Contact lenses exhibiting improved visual attributes - Patents.com

Abstract

Contact lenses containing high-energy visible (HEV) light absorbing compounds and their use to improve one or more visual attributes are described.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Patent Application No. 16 / 938,117, filed July 24, 2020, and U.S. Provisional Patent Application No. 62 / 893,996, filed August 30, 2019, which are incorporated by reference in their entireties.

[0002] FIELD OF THEINVENTION The present invention relates to contact lenses containing high energy visible (HEV) light absorbing compounds and their use to improve one or more visual attributes. [Background technology]

[0003] High energy light from the sun, such as UV light and high energy visible light, is known to be involved in cell damage. Most of the radiation with wavelengths below 280 nm is absorbed by the Earth's atmosphere, but photons with wavelengths in the range of 280-400 nm are associated with degenerative changes in the cornea, as well as several eye disorders, including age-related cataracts and macular degeneration. (See Statement on Ocular Ultraviolet Radiation Hazards in Sunlight, American Optometric Association, November 10, 1993). The human cornea absorbs some radiation up to 320 nm wavelength (30% transmission) (Doutch, JJ, Quantock, AJ, Joyce, NC, Meek, KM, Biophys. J, 2012, 102, 1258-1264), but is inefficient in protecting the back of the eye from radiation with wavelengths in the range of 320-400 nm.

[0004] Contact lens standards define the upper UV wavelength at 380 nm. The current Class I UV absorption standard defined by the American Optometric Association requires that >99% of radiation between 280 and 315 nm (UVB) and >90% of radiation between 316 and 380 nm (UVA) be absorbed by contact lenses. This standard effectively addresses corneal protection (<1% UVB transmission), but little attention is paid to the lower energy UV radiation (>380 and <400 nm) associated with retinal damage (Ham, WT, Mueller, HA, Sliney, DHNature 1976;260(5547):153-5) nor to the higher energy visible radiation.

[0005] High-energy visible (HEV) radiation can cause visual discomfort or disruption of circadian rhythms. For example, computer and electronic device screens, flat screen televisions, energy-efficient lights, and LED lights are known to emit HEV light. Long-term exposure to such HEV light sources can cause eye strain. It is also speculated that viewing devices that emit HEV light at night can disrupt natural circadian rhythms, leading to, for example, lack of sleep.

[0006] Absorption of high energy optical radiation before it reaches the eye remains a desirable goal in ophthalmology. However, the degree to which certain wavelength ranges are absorbed is also important. For example, in the UVA and UVB ranges, it may be desirable to absorb as much radiation as possible. On the other hand, since HEV light forms part of the visible spectrum, complete absorption of HEV light may have adverse effects on vision. Therefore, for HEV light, partial absorption may be more desirable. Summary of the Invention [Problem to be solved by the invention]

[0007] There is a need for materials that provide targeted absorption of undesirable wavelengths of high energy radiation and can be processed into functional products. Compounds that absorb or attenuate high energy radiation, when used in ophthalmic devices, can help protect the cornea, as well as internal cells in the ocular environment, from deterioration, fatigue, and / or disruption of circadian rhythms. [Means for solving the problem]

[0008] The present invention relates to contact lenses that are substantially transparent (e.g., greater than 80% transmission) at wavelengths longer than about 450 nm while filtering high energy visible (HEV) light and optionally UV light. The contact lenses provide significant improvements in many visual attributes when compared to contact lenses that do not filter HEV light, including improvements in one or more of photostress recovery time, glare discomfort, glare attenuation threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering.

[0009] Thus, in one aspect, the present invention provides a contact lens. The contact lens of the present invention is a free radical reaction product of a reactive mixture that includes one or more polymerizable compounds suitable for making a contact lens and a high energy visible (HEV) light absorbing compound, which may be a polymerizable HEV light absorbing compound. The contact lens may transmit 0 percent to 70 percent, or 1 percent to 70 percent of light over the wavelength range of 400 to 409 nm.

[0010] In another aspect, the invention provides a method for improving a visual attribute in a contact lens wearer, the method comprising providing to the contact lens wearer a contact lens that is a free radical reaction product of a reactive mixture that includes one or more polymerizable compounds suitable for making a contact lens and a visual attribute that improves the amount of a high energy visible (HEV) light absorbing compound, the visual attribute being selected from one or more of photostress recovery time, glare discomfort, glare impairment threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering.

[0011] In a further aspect, the present invention provides use of a contact lens for improving at least one visual attribute selected from photostress recovery time, glare discomfort, glare attenuation threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering, the contact lens being a free radical reaction product of a reactive mixture comprising one or more polymerizable compounds suitable for making a contact lens and an amount of a high energy visible light absorbing compound that improves the visual attribute. [Brief description of the drawings]

[0012] [Figure 1] 1 shows the UV-VIS transmission spectra of silicone hydrogel contact lenses of Examples 4A and 4B. [Diagram 2] 1 shows the UV-VIS transmission spectra of silicone hydrogel contact lenses of Examples 4A and 4C. [Diagram 3] 1 shows the UV-VIS transmission spectra of silicone hydrogel contact lenses of Examples 4A and 4D. [Figure 4] 1 shows the clinical results of glare discomfort for test lenses compared to control lenses in various age groups. [Diagram 5] 1 shows clinical results of glare reduction thresholds for test lenses compared to control lenses in various age groups. [Figure 6]1 shows the clinical results of heterochromatic contrast thresholds for test lenses compared to control lenses in various age groups. [Figure 7] 1 shows the clinical results of halos for test lenses compared to control lenses in various age groups. [Figure 8] 1 shows the clinical results of starburst for test lenses compared to control lenses in various age groups. [Figure 9] 1 shows the clinical results of light scattering for test lenses compared to control lenses in various age groups. [Figure 10] 1 shows the clinical results of light stress recovery time for test lenses compared to control lenses in various age groups. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] It is to be understood that the invention is not limited to the details of construction or process steps set forth in the following description, as the invention is capable of other embodiments and of being practiced or carried out in various ways using the teachings set forth herein.

[0014] The following definitions are provided for terms used in this disclosure.

[0015] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. The definition of polymer is consistent with the definition disclosed in Compendium of Polymer Terminology and Nomenclature, IUPAC Recommendations 2008, edited by: Richard G. Jones, Jaroslav Kahovec, Robert Stepto, Edward S. Wilks, Michael Hess, Tatsuki Kitayama, and W. Val Metanomski. All publications, patent applications, patents, and other references mentioned herein are incorporated herein by reference.

[0016] As used herein, the term "(meth)" refers to optional methyl substitution. Thus, a term such as "(meth)acrylate" refers to both methacrylate and acrylate.

[0017] Wherever a chemical structure is depicted, it should be understood that the disclosed options for the substituents in the structure may be combined in any combination. * and R ** and each of these contains a list of three possible groups, then 9 combinations are disclosed. The same is true for combinations of features.

[0018] General formula [ *** ] n When a subscript, such as "n" in: is used to denote the number of repeating units in a chemical formula for a polymer, the formula should be interpreted as representing the number average molecular weight of the macromolecule.

[0019] The term "individual" includes humans and vertebrate animals.

[0020] The term "contact lens" refers to an ophthalmic device that can be placed on the cornea of ​​an individual's eye. A contact lens can provide corrective, cosmetic, or therapeutic benefits, including wound healing, delivery of drugs or nutritional supplements, diagnostic evaluation or monitoring, ultraviolet light absorption, visible light or glare reduction, or any combination thereof. A contact lens can be of any suitable material known in the art and can be a soft lens, a hard lens, or a hybrid lens that contains at least two separate portions with different physical, mechanical, or optical properties, such as elastic modulus, water content, light transmission, or a combination thereof.

[0021] The lenses of the present invention may be comprised of silicone hydrogels or conventional hydrogels. Silicone hydrogels typically contain at least one hydrophilic monomer and at least one silicone-containing component covalently bonded to each other in the cured device.

[0022] "Target macromolecule" means a macromolecule that has been synthesized from a reactive monomer mixture that includes monomers, macromers, prepolymers, crosslinkers, initiators, additives, diluents, and the like.

[0023] The term "polymerizable compound" means a compound that contains one or more polymerizable groups. This term includes, for example, monomers, macromers, oligomers, prepolymers, crosslinkers, and the like.

[0024] A "polymerizable group" is a group capable of undergoing free radical and / or cationic polymerization, e.g., chain growth polymerization, such as a carbon-carbon double bond that can polymerize when subjected to radical polymerization initiation conditions. Non-limiting examples of free radical polymerizable groups include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, O-vinyl carbamates, O-vinyl carbonates, and other vinyl groups. Preferably, the free radical polymerizable groups include (meth)acrylates, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, and styryl functional groups, and mixtures of any of the foregoing. More preferably, the free radical polymerizable groups include (meth)acrylates, (meth)acrylamides, and mixtures thereof. The polymerizable group may be unsubstituted or substituted. For example, the nitrogen atom in (meth)acrylamides may be bonded to hydrogen, or the hydrogen may be substituted with alkyl or cycloalkyl (which may themselves be further substituted).

[0025] Any type of free radical polymerization can be used, including but not limited to bulk, solution, suspension, and emulsion, as well as any of the controlled radical polymerization techniques, such as stable free radical polymerization, nitric oxide mediated living polymerization, atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization, organotellurium mediated living radical polymerization, etc.

[0026] A "monomer" is a monofunctional molecule that can undergo chain growth polymerization, specifically free radical polymerization, thereby creating repeat units within the chemical structure of a target macromolecule. Some monomers have difunctional impurities that can act as crosslinkers. A "hydrophilic monomer" is also a monomer that, when mixed with deionized water at a concentration of 5 weight percent at 25°C, gives a clear, single-phase solution. A "hydrophilic component" is a monomer, macromer, prepolymer, initiator, crosslinker, additive, or polymer that, when mixed with deionized water at a concentration of 5 weight percent at 25°C, gives a clear, single-phase solution. A "hydrophobic component" is a monomer, macromer, prepolymer, initiator, crosslinker, additive, or polymer that is slightly soluble or insoluble in deionized water at 25°C.

[0027] A "macromolecule" is an organic compound having a number average molecular weight greater than 1500, and may be reactive or non-reactive.

[0028] A "macromonomer" or "macromer" is a macromolecule having one group capable of undergoing chain growth polymerization, specifically free radical polymerization, thereby creating repeat units within the chemical structure of a target macromolecule. Typically, the chemical structure of a macromer is different from the chemical structure of a target macromolecule, i.e., the repeat units of the pendant group of the macromer are different from the repeat units of the target macromolecule or its backbone. The only difference between a monomer and a macromer is one of the chemical structure of the pendant group, the molecular weight, and the molecular weight distribution. As a result, and as used herein, the patent literature sometimes defines a monomer as a polymerizable compound having a relatively low molecular weight of about 1,500 daltons or less, which essentially includes some macromers. Specifically, monomethacryloxypropyl 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. Additionally, the patent literature sometimes defines macromers as having one or more polymerizable groups, essentially expanding the general definition of macromer to include prepolymers. As a result, and as used herein, difunctional and multifunctional macromers, prepolymers, and crosslinkers may be used interchangeably.

