to which the linking group is connected. For example, if in formula A, L is indicated as -alkylene-cycloalkylene-, then Rg-L is preferably Rg-alkylene-cycloalkylene-.

[0077] The term "electron withdrawing group" (EWG) refers to a chemical group that withdraws electron density from the atom or group of atoms to which the electron withdrawing group is attached. Examples of EWGs include, but are not limited to, cyano, amide, ester, ketone, or aldehyde. A preferred EWG is cyano (CN).

[0078] The term "visible light absorbing compound" refers to a chemical material that absorbs light within the visible spectrum (e.g., in the range of 380 nm to 760 nm). "High energy radiation absorbers," "UV / HEV absorbers," or "high energy light absorbing compounds" are chemical materials that absorb various wavelengths of ultraviolet light, high energy visible light, or both. The term "mid-energy visible light" means the wavelength range of about 460 nm to about 660 nm. The ability of a material to absorb certain wavelengths of light can be determined by measuring its UV / visible transmission or absorption spectrum.

[0079] As used herein, if the transmission of a device or material is expressed as a percentage within a particular wavelength range, it is understood that the device or material exhibits that transmission percentage at all wavelengths within that range.

[0080] When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless otherwise specified, the compounds are intended to include cis, trans, Z-, and E-configurations. Likewise, all tautomeric and salt forms are also intended to be included.

[0081] The term "optional substituent" means that the hydrogen atoms in the following moiety are optionally replaced by substituents. Any substituent that is sterically practical and synthetically feasible at the substitution site can be used. The identification of suitable optional substituents is well within the capabilities of ordinary technicians. Examples of "optional substituents" include, but are not limited to, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl, halo, hydroxy, amino, NR 4 R 5 , benzyl, SO3H, SO3Na or -YP g , where R 4 and R 5 are independently H or C1-C6 alkyl, Y is a linking group; and P g is a polymerizable group. The aforementioned substituents may be optionally substituted by optional substituents (which are preferably not further substituted unless otherwise indicated). For example, an alkyl group may be substituted by a halo group (e.g., to produce CF3).

[0082] "Visible absorption maximum" refers to one or more wavelengths in the visible light range (380nm to 760nm) where light absorption peaks exist. A material may exhibit multiple absorption peaks in the visible light range, in which case the material has multiple visible absorption maxima. For materials that exhibit multiple visible absorption maxima, the peak showing the maximum absorbance among the multiple absorption maxima in the visible light range is called the "visible absorption maximum". This definition covers materials that exhibit overall absorption maxima outside the visible light range, such as in the UV region.

[0083] The term "photostable", "photostability" or similar expressions means that the compound (which, when measured, may optionally be embedded in an ophthalmic device, such as a hydrogel contact lens, and optionally measured inside or outside a blister pack or vial) exhibits no more than a 20% loss of absorbance at the visible light absorption maximum upon exposure to light under conditions such as those in the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guideline, "Q1B Photostability Testing for New Drug Substances and Products", published November 1996. Preferably, under the ICH photostability guideline, an Option 2 light source is used, preferably in a photostability chamber controlled at 25°C / Amb RH, at 1.5192×10 6 Estimated light exposure of Lux hours (168.8 hours exposure time) and 259.4 Wh / m 2 The lenses are exposed to an estimated UV radiation exposure of 16.2 hours (16.2 hours exposure time). After exposure, a UV / visible spectrum of the sample is collected and compared to the spectrum of the sample before exposure. The change in the visible light absorption maximum observed for the lens before exposure is calculated. By way of example, if the absorbance at the visible light absorption maximum before exposure is 4 absorbance units and after exposure is 2 absorbance units, the absorbance loss is 50%. In the present invention, the absorbance loss after light exposure is preferably no more than 15%, or no more than 10%, or no more than 7%, or no more than 5%, or no more than 4%, or no more than 3%, or no more than 2%, or no more than 1%, or no more than 0.5%, or no more than 0.1%.

[0084] The term "more photostable than macular pigment" or similar expressions 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 a blister pack) exhibits less loss of absorbance at the visible light absorption maximum than that observed with macular pigment after exposure to light under the ICH photostability guidelines, e.g., as described above.

[0085] The term full width at half maximum (FWHM) means the width of an absorption peak at half its maximum intensity.

[0086] The term "thermostable", "thermal stability" or similar expressions means that the compound (when measured, it may optionally be embedded in an ophthalmic device, such as a hydrogel contact lens, and optionally measured inside or outside a blister package or vial) exhibits no more than 20% loss of absorbance at the visible light absorption maximum after exposure for one month in a stability chamber at 89°C as described in the following examples. After exposure, the UV / visible spectrum of the sample is collected and compared with the spectrum of the sample before exposure. The change in the visible light absorption maximum observed for the lens before exposure is calculated. By way of example, if the absorbance at the visible light absorption maximum before exposure is 4 absorbance units, and after exposure is 2 absorbance units, the absorbance loss is 50%. In the present invention, the absorbance loss after heat exposure is preferably no more than 20%, or no more than 15%, or no more than 12%, or no more than 10%, or no more than 5%, or no more than 4%, or no more than 3%, or no more than 2%, or no more than 1%, or no more than 0.5%, or no more than 0.1%.

[0087] The term "more thermally stable than macular pigment" or similar expressions 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 a blister pack) exhibits less loss of absorbance at the visible light absorption maximum after heat exposure as described above than that observed with macular pigment.

[0088] Unless otherwise indicated, ratios, percentages, parts, etc. are by weight.

[0089] Unless otherwise indicated, a numerical range, such as, for example, "2 to 10" or "between 2 and 10" includes the numbers defining the range (eg, 2 and 10).

[0090] As described above, in one aspect, the present invention provides an ophthalmic device that is a free radical reaction product of a reactive mixture containing a first visible light filter compound and a second visible light filter compound. The first visible light filter compound used in the present invention substantially mimics the visible light absorption characteristics of the macular pigment. However, the compound is more photostable than the macular pigment, and thus, unlike the macular pigment, they can be used to make ophthalmic devices.

[0091] Thus, the first visible light compound of the present invention may have a visible light absorption maximum between 430 nm and 480 nm and a full width at half maximum (FWHM) of at least 35 nm and at most 150 nm at the visible light absorption maximum. The compound may be photostable (e.g., when measured according to ICH guideline Q1B). The compound may be more photostable than macular pigment.

[0092] The first visible light filter compound may have a visible light absorption maximum between 440 nm and 480 nm, or between 450 nm and 475 nm, or between 455 nm and 475 nm, or between 460 nm and 470 nm.

[0093] The first visible light filter compound may exhibit a FWHM 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 at the visible light absorption maximum. The first visible light filter compound may exhibit a FWHM of at most 125 nm, or at most 100 nm, or at most 95 nm, or at most 90 nm, or at most 85 nm, or at most 80 nm, or at most 75 nm, or at most 70 nm at the visible light absorption maximum. The FWHM of the first visible light filter compound at the visible light absorption maximum may be in the range of 35 nm to 150 nm, or 35 nm to 100 nm, or 45 nm to 90 nm, or 55 nm to 80 nm, or 60 nm to 75 nm, or 60 nm to 70 nm, or 62 nm to 67 nm.

[0094] The first visible light filter compound of the present invention may exhibit a molar extinction coefficient at the visible light absorption maximum of at least 5000, or at least 5500, or at least 6000, or at least 6500, or at least 7000, or at least 7500, or at least 7740, or at least 7800, or at least 8000, or at least 9000, or at least 10,000, or at least 11,000, or at least 12,000, or at least 12,500. The molar extinction coefficient is an intrinsic property of the material and can be calculated from the absorbance data using the Beer-Lambert law. The units are generally L.mol -1 .cm -1 .

[0095] The first visible light filter compound of the present invention may be a compound of formula I:

[0096]

[0097] wherein m and n are independently 0, 1, 2, 3 or 4; T is a bond, O or NR 6 , where R 6 is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or YP g ; R is H, C1-C8 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; Y is a linking group; P g is a polymerizable group; R 1 and R 2, when present, is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted by alkyl or halo), halo, hydroxy, amino, NR 3 R 4 , benzyl, SO3H or SO3M (M is a monovalent cation such as sodium or potassium), wherein R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 or R 2 The two adjacent groups are combined together with the carbon atoms to which they are attached to form a cycloalkyl or aryl ring; and EWG is an electron withdrawing group.

[0098] The compounds of formula I preferably contain one or two YP g More preferably, the compound contains a YP g Group.

[0099] Compounds of Formula I may include compounds of Formula I-1, which are compounds of Formula I wherein m and n are independently 0 or 1, or alternatively both are 0.

[0100] Compounds of formula I and I-1 may include compounds of formula I-2, which are compounds of formula I or I-1 wherein n is 0 and m is 1.

[0101] The compounds of Formula I, Formula I-1 and Formula I-2 may include compounds of Formula I-3, wherein n is 0, m is 1 and R 1 A compound of formula I, formula I-1 or formula I-2 which is a C1-C6 alkyl group or a C1-C6 alkoxy group.

[0102] The compounds of formula I, formula I-1, formula I-2 and formula I-3 may include compounds of formula I-4, which are compounds of formula I, formula I-1, formula I-2 or formula I-3 wherein R is H or C1-C8 alkyl. Preferably, R is C1-C6 alkyl.

[0103] The compounds of formula I, formula I-1, formula I-2, formula I-3 and formula I-4 may include compounds of formula I-5, wherein T is NR 6 And R 6 is a compound of formula I, formula I-1, formula I-2, formula I-3 or formula I-4 wherein R 6 For H.

[0104] The compounds of formula I, formula I-1, formula I-2, formula I-3, formula I-4 and formula I-5 may include compounds of formula I-6, wherein P g (Polymerizable group) is independently a compound of formula I, formula I-1, formula I-2, formula I-3, formula I-4 or formula I-5 at each occurrence of styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth) acrylate or (meth) acrylamide. The polymerizable group allows the compounds of the present invention to form covalent bonds when reacting with monomers, crosslinking agents and other components commonly used to make polymer devices. The compatibility of the compound with the reactive mixture can be controlled via the selection of the polymerizable group (and the linking group). Preferred polymerizable groups include (meth) acrylate or (meth) acrylamide. A more preferred polymerizable group is methacrylate.

[0105] The compound of formula I, I-1, I-2, I-3, I-4, I-5 and I-6 may include the compound of formula I-7, the compound of formula I-7 is the compound of formula I, I-1, I-2, I-3, I-4, I-5 and I-6 wherein Y (linking group) is alkylene, cycloalkylene, heterocycloalkylene, arylene (e.g., phenylene), heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene or any combination of the above groups. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propylene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene and C1-C8 alkylene-amine-C1-C8 alkylene. Particularly preferred is C1-C8 alkylene, especially ethylene (-CH2CH2-). When T in the compound of formula I is O, it is preferred that the carbon atom hinders the linking group to which O is attached. For example, if T is O and Y is alkylene, the preferred alkylene is -C(R H )2(CH2) x -, where R H are independently C1-C6 alkyl (preferably independently methyl or ethyl) and x is 1 to 5.

[0106] The compounds of formula I, I-1, I-2, I-3, I-4, I-5, I-6 and I-7 may include compounds of formula I-8, wherein T is a chemical bond or NR 6 (preferably NH)-containing compounds of formula I, I-1, I-2, I-3, I-4, I-5, I-6 or I-7.

[0107] The compounds of formula I, formula I-1, formula I-2, formula I-3, formula I-4, formula I-5, formula I-6, formula I-7 and formula I-8 may include compounds of formula I-9, which are compounds of formula I, formula I-1, formula I-2, formula I-3, formula I-4, formula I-5, formula I-6, formula I-7 or formula I-8 wherein EWG is cyano, amide, ester, keto or aldehyde. Preferably, EWG is cyano.

[0108] The first visible light filter compound of the present invention may have Formula IA:

[0109]

[0110] in:

[0111] T is a bond, O or NR 6 , where R 6 is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0112] R is H, C1-C8 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0113] Y is a linking group;

[0114] P g is a polymerizable group;

[0115] R 7 is H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted by alkyl or halogen), halogen, hydroxyl, amino, NR 3 R 4 , benzyl, SO3H or SO3M (M is a monovalent cation such as sodium or potassium), wherein R 3 and R 4 are independently H or C1-C6 alkyl; and

[0116] EWG is an electron withdrawing group.

[0117] The compound of formula IA may include a compound of formula IA-1, wherein R 7 A compound of formula IA wherein:

[0118] Compounds of Formula IA may include compounds of Formula IA-2, wherein the compound of Formula IA-2 is wherein R 7 The compound of formula IA is C1-C6 alkyl, C1-C6 alkoxy or C1-C6 thioalkyl.

[0119] The compounds of Formula IA and Formula IA-2 may include compounds of Formula IA-3, wherein R 7 The compound of formula IA or formula IA-2 is C1-C6 alkoxy (such as ethoxy or methoxy, preferably methoxy).

[0120] The compounds of formula IA, IA-1, IA-2 and IA-3 may include compounds of formula IA-4, which are compounds of formula IA, IA-1, IA-2 or IA-3 wherein R is H or a C1-C8 alkyl group. Preferably, R is a C1-C6 alkyl group, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl or sec-butyl. Preferably, R is n-propyl or n-butyl.

[0121] The compounds of Formula IA, Formula IA-1, Formula IA-2, Formula IA-3 and Formula IA-4 may include compounds of Formula IA-5, wherein T is NR 6 And R 6 is a compound of formula IA, IA-1, IA-2, IA-3 or IA-4 wherein R 6 For H.

[0122] The compounds of formula IA, IA-1, IA-2, IA-3, IA-4 and IA-5 may include compounds of formula IA-6, which are compounds of formula IA, IA-1, IA-2, IA-3, IA-4 or IA-5 wherein Pg (polymerizable group) independently includes styryl, ethylene carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth) acrylate or (meth) acrylamide at each occurrence. Preferred polymerizable groups include (meth) acrylate or (meth) acrylamide. More preferred polymerizable groups are methacrylate.

[0123] Compounds of formula IA, IA-1, IA-2, IA-3, IA-4, IA-5 and IA-6 may include compounds of formula IA-7, which are compounds of formula IA-1, IA-2, IA-3, IA-4, IA-5 and IA-6 wherein Y (linking group) is an alkylene, cycloalkylene, heterocycloalkylene, arylene (e.g., phenylene), heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene or a combination of any of the above groups. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propylene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene and C1-C8 alkylene-amine-C1-C8 alkylene. Particularly preferred are C1-C8 alkylene, especially ethylene (-CH2CH2-). When T in the compound of formula IA is O, it is preferred that the carbon atom hinders the linking group to which O is attached. For example, if T is O and Y is alkylene, the preferred alkylene is -C(R H )2(CH2) x -, where R H are independently C1-C6 alkyl (preferably independently methyl or ethyl) and x is 1 to 5.

[0124] The compounds of formula IA, IA-1, IA-2, IA-3, IA-4, IA-5, IA-6 and IA-7 may include compounds of formula IA-8, wherein T is a chemical bond or is NR 6 (preferably NH)-containing compounds of formula IA, IA-1, IA-2, IA-3, IA-4, IA-5, IA-6 or IA-7.

[0125] The compounds of formula IA, IA-1, IA-2, IA-3, IA-4, IA-5, IA-6, IA-7 and IA-8 may include a compound of formula IA-9, which is a compound of formula IA, IA-1, IA-2, IA-3, IA-4, IA-5, IA-6, IA-7 or IA-8 wherein EWG is cyano, amide, ester, keto or aldehyde. Preferably, EWG is cyano.

[0126] Specific examples of the first visible light filter compound of the present invention are shown in Table A.

[0127] Table A

[0128]

[0129]

[0130] The compound of formula I can be prepared as described in US20220194944A1 before authorization. For example, the compound can be prepared from N-substituted acridone by using triphenylphosphine dibromide. Triphenylphosphine dibromide can be generated "in situ" by adding bromine to triphenylphosphine in a suitable solvent. Adding N-substituted acridone after complete consumption of bromine avoids the potential oxidation of N-substituted acridone, and forms the desired product in high yield while significantly reducing the formation of by-products. An exemplary synthesis of a compound of formula I is shown in Scheme A.

[0131]

[0132] The reactive mixture for preparing the ophthalmic device of the present invention contains a second visible light filter compound in addition to the first visible light filter compound.

[0133] The second visible light filter compound may comprise a mid-energy visible light filter having one or more visible light absorption maxima between 550 nm and 660 nm or between 575 nm and 660 nm.

[0134] The mid-energy visible light filter may have a first visible light absorption maximum between 610 nm and 660 nm, preferably between 630 nm and 650 nm. The first visible light absorption maximum of the second visible light filter compound may optionally have a FWHM of at least 20 nm and at most 60 nm or optionally at least 30 nm and at most 50 nm.

[0135] The mid-energy visible light filter may optionally have a second visible light absorption maximum between 575 nm and 609 nm, preferably between 580 nm and 600 nm. The second visible light absorption maximum may optionally have a FWHM of from at least 60 nm to at most 120 nm or optionally from at least 80 nm to at most 100 nm.

[0136] When incorporated into the ophthalmic devices of the present invention, mid-energy visible light filters may be used to limit the transmittance of the device to between 50% and 95% in the wavelength range of 550 nm to 660 nm.

[0137] Preferably, when incorporated into an ophthalmic device, the mid-energy visible light filter limits the transmittance of the device to between 60% and 85% in the wavelength range of 575 nm to 650 nm.

[0138] The mid-energy visible light filter may contain at least one polymerizable group.

[0139] The medium energy visible light filter may be a compound of formula II:

[0140]

[0141] wherein Y is independently a linking group at each occurrence and P g is independently at each occurrence a polymerizable group.

[0142] Compounds of formula II may include compounds of formula II-1, which are compounds of formula II, wherein Y, at each occurrence, is independently alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination thereof.

[0143] The compounds of formula II and II-1 may include compounds of formula II-2, which are compounds of formula II or II-1, wherein P g Each occurrence independently comprises a styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate or (meth)acrylamide. Preferably, P g Contains at each occurrence a (meth)acrylate, more preferably a methacrylate.

[0144] The medium energy visible light filter may include 1,4-bis[2-methacryloyloxyethylamino]-9,10-anthraquinone, (9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl)bis(2-methyl acrylate), or N,N'-((((((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))diacrylamide.

[0145] Mid-energy visible light filter compounds are commercially available and / or they can be readily prepared by one skilled in the art, for example as described in US Pat. No. 4,997,897, which is incorporated herein by reference in its entirety.