[0029] A "silicone-containing component" is a monomer, macromer, prepolymer, crosslinker, initiator, additive, or polymer in the reactive mixture that has at least one silicon-oxygen bond, typically in the form of a siloxy group, a siloxane group, a carbosiloxane group, and mixtures thereof.

[0030] Examples of silicone-containing components useful in the present invention are disclosed in U.S. Pat. Nos. 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, 5,96 2,548, 5,965,631, 5,998,498, 6,367,929, 6,822,016, 6,943,203, 6,951,894, 7,052,131, No. 7,247,692, No. 7,396,890, No. 7,461,937, No. 7,468,398, No. 7,538,146, No. 7,553,880, No. 7,572,841, No. 7,666,921 , No. 7,691,916, No. 7,786,185, No. 7,825,170, No. 7,915,323, No. 7,994,356, No. 8,022,158, No. 8,163,206, No. 8,273, No. 802, No. 8,399,538, No. 8,415,404, No. 8,420,711, No. 8,450,387, No. 8,487,058, No. 8,568,626, No. 8,937,110, No. 8,9 37,111, 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 incorporated herein by reference in their entirety.

[0031] A "polymer" is a target macromolecule composed of repeating units of monomers used during polymerization.

[0032] A "homopolymer" is a polymer made from one monomer, a "copolymer" is a polymer made from two or more monomers, and a "terpolymer" is a polymer made from three monomers. A "block copolymer" is composed 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 macromer.

[0033] A "repeating unit" is the smallest grouping of atoms in a polymer that corresponds to the polymerization of a particular monomer or macromer.

[0034] An "initiator" is a molecule that is decomposable into radicals that can subsequently react with monomers to initiate a free radical polymerization reaction. Thermal initiators decompose at a specific rate depending on the temperature, and 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 by a photochemical process, and typical examples are derivatives of benzil, benzoin, acetophenone, benzophenone, camphorquinone, and mixtures thereof, as well as various monoacyl and bisacylphosphine oxides, and combinations thereof.

[0035] A "crosslinker" is a di- or polyfunctional monomer or macromer that can undergo free radical polymerization at two or more positions on the molecule, thereby creating branch points and polymer networks. Common examples are ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, methylene bisacrylamide, triallyl cyanurate, etc.

[0036] A "prepolymer" is a reaction product of monomers that contain remaining polymerizable groups that can be further reacted to form a polymer.

[0037] A "polymer network" is a cross-linked macromolecule that can swell but cannot dissolve in a solvent. A "hydrogel" is a polymer network that swells in water or an aqueous solution, typically absorbing at least 10 weight percent water. A "silicone hydrogel" is a hydrogel made from at least one silicone-containing component together with at least one hydrophilic component. The hydrophilic component may also include a non-reactive polymer.

[0038] "Conventional hydrogel" refers to a polymer network made from components that do not have any siloxy, siloxane, or carbosiloxane groups. Conventional hydrogels are prepared from reactive mixtures that include hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate ("HEMA"), N-vinylpyrrolidone ("NVP"), N,N-dimethylacrylamide ("DMA"), or vinyl acetate. U.S. Patent Nos. 4,436,887, 4,495,313, 4,889,664, 5,006,622, 5,039459, 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, lenefilcon, nesofilcon, omafilcon, polymacon, and vifilcon (including all variations thereof).

[0039] "Silicone hydrogel" refers to a polymer network made from at least one hydrophilic component and at least one silicone-containing component. Examples of silicone hydrogels include acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, and nafilcon. In addition to arafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon (including all variations thereof), U.S. Pat. Nos. 4,659,782, 4,659,783, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,998,498, 6,087,4 No. 15, No. 5,760,100, No. 5,776,999, No. 5,789,461, No. 5,849,811, No. No. 5,965,631, No. 6,367,929, No. 6,822,016, No. 6,867,245, No. 6,943, No. 203, No. 7,247,692, No. 7,249,848, No. 7,553,880, No. 7,666,921, No. No. 7,786,185, No. 7,956,131, No. 8,022,158, No. 8,273,802, No. 8,399, 538, 8,470,906, 8,450,387, 8,487,058, 8,507,577, No. 8,637,621, No. 8,703,891, No. 8,937,110, No. 8,937,111, No. 8,940 , No. 812, No. 9,056,878, No. 9,057,821, No. 9,125,808, No. 9,140,825, No. 9156,934, No. 9,170,349, No. 9,244,196, No. 9,244,197, No. 9,260,544, 9,297,928, 9,297,929, and silicone hydrogels such as those prepared in WO 03 / 22321, WO 2008 / 061992, and U.S. Patent Application Publication No. 2010 / 0048847, which are incorporated herein by reference in their entireties.

[0040] An "interpenetrating polymer network" includes two or more networks that are at least partially entangled on a molecular scale, but are not covalently bonded to each other and cannot be separated without a blocking chemical bond. A "semi-interpenetrating polymer network" includes one or more networks and one or more polymers that are characterized by some intermixing at the molecular level between at least one network and at least one polymer. A mixture of different polymers is a "polymer blend." Although semi-interpenetrating networks are technically polymer blends, in some cases the polymers are entangled in such a way that they cannot be easily removed.

[0041] The terms "reactive mixture" and "reactive monomer mixture" refer to a mixture of components (both reactive and non-reactive) that, when mixed together and subjected to polymerization conditions, form a conventional hydrogel or the silicone hydrogel of the present invention, as well as contact lenses made therefrom. The reactive monomer 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, dyes, and photochromic compounds (any of which may be reactive or non-reactive, but can be retained in the resulting contact lens, as well as pharmaceutical and nutraceutical compounds), and optional diluents. It is understood that a wide range of additives may be added based on the contact lens to be made and its intended use. The concentrations of the components of the reactive mixture are expressed as weight percentages of all components in the reactive mixture, excluding the diluent. If diluents are used, their concentrations are expressed as weight percentages based on the amount of all components and diluent in the reactive mixture.

[0042] A "reactive component" is a component of the reactive mixture that becomes part of the chemical structure of the polymer network of the resulting hydrogel through covalent bonds, hydrogen bonding, electrostatic interactions, formation of an interpenetrating polymer network, or any other means.

[0043] The term "silicone hydrogel contact lenses" refers to hydrogel contact lenses made from at least one silicone-containing component. Silicone hydrogel contact lenses generally have increased oxygen permeability compared to traditional hydrogels. Silicone hydrogel contact lenses use both their water content and polymer content to deliver oxygen to the eye.

[0044] The term "multifunctional" refers to a component having two or more polymerizable groups. The term "monofunctional" refers to a component having one polymerizable group.

[0045] The terms "halogen" or "halo" refer to fluorine, chlorine, bromine, and iodine.

[0046] "Alkyl" refers to an optionally substituted straight or branched chain alkyl group containing the specified number of carbon atoms. If no number is specified, the alkyl (including the optional substituents on the alkyl) may contain 1-16 carbon atoms. Preferably, the alkyl group contains 1-10 carbon atoms, alternatively 1-8 carbon atoms, alternatively 1-6 carbon atoms, or alternatively 1-4 carbon atoms. Examples of alkyl include methyl, ethyl, propyl, isopropyl, butyl, iso-, sec- and tert-butyl, pentyl, hexyl, heptyl, 3-ethylbutyl, and the like. Examples of substituents on alkyl include one, two, or three groups independently selected from hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, thioalkyl, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Alkylene" means a divalent alkyl group, such as -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH(CH3)CH2-, and -CH2CH2CH2CH2-.

[0047] "Haloalkyl" refers to an alkyl group as defined above substituted with one or more halogen atoms, each halogen being independently F, Cl, Br, or I. A preferred halogen is F. Preferred haloalkyl groups contain 1 to 6 carbons, more preferably 1 to 4 carbons, and even more preferably 1 to 2 carbons. "Haloalkyl" includes perhaloalkyl groups such as -CF3- or -CF2CF3-. "Haloalkylene" refers to a divalent haloalkyl group such as -CH2CF2-.

[0048] "Cycloalkyl" refers to an optionally substituted cyclic hydrocarbon containing the specified number of ring carbon atoms. If no number is specified, the cycloalkyl may contain 3 to 12 ring carbon atoms. Preferably, it is a C3-C8 cycloalkyl group, a C3-C7 cycloalkyl, more preferably a C4-C7 cycloalkyl, and even more preferably a C5-C6 cycloalkyl. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of substituents on cycloalkyl include one, two, or three groups independently selected from alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, thioalkyl, amido, carbamate, carbonate, halo, phenyl, benzyl, and combinations thereof. "Cycloalkylene" refers to a divalent cycloalkyl group, such as 1,2-cyclohexylene, 1,3-cyclohexylene, or 1,4-cyclohexylene.

[0049] "Heterocycloalkyl" refers to a cycloalkyl ring or ring system as defined above in which at least one ring carbon is replaced with a heteroatom selected from nitrogen, oxygen, and sulfur. The heterocycloalkyl ring is optionally fused or otherwise attached to other heterocycloalkyl rings and / or non-aromatic hydrocarbon rings and / or phenyl rings. Preferred heterocycloalkyl groups have 5 to 7 members. More preferred heterocycloalkyl groups have 5 or 6 members. Heterocycloalkylene refers to a divalent heterocycloalkyl group.

[0050] "Aryl" refers to an optionally substituted aromatic hydrocarbon ring system containing at least one aromatic ring. An aryl group contains a specified number of ring carbon atoms. If no number is specified, an aryl may contain 6 to 14 ring carbon atoms. The aromatic ring may be optionally fused or otherwise attached to other aromatic 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 an aryl include one, two, or three groups independently selected from alkyl, hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, thioalkyl, carbamate, carbonate, halo, phenyl, benzyl, and combinations thereof. "Arylene" refers to a divalent aryl group, such as 1,2-phenylene, 1,3-phenylene, or 1,4-phenylene.

[0051] "Heteroaryl" refers to an aryl ring or ring system, as defined above, in which at least one ring carbon atom is replaced with a heteroatom selected from nitrogen, oxygen, and sulfur. The heteroaryl ring may be fused or otherwise bonded to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings, or heterocycloalkyl rings. Examples of heteroaryl groups include pyridyl, furyl, and thienyl. "Heteroarylene" refers to a divalent heteroaryl group.

[0052] "Alkoxy" refers to 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. "Thioalkyl" refers to an alkyl group attached to the parent molecular moiety through a sulfur bridge. Examples of thioalkyl groups include, for example, methylthio, ethylthio, n-propylthio, and isopropylthio. "Aryloxy" refers to an aryl group attached to the parent molecular moiety through an oxygen bridge. Examples include phenoxy. "Cyclic alkoxy" refers to a cycloalkyl group attached to the parent moiety through an oxygen bridge.

[0053] "Alkylamine" refers to an alkyl group attached to the parent molecular moiety through an -NH bridge. Alkyleneamine refers to a divalent alkylamine group, such as -CHCHNH-.

[0054] "Siloxanyl" refers to a structure having at least one Si-O-Si bond. Thus, for example, a siloxanyl group refers to a group having at least one Si-O-Si group (i.e., a siloxane group), and a siloxanyl compound refers to a compound having at least one Si-O-Si group. "Siloxanyl" refers to monomeric (e.g., Si-O-Si) as well as oligomeric / polymeric structures (e.g., -[Si-O] n -, where n is 2 or 3 or more. Each silicon atom in the siloxanyl group is independently selected to complete their valence. A Group (R A is replaced by (as defined in options (b) to (i) of Formula A).

[0055] "Silyl" refers to a structure of formula RSi- and "siloxy" refers to a structure of formula RSi-O-, where each R in silyl or siloxy is independently selected from trimethylsiloxy, C1-C8 alkyl (preferably C1-C3 alkyl, more preferably ethyl or methyl), and C3-C8 cycloalkyl.

[0056] "Alkyleneoxy" refers to a group having the general formula -(alkylene-O-) p -or-(O-alkylene) p -, where alkylene is as defined above, p is 1-200, or 1-100, or 1-50, or 1-25, or 1-20, or 1-10, and each alkylene is independently optionally substituted with one or more groups independently selected from hydroxyl, halo (e.g., fluoro), amino, amido, ether, carbonyl, carboxyl, and combinations thereof. When p is greater than 1, each alkylene may be the same or different, and the alkyleneoxy may be in a block or random configuration. When the alkyleneoxy forms a terminal group in a molecule, the terminus of the alkyleneoxy may be, for example, hydroxy or alkoxy (e.g., HO-[CH2CHO] p - or CH3O-[CH2CH2O] p Examples of alkyleneoxy include polyethyleneoxy, polypropyleneoxy, polybutyleneoxy, and poly(ethyleneoxy-co-propyleneoxy).

[0057] "Oxaalkylene" refers to an alkylene group as defined above in which one or more non-adjacent CH groups are replaced with an oxygen atom, such as -CHCHOCH(CH)CH-. "Thiaalkylene" refers to an alkylene group as defined above in which one or more non-adjacent CH groups are replaced with a sulfur atom, such as -CHCHSCH(CH)CH-.

[0058] The term "linking group" refers to a moiety that connects a polymerizable group to a parent molecule. A linking group may be any moiety that is compatible with the compound of which it is a part, does not undesirably interfere with the polymerization of the compound, and is stable under the polymerization conditions as well as the conditions of processing and storage of the final product. For example, a linking group may be a bond or may include one or more alkylenes, haloalkylenes, amides, amines, alkyleneamines, carbamates, esters (-CO2-), arylenes, heteroarylenes, cycloalkylenes, heterocycloalkylenes, alkyleneoxys, oxaalkylenes, thiaalkylenes, haloalkyleneoxys (alkyleneoxys substituted with one or more halo groups, e.g., -OCF2-, -OCF2CF2-, -OCF2CH2-), siloxanyls, alkylenesiloxanyls, or combinations thereof. A linking group may be optionally substituted with one or more substituents. Suitable substituents can include those independently selected from alkyl, halo (e.g., fluoro), hydroxyl, HO-alkyleneoxy, MeO-alkyleneoxy, siloxanyl, siloxy, siloxy-alkyleneoxy-, siloxy-alkylene-alkyleneoxy- (wherein more than one alkyleneoxy group can be present, and each methylene in the alkylene and alkyleneoxy is independently optionally substituted with hydroxyl), ether, amine, carbonyl, carbamate, and combinations thereof. The linking group can also be substituted with a polymerizable group (in addition to the polymerizable group to which it is attached), such as (meth)acrylate.

[0059] Preferred linking groups include C1-C8 alkylene (preferably C2-C6 alkylene) and C1-C8 oxaalkylene (preferably C2-C6 oxaalkylene), each of which is optionally substituted with one or two groups independently selected from hydroxyl and siloxy. Preferred linking groups also include carboxylate, amide, C1-C8 alkylene-carboxylate-C1-C8 alkylene, or C1-C8 alkylene-amide C1-C8 alkylene.

[0060] When the linking group is composed of a combination of moieties as described above (e.g., alkylene and cycloalkylene), the moieties may be present in any order. For example, in formula E below, when L is shown to be -alkylene-cycloalkylene-, Rg-L may be either Rg-alkylene-cycloalkylene- or Rg-cycloalkylene-alkylene-. Regardless, the order listed represents the preferred order in which the moieties appear in the compound, starting from the terminal polymerizable group (Rg or Pg) to which the linking group is attached. For example, in formula E, L and L 2 and -L are preferably Rg-alkylene-cycloalkylene-, where -L 2 -Rg is preferably -cycloalkylene-alkylene-Rg.

[0061] The term "electron withdrawing group" (EWG) refers to a chemical group that withdraws electron density from the atom or group of atoms to which it is bonded. Examples of EWGs include, but are not limited to, cyano, amide, ester, keto, or aldehyde. A preferred EWG is cyano (CN).

[0062] The term "high energy visible light absorbing compound" or "HEV light absorbing compound" refers to a chemical material that absorbs one or more wavelengths of high energy visible light, for example in the range of 400-450 nm. The ability of a material to absorb light at a particular wavelength can be determined by measuring its UV / Vis transmission spectrum. A compound that exhibits no absorption at a particular wavelength exhibits substantially 100 percent transmission at that wavelength. Conversely, a compound that absorbs completely at a particular wavelength exhibits substantially 0% transmission at that wavelength. As used herein, when the amount of transmission of a contact lens is given as a percentage over a particular wavelength range, it is understood that the contact lens exhibits that transmission percentage at all wavelengths over that range. For purposes of the present invention, a material that has greater than 80 percent transmission over the wavelength range of 400-450 nm is not an HEV light absorbing material.

[0063] The term "photostable", "photostability", or similar expressions means that a contact lens (containing a HEV light absorbing compound) exhibits no substantial change in its visible light transmission spectrum after exposure to light when packaged in a transparent blister pack under the conditions of the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use guideline, Q1B Photostability Testing of New Drug Substances and Products, issued November 1996. Preferably, the exposure is at least 1.5192×10 6 Estimated illuminance exposure in lux hours (168.8 hours exposure time) and 259.4 watt-hours / m 2The measurements are performed under ICH photostability guidelines, preferably in a photostability chamber controlled at 25°C / Amb RH, using an Option2 light source with an estimated UV radiation exposure of 100 nm (16.2 hours exposure time). When measuring lenses in blister packs, the blister packs are exposed foil side down to maximize irradiation from the light source during exposure. After exposure, the UV / Vis spectrum of the test lens is collected and compared to a control lens (a lens not subjected to Q1B conditions). Photostability may be expressed as a percentage change in the average transmission of the test lens relative to the control lens in a selected wavelength range. The change may be calculated as the absolute value of the difference in average transmission (over a selected wavelength range) between the control lens and the test lens divided by the average transmission (over a selected wavelength range) of the control lens. For purposes of the present invention, a contact lens is considered to be photostable if the change in average transmission over a selected wavelength range (e.g., 380-450 nm) is 20 percent or less, or 15 percent or less, or 10 percent or less, or 7 percent or less, or 5 percent or less, or 2 percent or less. Measurements can be made, for example, with a -1.00 diopter contact lens.

[0064] The term "photochromic compound" refers to a material that, upon exposure to certain wavelengths of electromagnetic radiation, reversibly changes its absorption characteristics (i.e., color) caused by a photochemical reaction within the material. By way of example, a photochromic compound may exhibit a reversible change in average transmission of 5% or more, or 10% or more, or 20% or more percent in the visible portion of the electromagnetic spectrum (e.g., wavelength range from about 380 nm to about 760 nm) upon exposure to UV or HEV light. A "static compound" is a material that is not photochromic, and thus, the material does not undergo a photochemical reaction that reversibly changes its color.

[0065] Unless otherwise stated, ratios, percentages, parts, etc. are by weight.

[0066] Unless otherwise stated, a numerical range such as, for example, "2 to 10" is inclusive of the numbers defining the range (eg, 2 and 10).

[0067] As noted above, one aspect of the present invention provides a contact lens that is a free radical reaction product of a reactive mixture that includes one or more polymerizable compounds suitable for making a contact lens and a high energy visible (HEV) light absorbing compound.

[0068] The contact lens may transmit 0 percent to 70 percent, or 1 to 70 percent of light over the wavelength range of 400-409 nm. The transmission of the contact lens over the wavelength range of 400-409 nm may be at least 2 percent, or at least 3 percent, or at least 4 percent. The transmission of the contact lens over the range of 400-409 nm may be up to 60 percent, or up to 50 percent, or up to 40 percent, or up to 30 percent, or up to 20 percent.

[0069] The contact lens may transmit 10 percent or less of light over the wavelength range of 200-279 nm. The transmission of the contact lens over the wavelength range of 200-279 nm may be 5 percent or less, or 1 percent or less, or less than 1 percent.

[0070] The contact lens may transmit 45 percent or less of light over the wavelength range of 280-399 nm. The transmission of the contact lens over the wavelength range of 280-399 nm may be 35 percent or less, or 25 percent or less, or 20 percent or less, or 10 percent or less, or 5 percent or less, or 1 percent or less.

[0071] The contact lens may transmit at least 10 percent light over the wavelength range of 410-424 nm. The transmission of the contact lens over the wavelength range of 410-424 nm may be at least 15 percent. The transmission of the contact lens over the wavelength range of 410-424 nm may be up to 95 percent, up to 85 percent, up to 75 percent, or up to 65 percent.

[0072] The contact lens may transmit at least 50 percent light over the wavelength range of 425-449 nm. The transmission of the contact lens over the range of 425-449 nm may be at least 60 percent.

[0073] The contact lens may transmit at least 80 percent light over the wavelength range of 450-800 nm. The transmission of the contact lens over the wavelength range of 450-800 nm may be at least 85 percent.

[0074] The contact lenses may transmit between 1 and 70 percent of light over the wavelength range of 400 to 409 nm, and up to 45 percent of light over the wavelength range of 280 to 399 nm.

[0075] The contact lenses may transmit between 1 and 70 percent of light over the wavelength range of 400 to 409 nm, up to 45 percent of light over the wavelength range of 280 to 399 nm, and at least 80 percent of light over the wavelength range of 450 to 800 nm.