[0146] The second visible light filter compound may alternatively (or in addition) comprise a high energy visible light filter that limits the transmittance of the device in the wavelength range of 400 nm to 409 nm to between 0% and 70%, or between 0.2% and 70%, or between 0.5% and 70%, or between 1% and 70%. The high energy visible light filter may limit the transmittance of the device in the wavelength range of 400 nm to 409 nm to 0%, or at least 0.2%, or at least 0.5%, or at least 1%, or at least 2%, or at least 3%, or at least 4% and at most 60%, or at most 50%, or at most 40%, or at most 30%, or at most 20%, or at most 15%, or at most 10%. The high energy visible light filter may limit the transmittance of the device in the wavelength range of 400 nm to 409 nm to between 0% and 40%, or between 0.2% and 35%, or between 2% and 30%, or between 4% and 25%, or between 5% and 20%, or between 0.2% and 20%.

[0147] The high energy visible light filter may contain at least one polymerizable group.

[0148] The high energy visible light filter may be a compound of formula III:

[0149]

[0150] in:

[0151] m and n are independently 0, 1, 2, 3 or 4;

[0152] T is a chemical bond, O or NR;

[0153] Y is a linking group;

[0154] P g is a polymerizable group;

[0155] R is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or YP at each occurrence. g ;and

[0156] R 1 and R 2 , when present, is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted by alkyl or halo), halo, hydroxy, amino, NR 3 R 4 , or benzyl, where R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 or R 2The compound of formula III preferably contains one or two YP g More preferably, the compound contains a YP g Group.

[0157] The compound of formula III may include a compound of formula III-1, which is a compound of formula III wherein m and n are independently 0 or 1, or alternatively both are 0.

[0158] Compounds of formula III and III-1 may include compounds of formula III-2, wherein m is 1 and R 1 The compound of formula III or III-1 is C1-C6 alkyl, preferably ethyl or methyl.

[0159] The compounds of formula III, III-1 and III-2 may include compounds of formula III-3, wherein n is 1 and R 2 The compound of formula III, III-1 or III-2 is C1-C6 alkyl, preferably ethyl or methyl.

[0160] The compounds of formula III, III-1, III-2 and III-3 may include compounds of formula III-4, which are compounds of formula III, III-1, III-2 or III-3 wherein R is H or a C1-C6 alkyl group. Preferably, R in group T is H.

[0161] 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-1, III-2, III-3, or III-4 wherein Pg (polymerizable group) independently comprises styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth) acrylate or (meth) acrylamide at each occurrence. The polymerizable group allows the compounds of the present invention to form covalent bonds when reacting with monomers, crosslinkers and other components commonly used to make contact lenses. The compatibility of the compound with the reactive mixture can be controlled via the selection of the polymerizable group (and the linking group). Preferred polymerizable groups include (meth) acrylate or (meth) acrylamide. A more preferred polymerizable group is methacrylate.

[0162] Compounds of formula III, III-1, III-2, III-3, III-4 and III-5 may include compounds of formula III-6, which are compounds of formula III-1, III-2, III-3, III-4 or III-5 wherein Y (linking group) is an alkylene, cycloalkylene, heterocycloalkylene, arylene (e.g., phenylene), heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene or a combination of any of the above groups. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propylene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene and C1-C8 alkylene-amine-C1-C8 alkylene. Particularly preferred are C1-C8 alkylene, especially ethylene (-CH2CH2-). When T in the compound of formula III is O, it is preferred to hinder the carbon atom of the linking group to which O is attached. For example, if T is O and Y is alkylene, the preferred alkylene is -C(R H )2(CH2) x -, where R H are independently C1-C6 alkyl (preferably independently methyl or ethyl) and x is 1 to 5.

[0163] Compounds of formula III, III-1, III-2, III-3, III-4, III-5 and III-6 may include compounds of formula III-7, which are compounds of formula III, III-1, III-2, III-3, III-4, III-5 or III-6 wherein T is a chemical bond or NR (preferably NH).

[0164] The compound of formula III may include a compound of formula III-A:

[0165]

[0166] in:

[0167] m and n are independently 0, 1, 2, 3 or 4;

[0168] Y is a linking group;

[0169] P g is a polymerizable group;

[0170] R is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or YP at each occurrence. g ;as well as

[0171] R 1 and R 2, when present, is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted by alkyl or halo), halo, hydroxy, amino, NR 3 R 4 , or benzyl, where R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 or R 2 The compound of formula II preferably contains one or two YP g More preferably, the compound contains a YP g Group.

[0172] The compound of formula III-A may include a compound of formula III-A-1, which is a compound of formula III-A wherein m and n are independently 0 or 1, or alternatively both are 0.

[0173] The compounds of formula III-A and III-A-1 may include compounds of formula III-A-2, wherein m is 1 and R 1 The compound of formula III-A or III-A-1 is C1-C6 alkyl, preferably ethyl or methyl.

[0174] The compounds of formula III-A, III-A-1 and III-A-2 may include compounds of formula III-A-3, wherein n is 1 and R 2 The compound of formula III-A, III-A-1 or III-A-2 is C1-C6 alkyl, preferably ethyl or methyl.

[0175] The compounds of formula III-A, III-A-1, III-A-2 and III-A-3 may include compounds of formula III-A-4, which are compounds of formula III-A, III-A-1, III-A-2 or III-A-3 wherein R is independently H or C1-C6 alkyl at each occurrence. Preferably, R is H at each occurrence. Preferably, R in group T is H.

[0176] Compounds of formula III-A, III-A-1, III-A-2, III-A-3 and III-A-4 may include compounds of formula III-A-5, which are compounds of formula III-A-1, III-A-2, III-A-3 or III-A-4 wherein Pg (polymerizable group) independently includes styryl, ethylene carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth) acrylate or (meth) acrylamide at each occurrence. The polymerizable group allows the compounds of the present invention to form covalent bonds when reacting with monomers, crosslinking agents and other components commonly used to make polymer devices. The compatibility of the compound with the reactive mixture can be controlled via the selection of polymerizable groups (and linking groups). Preferred polymerizable groups include (meth) acrylate or (meth) acrylamide. More preferred polymerizable groups are methacrylate.

[0177] The compound of formula III-A, III-A-1, III-A-2, III-A-3, III-A-4 and III-A-5 may include the compound of formula III-A-6, which is a compound of formula III-A-1, III-A-2, III-A-3, III-A-4 or III-A-5 wherein Y (linking group) is an alkylene, cycloalkylene, heterocycloalkylene, arylene (e.g., phenylene), heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene or a combination of any of the above groups. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propylene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene and C1-C8 alkylene-amine-C1-C8 alkylene. Particularly preferred is C1-C8 alkylene, especially ethylene (-CH2CH2-).

[0178] Specific examples of compounds of Formula I include, but are not limited to, the compounds shown in Table B.

[0179] Table B

[0180]

[0181]

[0182]

[0183] Compounds of formula III can be readily prepared by one skilled in the art, for example as described in US20210061934, which is incorporated herein by reference in its entirety.

[0184] The high energy visible light filter may be a compound of formula IV:

[0185]

[0186] wherein m and n are independently 0, 1, 2, 3 or 4; R 1 and R 2 is independently at each occurrence H, an optional substituent or -YP g , or two adjacent R 1 or R 2 The groups, together with the atoms to which they are attached, combine to form an optionally -YP g substituted cycloalkyl or aryl ring; and EWG is independently an electron withdrawing group at each occurrence. g is independently a polymerizable group at each occurrence; Y is independently a linking group at each occurrence; wherein the compound of formula IV comprises at least one P g Group.

[0187] Compounds of Formula IV may include compounds of Formula IV-1, which is a compound of Formula IV wherein m and n are independently 0 or 1, or alternatively one is 0 and the other is 1.

[0188] Compounds of Formula IV and Formula IV-1 may include compounds of Formula IV-2, which are compounds of Formula IV or IV-1, wherein R 1 is H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl, halo, hydroxy, amino, NR 4 R 5 , benzyl, SO3H, or SO3Na, where R 4 and R 5 are independently H or C1-C6 alkyl.

[0189] The compounds of Formula IV, Formula IV-1 and Formula IV-2 may include compounds of Formula IV-3, which is wherein R 2 YP g A compound of Formula IV, Formula IV-1, or Formula IV-2.

[0190] Compounds of formula IV, IV-1, IV-2 and IV-3 may include compounds of formula IV-4, wherein Pg (polymerizable group) independently includes styryl, ethylene carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth) acrylate or (meth) acrylamide of formula IV, formula IV-1, formula IV-2 or formula IV-3 at each occurrence. The polymerizable group allows the compounds of the present invention to form covalent bonds when reacting with monomers, crosslinking agents and other components that can be used to make polymer devices. The compatibility of the compound with the reactive mixture can be controlled via the selection of polymerizable groups (and linking groups). Preferred polymerizable groups include (meth) acrylate or (meth) acrylamide. More preferred polymerizable groups are methacrylate.

[0191] The compound of formula IV, IV-1, IV-2, IV-3 and IV-4 may include the compound of formula IV-5, which is a compound of formula IV, IV-1, IV-2, IV-3 or IV-4 wherein Y (linking group) is an alkylene, cycloalkylene, heterocycloalkylene, arylene (e.g., phenylene), heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene or a combination of any of the above groups. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propylene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene and C1-C8 alkylene-amine-C1-C8 alkylene. Particularly preferred are oxa-C1-C8 alkylene, especially oxa-propylene (-O-CH2CH2CH2-).

[0192] The compounds of formula IV, IV-1, IV-2, IV-3, IV-4 and IV-5 may include a compound of formula IV-6, which is a compound of formula IV, IV-1, IV-2, IV-3, IV-4 or IV-5, wherein EWG is independently cyano, amide, ester, ketone or aldehyde at each occurrence. Preferably, EWG is cyano at each occurrence.

[0193] Compounds of formula IV, IV-1, IV-2, IV-3, IV-4, IV-5 and IV-6 may include compounds of formula IV-7, which is wherein the compound comprises one YP g A compound of formula IV, IV-1, IV-2, IV-3, IV-4, IV-5 or IV-6 containing a group.

[0194] Compounds of formula IV, IV-1, IV-2, IV-3, IV-4, IV-5, IV-6 and IV-7 may include compounds of formula IV-8, which is wherein m is 0 and R 2 YPg A compound of formula IV, IV-1, IV-2, IV-3, IV-4, IV-5, IV-6 or IV-7.

[0195] Specific examples of compounds of formula IV include, but are not limited to:

[0196]

[0197]

[0198]

[0199] The compound of Formula IV may exhibit a molar extinction coefficient of at least 5000, or at least 7500, or at least 10,000, or at least 12,500, or at least 15,000, or at least 17,500, or at least 19,000 at the visible light absorption maximum. The molar extinction coefficient is an intrinsic property of the material and can be calculated from the absorbance data using the Beer-Lambert law. The units are usually L.mol -1 .cm -1 .

[0200] Compounds of Formula IV can be readily prepared by one skilled in the art, for example as described in US20200407324 and U.S. Provisional Patent Application No. 63 / 265,706 filed on December 20, 2021, each of which is incorporated herein by reference in its entirety.

[0201] The high energy visible light (HEV) absorbing filters used in the present invention, including those of Formula III and Formula IV, are preferably photostable. Thus, the devices of the present invention, such as contact lenses comprising a high energy visible light filter as a second visible light filter compound, preferably exhibit a change in their average transmittance in the wavelength range of 380 nm to 450 nm of 20% or less, or 15% or less, or 10% or less, or 7% or less, or 5% or less, or 2% or less after exposure to ICH Q1B conditions.

[0202] As described above, the reactive mixture for preparing the ophthalmic device of the present invention contains, in addition to the first visible light filter compound, a second visible light filter compound. The second filter compound may comprise a mixture of a medium energy visible light filter as described above and a high energy visible light filter as described above. Thus, the second visible light filter compound may comprise a mixture of: (a) a medium energy visible light filter having one or more visible light absorption maxima between 550 nm and 660 nm; and (b) a high energy visible light filter that limits the transmittance of the device to between 0% and 70% in the wavelength range of 400 nm to 409 nm. The second visible light filter compound may be a mixture of a compound of formula II and a compound of formula III, or a mixture of a compound of formula II and a compound of formula IV, or a mixture of a compound of formula II and a compound of formula III and a compound of formula IV.

[0203] Other light absorbing compounds may be included in the reactive mixture for preparing the ophthalmic device of the present invention to provide additional desired absorption properties. For example, a preferred reactive mixture may contain a first visible light filter compound and a second visible light filter compound as described above, and 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, salicylic acid derivatives, benzoic acid derivatives, cinnamic acid derivatives, chalcone derivatives, acetophenone derivatives, crotonic acid derivatives, or any mixtures thereof. One class of preferred UV absorbing compounds is benzotriazoles, such as Norbloc (2-(2'-hydroxy-5-methacryloyloxyethylphenyl)-2H-benzotriazole).

[0204] The ophthalmic devices of the present invention may transmit 10% or less, or 5% or less, or 1% or less, or less than 1% of light in the wavelength range of 200 nm to 279 nm.

[0205] The ophthalmic device of the present invention may transmit 45% or less, or 35% or less, or 25% or less, or 20% or less, or 10% or less, or 5% or less, or 1% or less of light in the wavelength range of 280nm to 399nm.

[0206] The ophthalmic device of the present invention may transmit 0% to 70%, or 0.2% to 70% of light in the wavelength range of 400nm to 409nm. The transmittance of the device in the wavelength range of 400nm to 409nm may be at least 0.2%, or at least 2%, or at least 3%, or at least 4% and up to 60%, or up to 50%, or up to 40%, or up to 30%, or up to 20%. The transmittance of the device in the wavelength range of 400nm to 409nm may be between 0% and 40%, or between 0.2% and 40%, or between 2% and 30%, or between 4% and 25%, or between 5% and 20%, or between 0.1% and 20%.

[0207] The ophthalmic device of the present invention may transmit at least 10%, or at least 15%, or at least 20%, and at most 80%, or at most 70%, or at most 65% of light in the wavelength range of 410nm to 429nm. The transmittance of the device in the wavelength range of 410nm to 429nm may be between 10% and 75%, or between 15% and 70%, or between 20% and 65%.

[0208] The ophthalmic device of the present invention may transmit at least 55%, or at least 60%, and at most 85%, or at most 80% of light in the wavelength range of 430nm to 480nm. The transmittance of the device in the wavelength range of 430nm to 480nm may be between 55% and 85%, or between 60% and 80%.

[0209] The ophthalmic device of the present invention may transmit at least 65%, or at least 70%, and at most 98%, or at most 95% of light in the wavelength range of 481nm to 574nm. The transmittance of the device in the wavelength range of 481nm to 574nm may be between 70% and 98%, or between 75% and 95%.

[0210] The ophthalmic device of the present invention may transmit at least 50%, or at least 60%, or at least 70%, or at least 75%, and at most 95%, or at most 90%, or at most 85% of light in the wavelength range of 550nm to 660nm. The transmittance of the device in the wavelength range of 550nm to 660nm may be between 50% and 95%, or between 60% and 90%, or between 70% and 90%.

[0211] The ophthalmic device of the present invention may transmit at least 50%, or at least 60%, or at least 70%, or at least 75%, and at most 90%, or at most 85% of light in the wavelength range of 575nm to 650nm. The transmittance of the device in the wavelength range of 575nm to 650nm may be between 50% and 90%, or between 60% and 85%, or between 70% and 85%.

[0212] The ophthalmic device of the present invention may transmit at least 80% and at most 97% of light within the wavelength range of 651 nm to 666 nm.

[0213] The ophthalmic device of the present invention may transmit at least 90% of light within the wavelength range of 667 nm to 760 nm.

[0214] The ophthalmic devices of the present invention are preferably photostable. For example, the device, such as a contact lens, preferably exhibits a change in average transmittance of 20% or less, or 15% or less, or 10% or less, or 7% or less, or 5% or less, or 2% or less in the wavelength range of 400 nm to 660 nm after exposure to ICH Q1B conditions.

[0215] A variety of ophthalmic devices can be prepared, including spectacle lenses, sunglass lenses, hard contact lenses, soft contact lenses, corneal onlays, corneal inlays, intraocular lenses, or cover lenses. Preferably, the ophthalmic device is an intraocular lens or a soft contact lens. The soft contact lens can be made from conventional (non-silicone) hydrogels or from silicone hydrogels.

[0216] The foregoing transmission wavelengths and percentages can be measured on devices of various thicknesses. For example, if the device is a hydrogel contact lens (conventional or silicone), the center thickness can be 70 microns to 300 microns, or 80 microns to 230 microns, or 80 microns to 110 microns, or 90 microns to 110 microns. The concentration of one or more filter compounds can be adjusted to achieve the foregoing transmission properties. For example, the concentration can be at least 0.01%, or at least 0.1%, or at least 1%, or at least 2%, based on the weight percentage of all components in the reaction mixture excluding diluent; and at most 10% or at most 5%, based on the weight percentage of all components in the reaction mixture (excluding diluent). Typical concentrations can range from 1% to 5%.

[0217] The ophthalmic device of the present invention may include a free radical reaction product of a reactive mixture containing one or more monomers suitable for making a desired ophthalmic device (also referred to herein as device-forming monomers or hydrogel-forming monomers) and optional components. When polymerized, the reactive mixture results in the formation of a polymeric network, and the ophthalmic device may include the polymer network. The polymer network may, for example, be a hydrogel (e.g., a conventional hydrogel or a silicone hydrogel).

[0218] The visible light filter compounds of the present invention may be copolymerized with other components in the reactive mixture, in which case the reactive mixture may contain one or more of the visible light filter compounds in addition to one or more monomers (and any optional components) suitable for making the desired ophthalmic device.

[0219] Non-limiting examples of polymer networks into which visible light filtering compounds can be incorporated (e.g., as monomers) are described above and include, for example, etafilcon, genfilcon, hilafilcon, linefilcon, nesofilcon, omafilcon, polymacon, vifilcon, acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, lehfilcon, serafilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon and stenfilcon, including all variations thereof.

[0220] By way of further example, the polymer network may be made from a reactive mixture comprising one or more of a hydrophilic component, a hydrophobic component, a silicone-containing component, a wetting agent such as a polyamide, a crosslinking agent, and other components such as a diluent and an initiator. As described above, the reactive mixture also contains one or more of the first and second visible light filter compounds.

[0221] Hydrophilic component

[0222] Examples of suitable types of hydrophilic monomers that may be present in the reactive mixture include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl urethanes, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof.

[0223] 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, (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)acrylamide, N-3-aminopropyl (meth)acrylamide, N-2-aminopropyl (meth)acrylamide, N,N-bis-2-aminoethyl (meth)acrylamide, N,N-bis-3-aminopropyl (meth)acrylamide, N,N-bis-2-aminopropyl (meth)acrylamide, glyceryl methacrylate, polyethylene glycol monomethacrylate, (meth)acrylic acid, vinyl acetate, acrylonitrile, and mixtures thereof.

[0224] Hydrophilic monomers may also be ionic, including anions, cations, zwitterions, betaines, and mixtures thereof. Non-limiting examples of such charged monomers include (meth) acrylic acid, N-[(vinyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropionic acid (ACA1), 5-acrylamidovaleric acid (ACA2), 3-acrylamido-3-methylbutyric acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-1-propaneammonium inner salt (CBT), N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-1-propaneammonium inner salt (SBT), 4-hydroxy-N,N,N- trimethyl-9-oxo-4-oxide 3,5-dioxa-8-aza-4-phosphaundec-10-en-1-ammonium inner salt (9CI) (PBT), 2-methacryloyloxyethyl phosphorylcholine, 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), and 3-((3-(methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

[0225] Non-limiting examples of hydrophilic N-vinyl lactam and N-vinyl amide monomers include: N-vinyl pyrrolidone (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-vinyl acetamide (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 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.

[0226] Non-limiting examples of hydrophilic O-vinyl carbamate and O-vinyl carbonate monomers 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 disclosed in U.S. Pat. No. 5,070,215. Hydrophilic oxazolone monomers are disclosed in U.S. Pat. No. 4,910,277.

[0227] Other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, and 2-ethyloxazoline.

[0228] The hydrophilic monomer may also be a linear or branched macromonomer or prepolymer of poly(ethylene glycol), poly(propylene glycol) or a statistically random or block copolymer of ethylene oxide and propylene oxide with a polymerizable moiety such as (meth)acrylate, styrene, vinyl ether, (meth)acrylamide, N-vinylamide, etc. The macromonomers of these polyethers have one polymerizable group; the prepolymers may have two or more polymerizable groups.

[0229] 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.

[0230] Generally speaking, there is no particular limit on the amount of hydrophilic monomer present in the reactive monomer mixture. The amount of hydrophilic monomer can be selected based on the desired characteristics of the resulting hydrogel, including water content, light transmittance, wettability, protein absorption rate, etc. Wettability can be measured by contact angle, and the required contact angle is less than about 100°, less than about 80°, and less than about 60°. Based on the total weight of the reactive components in the reactive monomer mixture, the hydrophilic monomer can be, for example, in the range of about 0.1 wt % to about 100 wt %, alternatively in the range of about 1 wt % to about 80 wt %, alternatively in the range of about 5 wt % to about 65 wt %, alternatively in the range of about 40 to about 60 wt %, or alternatively in the range of about 55 wt % to about 60 wt %.

[0231] Silicone-containing ingredients

[0232] Silicone-containing components suitable for use in the present invention comprise one or more polymerizable compounds, wherein each compound independently comprises at least one polymerizable group, at least one siloxane group, and one or more linking groups linking the one or more polymerizable groups to the one or more siloxane groups. The silicone-containing component may, for example, contain from 1 to 220 siloxane repeating units, such as the groups defined below. The silicone-containing component may also contain at least one fluorine atom.

[0233] The silicone-containing component may comprise: one or more polymerizable groups as defined above; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units. The silicone-containing component may comprise: one or more polymerizable groups, the one or more polymerizable groups being independently (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, vinyl group, or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.

[0234] The silicone-containing component may include: one or more polymerizable groups that are independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinylamide, styryl, or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups that connect the polymerizable group to the siloxane unit.

[0235] The silicone-containing component may include: one or more polymerizable groups that are independently (meth)acrylates, (meth)acrylamides, or mixtures of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups that connect the polymerizable groups to the siloxane units.

[0236] The silicone-containing component may comprise one or more polymerizable compounds of formula A:

[0237]

[0238] in:

[0239] At least one R A Formula R g -L-, where R g is a polymerizable group, and L is a connecting group, and the remaining R A Each independently is:

[0240] (a)R g -L-,

[0241] (b) C1-C2 optionally substituted with one or more hydroxyl, amino, amide, oxa, carboxyl, alkylcarboxyl, carbonyl, alkoxy, amide, carbamate, carbonate, halo, phenyl, benzyl, or a combination thereof 16 alkyl,

[0242] (c) C3-C4 optionally substituted with one or more alkyl, hydroxy, amino, amide, oxa, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl or a combination thereof 12 Cycloalkyl,

[0243] (d) C6-C6 optionally substituted with one or more alkyl, hydroxy, amino, amide, oxa, carboxyl, alkylcarboxyl, carbonyl, alkoxy, amide, carbamate, carbonate, halo, phenyl, benzyl or a combination thereof 14 Aryl groups,

[0244] (e) a halo group,

[0245] (f) an alkoxy group, a cycloalkoxy group or an aryloxy group,

[0246] (g) silyloxy,

[0247] (h) an alkyleneoxy-alkyl or alkoxy-alkyleneoxy-alkyl, such as polyethyleneoxyalkyl, polypropyleneoxyalkyl or poly(ethyleneoxy-co-propyleneoxyalkyl), or

[0248] (i) a monovalent siloxane chain comprising 1 to 100 siloxane repeating units, the siloxane repeating units optionally substituted with alkyl, alkoxy, hydroxy, amino, oxa, carboxyl, alkylcarboxyl, alkoxy, amido, carbamate, halo, or combinations thereof;

[0249] and

[0250] n is 0 to 500, or 0 to 200, or 0 to 100, or 0 to 20, wherein it is understood that when n is not 0, n is a distribution with a mode equal to the specified value. When n is 2 or greater, the SiO units may have the same or different R A substituents, and if different R A Substituents, the n groups can be in random or block configuration.

[0251] In formula A, the three R A may each contain a polymerizable group, alternatively two R A may each contain a polymerizable group, or alternatively an R A A polymerizable group may be included.

[0252] Examples of silicone-containing components suitable for use in the present invention include, but are not limited to, the compounds listed in Table B. Where the compounds in Table B contain polysiloxane groups, unless otherwise specified, the number of SiO repeating units in such compounds is preferably 3 to 100, more preferably 3 to 40, or even more preferably 3 to 20.

[0253] Table B

[0254]

[0255]

[0256] Additional non-limiting examples of suitable silicone-containing components are listed in Table C. Unless otherwise indicated, where applicable, j2 is preferably 1 to 100, more preferably 3 to 40, or even more preferably 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.

[0257] Table C

[0258]

[0259]

[0260]

[0261] Mixtures of silicone-containing components may be used. By way of example, suitable mixtures may include, but are not limited to, mixtures of mono-(2-hydroxy-3-methacryloxypropoxy)-propyl terminated mono-n-butyl terminated polydimethylsiloxane (OH-mPDMS) having different molecular weights, such as mixtures of OH-mPDMS containing 4 and 15 SiO repeating units; mixtures of OH-mPDMS having different molecular weights (e.g., containing 4 and 15 repeating SiO repeating units) with silicone-based crosslinkers such as bis-3-acryloxy-2-hydroxypropoxypropyl polydimethylsiloxane (ac-PDMS); mixtures of 2-hydroxy-3-[3-methyl-3,3-bis(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA) and mono-methacryloxypropyl terminated mono-n-butyl terminated polydimethylsiloxane (mPDMS) such as mPDMS1000.

[0262] The silicone-containing components useful in the present invention may have an average molecular weight of from about 400 Daltons to about 4000 Daltons.

[0263] The one or more silicone-containing components may be present in an amount up to about 95 wt %, or about 10 wt % to about 80 wt %, or about 20 wt % to about 70 wt %, based on all reactive components of the reactive mixture (excluding diluent).

[0264] Polyamide

[0265] The reactive mixture may include at least one polyamide. As used herein, the term "polyamide" refers to polymers and copolymers comprising repeating units containing amide groups. Polyamides may include cyclic amide groups, acyclic amide groups, and combinations thereof, and may be any polyamide known to those skilled in the art. Acyclic polyamides include acyclic amide side groups and are capable of combining with hydroxyl groups. Cyclic polyamides include cyclic amide groups and are capable of combining with hydroxyl groups.

[0266] Examples of suitable acyclic polyamides include polymers and copolymers comprising repeating units of formula G1 and G2:

[0267]

[0268]

[0269] Where X is a direct bond, -(CO)- or -(CONHR 44 )-, where R 44 is a C1 to C3 alkyl group; R 40 R is selected from H, linear or branched substituted or unsubstituted C1 to C4 alkyl groups; 41 R is selected from H, a linear or branched substituted or unsubstituted C1 to C4 alkyl group, an amino group having up to two carbon atoms, an amide group having up to four carbon atoms and an alkoxy group having up to two carbon atoms; 42 R is selected from H, a linear or branched substituted or unsubstituted C1 to C4 alkyl group; or methyl, ethoxy, hydroxyethyl and hydroxymethyl; 43 is selected from H, a linear or branched substituted or unsubstituted C1 to C4 alkyl group; or methyl, ethoxy, hydroxyethyl and hydroxymethyl; wherein R 40 and R 41 The total number of carbon atoms in is 8 or less, including 7, 6, 5, 4, 3 or less; and wherein R 42 and R 43 The total number of carbon atoms in R is 8 or less, including 7, 6, 5, 4, 3 or less. 40 and R 41 The total number of carbon atoms in R may be 6 or less or 4 or less. 42 and R 43 The number of carbon atoms in the sum of may be 6 or less. As used herein, substituted alkyl groups include alkyl groups substituted with amine, amide, ether, hydroxyl, carbonyl or carboxyl groups, or combinations thereof.

[0270] R 40 and R 41 may be independently selected from H, substituted or unsubstituted C1 to C2 alkyl groups. X may be a direct bond, and R 40 and R 41 R may be independently selected from H, substituted or unsubstituted C1 to C2 alkyl groups. 42 and R 43 The radicals may be independently selected from H, substituted or unsubstituted C1 to C2 alkyl groups, methyl, ethoxy, hydroxyethyl and hydroxymethyl.

[0271] The acyclic polyamide of the present invention may contain a majority of repeating units of formula LV or formula LVI, or the acyclic polyamide may contain at least 50 mol % (including at least 70 mol % and at least 80 mol %) of repeating units of formula G or formula G1. 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-methyl-propionamide, N-vinyl-N,N'-dimethylurea, N,N-dimethylacrylamide, methacrylamide, and acyclic amides of formula G2 and G3:

[0272]

[0273] Examples of suitable cyclic amides that can be used to form cyclic polyamides include α-lactams, β-lactams, γ-lactams, δ-lactams, and ε-lactams. Examples of suitable cyclic polyamides include polymers and copolymers comprising repeating units of formula G4:

[0274]

[0275] Where R 45 is a hydrogen atom or a methyl group; wherein f is a number from 1 to 10; wherein X is a direct bond, -(CO)- or -(CONHR 46 )-, where R 46 is a C1 to C3 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. When X is a direct bond, f may be 2. In such cases, the cyclic polyamide may be polyvinylpyrrolidone (PVP).

[0276] The cyclic polyamide of the present invention may contain 50 mol% or more of the repeating unit of formula G4, or the cyclic polyamide may contain at least 50 mol% (including at least 70 mol% and at least 80 mol%) of the repeating unit of formula G4.

[0277] The polyamide may also be a copolymer comprising repeating units of both cyclic amides and acyclic amides. Additional repeating units may be formed from monomers selected from hydroxyalkyl (meth)acrylates, alkyl (meth)acrylates, other hydrophilic monomers, and siloxane-substituted (meth)acrylates. Any of the monomers (listed as suitable hydrophilic monomers) may be used as a co-monomer to form additional 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, and the like, and mixtures thereof. Ionic monomers may also be included. Examples of ionic monomers include (meth)acrylic acid, N-[(vinyloxy)carbonyl]-β-alanine (VINAL, CAS#148969-96-4), 3-acrylamidopropionic acid (ACA1), 5-acrylamidovaleric acid (ACA2), 3-acrylamido-3-methylbutyric acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-1-propaneammonium inner salt (CBT, carboxybetaine; CAS 79704-35-1), N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-1-propaneammonium inner salt (SBT, sulfobetaine, CAS 80293-60-3), 4-hydroxy-N,N,N-trimethyl-9-oxo-4-oxide 3,5-dioxa-8-aza-4-phosphaundec-10-en-1-ammonium inner salt (9CI) (PBT, phosphobetaine, CAS163674-35-9), 2-methacryloyloxyethyl phosphorylcholine, 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).

[0278] The reactive monomer mixture may include both acyclic polyamide and cyclic polyamide or their copolymers. Acyclic polyamide may be any of those acyclic polyamides described herein or their copolymers, and cyclic polyamide may be any of those cyclic polyamides described herein or their copolymers. Polyamide may be selected from polyvinyl pyrrolidone (PVP), polyvinyl methyl acetamide (PVMA), polydimethyl acrylamide (PDMA), polyvinyl acetamide (PNVA), poly (hydroxyethyl (methyl) acrylamide), polyacrylamide, and their copolymers and mixtures. Polyamide may be PVP (e.g., PVP K90) and PVMA (e.g., having an M of about 570 KDa). w ).

[0279] In all cases, the total amount of all polyamides in the reactive mixture can range from 1 wt % to about 35 wt %, including from about 1 wt % to about 15 wt % and from about 5 wt % to about 15 wt %, based on the total weight of the reactive components in the reactive monomer mixture.

[0280] Without intending to be bound by theory, the polyamide acts as an internal wetting agent when used with a silicone hydrogel. The polyamide of the present invention may be non-polymerizable, and in this case is incorporated into the silicone hydrogel as a semi-interpenetrating network. The polyamide is entrapped or physically retained within the silicone hydrogel. Alternatively, the polyamide of the present invention is polymerizable, for example as a polyamide macromer or prepolymer, and in this case is covalently incorporated into the silicone hydrogel. Mixtures of polymerizable and non-polymerizable polyamides may also be used.

[0281] When the polyamides are incorporated into the reactive monomer mixture, they may have a weight average molecular weight of at least 100,000 Daltons; greater than about 150,000; about 150,000 to about 2,000,000 Daltons; about 300,000 to about 1,800,000 Daltons. Higher molecular weight polyamides may be used if they are compatible with the reactive monomer mixture.

[0282] Crosslinking agent

[0283] It is generally desirable to add one or more crosslinking agents (also referred to as crosslinking monomers, multifunctional macromonomers, and prepolymers) to the reactive mixture. The crosslinking agent may be selected from a difunctional crosslinking agent, a trifunctional crosslinking agent, a tetrafunctional crosslinking agent, and mixtures thereof, including silicone-containing and silicone-free crosslinking agents. Silicone-free crosslinking agents include ethylene glycol dimethacrylate (EGDMA), tetraethylene glycol dimethacrylate (TEGDMA), trimethylolpropane trimethacrylate (TMPTMA), triallyl cyanurate (TAC), glycerol trimethacrylate, methacrylate oxyethyl vinyl carbonate (HEMAVc), allyl methacrylate, methylene bisacrylamide (MBA), and polyethylene glycol dimethacrylate (wherein the polyethylene glycol has a molecular weight of up to about 5000 Daltons). The crosslinking agent is used in the reactive mixture in conventional amounts (e.g., about 0.000415 moles to about 0.0156 moles per 100 grams of reactive formulation). Alternatively, if the hydrophilic monomers and / or silicone-containing components are multifunctional by molecular design or due to impurities, the addition of a crosslinker to the reactive mixture is optional. Examples of hydrophilic monomers and macromers that can act as crosslinkers and (when present) do not require the addition of an additional crosslinker to the reactive mixture include (meth)acrylates and (meth)acrylamide terminated polyethers. Other crosslinkers will be known to those skilled in the art and can be used to prepare the silicone hydrogels of the present invention.

[0284] It may be desirable to select a cross-linking agent that has a similar reactivity to one or more of the other reactive components in the formulation. In some cases, it may be desirable to select a mixture of cross-linking agents with different reactivities to control some physical, mechanical, or biological properties of the resulting silicone hydrogel. The structure and morphology of the silicone hydrogel may also be affected by the diluent or diluents used and the curing conditions.

[0285] Multifunctional silicone-containing components (including macromers, crosslinkers, and prepolymers) may also be included to further increase modulus and maintain tensile strength. Silicone-containing crosslinkers may be used alone or in combination with other crosslinkers. Examples of silicone-containing components that can act as crosslinkers and (when present) do not require the addition of crosslinking monomers to the reactive mixture include α,ω-bismethacryloxypropyl polydimethylsiloxane. Another example is bis-3-acryloxy-2-hydroxypropoxypropyl polydimethylsiloxane (ac-PDMS).

[0286] Crosslinkers having a rigid chemical structure and a polymerizable group that undergoes free radical polymerization may also be used. Non-limiting examples of suitable rigid structures include crosslinkers containing phenyl rings and benzyl rings, such as 1,4-phenylene diacrylate, 1,4-phenylene dimethacrylate, 2,2-bis(4-methacryloyloxyphenyl)-propane, 2,2-bis[4-(2-acryloyloxyethoxy)phenyl]propane, 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)-phenyl]propane and 4-vinylbenzyl methacrylate, and combinations thereof. The rigid crosslinker can be included in an amount between about 0.5 and about 15, or 2 to 10, 3 to 7, based on the total weight of all reactive components. By adjusting the components in the reactive mixture, the physical and mechanical properties of the silicone hydrogel of the present invention can be optimized for specific uses.

[0287] Non-limiting examples of silicone crosslinking agents also include the multifunctional silicone-containing components described in Table C above.

[0288] Additional components

[0289] The reactive mixture may contain additional components such as, but not limited to, diluents, initiators, UV absorbers, visible light absorbers, photochromic compounds, drugs, nutraceuticals, antimicrobial substances, tints, pigments, copolymerizable dyes, non-polymerizable dyes, release agents, visible tints, and combinations thereof.

[0290] Suitable classes of diluents for the silicone hydrogel reactive mixture include alcohols having 2 to 20 carbon atoms, amides derived from primary amines having 10 to 20 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. The diluents can be primary, secondary, and tertiary alcohols.

[0291] Generally, the reactive components are mixed in a diluent to form a reactive mixture. Suitable diluents are known in the art. Diluents suitable for silicone hydrogels are disclosed in WO 03 / 022321 and US 6020445, the disclosures of which are incorporated herein by reference. Classes of diluents suitable for silicone hydrogel reactive mixtures include alcohols having 2 to 20 carbons, amides derived from primary amines having 10 to 20 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. Primary and tertiary alcohols can be used. Preferred classes include alcohols having 5 to 20 carbons and carboxylic acids having 10 to 20 carbon atoms. Specific diluents that can be used include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropyl alcohol, 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, t-pentanol, t-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-propanol, 1-propanol, ethanol, 2-ethyl-1-butanol, (3-acetoxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methylsilane, 1-t-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-dimethylpropionamide and dimethylacetamide.

[0292] 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-pentanol, 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, and the like.