[0076] The contact lenses may transmit between 1 and 70 percent of light over the wavelength range of 400 to 409 nm, no more than 45 percent of light over the wavelength range of 280 to 399 nm, between 10 and 95 percent of light over the wavelength range of 410 to 424 nm, at least 50 percent of light over the wavelength range of 425 to 449 nm, and at least 80 percent of light over the wavelength range of 450 to 800 nm.

[0077] The contact lenses may be soft hydrogel contact lenses, preferably silicone hydrogel contact lenses. The aforementioned transmission wavelengths and percentages may be measured on lenses of various thicknesses. For example, the center thickness may be 70-300 microns, or 80-230 microns, or 80-110 microns, or 90-110 microns. The concentration of the one or more high energy visible absorbing compounds may be adjusted to achieve the aforementioned transmission characteristics. For example, the concentration may range from at least 0.01 percent, or at least 0.1 percent, or at least 1 percent, or at least 2 percent, and up to 10 percent or up to 5 percent, based on the weight percentage of all components in the reactive mixture excluding the diluent. Typical concentrations may range from 1 to 5 percent.

[0078] HEV light absorbing compounds for use in the contact lenses of the present invention can be compounds of Formula I,

[0079] [ka] During the ceremony, m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR; Y is a linking group; P g is a polymerizable group, R, at each occurrence, is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP g and R 1 and R 2 is, when present, independently at each occurrence C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halo), halo, hydroxy, amino, NR 3 R 4 or benzyl, R 3 and R4 are independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The groups, together with the carbon atom to which they are attached, are linked to form a cycloalkyl or aryl ring. Compounds of formula I preferably contain one or two YP g More preferably, the compound contains one YP group. g Contains a group.

[0080] I-1. Compounds of formula I may include compounds of formula I-1, which are compounds of formula I where m and n are independently 0 or 1, or alternatively both are 0.

[0081] I-2. Compounds of formula I and I-1 are those in which m is 1 and R 1 is a C1-C6 alkyl, preferably ethyl or methyl, or a compound of formula I-1, wherein I-2 is a compound of formula I-2.

[0082] I-3. Compounds of formula I, I-1, and I-2 are those in which n is 1 and R 2 is a compound of formula I, I-1, or I-2, wherein is C1-C6 alkyl, preferably ethyl or methyl.

[0083] The compounds of formula I, I-1, I-2, and I-3 may include compounds of formula I-4, which are compounds of formula I, I-1, I-2, or I-3, where R is H or C1-C6 alkyl. Preferably, R in the group T is H.

[0084] I-5. Compounds of formula I, I-1, I-2, I-3, and I-4 are P gThe compound may include compounds of formula I-5, where (polymerizable group) is a compound of formula I, I-1, I-2, I-3, or I-4, each occurrence of which is independently styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide. The polymerizable group allows the compound of the present invention to form a covalent bond when reacted with monomers, crosslinkers, and other components commonly used in making contact lenses. The compatibility of the compound with the reactive mixture can be controlled by the selection of the polymerizable group (and linking group). Preferred polymerizable groups include (meth)acrylate or (meth)acrylamide. More preferred polymerizable groups are methacrylates.

[0085] I-6. The compounds of formula I, I-1, I-2, I-3, I-4, and I-5 may include compounds of formula I-6, which are compounds of formula I, I-1, I-2, I-3, I-4, or I-5, where Y (the linking group) is an alkylene, a cycloalkylene, a heterocycloalkylene, an arylene (e.g., phenylene), a heteroarylene, an oxaalkylene, an alkylene-amide-alkylene, an alkylene-amine-alkylene, or a combination of any of the aforementioned 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 a compound of formula I is O, it is preferred that the carbon atom of the linking group to which O is attached is interrupted. For example, when T is O and Y is alkylene, a preferred alkylene is -C(R H )2(CH-2) x -(In the formula, R H are independently C1 to C6 alkyl (preferably independently methyl or ethyl), and x is 1 to 5).

[0086] I-7. Compounds of formula I, I-1, I-2, I-3, I-4, I-5, and I-6 may include compounds of formula I-7, which is a compound of formula I, I-1, I-2, I-3, I-4, I-5, or I-6, where T is a bond or NR (preferably NH).

[0087] Compounds of formula I may include compounds of formula II:

[0088] [ka] During the ceremony, m and n are independently 0, 1, 2, 3, or 4; Y is a linking group; P g is a polymerizable group, R, at each occurrence, is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP g and R 1 and R 2 is, when present, independently at each occurrence C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halo), halo, hydroxy, amino, NR 3 R 4 or benzyl, R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The groups, together with the carbon atom to which they are attached, are linked to form a cycloalkyl or aryl ring. Compounds of formula II preferably contain one or two YP g More preferably, the compound contains one YP group. g Contains a group.

[0089] II-1. Compounds of formula II may include compounds of formula II-1, which are compounds of formula II where m and n are independently 0 or 1, or alternatively both are 0.

[0090] II-2. Compounds of formula II and II-1 are those in which m is 1 and R 1 is a C1-C6 alkyl, preferably ethyl or methyl, or a compound of formula II-1.

[0091] II-3. Compounds of formula II, II-1, and II-2 are those in which n is 1 and R 2 is a C1-C6 alkyl, preferably ethyl or methyl, compound of formula II-3.

[0092] II-4. The compounds of formula II, II-1, II-2, and II-3 may include compounds of formula II-4, which are compounds of formula II, II-1, II-2, or II-3, where R is independently H or C1-C6 alkyl at each occurrence. Preferably, R is H at each occurrence. Preferably, R in the group T is H.

[0093] II-5. Compounds of formula II, II-1, II-2, II-3, and II-4 are P g The compounds of formula II-5 may include compounds of formula II-5, where (polymerizable group) is a compound of formula II, II-1, II-2, II-3, or II-4, each occurrence of which is independently 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 reacted with monomers, crosslinkers, and other components commonly used in the fabrication of polymeric devices. The compatibility of the compounds with the reactive mixture can be controlled by the selection of the polymerizable group (and linking group). Preferred polymerizable groups include (meth)acrylate or (meth)acrylamide. More preferred polymerizable groups are methacrylates.

[0094] II-6. The compounds of formula II, II-1, II-2, II-3, II-4, and II-5 may include compounds of formula II-6, which are compounds of formula II, II-1, II-2, II-3, II-4, or II-5, where Y (the linking group) is I, alkylene, cycloalkylene, heterocycloalkylene, arylene (e.g., phenylene), heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or any combination of the aforementioned 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-).

[0095] Specific examples of compounds of Formula I include, but are not limited to, the compounds shown in Table 1.

[0096] [Table 1-1]

[0097] [Table 1-2]

[0098] High energy visible (HEV) light absorbing compounds for use in the present invention are preferably photostable, such that a contact lens of the present invention containing a HEV light absorbing compound preferably exhibits no more than 20%, alternatively no more than 15%, alternatively no more than 10%, alternatively no more than 7%, alternatively no more than 5%, or alternatively no more than 2% change in its average transmission over the wavelength range of 380-450 nm after exposure under ICH Q1B conditions compared to a control lens.

[0099] The contact lenses of the present invention may contain other absorbing compounds in addition to the HEV light absorbing compound to provide the desired absorption characteristics. For example, a preferred composition may contain a HEV light absorbing compound and a compound that absorbs UV. Suitable UV absorbing compounds are known in the art and are classified into several classes, including, but not limited to, benzophenones, benzotriazoles, triazines, substituted acrylonitriles, salicylic acid derivatives, benzoic acid derivatives, cinnamic acid derivatives, chalcone derivatives, dipnone derivatives, crotonic acid derivatives, or any mixture thereof. A preferred class of UV absorbing compounds are benzotriazoles, such as Norbloc (2-(2'-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole).

[0100] A preferred composition comprises 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate and a UV absorbing compound such as a benzotriazole, for example, 2-(2'-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole).

[0101] Compounds of formula I can be prepared by those skilled in the art using literature methods. By way of example, various compounds of formula I may be prepared as shown in Scheme 1 and the associated description. Exemplary reagents and procedures for these reactions are provided in the Examples.

[0102] [ka]

[0103] Scheme 1 shows a method for preparing exemplary compounds of the present invention. Thus, the carbonyl moiety of the starting material is converted to a reactive dihalide intermediate, which is further reacted with an active methylene compound without further purification or separation. The reactive mixture is protected from air and moisture until the reaction with the cyanomethylamide derivative is completed. Other compounds of the present invention can be prepared by those skilled in the art using procedures similar to those shown in Scheme 1 with appropriate substitution of reagents.

[0104] A high energy visible light absorbing compound, such as a compound of formula I, can be included in the reactive mixture to form a contact lens. In general, the high energy visible light absorbing compound can be present in any amount, typically up to its solubility limit. For example, the compound can be present in an amount ranging from about 0.1% to about 10% by weight, or from about 0.5 to about 5% by weight, or from about 0.75% to about 4% by weight. The upper limit is typically determined by the solubility of the compound with other comonomers and / or diluents in the reactive monomer mixture.

[0105] Various contact lenses may be prepared, including hard contact lenses and soft contact lenses.Preferably, the contact lenses are soft contact lenses, which may be made from conventional hydrogel or silicone hydrogel formulations.Contact lenses with toric contact lenses, such as toric hydrogel contact lenses or toric silicone hydrogel contact lenses.Such lenses may be used to correct astigmatism in wearers who require astigmatism correction.

[0106] The present contact lenses comprise the free radical reaction product of a reactive mixture containing one or more high energy visible (HEV) light absorbing compounds, such as a compound of formula I, one or more polymerizable compounds suitable for making the desired ophthalmic device (also referred to herein as device-forming or hydrogel-forming polymerizable compounds), and optional ingredients. Thus, in addition to the high energy visible light absorbing compounds, such as those described above, the reactive mixture may include 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 additional ingredients such as diluents and initiators.

[0107] hydrophilic component Examples of suitable families of hydrophilic monomers 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.

[0108] 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 ... N-hydroxypropyl)(meth)acrylamide, N-(2-hydroxybutyl)(meth)acrylamide, N-(3-hydroxybutyl)(meth)acrylamide, N-(4-hydroxybutyl)(meth)acrylamide, 2-aminoethyl(meth)acrylate, 3-aminopropyl(meth)acrylate, 2-aminopropyl(meth)acrylate, N-2-aminoethyl(meth)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, glycerol methacrylate, polyethylene glycol monomethacrylate, (meth)acrylic acid, vinyl acetate, acrylonitrile, and mixtures thereof.