[0293] 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-butyl alcohol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, mixtures thereof, etc. If there is a diluent, there is usually no particular restriction on the amount of the diluent present. When using a diluent, based on the gross weight of a reactive mixture (including reactive and non-reactive formulations), the diluent can be present in an amount of about 2 wt % to about 70 wt % (including in the range of about 5 wt % to about 50 wt % and in the range of about 15 wt % to about 40 wt %). A mixture of diluents can be used.

[0294] A polymerization initiator may be used in the reactive mixture. The polymerization initiator may include, for example, at least one of lauroyl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, etc., which generate free radicals at moderately elevated temperatures; and a photoinitiator system such as aromatic α-hydroxy ketones, alkoxyoxybenzoin, acetophenone, acylphosphine oxide, diacylphosphine oxide, and tertiary amine plus diketone, mixtures thereof, and the like. Illustrative examples of photoinitiators are 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenylpropane-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 ester, and a combination of camphorquinone and ethyl 4-(N,N-dimethylamino)benzoate.

[0295] Commercially available visible light initiator systems (from IGM Resins BV, The Netherlands) include 819, 1700, 1800, 819, 1850 and TPO initiator. Commercially available UV photoinitiators (from IGM Resins BV) include 1173 and 2959. These and other photoinitiators that may be used are disclosed in Volume III, Photoinitiators for Free Radical Cationic & Anionic Photopolymerization, 2nd Edition, by J. V. Crivello & K. Dietliker; edited by G. Bradley; John Wiley and Sons; New York; 1998. The initiator is used in the reactive mixture in an effective amount to initiate photopolymerization of the reactive mixture (e.g., from about 0.1 parts by weight to about 2 parts by weight per 100 parts of reactive monomer mixture). Polymerization of the reactive mixture may be initiated using appropriately selected heat or visible or ultraviolet light or other means, depending on the polymerization initiator used. Alternatively, initiation may be carried out using an electron beam in the absence of a photoinitiator. However, when a photoinitiator is used, the preferred initiator is a diacylphosphine oxide, such as bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide ( 819) or a combination of 1-hydroxycyclohexyl phenyl ketone and bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentylphosphine oxide (DMBAPO). Thermally initiated polymerization can be carried out, for example, as described in US20200399429, which is incorporated herein by reference in its entirety. A combination of photocuring and thermal curing can be used.

[0296] The reactive mixture used to make the ophthalmic devices of the present invention may contain, in addition to the first and second visible light filter compounds, any of the polymerizable compounds and optional components described above.

[0297] The reactive mixture may include: first and second visible light filter compounds, and a hydrophilic component.

[0298] The reactive mixture may comprise: first and second visible light filter compounds, and a hydrophilic component selected from the group consisting of DMA, NVP, HEMA, VMA, NVA, methacrylic acid, and mixtures thereof. Preferred is a mixture of HEMA and methacrylic acid.

[0299] The reactive mixture may include: first and second visible light filter compounds, a hydrophilic component, and a silicone-containing component.

[0300] The reactive mixture may comprise: a first and a second visible light filter compound, a hydrophilic component selected from DMA, HEMA, and mixtures thereof; a silicone-containing component selected from 2-hydroxy-3-[3-methyl-3,3-bis(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA), mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxane (mPDMS), mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether-terminated mono-n-butyl-terminated polydimethylsiloxane (OH-mPDMS), and mixtures thereof; and a wetting agent (preferably PVP or PVMA). For the hydrophilic component, a mixture of DMA and HEMA is preferred. For the silicone-containing component, a mixture of SiMAA and mPDMS is preferred.

[0301] The reactive mixture may comprise: a first and a second visible light filter compound, a hydrophilic component comprising a mixture of DMA and HEMA; a silicone-containing component comprising a mixture of OH-mPDMS having 2 to 20 repeating units (preferably a mixture of 4 and 15 repeating units). Preferably, the reactive mixture also comprises a silicone-containing crosslinker, such as ac-PDMS. Also preferably, the reactive mixture contains a wetting agent (preferably DMA, PVP, PVMA or a mixture thereof).

[0302] The reactive mixture may include: first and second visible light filter compounds; between about 1 wt % and about 15 wt % of at least one polyamide (e.g., an acyclic polyamide, a cyclic polyamide, or a mixture thereof); at least one first monofunctional hydroxy-substituted poly(disubstituted siloxane) having 4 to 8 siloxane repeating units (e.g., OH-mPDMS, wherein n is 4 to 8, preferably n is 4); at least one second hydroxy-substituted poly(disubstituted siloxane) having 10 to 200, or 10 to 10 0, or 10 to 50, or 10 to 20 siloxane repeating units (e.g., OH-mPDMS, wherein n is 10 to 200, or 10 to 100, or 10 to 50, or 10 to 20, preferably n is 15); about 5 wt % to about 35 wt % of at least one hydrophilic monomer; and optionally a multifunctional hydroxy-substituted poly(disubstituted siloxane) having 10 to 200 or 10 to 100 siloxane repeating units (e.g., ac-PDMS). Preferably, the first monofunctional hydroxy-substituted poly(disubstituted siloxane) and the second hydroxy-substituted poly(disubstituted siloxane) are present in a concentration such that the ratio of the weight percent of the first monofunctional hydroxy-substituted poly(disubstituted siloxane) to the weight percent of the second hydroxy-substituted poly(disubstituted siloxane) is 0.4 to 1.3 or 0.4 to 1.0.

[0303] The foregoing reactive mixture may contain optional ingredients such as, but not limited to, one or more initiators, internal wetting agents, crosslinking agents, other UV or HEV absorbers, and diluents.

[0304] Curing of hydrogels and lens fabrication

[0305] The reactive mixture can be formed by any of the methods known in the art, such as shaking or agitation, and used to form a polymeric article or device by known methods.The reactive components are mixed together with or without a diluent to form a reactive mixture.

[0306] For example, an ophthalmic device may be prepared by mixing the reactive components and optionally one or more diluents with a polymerization initiator and curing by appropriate conditions to form a product, which may then be formed into an appropriate shape by lathing, cutting, etc. Alternatively, the reactive mixture may be placed in a mold and then cured into an appropriate article.

[0307] A method of making a molded ophthalmic device such as a silicone hydrogel contact lens may include: preparing a reactive monomer mixture; transferring the reactive monomer mixture to a first mold; placing a 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 shape of a contact lens.

[0308] The reactive mixture can be cured via any known process for molding reactive mixtures in the production of contact lenses, including spin casting and static casting. Spin casting is disclosed in U.S. Pat. Nos. 3,408,429 and 3,660,545, and static casting is disclosed in U.S. Pat. Nos. 4,113,224 and 4,197,266. The contact lenses of the present invention can be formed by direct molding of the hydrogel, which is both economical and allows precise control of the final shape of the hydrated lens. For this method, the reactive mixture is placed in a mold having the shape of the final desired hydrogel, and the reactive mixture is subjected to conditions that polymerize the monomers, thereby producing a polymer having the approximate shape of the final desired product.

[0309] After curing, the lens can be extracted to remove unreacted components and release the lens from the lens mold. The extraction can be performed using a conventional extraction liquid (eg, an organic solvent such as alcohol), or an aqueous solution can be used.

[0310] An aqueous solution is a solution comprising water. The aqueous solution of the present invention may comprise at least about 20% by weight of water, or at least about 50% by weight of water, or at least about 70% by weight of water, or at least about 95% by weight of water. The aqueous solution may also comprise additional water-soluble formulations, such as inorganic salts or release agents, wetting agents, lubricants, pharmaceutical and nutritional formulations, combinations thereof, and the like. A release agent is a compound or mixture of compounds that, when combined with water, reduces the time required to release a contact lens from a mold compared to the time required to release a contact lens from a mold using an aqueous solution without the release agent. The aqueous solution may not require specialized treatment, such as purification, recycling, or special disposal procedures.

[0311] Extraction can be achieved, for example, by immersing the lens in an aqueous solution or exposing it to a flowing aqueous solution. Extraction can also include, for example, one or more of the following: heating the aqueous solution; stirring the aqueous solution; increasing the level of a release aid in the aqueous solution to a level sufficient to release the lens; mechanically or ultrasonically agitating the lens; and incorporating at least one filtration or extraction aid into the aqueous solution to a level sufficient to promote adequate removal of unreacted components from the lens. The above operations can be performed in a batch or continuous process, with or without heating, stirring, or both.

[0312] It may be desirable to apply physical agitation to facilitate leaching and demolding. For example, the lens mold part to which the lens is adhered may be vibrated or moved back and forth in the aqueous solution. Other methods may include passing ultrasound through the aqueous solution.

[0313] The lenses may be sterilized by known means such as, but not limited to, autoclaving.

[0314] As described above, the preferred ophthalmic device is a contact lens, more preferably a soft hydrogel contact lens. The transmission wavelengths and percentages described herein can be measured for lenses of various thicknesses using methods such as those described in the Examples. By way of example, the preferred center thickness for measuring the transmission spectrum in a soft contact lens can be 80 microns to 100 microns, or 90 microns to 100 microns, or 90 microns to 95 microns. Typically, measurements can be made at the center of the lens using an instrument slit width of, for example, 4 nm.

[0315] When the ophthalmic device of the present invention is a contact lens, the residues of the first and second visible light filter compounds in the final lens may be evenly distributed throughout the lens, or they may be more concentrated in the central region of the lens than in the peripheral regions. Since the compounds absorb visible light, they tend to be colored, so it is straightforward to determine when the residues are concentrated in the central region simply by observing the stronger color in the central region. Alternatively, US / Vis spectroscopy may be used, whereby greater absorbance of a particular residue in the central region generally indicates greater concentration based on Beer's law.

[0316] Various techniques can be used to prepare lenses in which the residues of visible light filtering compounds are concentrated in the central area. One such technique is described in U.S. Provisional Patent Application Serial No. 63 / 265,705 filed on December 20, 2021, which is incorporated herein by reference in its entirety.

[0317] Thus, local concentration of residues of the first and second visible light filter compounds can be achieved by selectively derivatizing the residues in areas where their light absorbing properties are not needed or desired, for example in the peripheral areas of the lens. The selective derivatization is preferably achieved chemically. More preferably, the derivatization is via chemical oxidation of one or more functional groups in the visible light filter compounds, producing, as a result of the oxidation, a material having a greater visible light transmittance than the parent chromophore.

[0318] In the case of derivatization by chemical oxidation, the visible light filter compound preferably contains functional groups that can readily undergo oxidation reactions under conditions that produce a material having a higher light transmission than the parent. Exemplary functional groups for such oxidation include S, NR and Se. Thus, preferred visible light filter compounds include the above materials containing oxidizable functional groups (e.g., oxidizable sulfur, selenium or amine moieties).

[0319] Chemical oxidation can be performed, for example, by bleaching. A variety of agents can be used for oxidation, including but not limited to hypochlorite, Dimethyl dioxirane, hydrogen peroxide and / or chlorite.

[0320] In order to form the derivative of the visible light filtering compound residue in selected areas of the lens, the areas of the lens that do not require derivatization are masked from the derivatization conditions. For example, if the derivatization is by chemical means, such as by chemical oxidation, the central area of ​​the lens can be masked from the derivatization reagent using, for example, a cup of appropriate size to exclude the derivatization reagent from that area. Preferably, such a cup is formed of a material such as silicone that provides adequate shielding of the area but does not damage the underlying lens. Other masking techniques or equipment can readily be used.

[0321] Once the central region of the lens is appropriately masked, the derivatization step is then performed. For example, if derivatization is performed by chemical means, the derivatization reagent may be applied so that it contacts the peripheral region without significantly contacting the central region. Contact of the reagent with the peripheral region may continue until the desired level of derivatization has been achieved, and then the reagent is removed, for example, by washing.

[0322] Derivatization as described above is preferably performed while the contact lens is still in the mold (preferably one of the mold halves is removed to allow access to the lens in the other mold half). After derivatization, the lens may be subjected to processing methods commonly used to produce contact lenses, including extraction to remove unreacted components and release the lens from the lens mold. Extraction may be performed using conventional extraction fluids (including organic solvents such as alcohols), or aqueous extraction may be used. Extraction may also be performed prior to the derivatization step.

[0323] Other techniques may be used to make lenses in which the residues of the first and second visible light filter compounds are concentrated in the central region of the lens, and include, for example, the method described in US8697770, which is incorporated herein by reference in its entirety. For example, the technique uses multiple doses of a reactive monomer mixture into a lens mold, wherein a first higher viscosity mixture containing the first and second visible light filter compounds is dosed over the central region of the mold, and a lower viscosity reactive mixture without the first and second visible light filter compounds is dosed at or about the first dose. The mold halves are then brought together and the reactive monomer mixture is subsequently cured.

[0324] When the device of the present invention is a silicone hydrogel contact lens, the lens preferably exhibits the following properties. All values ​​are preceded by "about", and the lens may have any combination of the listed properties. These properties can be determined by methods known to those skilled in the art, for example, as described in U.S. Pre-Grant Publication US20180037690, which is incorporated herein by reference.

[0325] Water concentration %: at least 20% or at least 25% and at most 80% or at most 70%

[0326] Haze: 30% or less, or 10% or less

[0327] Advancing dynamic contact angle (Wilhelmy plate method): 100° or less, or 80° or less, or 50° or less

[0328] Tensile modulus (psi): 120 or less, or 80 to 120

[0329] Edge-corrected oxygen permeability (Dk, Baler): at least 50, or at least 60, or at least 80, or at least 100, or at least 120

[0330] Elongation at break: at least 100

[0331] For ionic silicone hydrogels, the following properties (in addition to those described above) may also be preferred:

[0332] Lysozyme absorption rate (μg / lens): at least 100, or at least 150, or at least 500, or at least 700

[0333] Polyquaternium 1 (PQ1) intake (%): 15 or less, or 10 or less, or 5 or less

[0334] In addition to ophthalmic devices, the visible light filter compounds described herein can also be used with other products. For example, the compounds can be used in windows (e.g., vehicle or building windows) or optical devices such as binoculars and cameras. In such uses, the compounds can be coated on the surface of the device, for example. To facilitate coating, the compounds can be dissolved in a solvent.

[0335] The following clauses set forth non-limiting embodiments of the present disclosure:

[0336] 1. An ophthalmic device, the ophthalmic device being the free radical reaction product of a reactive mixture comprising: one or more monomers suitable for making the ophthalmic device; and a visible light filtering compound, wherein the device transmits:

[0337] between 0% and 70%, or between 0.2% and 70%, or between 1% and 70%, or between 2% and 30%, or between 4% and 25%, or between 5% and 20% of light in the wavelength range of 400 nm to 409 nm;

[0338] between 55% and 85%, or between 60% and 80% of light in the wavelength range of 430nm to 480nm; and

[0339] Between 50% and 90%, or between 60% and 85%, or between 70% and 85% of the light in the wavelength range of 575nm to 650nm.

[0340] 2. The ophthalmic device of clause 1, wherein the device further transmits between 10% and 75%, or between 15% and 70%, or between 20% and 65% of light in the wavelength range of 410 nm to 429 nm.

[0341] 3. An ophthalmic device according to any of the preceding clauses, wherein the device transmits between 70% and 98% of light, or between 75% and 95% of light in the wavelength range of 481 nm to 574 nm.

[0342] 4. An ophthalmic device according to any of the preceding clauses, wherein the device transmits at least 80% and at most 97% of light in the wavelength range of 651 nm to 666 nm.

[0343] 5. An ophthalmic device according to any of the preceding clauses, wherein the device transmits at least 90% of light in the wavelength range of 667 nm to 760 nm.

[0344] 6. An ophthalmic device according to any of the preceding clauses, wherein the device transmits 10% or less, or 5% or less, or 1% or less, or less than 1% of light in the wavelength range of 200 nm to 279 nm.

[0345] 7. An ophthalmic device according to any of the preceding clauses, wherein the device transmits 45% or less, or 35% or less, or 25% or less, or 20% or less, or 10% or less, or 5% or less, or 1% or less of light in the wavelength range of 280nm to 399nm.

[0346] 8. An ophthalmic device according to any of the preceding clauses, wherein the polymerizable compound suitable for use in making the device comprises a hydrophilic component, a silicone-containing component, or a mixture thereof.

[0347] 9. An ophthalmic device according to any of the preceding clauses, wherein the device is a silicone hydrogel contact lens having a contact angle of about 100° or less, a water content of at least about 25% by weight, and an oxygen permeability of at least about 80 barrers.

[0348] 10. An ophthalmic device according to any of the preceding clauses, wherein the visible light filter compound comprises a first visible light filter compound and a second visible light filter compound.

[0349] 11. The ophthalmic device according to clause 10, wherein the first visible light filter compound comprises a compound of formula I.

[0350] 12. An ophthalmic device according to any one of Clauses 11 to 12, wherein the second visible light filter compound comprises a compound of Formula II.

[0351] 13. An ophthalmic device according to any one of Clauses 11 to 12, wherein the second visible light filter compound comprises a compound of Formula III or a compound of Formula IV.

[0352] 14. An ophthalmic device according to any one of Clauses 11 to 12, wherein the second visible light filter compound comprises a mixture of a compound of Formula II and (a) a compound of Formula III; or (b) a compound of Formula IV.

[0353] 15. An ophthalmic device, the ophthalmic device being the free radical reaction product of a reactive mixture, the reactive mixture comprising: one or more monomers, the one or more monomers suitable for making the ophthalmic device; a first visible light filter compound comprising a compound of formula I; and a second visible light filter compound, the second visible light filter compound comprising: a compound of formula II; or a compound of formula III; or a compound of formula IV; or a mixture of a compound of formula II and a compound of formula III; or a mixture of a compound of formula II and a compound of formula IV.

[0354] Some embodiments of the present invention will now be described in detail in the following examples.

[0355] Example

[0356] Test Method

[0357] The UV-visible spectra of the compounds in solution were measured on a Perkin Elmer Lambda 45, Agilent Cary 6000i, or Ocean Optics QE65PRO (DH-2000-BAL light source) UV-VIS scanning spectrometer. The instrument was thermally equilibrated for at least thirty minutes before use. For the Perkin Elmer instrument, the scan range was 200nm to 800nm; the scan speed was 960nm / min; the slit width was 4nm; the mode was set to transmittance or absorbance; and baseline correction was selected. For the Cary instrument, the scan range was 200nm to 800nm; the scan speed was 600nm / min; the slit width was 2nm; the mode was transmittance or absorbance; and baseline correction was selected. For the Ocean Optics instrument, the scan range was 200nm-800nm; the slit width was 10μm; the mode was transmittance or absorbance; and baseline correction was selected. Baseline correction was performed before analyzing the sample using the autozero function.

[0358] The UV-visible spectra of contact lenses formed in part from the claimed compositions were measured on a Perkin Elmer Lambda 45UV / VIS, Agilent Cary 6000i or OceanOptics UV-VIS scanning spectrometer using a wetting solution. The instrument was thermally equilibrated for at least thirty minutes before use. Baseline correction was performed using a cuvette comprising a plastic two-piece lens holder and the same solvent. These two-piece contact lens holders are designed to hold the sample in the quartz cuvette at the position through which the incident beam passes. The reference cuvette also includes a two-piece holder. To ensure that the thickness of the sample is constant, all lenses are made using the same mold. The center thickness of the contact lens is measured using an electronic thickness gauge. The reported center thickness and transmittance spectrum percentage are obtained by averaging the data for three individual lenses.

[0359] It is important to ensure that the outer surface of the cuvette is completely clean and dry and that there are no bubbles trapped in the cuvette. The repeatability of measurements is improved when the reference cuvette and its lens holder remain unchanged and when the same sample cuvette and its lens holder are used for all samples, ensuring that both cuvettes are inserted correctly into the instrument.

[0360] The refractive index ("RI") of the contact lenses is measured by a Leica ARIAS 500 Abbe refractometer in manual mode or by a Reichert ARIAS 500 Abbe refractometer in automatic mode with a prism gap distance of 100 microns. The instrument is calibrated at 20°C (±0.2°C) with deionized water. The prism assembly is opened and the test lens is placed on the lower prism between the magnetic dots closest to the light source. If the prism is dry, a few drops of saline are applied to the bottom prism. The front curve of the lens is against the bottom prism. The prism assembly is then closed. The control is adjusted so that the light and dark boundary line appears behind the crosshair area and the refractive index is measured. The RI measurement is performed on five test lenses. The average RI calculated from the five measurements is recorded as the refractive index and its standard deviation.

[0361] The water content is determined gravimetrically. Allow the lenses to equilibrate in the wetting solution for 24 hours. Remove each of the three test lenses from the wetting solution with a cotton swab and place it on an absorbent towel that has been soaked with the wetting solution. Both sides of the lens are in contact with the absorbent towel. Use tweezers to place the test lens in a tared weighing pan and weigh it. Prepare two additional samples and weigh them. All weight measurements are performed in triplicate and the average of those values ​​is used for calculations. The wet weight is defined as the total weight of the pan and wet lens minus the weight of the pan weighed alone.

[0362] Dry weight is measured by placing the sample pan into a vacuum oven that has been preheated to 60°C for 30 minutes. Apply vacuum until the pressure reaches at least 1 inch of mercury (Hg); lower pressures are allowed. Close the vacuum valve and pump, and dry the lenses for at least 12 hours, usually overnight. Open the vent valve to allow dry air or dry nitrogen to enter. Allow the oven to reach atmospheric pressure. Remove the pan and weigh it. Dry weight is defined as the total weight of the pan and dry lens minus the weight of the pan weighed alone. Calculate the water content of the test lens as follows: % Water Content = (Wet Weight - Dry Weight) / Wet Weight x 100.

[0363] The mean and standard deviation of the water content were calculated and the mean was reported as the % water content of the test lenses.

[0364] Oxygen permeability ("D k ”). The measurements were performed in an environment containing 2.1% oxygen, created by equipping the test chamber with nitrogen and air inputs set in appropriate ratios, e.g. 1800 ml / min nitrogen and 200 ml / min air. The adjusted oxygen concentration was used to calculate t / Dk. A borate buffered saline solution was used. The dark current was measured by using a humidified pure nitrogen environment without applying the MMA lens. The lens was not blotted before the measurement. Four lenses were stacked instead of using lenses with different thicknesses (t) measured in centimeters. A curved sensor was used instead of a flat sensor; the radius was 7.8 mm. The calculations for a sensor with a 7.8 mm radius and a 10% (v / v) airflow are as follows:

[0365] D k / t=(measured current – ​​dark current)×(2.97×10-8mL O2 / (μA-sec-cm 2 -mm Hg)

[0366] Edge correction and material D k related.

[0367] For all D less than 90 bar k value:

[0368] t / D k (Edge correction) = (1 + (5.88 × t)) × (t / D k )

[0369] For D between 90 bar and 300 bar k value:

[0370] t / D k (Edge correction) = (1 + (3.56 × t)) × (t / D k)

[0371] For D greater than 300 bar k value:

[0372] t / D k (Edge correction) = (1 + (3.16 × t)) × (t / D k )

[0373] The un-edge-corrected D was calculated from the inverse of the slope obtained from the linear regression analysis of the data. k , where the x variable is the center thickness in centimeters and the y variable is t / D k On the other hand, the edge correction D is calculated based on the inverse of the slope obtained from the linear regression analysis of the data. k (“EC D k ”), where the x variable is the center thickness in centimeters and the y variable is the edge-corrected t / D k Value. The obtained D k Values ​​are reported in balers.

[0374] The wettability of the lens is determined by a modified Wilhelmy plate method at room temperature (23 ± 4 ° C) using a calibrated Kruss K100 tensiometer and using borate buffered saline without surfactant as the probe solution. All equipment must be clean and dry; vibration around the instrument must be minimal during testing. Wettability is usually reported as an advancing contact angle ("Kruss DCA"). The tensiometer is equipped with a humidity generator, and a temperature and humidity meter are placed in the tensiometer chamber. Relative humidity is maintained at 70 ± 5%. The experiment is performed by immersing a lens specimen of known circumference in a wetting solution of known surface tension, while measuring the force exerted on the sample due to wetting by a sensitive balance. Based on the force data collected during the sample immersion, the advancing contact angle of the packaging solution on the lens is determined. The receding contact angle is determined from the force data while the sample is removed from the liquid. The Wilhelmy plate method is based on the following formula: Fg = γρcosθ-B, where F = the wetting force between the liquid and the lens (mg), g = the acceleration due to gravity (980.665 cm / sec 2), γ = surface tension of the probe liquid (dyne / cm), ρ = circumference of the contact lens at the liquid / lens meniscus (cm), θ = dynamic contact angle (degrees), and B = buoyancy (mg). B is zero when the immersion depth is zero. Typically, test strips are cut from the center area of ​​the contact lens. Each strip is approximately 5 mm wide and 14 mm long, attached to a metal fixture using plastic tweezers, pierced with a metal wire hook, and equilibrated in the wetting solution for at least 3 hours. Each sample is then cycled four times, and the results are averaged to obtain the advancing and receding contact angles of the lens. The typical measurement speed is 12 mm / min. The sample is kept completely immersed in the wetting solution during data acquisition and analysis, without contacting the metal clamp. The values ​​of five individual lenses are averaged to obtain the reported advancing and receding contact angles of the experimental lenses.

[0375] The wettability of the lens was determined by the sessile drop technique using a Kruss K100 TM instrument at room temperature and deionized water as the probe solution (Sessile Drop). The lenses to be tested were rinsed in deionized water to remove residual wetting solution. Each test lens was placed on a non-linting absorbent towel soaked with the wetting solution. Both sides of the lens were contacted with the absorbent towel to remove surface moisture without drying the lens. To ensure proper flattening, the lens was placed "bowl side down" on the convex surface of the contact lens plastic mold. The plastic mold and lens were placed on the sessile drop instrument holder, ensuring that the syringe was correctly centered. A 3 to 4 microliter deionized water droplet was formed on the tip of the syringe using the DSA 100-Drop Shape Analysis software, ensuring that the droplet was suspended from the lens. The droplet was released smoothly on the lens surface by moving the needle downward. After dispensing the droplet, the needle was immediately withdrawn. The droplet was allowed to balance on the lens for 5 to 10 seconds, and the contact angle was measured between the droplet image and the lens surface. Three to five lenses were usually evaluated, and the average contact angle was reported. The contact angles were measured on both the front and back surfaces of the lenses, as indicated in the table as Front Curve ("FC") and Base Curve ("BC").

[0376] The mechanical properties of contact lenses are measured using a tensile testing machine, such as an Instron Model 1122 or 5542 equipped with a load cell and pneumatic gripping control. A minus one diopter lens is the preferred lens geometry because of its uniform thickness distribution at the center. A dog-bone shaped sample slice taken from a minus one diopter spherical lens having a length of 0.522 inches, a "ear" width of 0.276 inches, and a "neck" width of 0.213 inches is loaded into a fixture and stretched at a constant strain rate of 2 inches / minute until it breaks. Prior to testing, the center thickness of the dog-bone sample is measured using an electronic thickness gauge. The initial gauge length (L) of the sample is measured. o ) and the length at break (L f). At least five specimens of each composition were measured and the average value was used to calculate the percent elongation at break: Percent elongation = [(L f –L o ) / L o ] × 100. Tensile modulus is calculated as the slope of the initial linear portion of the stress-strain curve; modulus is measured in pounds per square inch or psi. Tensile strength is calculated from peak load and initial cross-sectional area: Tensile strength = peak load divided by initial cross-sectional area; tensile strength is measured in psi. Toughness is calculated from fracture energy and initial sample volume: Toughness = fracture energy divided by initial sample volume; toughness is measured in in-lbs / in 3 .

[0377] Contact lens parameters are measured in a wetting solution using a calibrated dual interferometry method. These parameters include equivalent spherical power (diopters or D) at multiple apertures, cylindrical power (diopters or D) at multiple apertures, diameter (millimeters or mm), center thickness (millimeters or mm), sagittal height (millimeters or mm), and root mean square (RMS) optical path wavefront deviation from the lens design target in micrometers (micrometer or micron) (μm), where spherical power / cylindrical power and coma are removed as measured using a 6.5 mm aperture. The instrument consists of a custom-made propionic acid interferometer for measuring wavefront parameters and a Lumetrics 3D interferometer for measuring the dimensional parameters of sagittal height and center thickness. II low coherence interferometer. The combination of two separate instruments is similar to the Lumetrics Clearwave TM Plus, and software similar to Lumetrics OptiGaugeControl Center v7.0 or higher. Utilizes Clearwave TM Plus, a camera is used to find the lens edge and then calculate the lens center, which is then used to align a 1310 nanometer interferometer probe at the center of the lens for measuring sagittal height and center thickness. The transmitted wavefront is also collected in series using a wavefront sensor (Shack-Hartmann sensor). Multiple parameters of the transmitted wavefront from the contact lens are measured and other parameters are calculated from those measurements.

[0378] Based on the collected data, differential terms are calculated by comparing the measured values ​​to the targets. These include the root mean square optical path wavefront deviation (spherical power / cylinder and coma removed) from the lens design target in μm as measured using a 6.5 mm aperture (RMS_65), the second equivalent spherical power deviation (PW2EQD) from the lens design target in diopters (D) as measured using a 5 mm aperture, the deviation from the lens design target diameter in mm (DMD), the deviation from the lens design target base curve radius in mm (BCD) as calculated from the sagittal height measured according to ISO 18369-3 and the target lens diameter, and the deviation from the lens design target center thickness in mm (CTD).

[0379] The following abbreviations will be used throughout the examples and figures and have the following meanings:

[0380] L: Lift

[0381] mL: milliliters

[0382] Equiv. or eq.: equivalent

[0383] kg: kilogram

[0384] g: grams

[0385] mg: milligram

[0386] mol: mole

[0387] mmol: millimole

[0388] M: Moore

[0389] Da: Dalton or g / mole

[0390] kDa: Kilodalton or atomic mass unit equal to 1,000 Daltons

[0391] min: minutes

[0392] mm: millimeters

[0393] cm: centimeters

[0394] μm: micrometer

[0395] nm: nanometer

[0396] λ: wavelength

[0397] wt.%: weight %

[0398] Cmpd: Compound

[0399] TLC: Thin layer chromatography

[0400] 1 H NMR: proton nuclear magnetic resonance spectroscopy

[0401] UV-VIS: Ultraviolet-visible spectroscopy

[0402] HEV: High Energy Visible (light)

[0403] LED: Light Emitting Diode

[0404] mW: milliwatt

[0405] AU: Absorbance Unit

[0406] %T: Percent Transmission

[0407] BC: Base Curve Plastic Mold

[0408] FC: Front Curve Plastic Mold

[0409] PP: Polypropylene, a homopolymer of propylene

[0410] TT: Tuftec, hydrogenated styrene butadiene block copolymer (Asahi Kasei Chemicals)

[0411] Z: Zeonor, polycycloolefin thermoplastic polymer (Nippon Zeon Co Ltd)

[0412] DMA: N,N-dimethylacrylamide (Jarchem)

[0413] HEMA: 2-Hydroxyethyl Methacrylate (Bimax)

[0414] PVP K90: Poly(N-vinylpyrrolidone) (ISP Ashland)

[0415] EGDMA: Ethylene glycol dimethacrylate (Esstech)

[0416] TEGDMA: Tetraethylene glycol dimethacrylate (Esstech)

[0417] Tegomer MA: Bis-3-methacryloyloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (M n =2000 g / mol, n=20) (Shin Etsu)

[0418]

[0419] Omnirad 1870: bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide blended with 1-hydroxycyclohexylphenylketone (IGM Resins or BASF or Ciba Specialty Chemicals)

[0420] AIBN: Azobisisobutyronitrile [CAS 78-67-1]

[0421] mPDMS: mono-n-butyl-terminated mono-methacryloxypropyl-terminated polydimethylsiloxane (M n =800 Daltons-1500 Daltons)(Gelest)

[0422] HO-mPDMS: mono-(2-hydroxy-3-methacryloxypropoxy)-propyl-terminated polydimethylsiloxane (M n =400 to 1400 g / mol) (Ortec or DSM-Polymer Technology Group)

[0423] OH-mPDMS (n=4):

[0424]

[0425] OH-mPDMS (n=15), which is an oligomeric macromonomer with a number average degree of polymerization DP=15:

[0426]

[0427] SiMAA: 2-Propylene glycol, 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

[0428] Norbloc: 2-(2'-Hydroxy-5-methacryloyloxyethylphenyl)-2H-benzotriazole (Janssen)

[0429] RB247: 1,4-bis[2-methacryloyloxyethylamino]-9,10-anthraquinone

[0430]

[0431] Compound B: 2-(2-cyano-2-(2-methoxy-10-butylacridin-9(10H)-ylidene)acetamido)ethyl methacrylate

[0432]

[0433] Compound C: 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate (prepared as described in US20210061934)

[0434]

[0435] Compound D: 3-((9-(dicyanomethylidene)-9H-xanthen-3-yl)oxy)propyl methacrylate

[0436]

[0437] D3O: 3,7-dimethyl-3-octanol (Vigon)

[0438] DIW: Deionized water

[0439] IPA: Isopropyl alcohol

[0440] CDCl3: deutrochloroform

[0441] HCl: hydrochloric acid

[0442] Borate Buffered Wetting Solution: Dissolve 18.52 g (300 mmol) of boric acid, 3.7 g (9.7 mmol) of sodium borate decahydrate, and 28 g (197 mmol) of sodium sulfate in enough deionized water to fill a 2 liter volumetric flask.

[0443] Example 1: 2-(2-cyano-2-(2-methoxy-10-propylacridin-9(10H)-ylidene)ethyl Synthesis of ethyl methacrylate (compound A)

[0444]

[0445] 2-Iodobenzoic acid (12.40 g, about 0.05 mol), 12.32 g 4-methoxyaniline (about 2 equivalents), 6.91 g anhydrous potassium carbonate (about 0.05 mol) and 300 mg copper powder (4.76 mmol) were charged into a 100 mL three-necked round-bottom flask equipped with a magnetic stirring bar and a reflux condenser. Deionized water (30 mL) was added to the solid mixture, and the system was heated under reflux for 6 hours with constant stirring. The mixture solidified when cooled to room temperature. The system was diluted with deionized water and gradually poured into 1 equivalent of aqueous hydrochloric acid solution with stirring. The mixture was stirred at room temperature for 30 minutes, after which it was filtered on a sintered glass funnel and dried in a vacuum oven at 60°C. The residue 2-((4-methoxyphenyl)amino)benzoic acid was washed with 3×100 mL deionized water and used "as is" for intramolecular cyclization. 1H NMR(CDCl3)-δ3.81(3H,s), 6.66(1H,t), 6.89-6.93(3H,m), 7.16(2H,d), 7.27(1H,t), 7.99(1H,d), 9.12(1H,bs).

[0446] A 250 mL round bottom flask equipped with a magnetic stirring bar and a reflux condenser was charged with 12.5 g of 2-((4-methoxyphenyl)amino)benzoic acid and 100 mL of Eaton's acid (10 wt % P2O5 in methanesulfonic acid). The mixture was heated at 90°C (mantle temperature) for 5 hours with constant stirring while monitoring the progress by TLC. Upon cooling to room temperature, the reaction mixture was poured onto ice, stirred for 30 minutes, and filtered on a sintered glass funnel. The residual 2-methoxyacridin-9(10H)-one was washed with 3×100 mL of deionized water, then with acetonitrile, and dried in a vacuum oven at 60°C. 1 H NMR(DMSO d6)-δ3.86(3H,s), 7.23(1H,t), 7.41(1H,dd), 7.52(1H,d), 7.53(1H,d), 7.63(1H,d), 7.70(1H,dt), 8.23(1H,d).

[0447] A 250 mL round bottom flask equipped with a magnetic stir bar and a reflux condenser was charged with 5.4 g of 2-methoxyacridin-9(10H)-one (0.0244 mole) and 12.9 g of cesium carbonate (about 1.5 equivalents). The solid was dried at 80°C under vacuum, after which the system was placed under a nitrogen blanket and 80 mL of anhydrous N,N-dimethylformamide was added to the flask. 1-Bromopropane (6.0 g, about 2 equivalents) was added to the flask, and the mixture was heated at 50°C (hood temperature) for 36 hours. TLC indicated the presence of two compounds (O-alkylated and N-alkylated). The organics were poured into 200 mL of deionized water and extracted into about 150 mL of ethyl acetate. The organics were then washed with 3×100 mL of water, followed by 3×100 mL of dilute aqueous HCl to remove the O-alkylated acridinium byproduct, and finally washed with deionized water. TLC of the organics indicated the presence of a single compound at this point, 2-methoxy-10-propylacridin-9(10H)-one, which was dried under reduced pressure and used in subsequent transformations. 1 H NMR(CDCl3)-δ1.12(3H,t), 1.93(2H,m), 4.28(2H,dd), 7.25(1H,ddd), 7.35(1H,dd), 7.45(1H,dd), 7.66(1H,m), 7.96(1H,d), 7.57(1H,dd).