[0109] The hydrophilic monomers may also be ionic, including anionic, cationic, zwitterionic, betaine, and mixtures thereof. Non-limiting examples of such charged monomers include (meth)acrylic acid, N-[(ethenyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropanoic acid (ACA1), 5-acrylamidopropanoic acid (ACA2), 3-acrylamido-3-methylbutanoic acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, inner salt (CBT), 1-propanaminium, N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-, inner salt (SBT), 3,5-dioxa- 8-Aza-4-phosphane-10-en-1-aminium, 4-hydroxy-N,N,N-trimethyl-9-oxo-, inner salt, 4-oxide (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 methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

[0110] 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-methyl acetamide (VMA), N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, N-vinyl-N-methyl propionamide, N-vinyl-N-methyl-2-methyl propionamide, N-vinyl ... N-methylpropionamide, N-vinyl-N,N'-dimethylurea, 1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-N-propyl-3-methylene-2-pyrrolidone, 1-N-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N-vinylformamide, N-vinylisopropylamide, N-vinylcaprolactam, N-vinylimidazole, and mixtures thereof.

[0111] 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. Further examples of hydrophilic vinyl carbonate or vinyl carbamate monomers are disclosed in U.S. Patent No. 5,070,215. Hydrophilic oxazolone monomers are disclosed in U.S. Patent No. 4,910,277.

[0112] Other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, and 2-ethyloxazoline.

[0113] The hydrophilic monomer may also be a macromer or prepolymer of linear or branched poly(ethylene glycol), poly(propylene glycol), or statistical random or block copolymers of ethylene oxide and propylene oxide, having polymerizable moieties such as (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl amides, etc. Macromers of these polyethers have one polymerizable group and prepolymers may have two or more polymerizable groups.

[0114] 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.

[0115] Generally, there is no particular limitation regarding 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, transparency, wettability, protein uptake, and the like. Wettability can be measured by contact angle, with desirable contact angles being less than about 100°, less than about 80°, and less than about 60°. The hydrophilic monomer can be present in an amount ranging from, for example, about 0.1 to about 100 weight percent, alternatively from about 1 to about 80 weight percent, alternatively from about 5 to about 65 weight percent, alternatively from about 40 to about 60 weight percent, or alternatively from about 55 to about 60 weight percent, based on the total weight of the reactive components in the reactive monomer mixture.

[0116] Silicone-containing ingredients Silicone-containing components suitable for use in the present invention include one or more polymerizable compounds, each compound independently including at least one polymerizable group, at least one siloxane group, and one or more linking groups connecting the polymerizable group(s) to the siloxane group(s). The silicone-containing component may contain, for example, 1 to 220 siloxane repeat units, such as those defined below. The silicone-containing component may also contain at least one fluorine atom.

[0117] 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, one or more optionally repeating siloxane units, and one or more linking groups connecting the polymerizable groups to the siloxane units, which are independently (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, vinyl groups, or mixtures of the foregoing.

[0118] The silicone-containing component may independently comprise one or more polymerizable groups that are (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, styryl, or mixtures of the foregoing, one or more optionally repeating siloxane units, and one or more linking groups connecting the polymerizable groups to the siloxane units.

[0119] The silicone-containing component may independently comprise one or more polymerizable groups that are (meth)acrylate, (meth)acrylamide, or mixtures of the foregoing, one or more optionally repeating siloxane units, and one or more linking groups connecting the polymerizable groups to the siloxane units.

[0120] Formula A. The silicone-containing component may include one or more polymerizable compounds of formula A:

[0121] [ka] During the ceremony, At least one R A is the formula R g -L group, where R g is a polymerizable group, L is a linking group, and the remaining R A are each independently (a)R g -L-, (b) C1-C optionally substituted with one or more hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof. 16 Alkyl, (c) C-C optionally substituted with one or more alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof. 12 Cycloalkyl, (d) C-C optionally substituted with one or more alkyl, hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof. 14 Aryl groups, (e) halo, (f) alkoxy, cyclic alkoxy, or aryloxy, (g) siloxy, (h) alkyleneoxy-alkyl or alkoxy-alkyleneoxy-alkyl, such as polyethyleneoxyalkyl, polypropyleneoxyalkyl, or poly(ethyleneoxy-co-propyleneoxyalkyl); or (i) a monovalent siloxane chain comprising 1 to 100 siloxane repeat units optionally substituted with alkyl, alkoxy, hydroxy, amino, oxa, carboxy, alkylcarboxy, alkoxy, amido, carbamate, halo, or combinations thereof; n is 0 to 500, or 0 to 200, or 0 to 100, or 0 to 20, and when n is other than 0, it is understood that n is a distribution having a mode equivalent to the indicated value. When n is 2 or more, the SiO units may be the same or different R A may carry substituents, different R A When substituents are present, the n groups may be in a random or block configuration.

[0122] In formula A, three R A may each contain a polymerizable group, alternatively two R A may each contain a polymerizable group, or alternatively one R A may contain a polymerizable group.

[0123] Examples of silicone-containing components suitable for use in the present invention include, but are not limited to, the compounds listed in Table 2. When a compound in Table 2 contains a polysiloxane group, the number of SiO repeat units in such compound is preferably 3 to 100, more preferably 3 to 40, or even more preferably 3 to 20, unless otherwise specified.

[0124] [Table 2-1]

[0125] [Table 2-2]

[0126] Additional non-limiting examples of suitable silicone-containing components are listed in Table 3. Unless otherwise stated, 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.

[0127] [Table 3-1]

[0128] [Table 3-2]

[0129] Mixtures of silicone-containing components may also be used.For example, suitable mixtures may include, but are not limited to, mixtures of mono-(2-hydroxy-3-methacryloxypropyloxy)-propyl-terminated mono-n-butyl-terminated polydimethylsiloxanes (OH-MPDMS) with different molecular weights, such as mixtures of OH-mPDMS containing 4 and 15 repeating SiO units; mixtures of OH-mPDMS with different molecular weights (e.g., containing 4 and 15 repeating SiO units) and silicone-based crosslinkers, such as bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxanes (ac-PDMS); mixtures of 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA) and mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxanes (mPDMS), such as mPDMS1000.

[0130] Silicone-containing components for use in the present invention can have an average molecular weight of from about 400 to about 4000 daltons.

[0131] The silicone-containing component(s) may be present in an amount up to about 95%, or from about 10 to about 80%, or from about 20 to about 70% by weight of the reactive mixture (excluding diluent), based on all reactive components.

[0132] polyamide The reactive mixture may include at least one polyamide. As used herein, the term "polyamide" refers to polymers and copolymers that include repeating units that contain amide groups. The polyamide may include cyclic amide groups, non-cyclic amide groups, and combinations thereof, and may be any polyamide known to those skilled in the art. Non-cyclic polyamides include pendant non-cyclic amide groups and are capable of association with hydroxyl groups. Cyclic polyamides include cyclic amide groups and are capable of association with hydroxyl groups.

[0133] Examples of suitable acyclic polyamides include polymers and copolymers comprising repeat units of formulae G1 and G2,

[0134] [ka] In the formula, X is a direct bond, -(CO)-, or -(CONHR 44 )- and R 44 is a C1-C3 alkyl group, and R 40 is selected from H, linear or branched, substituted or unsubstituted C1-C4 alkyl groups, R 41 is selected from H, a linear or branched substituted or unsubstituted C1-C4 alkyl group, an amino group having up to 2 carbon atoms, an amido group having up to 4 carbon atoms, and an alkoxy group having up to 2 carbon atoms; R 42 is selected from H, a linear or branched, substituted or unsubstituted C1-C4 alkyl group, or methyl, ethoxy, hydroxyethyl, and hydroxymethyl; R 43 is selected from H, a linear or branched, substituted or unsubstituted C1-C4 alkyl group, or methyl, ethoxy, hydroxyethyl, and hydroxymethyl; R 40 and R41 The total number of carbon atoms in R is 8 or less, including 7, 6, 5, 4, 3, or less; 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 may have a total of up to 6 carbon atoms. As used herein, a substituted alkyl group includes an alkyl group substituted with an amine group, an amide group, an ether group, a hydroxyl group, a carbonyl group, or a carboxyl group, or combinations thereof.

[0135] R 40 and R 41 may be independently selected from H, a substituted or unsubstituted C1-C2 alkyl group; X may be a direct bond, and R 40 and R 41 R may be independently selected from H, a substituted or unsubstituted C1-C2 alkyl group. 42 and R 43 may be independently selected from H, substituted or unsubstituted C1-C2 alkyl groups, methyl, ethoxy, hydroxyethyl, and hydroxymethyl.

[0136] The acyclic polyamides of the present invention may comprise a majority of repeat units of formula LV or formula LVI, or the acyclic polyamides may comprise at least 50 mole percent of repeat units of formula G or formula G1, including at least about 70 mole percent, and at least 80 mole percent. Specific examples of repeat units of formula G and formula G1 include repeat 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 the acyclic amides of formula G2 and G3.

[0137] [ka]

[0138] Examples of suitable cyclic amides that can be used to form the cyclic polyamides include α-lactams, β-lactams, γ-lactams, δ-lactams, and ε-lactams. Examples of suitable cyclic polyamides include polymers and copolymers comprising repeat units of formula G4:

[0139] [ka] In the formula, R 45 is a hydrogen atom or a methyl group, f is a number from 1 to 10, and X is a direct bond, -(CO)-, or -(CONHR 46 )- and R 46 is a C1-C3 alkyl group. In formula LIX, f can be 8 or less, including 7, 6, 5, 4, 3, 2, or 1. In formula G4, f can be 6 or less, including 5, 4, 3, 2, or 1. In formula G4, f can be 2-8, including 2, 3, 4, 5, 6, 7, or 8. In formula LIX, f can be 2 or 3. When X is a direct bond, f can be 2. In such cases, the cyclic polyamide can be polyvinylpyrrolidone (PVP).

[0140] The cyclic polyamides of the present invention may comprise 50 mole percent or more of repeat units of formula G4, or the cyclic polyamides may comprise at least 50 mole percent of repeat units of formula G4, including at least 70 mole percent, and at least 80 mole percent.