[0448] 4.5g2-methoxy-10-propylacridine-9 (10H)-one (0.017 mole) and 6.4g N-2-methacryloyloxyethyl-2-cyanoacetamide (0.033 mole) are loaded into the 250mL three-necked round-bottom flask equipped with a magnetic stirring bar and a reflux condenser. The system is placed under a nitrogen blanket, and 20mL of dichloromethane is added to the mixture, stirring is until uniform. After cooling the system in an ice bath, titanium tetrachloride (4.5mL, 7.78g, 0.041 mole) is added to the mixture in a dropwise manner, and stirring is continued for another 15 minutes. 5mL of pyridine (4.9g, 0.06 mole) is added to the mixture, it is warming up to ambient temperature, then heated to reflux for 8 hours. After the mixture is cooled to room temperature, it is poured on the dilute HCl aqueous solution, and the product mixture is extracted into dichloromethane. Volatiles are evaporated under reduced pressure, and the product compound A is purified by flash chromatography. 1 H NMR (CDCl3) -δ 1.07 (3H, t), 1.87 (3H, s), 1.91 (2H, m), 3.58 (2H, dd), 3.85 (3H, s), 4.07 (2H, dd), 4.18 (2H, t), 5.5 (1H, dd), 6.03 (1H, ss), 6.07 (1H, t), 7.07 (1H, t), 7.14 (1H, dd), 7.23 (2H, two doublets), 7.48 (1H, m), 7.92 (1H, bs).

[0449] Example 2: 2-(2-cyano-2-(2-methoxy-10-butylacridin-9(10H)-ylidene)ethyl Synthesis of ethyl methacrylate (compound B)

[0450]

[0451] 10.0g 2-methoxyacridine-9 (10H) -one (0.044 mole) and 19.6g cesium carbonate (about 1.25 equivalents) are loaded into a 200mL round-bottom flask equipped with a magnetic stirring bar and a reflux condenser. The solid is dried under vacuum at 80°C, after which the system is placed under a nitrogen blanket and 60mL anhydrous DMSO is added to the flask. 1-bromobutane (7.55g, about 1.25 equivalents) is added to the flask, and the mixture is heated at 110°C (hood temperature) for 6 hours. Two products are observed by TLC, and the retention factors of the two products are very close and inseparable by chromatography. The cooling suspension is poured in 500mL deionized water, and the mixture is stirred at room temperature for 30 minutes. Organic matter is extracted into ethyl acetate, and washed with 3 × 200mL deionized water. NMR of the organic material indicated the presence of an O-alkylated acridinium derivative in addition to the desired compound 2-methoxy-10-butylacridin-9(10H)-one. This material can be used "as is" for the Knoevenagel condensation. Preferably, the crude product is washed with dilute aqueous HCl to remove the O-alkylated acridinium derivative, thereby obtaining pure 2-methoxy-10-butylacridin-9(10H)-one. 1 HNMR(CDCl3)-δ1.05(3H,t), 1.55(2H,m), 1.82(2H,m), 4.31(2H,dd), 7.25(1 H,ddd), 7.34(1H,dd), 7.45(1H,dd), 7.68(1H,m), 7.96(1H,d), 8.56(1H,dd).

[0452] Into a 250mL three-necked round-bottom flask equipped with a magnetic stirring bar and a reflux condenser, 10.0g of a crude product mixture containing 2-methoxy-10-butylacridine-9 (10H)-one and 15g of N-2-methacryloyloxyethyl-2-cyanoacetamide were loaded. The system was placed under a nitrogen blanket, 150mL of dichloromethane was added to the mixture, and stirring was until uniform. After cooling the system in an ice bath, titanium tetrachloride (10mL, 17.3g, 1.092 moles) was added to the mixture in a dropwise manner, and stirring was continued for another 15 minutes. 10mL of pyridine (9.82g, 0.12 mole) was added to the mixture, it was warmed to ambient temperature, and then heated to reflux for 8 hours. TLC showed the presence of several compounds, including the unreacted O-alkylated derivatives present in the starting material mixture. The major product, compound B, is a slightly more polar dark brown-orange species that is isolated after quenching the system in dilute aqueous HCl, followed by water extraction and chromatography. 1H NMR (CDCl3) -δ 1.04 (3H, t), 1.51 (2H, m), 1.87 (3H, s, 2H, m), 3.58 (2H, dd), 3.84 (3H, s), 4.12 (2H, dd), 4.19 (2H, t), 5.55 (1H, dd), 6.03 (1H, bs), 6.07 (1H, t), 7.07 (1H, t), 7.15 (1H, dd), 7.25 (2H, two doublets), 7.48 (1H, t), 7.75 (1H, bs), 7.92 (1H, bs).

[0453] An alternative synthesis of compound B is shown in Scheme 3

[0454]

[0455] Synthesis of ethyl 2-(2-(10-butyl-2-methoxyacridin-9(10H)-ylidene)-2-cyanoacetamido)methacrylate or compound B when R is n-butyl: A 3-neck 500 mL RBF equipped with a magnetic stir bar and reflux condenser was charged with 9.43 g of triphenylphosphine (36 mmol) and 120 mL of anhydrous dichloromethane. Bromine (5.76 g, 33 mmol) was added dropwise to the solution, which was stirred at room temperature for another 30 minutes, after which 10-butyl-2-methoxyacridin-9(10H)-one (8.43 g, 30 mmol) was added to the mixture and heated to reflux for 18 hours. Ethyl 2-(2-cyanoacetamido)methacrylate (8.23 g, 36 mmol, 1.4 equiv) was added to the reaction mixture, which was heated and stirred for another 8 hours. 4-(4-(4-(4-(4-chloro-2-yl)-1-yl)-2-nitropropene ...

[0456] Selected absorption properties of Compound A and Compound B are shown in Table 1.

[0457] Table 1

[0458]

[0459] 1λ 最大值The full width at half maximum (FWHM)

[0460] exist Figure 1 The UV-VIS absorption spectra of 0.1 mM methanol solutions of Compound A and Compound B are shown in FIG, and are superimposed on the literature spectrum of macular pigment.

[0461] Example 3: Contact Lenses

[0462] A reactive monomer mixture was prepared consisting of 77 wt% of the formulation listed in Table 2 and 23 wt% of the diluent D30. The reactive monomer mixture was filtered under pressure through a 3 μm filter using a stainless steel syringe.

[0463] Table 2

[0464]

[0465]

[0466] The reactive monomer mixture was degassed at ambient temperature by applying a vacuum (40 Torr) for at least 20 minutes. Then, in a glove box with a nitrogen atmosphere and less than about 0.1% to 0.2% oxygen, about 75 μL of the reactive mixture was dosed into a FC made of a 90:10 (weight / weight) Z / TT blend using an Eppendorf pipette at room temperature. The BC made of a 90:10 (w / w) Z:TT blend was then placed on the FC. Prior to dosing, the mold was equilibrated in the glove box for a minimum of twelve hours. The pallets, each containing eight mold assemblies, were transferred to an adjacent glove box maintained at 62°C and heated to about 2.0 mW / cm 2 The lenses were cured from the top and bottom for 10 minutes using 405nm LED light.

[0467] The lenses were manually demolded and released by suspending the lenses in about one liter of 70% IPA for about one hour, then soaking them twice more in fresh 70% IPA for 30 minutes; then overnight in DIW; then treated with fresh DIW for 30 minutes; and then soaked in the wetting solution for 30 minutes. Finally, the lenses were equilibrated and stored in a borate buffered wetting solution. One of ordinary skill in the art recognizes that the exact lens release process can vary depending on the lens formulation and molding material in terms of the concentration of the aqueous isopropyl alcohol solution, the number of washes with each solvent, and the duration of each step. The goal of the lens release process is to have all lenses released without defects and transition from a diluent-swollen network to a wetting solution-swollen hydrogel.

[0468] exist Figure 2Shown in FIG. 5 are the UV-VIS transmission spectra of two different sets of lenses (Example 3A and Example 3B) in borate buffered wetting solution.

[0469] Example 4: Thermal stability and photochemical stability test

[0470] A reactive monomer mixture was prepared, which consisted of 77 wt% of the formulation listed in Table 3 and 23 wt% of the diluent D3O. Lenses were manufactured from this reactive monomer mixture on a pilot line using an intensity of 1.5 mW / cm 2 The lenses were cured for 4 minutes using a double-sided 395nm LED and then at an intensity of 5mW / cm 2 The lenses were cured with a dual-sided 395 nm LED for 4 minutes. The lenses were packaged in standard blister packs with a borate buffered wetting solution containing about 50 ppm methyl ether cellulose; and the lenses (Example 4A) were sterilized at 121° C. for about 18 minutes.

[0471] Table 3

[0472] Components (weight %) Example 4A mPDMS 31 SiMAA 28 DMA 24.01 HEMA 6 TEGDMA 1.5 PVP K90 7 Omnirad 1870 0.34 Norbloc 2 Visible hue 0.06 Compound B 0.09

[0473] Example 4A (control lenses) were removed from their original blister packaging and placed into individual glass vials containing 5 mL of borate buffered wetting solution. The vials containing these lenses were stored in a stability chamber at 89°C for one month. The lens parameters, mechanical properties, and UV-VIS spectral properties (average percent transmission over a range of wavelengths) of these heat treated lenses (Example 4B) were subsequently measured and compared to the control lenses. These data are shown in Tables 4-6. Standard deviations are shown in parentheses. Figure 3 The UV-VIS spectra of Example 4A and Example 4B are shown in FIG.

[0474] The blister package containing the Example 4A lenses was placed in a controlled light stability chamber (foil side down, bowl side up so that the lenses in the bowl could be exposed to light). The light stability chamber was maintained at 25°C ± 2°C and ambient relative humidity. The lenses were then sequentially exposed to 1.5 million lux hours of visible light (168.8 hours of exposure) and 259.4 watt-hours / m 2 16.2 hours of UV light (16.2 hours of exposure). The lens parameters, mechanical properties and UV-VIS spectral properties (average transmission percentage over a wavelength range) of these light-stressed lenses (Example 4C) were then measured and compared to the control lenses. These data are shown in Tables 4-7. Standard deviations are shown in parentheses. The UV-VIS spectrum of Example 4C is also shown in Table 4-7. Figure 3 Shown in.

[0475] Table 4: Lens parameters

[0476]

[0477]

[0478] Table 5. Mechanical properties

[0479] Mechanical properties Example 4A Example 4B Example 4C Modulus (psi) 99(5) 113(9) 100(5) Elongation(%) 214(48) 162(39) 231(57) Tensile Strength (psi) 106(24) 96(20) 110(26) <![CDATA[Toughness (in-lb / in 3 )]]> 113(41) 84(34) 135(48) Water (wt%) 38.2(0) 38.7(0) 39.8(0)

[0480] Table 6: Spectral properties

[0481]

[0482] Table 7: Thermal and photostability at visible light absorption maximum

[0483]

[0484] 1 At the maximum absorption of visible light

[0485] Chromophores having Formula I, such as Compound B, exhibit thermal and photostability in contact lenses, while substantially mimicking the UV-VIS spectrum of macular pigment, as shown by minor changes in lens parameters, mechanical properties, and UV-VIS transmission spectra after heat treatment or light exposure.

[0486] Example 5

[0487] Reactive monomer mixtures were prepared consisting of 77 wt% of the formulation listed in Table 8 and 23 wt% of the diluent D3O. Lenses were manufactured from those reactive monomer mixtures on a pilot line using an intensity of 0.5 mW / cm2 at 70°C and an oxygen concentration of less than 5% (v / v). 2 The lenses were cured with a double-sided 395nm LED for 4 minutes and then with an intensity of 3mW / cm 2 The lenses were cured for 4 minutes using a double-sided 395nm LED. FC was made from a 90:10 (w / w) Z / TT blend and BC was made from a 90:10 (w / w) Z:TT blend. The lenses were demolded and peeled by suspending the mold assembly in 70% IPA for approximately one hour, then soaking twice more in fresh 70% IPA for 30 minutes, and then washing several times with DIW. The lenses were finally packaged in standard blister packs with a borate buffered wetting solution containing approximately 50 ppm methyl ether cellulose. The lenses of Example 5 were sterilized by autoclaving at 121°C for approximately 18 minutes.

[0488] The physical and mechanical properties of the lens of Example 5 were measured and are listed in Table 8. The UV-VIS transmission spectrum of the lens of Example 5 was measured and is shown in Figure 4 middle.

[0489] Example 6

[0490] Reactive monomer mixtures were prepared consisting of 77 wt% of the formulation listed in Table 8 and 23 wt% of the diluent D3O. Lenses were manufactured from those reactive monomer mixtures on a pilot line using an intensity of 2 mW / cm2 at 70°C and an oxygen concentration of less than 5% (v / v). 2 The lenses were cured with a double-sided 435nm LED for 4 minutes and then with an intensity of 12mW / cm 2 The lenses were cured for 4 minutes using a double-sided 435nm LED. FC was made from a 90:10 (w / w) Z / TT blend and BC was made from a 90:10 (w / w) Z:TT blend. The lenses were demolded and peeled by suspending the mold assembly in 70% IPA for approximately one hour, then soaking twice more in fresh 70% IPA for 30 minutes, and then washing several times with DIW. The lenses were finally packaged in standard blister packs with a borate buffered wetting solution containing approximately 50 ppm methyl ether cellulose. The lenses of Example 6 were sterilized by autoclaving at 121°C for approximately 18 minutes.

[0491] The physical and mechanical properties of the lens of Example 6 were measured and are listed in Table 8. The UV-VIS transmission spectrum of the lens of Example 6 was measured and is shown in Figure 4 middle.

[0492] Example 7

[0493] A reactive monomer mixture was prepared consisting of 77 wt% of the formulation listed in Table 8 and 23 wt% of the diluent D3O. Lenses were made from the reactive monomer mixture by thermal curing with AIBN at 90°C for 180 minutes in a glove box and nitrogen atmosphere. Both FC and BC were made from 1430R Zeonor. The lenses were demolded and peeled by suspending the mold assembly in 70% IPA for about one hour, then soaking it twice more with fresh 70% IPA for 30 minutes, and then washing it with DIW several times. The lenses were finally packaged in standard blister packs with a borate buffered wetting solution containing about 50 ppm of methyl ether cellulose. The lenses were sterilized by autoclaving at 121°C for about 18 minutes.

[0494] The physical and mechanical properties of the lens of Example 7 were measured and are listed in Table 8. The spectral properties of the lenses of Examples 1-3 are listed in Table 9. The UV-VIS transmission spectra of the lenses were measured and are shown in Table 10. Figure 4The UV-VIS spectrum of the thermally cured Example 7 lens is almost identical to the UV-VIS spectrum of the photochemically cured Example 6 lens made from the same formulation. In addition, the Example 6 lens and the Example 7 lens absorb significantly more HEV light than the Example 5 lens.

[0495] Table 8: Formulation and physical properties

[0496] Components (weight %) Example 5 Example 6 Example 7 mPDMS 31 30 30 SiMAA 28 27.6 27.6 DMA 24.01 24 24 HEMA 5.85 5.85 5.82 TEGDMA 1.65 1.65 1.65 PVP K90 7 7 7 Omnirad 1870 0.34 0.34 0 AIBN 0 0 0.37 Norbloc 2 1 1 RB247 0.06 0.06 0.06 Compound B 0.09 0.09 0.09 Compound C 0 2.41 2.41 Total of components 100 100 100 nature Example 5 Example 6 Example 7 WC (weight %) 38(0) 39(0) 38(0) EC Dk(Bale) 101 94 91 TS(psi) 102(23) 132(15) 109(30) ETB(%) 230(51) 264(23) 235(42) TM(psi) 92(5) 95(5) 94(11) <![CDATA[Toughness (in*lb / in 3 )]]> 123(45) 176(29) 134(51) Kruss DCA(°) 52(1) 50(1) 53(4) Sessile drop method(°) FC=39(4); BC=38(3) FC=32(0);BC=33(2) FC=35(1) RI 1.4145 1.4193 1.388

[0497] Table 9. Spectral transmission properties

[0498]

[0499] Example 8

[0500] A reactive monomer mixture was prepared, which consisted of 77 wt % of the formulation listed in Table 10 and 23 wt % of the diluent D3O. Lenses were manufactured from the reactive monomer mixture by thermal curing with AIBN at 90°C for 180 minutes in a glove box and nitrogen atmosphere. Both FC and BC were made of 1430R Zeonor. The lenses were demolded and peeled off by suspending the mold assembly in 70% IPA for about one hour, then soaking it twice with fresh 70% IPA for 30 minutes, and then washing it with DIW several times. Finally, the lenses were packaged in standard blister packs with a borate buffered wetting solution containing about 50 ppm methyl ether cellulose. The lenses were sterilized by autoclaving at 121°C for about 18 minutes. The physical and mechanical properties of the lenses of Example 8 were measured and listed in Table 10. The spectral properties of the lenses of Example 8 are listed in Table 11. The UV-VIS transmittance spectrum of the lenses was measured and shown in Figure 5 middle.

[0501] Table 10: Formulation and physical properties

[0502]

[0503]

[0504] Table 11. Spectral transmission properties

[0505] Spectral range Wavelength range (nm) Example 8 (%T) visible 380-780 77.6 UVA 315-380 0.1 UVB 289-315 0 HEV 380-450 33.1

[0506] Example 9

[0507] Reactive monomer mixtures 9A and 9B were formed by mixing the reactive components listed in Table 12 with a diluent D3O, wherein the weight ratio of the reactive components to the diluent was 77:23 (w / w). The resulting formulations were filtered independently through a 3 μm filter and degassed by applying a vacuum (about 40 mm Hg). The target spherical power of the mold design was nominally minus one diopter. Both FC and BC were made from a 90:10 (w / w) Z / TT blend. Before dosing, the mold was equilibrated in a glove box for a minimum of twelve hours. The lenses were manufactured on a pilot production line using double-sided 435nm LED curing. In a nitrogen atmosphere and about 0.8% oxygen, about 5 μL of reactive mixture 9A was dosed into FC at room temperature. Then, about 75 μL of reaction mixture 9B was metered onto the top of the 9A micro-dose. BC was placed on top of FC. The mold assembly was equilibrated at 70°C for 6-7 minutes and then heated to 2 mW / cm 2 435nm LED light from the top and bottom for 6-7 minutes, followed by 5mW / cm 2 Curing for 6-7 minutes. The lenses were demolded and peeled by suspending the mold assembly in 70% IPA for about one hour, then soaking twice more in fresh 70% IPA for 30 minutes, and then washing several times with DIW. The lenses were finally packaged in standard blister packs with a borate buffered wetting solution containing about 50 ppm methyl ether cellulose. The lenses were sterilized by autoclaving at 121°C for about 18 minutes.

[0508] The physical and mechanical properties of the sterile Example 9C lenses were measured and are listed in Table 12. The UV-VIS transmission spectra of the Example 9C lenses were measured and are shown in Figure 6 middle.

[0509] Table 12: Formulation and physical properties

[0510]

[0511] Example 10: 3-((9-(dicyanomethylidene)-9H-xanthen-3-yl)oxymethacrylate as shown in Scheme 4 Synthesis of 2-(4-(2-aminopropyl)propane ester (Compound D)

[0512]

[0513] Synthesis of 3-((9-oxo-9H-xanthene-3-yl)oxy)propyl acetate:

[0514] A suspension of 3-hydroxy-9H-xanthene-9-one (42.4 g, 0.2 mol), 70.0 g of Cs2CO3 (0.2 mol) and sodium iodide (catalytic amount 200 mg) was dried in a 500 mL round-bottom flask containing a magnetic stirring bar under vacuum. Anhydrous DMSO (250 mL) was added, followed by 2-chloroethyl methacrylate (30.0 g, 0.2 mol). The reaction mixture was heated at 70 ° C overnight. Monitoring by TLC indicated that the hydroxyxanthene was completely consumed, while a less polar derivative was formed. The reaction mixture was cooled to room temperature and slowly poured into a dilute aqueous hydrochloric acid solution under continuous stirring. After stirring for thirty minutes, the off-white solid was separated by vacuum filtration using a sintered glass funnel. The filter cake was washed with deionized water and then washed twice with 200 mL of hexane. 3-((9-oxo-9H-xanthene-3-yl)oxy)propyl acetate was dried in vacuum at 60 ° C to constant weight.

[0515] Synthesis of 3-((9-oxo-9H-xanthen-3-yl)oxy)propanol :

[0516] 27 grams of 3-((9-oxo-9H-xanthene-3-yl)oxy)propyl acetate was stirred in about 700 mL of methanol at room temperature, during which time 20 mL of 10N aqueous sodium hydroxide solution was added to the mixture, followed by about 30 mL of deionized water. TLC monitoring indicated that the hydrolysis reaction was complete within a few minutes. The mixture was slowly acidified by the addition of dilute aqueous hydrochloric acid, and then 150 mL of deionized water was added while the system was continuously stirred. 3-((9-oxo-9H-xanthene-3-yl)oxy)propanol was isolated by vacuum filtration using a sintered glass funnel, washed with additional amounts of water, and finally dried in a vacuum oven at 60°C.

[0517] Synthesis of 3-((9-oxo-9H-xanthene-3-yl)oxy)propyl methacrylate :

[0518] In a one-liter three-necked round-bottom flask equipped with a magnetic stirring bar and a reflux condenser, 25 grams of 3-((9-oxo-9H-xanthene-3-yl)oxy)propanol and 15 mL (10.89 grams) of triethylamine were stirred in 300 mL of anhydrous acetonitrile. Methacryloyl chloride (9.9 grams) was added dropwise to the flask and the mixture was stirred for one hour. The volatile components were evaporated under reduced pressure and the resulting solid was washed and filtered on a sintered glass funnel and rinsed with deionized water. The residue was further washed with dilute aqueous hydrochloric acid, then with deionized water and finally with hexane. The methacrylate 3-((9-oxo-9H-xanthene-3-yl)oxy)propyl ester was then dried in a rotary evaporator with the bath temperature maintained below 20°C.

[0519] Synthesis of 3-((9-(dicyanomethylidene)-9H-xanthen-3-yl)oxy)propyl methacrylate (Compound D) :

[0520] In a round bottom flask equipped with a magnetic stir bar and reflux condenser, 6.76 grams of 3-((9-oxo-9H-xanthene-3-yl)oxy)propyl methacrylate and 15 mL of thionyl chloride were heated at 65°C (mantle temperature) for 2 hours. The mixture was cooled to room temperature and the excess thionyl chloride was evaporated under reduced pressure while keeping the bath temperature below 20°C. 3.96 grams of malononitrile was added to the flask, followed by 25 mL of anhydrous dichloromethane, and the mixture was stirred and heated under gentle reflux for two hours. The mixture was cooled to room temperature and then rinsed through a short plug of silica gel, eluting with dichloromethane. The volatile components were evaporated under reduced pressure, keeping the temperature below 20°C, after which the solid was suspended in cold methanol (100 mL) and stirred for 20 minutes. The crude product was isolated by vacuum filtration and the filter cake was washed with additional cold methanol. 3-((9-(dicyanomethylidene)-9H-xanthene-3-yl)oxy)propyl methacrylate was further purified by passing through a silica gel column eluting with dichloromethane. 1 H NMR (500MHz, CDCl3)-δ1.95 (3H, CH3), 2.25 (2H, m, CH2), 4.20 (2H, t, CH2 benzyl), 4.37 (2H, t, CH2O ester), 5.59 (1H, m, vinyl), 6.12 (1H, m, vinyl), 6.90 (1H, dAr-H), 6.97 (1H, dd, Ar-H), 7.40 (1H, ddd, Ar-H), 7.45 (1H, dd, Ar-H), 7.68 (1H, ddd, Ar-H), 8.50 (1H, d, Ar-H), 8.57 (1H, dd, Ar-H). Figure 7 The UV-VIS absorption spectra of compound C and compound D are shown in FIG. Compound D exhibits a 19,341 L·mol -1 cm -1 The molar extinction coefficient, as in λ max = calculated at 396 nm in 0.2 mM dichloromethane.

[0521] Example 11: Synthesis of (9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl)bis(2-methyl acrylate) as shown in Scheme 5.

[0522]

[0523] Anthracene-1,4,9,10-tetrol (75 g, 0.3096 mol), 2-ethoxyethanol (225 mL), 2-(2-(2-aminoethoxy)ethoxy)ethan-1-ol (161.58 g, 1.083 mol) and sodium dithionite (107.81 g, 0.6192 mol) were added to the autoclave chamber under nitrogen atmosphere and ambient temperature conditions. The reaction mixture was vigorously stirred at 85°C under 5 kg nitrogen pressure for 16 hours. The progress of the reaction was monitored by thin layer chromatography (5% methanol in dichloromethane). When the reaction was complete, the reaction mixture was cooled to ambient temperature. Dichloromethane (2000 mL) and deionized water (1000 mL) were added and the reaction mixture was stirred for 5-7 minutes. The organic layer was separated and the aqueous layer was extracted with dichloromethane (500 mL). The combined organic extracts were washed with water (2×1000 mL) and brine (2×1000 mL). Activated carbon (75 g) was added to the organic layer and stirred overnight at room temperature. The activated carbon was removed by filtration through diatomaceous earth and washed with dichloromethane (3000 mL). The filtrate was dried over sodium sulfate and filtered. The solvent was removed under reduced pressure to give a crude product of 1,4-bis((2-(2-(2-hydroxyethoxy)ethoxy)ethyl)amino)anthracene-9,10-dione (126 g). The crude product was stirred in ethyl acetate (1000 mL) at 60° C. for one hour and then at ambient temperature for 14-16 hours. The solid was filtered and washed with ethyl acetate (300 mL), and the residue was air-dried at 45 °C for 14-16 h to afford 1,4-bis((2-(2-hydroxyethoxy)ethoxy)ethyl)amino)anthracene-9,10-dione (100.0 g; yield = 64%) as a blue solid. 1 H-NMR (DMSO-d 6 ,400MHz): δ3.70-3.45(m,24H),7.51(s,2H),7.78(m,2H),8.25(m,2H),10.89(br s,2H).

[0524] To a solution of 1,4-bis((2-(2-(2-hydroxyethoxy)ethoxy)ethyl)amino)anthracene-9,10-dione (75.0 g, 0.1493 mol) in tetrahydrofuran (1500 mL) was added triethylamine (302.1 g, 414.97 mL, 2.9866 mol) at room temperature. After stirring for 15 minutes, a solution of methacryloyl chloride (62.43 g, 58.35 mL, 0.5973 mol) in tetrahydrofuran (150 mL) was added dropwise while maintaining the reaction temperature between 0°C and -5°C. The reaction mixture was stirred at 0°C to -5°C for 1 hour and the progress of the reaction was monitored by thin layer chromatography (5% methanol in dichloromethane). Upon completion of the reaction, ethyl acetate (3000 mL) and deionized water (2000 mL) were added at 10°C-15°C and the reaction mixture was stirred for 8-10 minutes. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×1000 mL). The combined organic layers were washed with deionized water (4×2000 mL) and brine (1000 mL), dried over sodium sulfate, and filtered. The solvent was removed under reduced pressure to give a crude product (86 g), which was then purified by column chromatography using 230-400 mesh silica gel (2.8 kg) eluting with 0.1%-0.5% methanol in dichloromethane to give (9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl)bis(2-acrylic acid methyl ester) (22 g; yield = 23%) as a blue solid. 1 H-NMR (DMSO-d 6 ,400MHz): δ1.83(s,6H),4.20-4.16(m,20H),4.21(m,4H),5.62(s,2H),5.9 8(s,2H),7.5(s,2H),7.77(m,2H),8.23(m,2H),10.87(t,2H,J=5.2,5.6Hz). Figure 8 Shown is the UV-VIS absorption spectrum of (9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl)bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl)bis(methyl 2-acrylate) in a 0.2 mM methanol solution.

[0525] Example 12. N,N′-(((((((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(1,4-diyl)-1,4-diyl)-1,4-diyl)-1,4-diyl (azadiyl)bis(ethane-2,1-diyl)bis(oxy)bis(ethane-2,1-diyl)bis(oxy)bis(ethane-2,1-diyl)bis(oxy)bis(ethane-2,1-diyl) Synthesis of diacrylamide .

[0526]

[0527] Anthracene-1,4,9,10-tetrol (10.0 g, 0.042 mol), 2,2'-(ethane-1,2-diylbis(oxy))bis(ethane-1-amine) (61.17 g, 0.413 mol) and sodium bisulfite (10.0 g, 0.058 mol) were added to the tube at ambient temperature and then sealed. The reaction mixture was stirred at 85°C for 16 hours. The progress of the reaction was monitored by thin layer chromatography (20% methanol in dichloromethane). After the reaction was complete, the reaction mixture was cooled to room temperature and deionized water (250 mL) and dichloromethane (250 mL) were added. The aqueous layer was re-extracted with dichloromethane (250 mL). The combined organic extracts were washed with deionized water (250 mL) and brine (250 mL). The organic phase was then dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to give a crude product (23 g) which was used in the next step without further purification.

[0528] To a solution of 1,4-bis((2-(2-(2-aminoethoxy)ethoxy)ethyl)amino)anthracene-9,10-dione (23.0 g, 0.046 mole) in dichloromethane (690 mL) was slowly added triethylamine (46.5 grams, 64 mL, 0.46 mole) at room temperature, followed by dropwise addition of a solution of acryloyl chloride (12.4 grams, 10.8 mL, 0.1379 mole) in dichloromethane (46 mL) while maintaining the reaction temperature between 0°C and 5°C, followed by stirring for two hours. The progress of the reaction was monitored by thin layer chromatography (5% methanol in dichloromethane). Upon completion of the reaction, saturated sodium bicarbonate solution (300 mL) was added to the reaction mixture at 0-5°C. The organic layer was separated and the aqueous layer was extracted again with dichloromethane (2×230 mL). The combined organic extracts were washed with deionized water (460 mL) and brine (460 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure at 30° C. to give N,N′-((((((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))diacrylamide (27 g). The crude product was then purified by column chromatography using 100-200 mesh size silica gel eluting with 0.2%-0.6% methanol / dichloromethane to give a blue solid (65% yield). 1 H-NMR (DMSO-d 6 ,400MHz): δ3.71-3.28(m,24H),5.56(s,J=10.8Hz,2H),6.09(d,J=16.8Hz ,2H),6.24(m,2H),7.47(s,2H),7.85(m,2H),8.24-8.15(m,4H),10.86(br s,2H).

[0529] Example 13: As shown in Scheme 7, 1-cyano-2-oxo-1-(9H-thioxanthen-9-ylidene)-6,9, Synthesis of 12,15,18-pentaoxa-3-azepin-20-yl esters (hypothetical example).

[0530]

[0531] Synthesis of 2-cyano-N-(17-hydroxy-3,6,9,12,15-pentaoxyheptadecyl)acetamide

[0532] Under nitrogen environment, a solution of 17-amino-3,6,9,12,15-five oxa heptadecan-1-ol (0.98 equivalent) in dichloromethane (25mL) was added to a solution of methyl cyanoacetate (1.0 equivalent) in methyl chloride (50mL) in a 100mL three-necked round-bottom flask equipped with a reflux condenser using a charging funnel. As the reaction temperature rises, the reaction mixture begins to reflux. After the exothermic stop, external heat is applied to continue reflux for a total of two hours, after which 17-amino-3,6,9,12,15-five oxa heptadecan-1-ol is not observed by thin layer chromatography. The reaction can also be carried out at room temperature, but it needs to be carried out for several hours. The mixture is cooled to room temperature, and dichloromethane is removed by rotary evaporation under reduced pressure. The residual oil is washed three times with 50mL ethyl acetate to remove unreacted starting material and non-polar impurities. The residual ethyl acetate is then removed by rotary evaporation under reduced pressure, and the resulting oil (Compound E) is used for subsequent acylation without any further purification.

[0533] Synthesis of 1-cyano-2-oxo-6,9,12,15,18-pentaoxa-3-aza-20-yl methacrylate

[0534] In a three-necked round-bottom flask equipped with a reflux condenser, a charging funnel and a magnetic stirring bar, compound E was dissolved in 150mL of dichloromethane containing pyridine (2.5 equivalents). The flask was immersed in an ice bath and cooled to 0°C, and methacryloyl chloride (1.5 equivalents) was added dropwise from the charging funnel. The resulting reaction mixture was warmed to room temperature while the system was constantly stirred. Methanol (20mL) was then added to the flask to quench any unreacted methacryloyl chloride. The volatile components were removed by rotary evaporation under reduced pressure, and the crude product was dissolved in 800mL of dilute hydrochloric acid aqueous solution. The resulting aqueous solution was extracted three times with 100mL of hexane in a separatory funnel to remove any non-polar impurities. The organic layer was discarded. Sodium chloride was added to the aqueous layer, which was then extracted three times with 300mL of ethyl acetate. About 50 mg of butylated hydroxytoluene (BHT) or 2,6-di-tert-butyl-4-methylphenol was added as an inhibitor to the combined organic fractions, and ethyl acetate was removed by rotary evaporation under reduced pressure. During the removal of the solvent, the crude product crystallized from the solution. When about 100 mL of ethyl acetate remained in the flask, 250 mL of hexane was added, and the crude product was separated by vacuum filtration using a sintered glass funnel. The filter cake was washed twice with 150 mL of hexane and then dried in vacuo at 40 ° C to obtain 1-cyano-2-oxo-6,9,12,15,18-pentaoxa-3-aza-20-yl methacrylate (Compound F).

[0535] Methacrylic acid 1-cyano-2-oxo-1-(9H-thioxanthen-9-ylidene)-6,9,12,15,18-pentaoxa-3-nitropropene Synthesis of hetero-20-yl esters

[0536] Under nitrogen atmosphere, a mixture of 9H-thioxanthen-9-one (1.0 equivalent) and thionyl chloride (7.0 equivalent) was refluxed in a 100mL round-bottom flask while stirring continuously. After two hours, the red solution was evaporated to dryness to remove excess thionyl chloride from the system. Compound F (1.17 equivalents) was dissolved in 25mL dichloromethane and then added to a flask. The resulting reaction mixture was heated to reflux under nitrogen blanketing. The reaction was monitored by thin layer chromatography until the reaction was complete. The reaction mixture was cooled to room temperature. The desired product, methacrylic acid 1-cyano-2-oxo-1-(9H-thioxanthen-9-subunit)-6,9,12,15,18-pentaoxa-3-aza-20-yl ester, was separated as yellow crystals after passing through a short silica gel column (dichloromethane, followed by a 5% methanol solution in dichloromethane).

[0537] Example 14: Methacrylic acid 1-(10-butyl-2-methoxyacridin-9(10H)-ylidene)- 1-Cyano-2-oxo-6,9,12,15,18-pentaoxa-3-aza-20-yl ester (hypothetical example)

[0538]

[0539] Synthesis of 2-((4-methoxyphenyl)amino)benzoic acid

[0540] 2-Iodobenzoic acid (1.0 eq.), 4-methoxyaniline (2 eq.), potassium carbonate (1.0 eq.) and 300 mg of copper powder were charged into a 100 mL three-necked round bottom flask equipped with a magnetic stirring bar and a reflux condenser. Deionized water (30 mL) was added to the solid mixture, and the reaction mixture was then heated under reflux for 6 hours with constant stirring. The mixture solidified upon cooling to room temperature. The reaction mixture was diluted with deionized water and gradually poured into 1 equivalent of aqueous hydrochloric acid solution with stirring. The reaction mixture was stirred at room temperature for 30 minutes, after which it was filtered on a sintered glass funnel and dried in a vacuum oven at 60°C. The resulting 2-((4-methoxyphenyl)amino)benzoic acid was washed with deionized water (3×100 mL) and used “as is” for intramolecular cyclization.

[0541] Synthesis of 2-Methoxyacridin-9(10H)-one

[0542] A 250 mL round bottom flask equipped with a magnetic stirring bar and a reflux condenser was charged with 12.5 g of 2-((4-methoxyphenyl)amino)benzoic acid and 100 mL of Eton's acid (10 wt % P2O5 in methanesulfonic acid). The mixture was heated at 90°C (mantle temperature) for 5 hours with constant stirring while the progress of the reaction was monitored by thin layer chromatography. Upon cooling to room temperature, the reaction mixture was poured onto crushed ice, stirred for 30 minutes, and filtered on a sintered glass funnel. The resulting 2-methoxyacridin-9(10H)-one was washed with deionized water (3×100 mL), then with acetonitrile, and dried in a vacuum oven at 60°C.

[0543] Synthesis of 2-Methoxy-10-butylacridin-9(10H)-one

[0544] A 250 mL round bottom flask equipped with a magnetic stir bar and reflux condenser was charged with 5.4 g of 2-methoxyacridin-9(10H)-one (0.0244 mol) and 12.9 g of cesium carbonate (1.5 eq.). The solid was dried at 80 °C under vacuum, after which the system was placed under a nitrogen blanket and 80 mL of anhydrous N,N-dimethylformamide was added to the flask. 1-Bromobutane (6.0 g, 2 eq.) was added to the flask, and the mixture was heated at 50 °C (hood temperature) for 36 hours. Thin layer chromatography indicated the presence of two compounds (O-alkylated and N-alkylated). The organics were poured into 200 mL of deionized water and extracted into approximately 150 mL of ethyl acetate. The organics were then washed with deionized water (3×100 mL), followed by dilute aqueous HCl (3×100 mL) to remove the O-alkylated acridinium byproduct, and the final water was then washed with deionized water. Thin layer chromatography of the organic fraction confirmed the presence of a single compound at this point, 2-methoxy-10-propylacridin-9(10H)-one, which was dried under reduced pressure and used in subsequent transformations.