[0141] Polyamides may also be copolymers containing both cyclic and non-cyclic amide repeat units. The additional repeat 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 comonomers to form the additional repeat units. Specific examples of additional monomers that may 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-[(ethenyloxy)carbonyl]-β-alanine (VINAL, CAS#148969-96-4), 3-acrylamidopropanoic acid (ACA1), 5-acrylamidopentanoic acid (ACA2), 3-acrylamido-3-methylbutanoic acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methyl Propanesulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, inner salt (CBT, carboxybetaine, CAS 79704-35-1), 1-propanaminium, N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-, inner salt (SBT, sulfobetaine, CAS 8029 3-60-3), 3,5-dioxa-8-aza-4-phosphanundeca-10-en-1-aminium, 4-hydroxy-N,N,N-trimethyl-9-oxo-, inner salt, 4-oxide (9CI) (PBT, phosphobetaine, CAS 163674-35-9, 2-methacryloyloxyethyl phosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamin Examples of such compounds include 3-((3-(methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS), and methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

[0142] The reactive monomer mixture may include both acyclic and cyclic polyamides or copolymers thereof. The acyclic polyamide may be any of the acyclic polyamides described herein or copolymers thereof, and the cyclic polyamide may be any of the cyclic polyamides described herein or copolymers thereof. The polyamide may be selected from the group of polyvinylpyrrolidone (PVP), polyvinylmethyacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof. The polyamide may be a combination of PVP (e.g., PVP K90) and PVMA (e.g., PVMA with an M of about 570 KDa). w The mixture may be

[0143] The total amount of all polyamides in the reactive mixture can range from 1 weight percent to about 35 weight percent, including the range of 1 weight percent to about 15 weight percent, and the range of about 5 weight percent to about 15 weight percent, in all cases based on the total weight of the reactive components of the reactive monomer mixture.

[0144] Without being bound by theory, when used with silicone hydrogels, polyamides function as internal wetting agents. The polyamides of the present invention may be non-polymeric, in which case they are incorporated into the silicone hydrogel as a semi-interpenetrating network. The polyamides are encapsulated or physically held within the silicone hydrogel. Alternatively, the polyamides of the present invention may be polymeric, for example as polyamide macromers or prepolymers, in which case they are covalently incorporated into the silicone hydrogel. Mixtures of polymeric and non-polymeric polyamides may also be used.

[0145] When a polyamide is incorporated within the reactive monomer mixture, the polyamide may have a weight average molecular weight of at least 100,000 Daltons, greater than about 150,000, from about 150,000 to about 2,000,000 Daltons, from about 300,000 Daltons to about 1,800,000 Daltons. Higher molecular weight polyamides can be used if compatible with the reactive monomer mixture.

[0146] Crosslinking Agent It is generally desirable to add one or more crosslinking agents, also referred to as crosslinking monomers, multifunctional macromers, and prepolymers, to the reactive mixture. The crosslinking agents may be selected from difunctional crosslinkers, trifunctional crosslinkers, tetrafunctional crosslinkers, and mixtures thereof, including silicone-containing and non-silicone-containing crosslinkers. Non-silicone-containing crosslinkers include ethylene glycol dimethacrylate (EGDMA), tetraethylene glycol dimethacrylate (TEGDMA), trimethylolpropane trimethacrylate (TMPTMA), triallyl cyanurate (TAC), glycerol trimethacrylate, methacryloxyethyl vinyl carbonate (HEMAVc), allyl methacrylate, methylene bisacrylamide (MBA), and polyethylene glycol dimethacrylate, where the polyethylene glycol has a molecular weight of up to about 5000 Daltons. The crosslinking agents are used in the reactive mixture in conventional amounts, for example, from about 0.000415 to about 0.0156 moles per 100 grams of reactive formulation. Alternatively, if the hydrophilic monomer and / or silicone-containing component is multifunctional due to molecular design or impurities, adding a crosslinker to the reactive mixture is optional. Examples of hydrophilic monomers and macromers that can act as crosslinkers and do not require the addition of additional crosslinkers to the reactive mixture when present include (meth)acrylate and (meth)acrylamide end-capped polyethers. Other crosslinkers will be known to those skilled in the art and can be used to make the silicone hydrogel of the present invention.

[0147] It may be desirable to select a crosslinker that has a similar reactivity with one or more of the other reactive components in the formulation. In some cases, it may be desirable to select a mixture of crosslinkers 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(s) and curing conditions used.

[0148] 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. An example of a silicone-containing component that can act as a crosslinker and does not require the addition of a crosslinking monomer to the reactive mixture when present includes α,ω-bismethacryloxypropyl polydimethylsiloxane. Another example is bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (ac-PDMS).

[0149] Crosslinkers with hard chemical structures and polymerizable groups that undergo free radical polymerization may also be used. Non-limiting examples of suitable hard structures include crosslinkers containing phenyl and benzyl rings, such as 1,4-phenylenediacrylate, 1,4-phenylenedimethacrylate, 2,2-bis(4-methacryloxyphenyl)-propane, 2,2-bis[4-(2-acryloxyethoxy)phenyl]propane, 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl]propane, and 4-vinylbenzyl methacrylate, and combinations thereof. Hard crosslinkers may be included in an amount of about 0.5 to about 15, or about 2 to 10, 3 to 7, based on the total weight of all reactive components. The physical and mechanical properties of the silicone hydrogels of the present invention may be optimized for a particular application by adjusting the components in the reactive mixture.

[0150] Non-limiting examples of silicone crosslinkers also include the multifunctional silicone-containing components described above, such as compounds of Formula E (and subformulas thereof) and the multifunctional compounds shown in Table 3.

[0151] Further components The reactive mixture may contain additional components such as, but not limited to, diluents, initiators, UV absorbers, visible light absorbers, photochromic compounds, pharmaceuticals, nutritional supplements, antimicrobial substances, colorants, pigments, copolymerizable dyes, non-polymerizable dyes, release agents, and combinations thereof.

[0152] Suitable classes of diluents for silicone hydrogel reactive mixtures 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.

[0153] Generally, reactive components are mixed in a diluent to form a reactive mixture. Suitable diluents are known in the art. For silicone hydrogels, suitable diluents are disclosed in WO 03 / 022321 and U.S. Patent No. 6,020,445, the disclosures of which are incorporated herein by reference.

[0154] Suitable classes of diluents for silicone hydrogel reactive mixtures include alcohols having 2-20 carbons, amides having 10-20 carbon atoms derived from primary amines, and carboxylic acids having 8-20 carbon atoms. Primary and tertiary alcohols can be used. Preferred classes include alcohols having 5-20 carbons and carboxylic acids having 10-20 carbon atoms.

[0155] Specific diluents that may be used include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropanol, 3,7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-octanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, tert-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2 ... Examples of diluents include ethanol, 2-propanol, 1-propanol, ethanol, 2-ethyl-1-butanol, (3-acetoxy-2-hydroxypropyloxy)-propylbis(trimethylsiloxy)methylsilane, 1-tert-butoxy-2-propanol, 3,3-dimethyl-2-butanol, tert-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.

[0156] 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, t-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, mixtures thereof, and the like.

[0157] More preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 1-dodecanol, 3-methyl-3-pentanol, 1-pentanol, 2-pentanol, t-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, mixtures thereof, and the like.

[0158] When a diluent is present, there is generally no particular restriction as to the amount of diluent present. When a diluent is used, it may be present in an amount ranging from about 2 to about 70 weight percent, including from about 5 to about 50 weight percent and from about 15 to about 40 weight percent, based on the total weight of the reactive mixture (including reactive and non-reactive compounds). Mixtures of diluents may also be used.

[0159] A polymerization initiator may be used in the reactive mixture. The polymerization initiator may include at least one of those that generate free radicals at moderately high temperatures, such as lauryl peroxide, benzoyl peroxide, iso-propyl percarbonate, azobisisobutyronitrile, and photoinitiator systems, such as aromatic α-hydroxyketones, alkoxyoxybenzoins, acetophenones, acylphosphine oxides, bisacylphosphine oxides, and tertiary amines + diketones, mixtures thereof. Specific examples of photoinitiators include 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenyl-propan-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.

[0160] Commercially available (from IGM Resins BV, The Netherlands) visible light initiator systems include Irgacure® 819, Irgacure® 1700, Irgacure® 1800, Irgacure® 819, Irgacure® 1850, and Lucrin® TPO initiators. Commercially available (from IGM Resins BV) UV photoinitiators include Darocur® 1173 and Darocur® 2959. These and other photoinitiators that may be used are disclosed in Volume III, Photoinitiators for Free Radical Cationic & Anionic Photopolymerization, 2nd Edition by JV Crivello & K. Dietliker; edited by G. Bradley; John Wiley and Sons; New York; 1998. The initiator is used in the reactive mixture in an amount effective to initiate photopolymerization of the reactive mixture, for example, from about 0.1 to about 2 parts by weight per 100 parts of the reactive monomer mixture. Polymerization of the reactive mixture can be initiated using heat or visible or ultraviolet light or other means, appropriately selected depending on the polymerization initiator used. Alternatively, initiation can be carried out using an electron beam without a photoinitiator. However, when a photoinitiator is used, the preferred initiator is a bisacylphosphine oxide, such as bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure® 819), or a combination of 1-hydroxycyclohexyl phenyl ketone and bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentylphosphine oxide (DMBAPO).

[0161] The reactive mixture for making the ophthalmic devices of the present invention may include, in addition to the high energy visible light absorbing compound, any of the polymerizable compounds and optional ingredients described above.

[0162] A preferred reactive mixture can include a high energy visible light absorbing compound, such as a compound of formula I, and a hydrophilic component.

[0163] A preferred reactive mixture may include a high energy visible light absorbing compound, such as a compound of formula I, and a hydrophilic component selected from DMA, NVP, HEMA, VMA, NVA, methacrylic acid, and mixtures thereof. A mixture of HEMA and methacrylic acid is preferred.

[0164] A preferred reactive mixture can include a high energy visible light absorbing compound, such as a compound of Formula I, a hydrophilic component, and a silicone-containing component.

[0165] A preferred reactive mixture may include a high energy visible light absorbing compound, such as a compound of Formula I, a hydrophilic component, and a silicone-containing component that includes a compound of Formula A.

[0166] A preferred reactive mixture may include a high energy visible light absorbing compound, such as a compound of formula I, a hydrophilic component selected from DMA, NVP, HEMA, VMA, NVA, and mixtures thereof, a silicone-containing component, such as a compound of formula A, and an internal wetting agent.

[0167] A preferred reactive mixture may include a high energy visible light absorbing compound such as a compound of formula I, a hydrophilic component selected from DMA, HEMA, and mixtures thereof, a silicone-containing component selected from 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA), 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.

[0168] A preferred reactive mixture may include a high energy visible light absorbing compound, such as a compound of formula I, a hydrophilic component including a mixture of DMA and HEMA, and a silicone-containing component including a mixture of OH-mPDMS having 2-20 repeat units, preferably a mixture of 4 and 15 repeat units. Preferably, the reactive mixture further includes a silicone-containing crosslinker, such as ac-PDMS. Also preferably, the reactive mixture includes a wetting agent, preferably DMA, PVP, PVMA, or a mixture thereof.