[0545] Methacrylic acid 1-(10-butyl-2-methoxyacridin-9(10H)-ylidene)-1-cyano-2-oxo-6,9,12, Synthesis of 15,18-pentaoxa-3-aza-20-yl ester

[0546] 2-methoxy-10-butylacridine-9(10H)-one (1.0 equivalent), methacrylic acid 1-cyano-2-oxo-6,9,12,15,18-pentaoxa-3-aza-20-yl ester (Compound F, 2.0 equivalent) and 20mL dichloromethane were loaded into a 250mL three-necked round-bottom flask equipped with a magnetic stirring bar and a reflux condenser. The system was placed under a nitrogen seal and the reaction mixture was stirred until uniform. After cooling the system in an ice bath, titanium tetrachloride (2.5 equivalents) was added to the reaction mixture in a dropwise manner and stirred for another 15 minutes. 5mL pyridine (0.33 equivalents) was added to the reaction mixture, which was warmed to ambient temperature and then heated to reflux for 8 hours. After the reaction mixture was cooled to room temperature, the reaction mixture was poured into a dilute aqueous hydrochloric acid solution and the aqueous phase was extracted with dichloromethane. The organic fractions were combined and the volatile components were removed by rotary evaporation under reduced pressure. The desired product, 1-(10-butyl-2-methoxyacridin-9(10H)-ylidene)-1-cyano-2-oxo-6,9,12,15,18-pentaoxa-3-azepin-20-yl methacrylate, was purified by flash chromatography to give a dark yellow solid.

[0547] Example 15: 17-((9-(dicyanomethylene)-9H-xanthen-3-yl)methacrylate as shown in Scheme 9 Synthesis of 3,6,9,12,15-pentaoxyheptadecyl ester (hypothetical example).

[0548]

[0549] Synthesis of 17-chloro-3,6,9,12,15-pentaoxyheptadecyl methacrylate

[0550] 17-Chloro-3,6,9,12,15-pentaoxaheptadecan-1-ol (1.0 equivalent) and some 4-(dimethylamino)-pyridine crystals (catalytic amount) were dissolved in dichloromethane (500 mL) in a round-bottom flask equipped with a pressure equalizing addition funnel and a nitrogen seal. The reaction mixture was cooled to 0°C using an ice bath, and triethylamine (4.0 equivalents) was then added. Acryloyl chloride (1.1 equivalents) containing about 400 parts per million (ppm) of butylated hydroxytoluene (BHT) or 2,6-di-tert-butyl-4-methylphenol was then added dropwise, and the reaction mixture was stirred at 0°C for two hours, then warmed to ambient temperature and stirred for about 6 hours. The reaction mixture was quenched with 150 mL of deionized water, then poured into 200 mL of 1 molar hydrochloric acid and stirred. After adding some saturated sodium chloride solution, the phases were separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with saturated sodium bicarbonate solution and saturated sodium chloride solution. After adding about 100 ppm BHT per gram of desired product, the organic phase was concentrated by rotary evaporation under reduced pressure to obtain a crude product. The crude product was dissolved in 30% (v / v) ethyl acetate in n-hexane and passed through a short silica gel column, eluted with 30% (v / v) ethyl acetate in n-hexane to obtain 17-chloro-3,6,9,12,15-pentahydroheptadecyl methacrylate.

[0551] 17-((9-oxo-9H-xanthen-3-yl)oxy)-3,6,9,12,15-pentaoxyheptadecyl methacrylate synthesis

[0552] A suspension of 3-hydroxy-9H-xanthene-9-one (1.0 equivalent), Cs2CO3 (1.0 equivalent) and sodium iodide (catalytic amount, about 200 mg) was dried under vacuum in a 500 mL round-bottom flask containing a magnetic stirring bar. Anhydrous dimethyl sulfoxide (DMSO) (250 mL) was added, followed by 17-chloro-3,6,9,12,15-pentahydrogen heptadecanyl methacrylate (1.0 equivalent). The reaction mixture was heated at 70 ° C overnight and monitored by thin layer chromatography. The reaction mixture was cooled to room temperature and slowly poured into a dilute aqueous hydrochloric acid solution under continuous stirring. After stirring for thirty minutes, a sintered glass funnel was used to separate the off-white solid by vacuum filtration. The filter cake was then washed with deionized water and then washed twice with 200 mL of hexane. The obtained 17-((9-oxo-9H-xanthene-3-yl)oxy)-3,6,9,12,15-pentaoxoheptadecyl methacrylate was dried under vacuum at 60° C. to a constant weight.

[0553] Methacrylate 17-((9-(dicyanomethylene)-9H-xanthen-3-yl)oxy)-3,6,9,12,15-pentaoxodecaproic acid Synthesis of Heptaalkyl Esters

[0554] Methacrylate 17-((9-oxo-9H-xanthen-3-yl)oxy)-3,6,9,12,15-pentahydroheptadecyl ester (1.0 equiv) and thionyl chloride (7.0 equiv) were dissolved in dichloromethane (50 mL) and the resulting reaction mixture was refluxed under nitrogen for 2 hours. The reaction mixture was cooled to room temperature and excess thionyl chloride and dichloromethane were removed by rotary evaporation under reduced pressure while keeping the bath temperature below 20°C. Excess malononitrile (10.0 equiv) was added to the flask, followed by 25 mL of anhydrous dichloromethane, and the reaction mixture was stirred and heated to reflux for two hours. The mixture was cooled to room temperature and then rinsed through a short silica gel plug, eluting with 5% methanol (v / v) in dichloromethane. The volatile components were evaporated under reduced pressure, the temperature was maintained below 20°C, and the solid was then suspended in cold methanol (100 mL) and stirred for 20 minutes. The crude product was isolated by vacuum filtration and the filter cake was washed with additional cold methanol. Methacrylate 17-((9-(dicyanomethylidene)-9H-xanthene-3-yl)oxy)-3,6,9,12,15-pentaoxoheptadecyl ester was further purified by silica gel column eluting with 5% methanol in dichloromethane (v / v) to give a light yellow solid.

Claims

1. An ophthalmic device, the ophthalmic device being a free radical reaction product of a reactive mixture, the reactive mixture comprising: one or more monomers suitable for making the ophthalmic device; A first visible light filter compound having a visible light absorption maximum between 430 nm and 480 nm and having a full width at half maximum (FWHM) of at least 35 nm and at most 150 nanometers at said visible light absorption maximum, wherein said compound is photostable, and wherein said compound has at least 7740 L.mol -1 .cm -1 The molar extinction coefficient of A second visible light filtering compound.

2. The ophthalmic device of claim 1, wherein the visible light absorption maximum of the first visible light filter compound is between 440 nm and 470 nm.

3. The ophthalmic device according to any of the preceding claims, wherein the FWHM at the visible light absorption maximum of the first visible light filter compound is at least 40 nm and at most 95 nm.

4. The ophthalmic device of any one of the preceding claims, wherein photostability comprises no more than a 20% loss in absorbance at the visible light absorption maximum.

5. The ophthalmic device of any of the preceding claims, wherein photostable comprises more photostable than macular pigment.

6. The ophthalmic device according to any one of the preceding claims, wherein the first visible light filter compound is thermally stable.

7. The ophthalmic device according to any one of the preceding claims, wherein the first visible light filter compound is more thermally stable than macular pigment.

8. An ophthalmic device according to any one of the preceding claims, wherein the second visible light filter compound comprises a mid-energy visible light filter having one or more visible light absorption maxima between 550 nm and 660 nm.

9. The ophthalmic device of claim 8, wherein the mid-energy visible light filter has a first visible light absorption maximum between 610 nm and 660 nm, preferably between 630 nm and 650 nm, optionally with a FWHM of at least 20 nm and at most 60 nm or optionally at least 30 nm and at most 50 nm.

10. The ophthalmic device of claim 9, wherein the mid-energy visible light filter has a second visible light absorption maximum intermediately between 575 nm and 609 nm, preferably intermediately between 580 nm and 600 nm, optionally having a FWHM of at least 60 nm and at most 120 nm or optionally at least 80 nm and at most 100 nm.

11. The ophthalmic device of any one of claims 8 to 10, wherein the mid-energy visible light filter limits the transmittance of the device in the wavelength range of 550 nm to 660 nm to between 50% and 95%.

12. An ophthalmic device according to any of the preceding claims, wherein the second visible light filtering compound comprises a high energy visible light filter which limits the transmittance of the device in the wavelength range of 400 nm to 409 nm to between 0% and 70%, preferably to between 0.2% and 40%.

13. The ophthalmic device of any of the preceding claims, wherein the second visible light absorbing compound comprises the following compounds: (a) a mid-energy visible light filter having one or more visible light absorption maxima between 550 nm and 660 nm; and (b) a high-energy visible light filter that limits the transmittance of the device to between 0% and 70% in the wavelength range of 400 nm to 409 nm.

14. The ophthalmic device according to any one of the preceding claims, wherein the first visible light filter compound and the second visible light filter compound independently comprise at least one polymerizable group.

15. The ophthalmic device of any one of the preceding claims, wherein the reactive mixture further comprises a UV absorbing compound.

16. An ophthalmic device according to any one of the preceding claims, wherein the device has a transmittance of: (a) between 0% and 70% in the wavelength range of 400 nm to 409 nm; (b) between 60% and 80% in the wavelength range of 430 nm to 480 nm; (c) between 50% and 95% in the wavelength range of 550 nm to 660 nm; and (d) At least 90% in the wavelength range from 665 nm to 760 nm.

17. The ophthalmic device of claim 16, wherein the device has a transmittance of: (e) at least 90% in the wavelength range of 515 nm to 530 nm.

18. The ophthalmic device of any one of claims 16 to 17, wherein the device has a transmittance of: (f) 35% or less in the wavelength range of 280 nm to 399 nm.

19. The ophthalmic device according to any one of the preceding claims, wherein the first visible light filter compound has Formula I: wherein m and n are independently 0, 1, 2, 3 or 4; T is a bond, O or NR 6 , where R 6 is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or YP g ; R is H, C1-C8 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; Y is a linking group; P g is a polymerizable group; R 1 and R 2 , when present, is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted by alkyl or halo), halo, hydroxy, amino, NR 3 R 4 , benzyl, SO3H or SO3M (M is a monovalent cation such as sodium or potassium), wherein R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 or R 2 The two adjacent groups are combined together with the carbon atoms to which they are attached to form a cycloalkyl or aryl ring; and EWG is an electron withdrawing group.

20. The ophthalmic device of claim 19, wherein m and n are each independently 0 or 1.

21. The ophthalmic device of any one of claims 19 to 20, wherein Y at each occurrence is independently alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination thereof.

22. An ophthalmic device according to any one of claims 19 to 21, wherein P g These include styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide.

23. The ophthalmic device of any one of claims 19 to 22, wherein EWG is a cyano group, an amide group, an ester group, a ketone group, or an aldehyde group.

24. The ophthalmic device of any one of claims 19 to 23, wherein EWG is cyano.

25. The ophthalmic device of any one of the preceding claims, wherein the first visible light filter compound comprises: 2-(2-cyano-2-(2-methoxy-10-propylacridin-9(10H)-ylidene)acetamido)ethyl methacrylate 2-(2-cyano-2-(2-methoxy-10-butylacridin-9(10H)-ylidene)acetamido)ethyl methacrylate 1-(10-butyl-2-methoxyacridin-9(10H)-ylidene)-1-cyano-2-oxo-6,9,12,15,18-pentaoxa-3-azepin-20-yl methacrylate; or A mixture of them.

26. The ophthalmic device according to any one of the preceding claims, wherein the second visible light filter compound comprises a mid-energy visible light filter of Formula II: wherein Y is independently a linking group at each occurrence and P g is independently at each occurrence a polymerizable group.

27. The ophthalmic device of claim 26, wherein Y at each occurrence is independently alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination thereof.

28. An ophthalmic device according to any one of claims 26 to 27, wherein P g Each occurrence independently includes styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide.

29. The ophthalmic device of claim 26, wherein the mid-energy visible light filter comprises 1,4-bis[2-methacryloyloxyethylamino]-9,10-anthraquinone, (9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl)bis(2-methyl acrylate), or N,N′-((((((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))diacrylamide.

30. The ophthalmic device according to any one of the preceding claims, wherein the second visible light filter compound comprises a high energy visible light filter of formula III: in: m and n are independently 0, 1, 2, 3 or 4; T is a chemical bond, O or NR; Y is a linking group; P g is a polymerizable group; R is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or YP at each occurrence. g ;and R 1 and R 2 , when present, is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted by alkyl or halo), halo, hydroxy, amino, NR 3 R 4 , or benzyl, where R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 or R 2 The two adjacent groups, together with the carbon atoms to which they are attached, combine to form a cycloalkyl or aryl ring.

31. The ophthalmic device of claim 30, wherein m and n are each independently 0 or 1.

32. The ophthalmic device of any one of claims 30 to 31, wherein Y at each occurrence is independently alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination thereof.

33. An ophthalmic device according to any one of claims 30 to 32, wherein P g These include styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide.

34. The ophthalmic device of claim 30, wherein the high energy visible light filter comprises: 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate; 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl acrylate; N-(2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl)methacrylamide; N-(2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl)acrylamide; 2-(2-cyano-N-methyl-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate; 2-Cyano-2-(9H-thioxanthen-9-ylidene)-N-(2-(N-vinylacetamido)ethyl)acetamide; 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)-2-methylpropyl methacrylate; 2-(2-cyano-2-(2,4-dichloro-9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate; 2-(2-(2-chloro-9H-thioxanthen-9-ylidene)-2-cyanoacetamido)ethyl methacrylate; 2-(2-cyano-2-(2-isopropyl-9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate; 2-(2-cyano-2-(4-isopropyl-9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate; 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetoxy)ethyl methacrylate; 1-Cyano-2-oxo-1-(9H-thioxanthen-9-ylidene)-6,9,12,15,18-pentaoxa-3-azepin-20-yl methacrylate; or A mixture of two or more of them.

35. The ophthalmic device according to any one of the preceding claims, wherein the second visible light filter compound comprises a high energy visible light filter of formula IV: wherein m and n are independently 0, 1, 2, 3 or 4; R 1 and R 2 is independently at each occurrence H, an optional substituent or -YP g , or two adjacent R 1 or R 2 The groups, together with the atoms to which they are attached, combine to form an optionally -YP g substituted cycloalkyl or aryl rings; EWG is independently an electron withdrawing group at each occurrence; P g is independently at each occurrence a polymerizable group; and Y at each occurrence is independently a linking group; wherein the compound of formula II comprises at least one P g Group.

36. The ophthalmic device of claim 35, wherein m and n are independently 0 or 1.

37. An ophthalmic device according to any one of claims 35 to 36, wherein R 1 is H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl, halo, hydroxy, amino, NR 4 R 5 , benzyl, SO3H or SO3Na, where R 4 and R 5 are independently H or C1-C6 alkyl.

38. An ophthalmic device according to any one of claims 35 to 37, wherein R 2 YP g .

39. An ophthalmic device according to any one of claims 35 to 38, wherein P g Each occurrence independently includes styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide.

40. The ophthalmic device of any one of claims 35 to 39, wherein Y at each occurrence is independently alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination of any of the foregoing.

41. The ophthalmic device of any one of claims 35 to 40, wherein EWG at each occurrence is independently cyano, amide, ester, ketone, or aldehyde.

42. An ophthalmic device according to any one of claims 35 to 41, wherein the compound comprises one YP g Group.

43. The ophthalmic device of claim 35, wherein the high energy visible light filter comprises: 3-((9-(dicyanomethylidene)-9H-xanthen-3-yl)oxy)propyl methacrylate; 3-((9-(dicyanomethylidene)-9H-xanthene-2-yl)oxy)propyl methacrylate; 1-((9-(dicyanomethylidene)-9H-xanthen-3-yl)oxy)propan-2-yl methacrylate; 4-((9-(dicyanomethylidene)-9H-xanthen-3-yl)oxy)butyl methacrylate; 3-((9-(dicyanomethylidene)-9H-xanthene-3-yl)oxy)propyl acrylate; 1-((9-(dicyanomethylidene)-9H-xanthene-3-yl)oxy)propan-2-yl acrylate; 4-((9-(dicyanomethylidene)-9H-xanthene-3-yl)oxy)butyl acrylate; N-(3-((9-(dicyanomethylidene)-9H-xanthen-3-yl)oxy)propyl)methacrylamide; N-(3-((9-(dicyanomethylidene)-9H-xanthen-3-yl)oxy)propyl)acrylamide; 3-((9-(dicyanomethylidene)-9H-xanthene-3-yl)amino)propyl methacrylate; 17-((9-(dicyanomethylidene)-9H-xanthene-3-yl)oxy)-3,6,9,12,15-pentaoxoheptadecyl methacrylate; or a mixture of two or more thereof.

44. The ophthalmic device of any preceding claim formed by photocuring of the reactive mixture.

45. The ophthalmic device of any one of Claims 1 to 43 formed by thermal curing of the reactive mixture.

46. ​​The ophthalmic device of any one of Claims 1 to 43, formed by a combination of photo-curing and thermal-curing of the reactive mixture.

47. The ophthalmic device of any preceding claim being a contact lens having a central region and a peripheral region.

48. The ophthalmic device of Claim 47, wherein the residues of the first visible light filter compound and the residues of the second visible light filter compound are evenly distributed throughout the central region and the peripheral region.

49. The ophthalmic device of Claim 47, wherein the residues of the first visible light filter compound and the residues of the second visible light filter compound are present in the central region at a higher molar concentration than in the peripheral region.

50. The ophthalmic device of any of the preceding claims, wherein the reactive mixture further comprises a UV absorbing compound, wherein the UV absorbing compound comprises benzophenone, benzotriazole, triazine, substituted acrylonitrile, salicylic acid derivatives, benzoic acid derivatives, cinnamic acid derivatives, chalcone derivatives, acetophenone derivatives, crotonic acid derivatives, or mixtures thereof.

51. The ophthalmic device of any preceding claim, wherein the polymerizable compound suitable for use in making the contact lens comprises a hydrophilic component, a silicone-containing component, or a mixture thereof.

52. The ophthalmic device of any of the preceding claims, wherein the device is a silicone hydrogel contact lens having a contact angle of about 100° or less, a water content of at least about 25% by weight, and an oxygen permeability (edge ​​corrected) of at least about 60 barrers.

53. The ophthalmic device of any one of the preceding claims, wherein the second visible light filter compound: (a) limiting the transmittance of the device within the wavelength range of 550 nm to 660 nm to between 50% and 95%; or (b) limiting the transmittance of the device in the wavelength range of 400 nm to 409 nm to between 0% and 70%; or (c) Both (a) and (b).

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