[0169] A preferred reactive mixture comprises a high energy visible light absorbing compound, such as a compound of Formula I, from about 1 to about 15 weight percent of at least one polyamide (e.g., acyclic polyamide, cyclic polyamide, or mixtures thereof), at least one first monofunctional hydroxyl-substituted poly(disubstituted siloxane) having 4 to 8 siloxane repeat units (e.g., OH-mPDMS, where n is 4 to 8, preferably n is 4), and at least one second hydroxyl-substituted poly(disubstituted siloxane) that is a monofunctional hydroxyl-substituted poly(disubstituted siloxane) having 10 to 200, or 10 to 100, or 10 to 50, or 10 to 20 siloxane repeat units (e.g., OH-mPDMS, where n is 10 to 20, preferably OH-mPDMS, where n is 10 to 20, more preferably OH-mPDMS, where n is 10 to 20, more preferably OH-mPDMS, where n is 10 to 20, most ... 200, or 10-100, or 10-50, or 10-20, preferably n is 15), about 5 to about 35 weight percent of at least one hydrophilic monomer, and optionally a multifunctional hydroxyl-substituted poly(disubstituted siloxane) (e.g., ac-PDMS) having 10-200 or 10-100 siloxane repeat units. Preferably, the first monofunctional hydroxyl-substituted poly(disubstituted siloxane) and the second hydroxyl-substituted poly(disubstituted siloxane) are present in concentrations to provide a ratio of the weight percent of the first monofunctional hydroxyl-substituted poly(disubstituted siloxane) to the weight percent of the second hydroxyl-substituted poly(disubstituted siloxane) of 0.4 to 1.3, or 0.4 to 1.0.

[0170] The aforementioned reactive mixture may contain optional components such as, but not limited to, one or more initiators, internal wetting agents, crosslinkers, other UV or HEV absorbers, and diluents.

[0171] Curing of Hydrogels and Manufacturing of Lenses The reactive mixture may be formed by any method known in the art, such as shaking or stirring, and used to form a polymeric article or device by known methods. The reactive components are mixed together, either with or without a diluent, to form the reactive mixture.

[0172] For example, an ophthalmic device can be prepared by mixing the reactive components and optionally a diluent(s) with a polymerization initiator and curing under appropriate conditions to form a product that can later be molded into a suitable shape by lathing, cutting, etc. Alternatively, the reactive mixture can be placed in a mold and then cured into a suitable article.

[0173] 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 over 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.

[0174] The reactive mixture may be cured via any known process for shaping the reactive mixture in the production of contact lenses, including rotational molding and static molding. Rotational molding methods are disclosed in U.S. Patents 3,408,429 and 3,660,545, and static molding methods are disclosed in U.S. Patents 4,113,224 and 4,197,266. The contact lenses of the present invention may be formed by direct molding of silicone hydrogels, which is economical and allows precise control of the final shape of the hydrated lens. In this method, the reactive mixture is placed into a mold having the shape of the desired final silicone hydrogel, and the reactive mixture is subjected to conditions that polymerize the monomers, thereby producing a polymer of the approximate shape of the desired final product.

[0175] After curing, the lens may be subjected to extraction to remove unreacted components and release the lens from the lens mold. Extraction may be performed using conventional extraction fluids, such as organic solvents, such as alcohols, or may be extracted using aqueous solutions.

[0176] An aqueous solution is a solution that includes water. The aqueous solution of the present invention may include at least about 20 percent by weight water, or at least about 50 percent by weight water, or at least about 70 percent by weight water, or at least about 95 percent by weight water. The aqueous solution may also include additional water-soluble ingredients, such as inorganic salts or release agents, wetting agents, slip agents, pharmaceutical ingredients and nutritional supplements, combinations thereof. 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 when compared to the time required to release a contact lens using an aqueous solution that does not include a release agent. The aqueous solution may not require special handling, such as purification, recycling, or special waste disposal.

[0177] Extraction may occur, for example, via immersion of the lens in an aqueous solution or exposure to a stream of an aqueous solution. Extraction may also include, for example, one or more of heating the aqueous solution, agitating the aqueous solution, increasing the level of release agent in the aqueous solution to a level sufficient to cause release of the lens, mechanical or ultrasonic agitation of the lens, and incorporating at least one leaching or extraction aid into the aqueous solution to a level sufficient to facilitate adequate removal of unreacted components from the lens. The foregoing may be performed in a batch or continuous process, with or without the addition of heat, vibration, or both.

[0178] To facilitate leaching and demolding, it may be desirable to apply physical agitation. For example, the lens mold part to which the lens is attached can be vibrated or moved back and forth in the aqueous solution. Other methods may include passing ultrasound through the aqueous solution.

[0179] The lenses may be sterilized by known means, such as, but not limited to, high pressure steam treatment.

[0180] As mentioned 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 on lenses of various thicknesses, for example, using the methods described in the Examples. By way of example, a preferred center thickness for measuring the transmission spectrum in a soft contact lens can be 80-100 microns, or 90-100 microns, or 90-95 microns. Typically, measurements can be made at the center of the lens, for example, using an instrument slit width of 4 nm. Various concentrations of one or more polymerizable high energy visible light absorbing compounds can be used to achieve the above-mentioned transmission characteristics. For example, the concentrations can range from at least 1 percent, or at least 2 percent, and up to 10 percent or up to 5 percent, based on the weight percentage of all components in the reactive mixture excluding the diluent. Typical concentrations can range from 3 to 5 percent.

[0181] Silicone hydrogel ophthalmic devices (e.g., contact lenses) according to the present invention preferably exhibit the following properties. All values ​​are preceded by "about" and the device can have any combination of the listed properties. Properties can be determined by methods known to those of skill in the art, for example, as described in U.S. Pre-Grant Publication No. 2018 / 0037690, which is incorporated herein by reference. Water concentration %: at least 20%, or at least 25% and at most 80%, or at most 70% Haze: 30% or less, or 10% or less Advancing dynamic contact angle (Wilhelmy plate method): 100° or less, or 80° or less, or 50° or less Tensile modulus (psi): 150 or less, or 135 or less, or 120 or less, or 80 to 135 Oxygen permeability (Dk, Barrer): at least 60 Barrer, or at least 80, or at least 100, or at least 150, or at least 200 Elongation at break: at least 100

[0182] For ionic silicone hydrogels, the following properties may also be preferred (in addition to those mentioned above): Lysozyme uptake (μg / lens): at least 100, or at least 150, or at least 500, or at least 700 Polyquaternium 1 (PQ1) uptake (%): ≦15, or ≦10, or ≦5.

[0183] The contact lenses of the present invention may be used to improve one or more visual attributes in a contact lens wearer. The visual attribute may be photostress recovery time. The visual attribute may be glare discomfort. The visual attribute may be glare attenuation threshold. The visual attribute may be heterochromatic contrast threshold. The visual attribute may be halo size. The visual attribute may be starburst size. The visual attribute may be light scattering. The visual attribute may be one or more of photostress recovery time, glare discomfort, glare attenuation threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering. Further details regarding the improvement of visual attributes are provided in the examples below.

[0184] The following items list non-limiting embodiments of the present disclosure. 1. A method for improving a visual attribute in a contact lens wearer, comprising providing to the contact lens wearer a contact lens that is a free radical reaction product of a reactive mixture comprising one or more polymerizable compounds suitable for making contact lenses and a high energy visible (HEV) light absorbing compound, wherein the visual attribute is selected from one or more of the following: photostress recovery time, glare discomfort, glare impairment threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering. 2. The method of claim 1, wherein the contact lens transmits between 0 percent and 70 percent of light over the wavelength range of 400 to 409 nm. 3. The method of claim 1 or 2, wherein the contact lens transmits 45 percent or less of light over the wavelength range of 280 to 399 nm. 4. The method of any one of items 1 to 3, wherein the contact lens transmits at least 80 percent of light over the wavelength range of 450 to 800 nm. 5. The method according to any one of items 1 to 4, wherein the contact lens is photostable. 6. The method according to any one of items 1 to 5, wherein the high-energy visible light absorbing compound is a static compound. 7. The high energy visible light absorbing compound comprises a compound of formula I,

[0185] [ka] During the ceremony, m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR; Y is a linking group; P g is a polymerizable group, R, at each occurrence, is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP g and R 1 and R 2 when present, independently at each occurrence is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halo), halo, hydroxy, amino, NR 3 R 4 or benzyl, R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The method according to any one of items 1 to 6, wherein the groups, together with the carbon atom to which they are attached, are linked to form a cycloalkyl or aryl ring. The compound of formula I preferably comprises one or two YP g More preferably, the compound contains one YP group. g Contains a group. 8. The method according to item 7, wherein m and n are each independently 0 or 1. 9. The method of claim 7 or 8, wherein Y, at each occurrence, is independently alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination thereof. 10. P g comprises styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide. 11. Use of a contact lens to improve at least one visual attribute selected from photostress recovery time, glare discomfort, glare attenuation threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering, wherein the contact lens is a free radical reaction product of a reactive mixture comprising one or more polymerizable compounds suitable for making contact lenses and a high energy visible light absorbing compound. 12. The use according to item 11, wherein the contact lens transmits between 0 percent and 70 percent of light over the wavelength range of 400 to 409 nm. 13. The use according to item 11 or 12, wherein the contact lens transmits 45 percent or less of light over the wavelength range of 280 to 399 nm. 14. The use according to any one of items 11 to 13, wherein the contact lens transmits at least 80 percent of light over the wavelength range of 450 to 800 nm. 15. The use according to any one of items 11 to 14, wherein the contact lenses are photostable. 16. The use according to any one of items 11 to 15, wherein the high-energy visible light absorbing compound is a static compound. 17. The high energy visible light absorbing compound comprises a compound of formula I,

[0186] [ka] During the ceremony, m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR; Y is a linking group; P g is a polymerizable group, R, at each occurrence, is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP g and R 1 and R 2 when present, independently at each occurrence is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halo), halo, hydroxy, amino, NR 3 R 4 or benzyl, R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The use according to any one of items 11 to 16, wherein the groups, together with the carbon atom to which they are attached, are linked to form a cycloalkyl or aryl ring. The compounds of formula I preferably contain one or two YP g More preferably, the compound contains one YP group. g Contains a group. 18. The use according to item 17, wherein m and n are each independently 0 or 1. 19. The use according to item 17 or 18, wherein Y, at each occurrence, is independently alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination thereof. 20. P g comprises styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide. 21. A contact lens comprising: one or more polymerizable compounds suitable for making contact lenses; a high energy visible (HEV) light absorbing compound; and a free radical reaction product of a reactive mixture comprising the contact lens, wherein the contact lens is a toric contact lens. 22. The contact lens of item 21, which transmits between 0 percent and 70 percent of light over the wavelength range of 400 to 409 nm. 23. The contact lens according to item 21 or 22, which transmits 45 percent or less of light over the wavelength range of 280 to 399 nm. 24. A contact lens according to any one of items 21 to 23, which transmits at least 80 percent of light over the wavelength range of 450 to 800 nm. 25. The contact lens of any one of items 21 to 24, which is photostable. 26. The contact lens according to any one of items 21 to 25, wherein the high-energy visible light absorbing compound is a static compound. 27. The high energy visible light absorbing compound comprises a compound of formula I,

[0187] [ka] During the ceremony, m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR; Y is a linking group; P g is a polymerizable group, R, at each occurrence, is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP g and R 1 and R 2when present, independently at each occurrence is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halo), halo, hydroxy, amino, NR 3 R 4 or benzyl, R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 27. The contact lens of any one of items 21 to 26, wherein the groups, together with the carbon atom to which they are attached, are linked to form a cycloalkyl or aryl ring. 28. The contact lens according to item 27, wherein m and n are each independently 0 or 1. 29. The contact lens according to item 27 or 28, wherein Y, at each occurrence, is independently alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or combinations thereof. 30. P g 30. The contact lens according to any one of items 27 to 29, wherein comprises styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide. 31. The contact lens of any one of items 21 to 30, further comprising a UV absorbing compound. 32. The contact lens of item 31, wherein the UV absorbing compound comprises a compound of formula I, a benzophenone, a benzotriazole, a triazine, a substituted acrylonitrile, a salicylic acid derivative, a benzoic acid derivative, a cinnamic acid derivative, a chalcone derivative, a dipnone derivative, a crotonic acid derivative, or a mixture thereof. 33. A contact lens according to any one of items 21 to 32, wherein the polymerizable compound suitable for making a contact lens comprises a hydrophilic component, a silicone-containing component, or a mixture thereof.

[0188] Some embodiments of the present invention will now be described in detail in the following examples. EXAMPLES

[0189] Test Method The ultraviolet-visible spectra of the compounds in solution were measured on a Perkin Elmer Lambda 45 or Agilent Cary 6000i UV / VIS scanning spectrometer. The instruments were allowed to thermally equilibrate for at least 30 min before use. For the Perkin Elmer instruments, the scan range was 200-800 nm, the scan speed was 960 nm per minute, the slit width was 4 nm, the mode was set to transmission or absorbance, and baseline correction was selected. For the Cary instruments, the scan range was 200-800 nm, the scan speed was 600 nm / min, the slit width was 2 nm, the mode was transmission or absorbance, and baseline correction was selected. Baseline correction was performed before analyzing the samples using the autozero function.

[0190] The UV-visible spectra of contact lenses partially formed from the claimed compositions were measured using packing solutions on a Perkin Elmer Lambda 45 UV / VIS or Agilent Cary 6000i UV / VIS scanning spectrometer. Prior to use, the instruments were allowed to thermally equilibrate for at least 30 minutes. For the Perkin Elmer instruments, the scan range was 200-800 nm, the scan speed was 960 nm per minute, the slit width was 4 nm, the mode was set to transmission, and baseline correction was selected. Baseline correction was performed using plastic two-piece lens holders and cuvettes containing the same solvent. These two-piece contact lens holders were designed to hold the samples in the quartz cuvette at a position traversed by the incident light beam. A reference cuvette also housed the two-piece holder. To ensure that the thickness of the samples was consistent, all lenses were made using the same mold. The center thickness of the contact lenses was measured using an electronic thickness gauge. The reported center thickness and percent transmission spectra are obtained by averaging three individual lens data.

[0191] It is important to ensure that the exterior surface of the cuvette is completely clean and dry and that there are no air bubbles within the cuvette. Measurement reproducibility is improved when the reference cuvette and its lens holder remain constant and all samples use the same sample cuvette and its lens holder, ensuring that both cuvettes are properly inserted into the instrument.

[0192] The following abbreviations are used throughout the examples and figures and have the following meanings: BC: Back or base curve plastic mold FC: Front curve plastic mold DMA: N,N-dimethylacrylamide (Jarchem) HEMA: 2-hydroxyethyl methacrylate (Bimax) PVP: Poly(N-vinylpyrrolidone) (ISP Ashland) PDMA: Polydimethylacrylamide PVMA: Polyvinylmethyacetamide EGDMA: Ethylene glycol dimethacrylate (Esstech) TEGDMA: Tetraethylene glycol dimethacrylate (Esstech) Irgacure 819: Bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (BASF or Ciba Specialty Chemicals) Irgacure 1870: A blend of bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide and 1-hydroxycyclohexyl phenyl ketone (BASF or Ciba Specialty Chemicals) mPDMS: mono-n-butyl terminated, monomethacryloxypropyl terminated polydimethylsiloxane (M n =800~1000 Daltons) (Gelest) HO-mPDMS: mono-n-butyl terminated mono-(2-hydroxy-3-methacryloxypropyloxy)-propyl terminated polydimethylsiloxane (M n =400~1500 Daltons) (Ortec or DSM-Polymer Technology Group) ac-PDMS: bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (Tegomer V-Si 2250 from Evonik) Blue HEMA: 1-amino-4-[3-(4-(2-methacryloyloxyethoxy)-6-chlorotriazin-2-ylamino)-4-sulfophenylamino]anthraquinone-2-sulfonic acid, as described in U.S. Pat. No. 5,944,853. Da: Daltons or g / mol kDa: kilodalton, or atomic mass unit equal to 1,000 daltons SiMAA: 2-Propenoic acid, 2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl ester (Toray), or 3-(3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy)-2-hydroxypropyl methacrylate RB247: 1,4-Bis[2-methacryloxyethylamino]-9,10-anthraquinone BHT: Butylated hydroxytoluene D3O: 3,7-dimethyl-3-octanol (Vigon) DIW: Deionized water MeOH: Methanol IPA: Isopropyl alcohol HCl: Hydrochloric acid CH2Cl2 or DCM: methylene chloride or dichloromethane SOCl2: Thionyl chloride mCPBA: m-chloroperbenzoic acid EtOAc: ethyl acetate NH2CH2CH2OH: Ethanolamine or 2-aminoethanol Norbloc: 2-(2'-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole (Janssen) PP: Polypropylene, a homopolymer of propylene TT: Tuftec (Asahi Kasei Chemicals), a hydrogenated styrene butadiene block copolymer Z: Zeonor (Nippon Zeon Co Ltd), a polycycloolefin thermoplastic polymer TL03 Light: Phillips TLK 40W / 03 bulb LED: Light Emitting Diode 1 N NMR: Proton nuclear magnetic resonance spectroscopy UV-VIS: Ultraviolet-visible spectroscopy L: Liters mL: milliliter Equiv. or eq.: equivalent kg: kilogram g: grams mol: mole mmol: millimolar min:minutes nm: nanometer TLC: Thin Layer Chromatography Borate Buffer Packing Solution: 18.52 grams (300 mmol) of boric acid, 3.7 grams (9.7 mmol) of sodium borate decahydrate, and 28 grams (197 mmol) of sodium sulfate were dissolved in enough deionized water to fill a 2 liter volumetric flask.

[0193] Example 1 - Synthesis of 2-(2-cyanoacetamido)ethyl methacrylate (A) and 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate (B) as shown in Scheme 2

[0194] [ka] Methyl cyanoacetate (40 grams, 0.4037 moles) and 25 mL of dichloromethane were stirred in a three-necked 500 mL round bottom flask equipped with a reflux condenser under a nitrogen environment. After 2-aminoethanol (23.8 grams, 0.3897 moles, approximately 0.97 equivalents) was added to the solution via an addition funnel, the temperature rose and the methylene chloride began to reflux. After the exotherm ceased, external heat was applied to continue the gentle reflux for a total of 2 hours after which no ethanolamine was observed by thin layer chromatography.

[0195] The reaction may also be carried out at room temperature and is complete within a few hours.

[0196] The mixture was cooled to room temperature and all methylene chloride was evaporated under reduced pressure. The residual oil was washed with 50 mL of ethyl acetate three times to remove unreacted starting material and non-polar impurities. The residual ethyl acetate was then removed under reduced pressure and the resulting oil was used for acylation without further purification.

[0197] The crude N-2-hydroxyethylacetamide derivative was dissolved in 150 mL of dichloromethane containing 40 grams of pyridine (about 0.5 moles) in a three-necked round-bottom flask equipped with a reflux condenser, an addition funnel, and a magnetic stir bar. The flask was immersed in an ice bath and cooled to about 0° C. Methacryloyl chloride (45.76 g, about 0.44 moles) was added dropwise through the addition funnel, and the resulting reactive mixture was allowed to warm to room temperature while the system was constantly stirred. Methanol (20 mL) was 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 800 mL of dilute aqueous HCl. The resulting aqueous solution was extracted three times with 100 mL 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 300 mL of ethyl acetate. Approximately 50 milligrams of BHT was added as an inhibitor to the combined organic fractions, and the ethyl acetate was removed by rotary evaporation under reduced pressure. The crude product crystallized out of solution during solvent removal. When approximately 100 mL of ethyl acetate remained in the flask, 250 mL of hexane was added, and the crude product was isolated by vacuum filtration using a fritted glass funnel. Thin layer chromatography indicated the presence of a single compound. The filter cake was washed twice with 150 mL of hexane, then dried under vacuum at 40° C. to give 53 grams (approximately 70% yield) of 2-(2-cyanoacetamido)ethyl methacrylate (A). 1 H NMR (500MHz, CDCl3) δ1.93(3H,s,CH3), 3.36(2H,s,CNCH2), 3.60(2H,dd,CH2NH), 4.26(2H,t,CH2OC=O), 5.59(1H,m,vinylic), 6.11(1H,bs,vinylic), 6.52(1H,bs,NH).

[0198] A mixture of 9H-thioxanthen-9-one (2.12 grams, 0.01 mole) and thionyl chloride (5 mL, 8.2 grams, approximately 0.07 mole) was refluxed in a 50 mL round bottom flask under constant stirring under a nitrogen atmosphere. After 2 hours, the red solution was evaporated to dryness to ensure that all unreacted thionyl chloride was removed from the system. 2-(2-cyanoacetamido)ethyl methacrylate (A) (2.3 grams, 0.0117 mole, approximately 1.17 equivalents) and 15 mL of dichloromethane were added and the resulting reactive mixture was heated to reflux under a nitrogen blanket. The reaction was monitored by thin layer chromatography. After 2 hours, no change was observed in the chromatogram so the reactive mixture was cooled to room temperature. After passage through a short silica gel column (CHCl followed by 8 wt% EtOAc in CHCl), 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate (B) was isolated as yellow crystals (3.2 grams, 82% yield). The UV-VIS transmission spectrum of a 0.2 mM solution of compound B in methanol is shown in Figure 1. 1 H NMR(500MHz,CDCl3)δ1.84(3H,s,CH3), 3.47(2H,m,CH2NH), 4.01(2H,t,CH2OC=O), 5.55(1H,m,vinylic), 5.91(1H,bs,NH), 5.98(1H,bs,vin ylic), 7.24(1H,t,Ar-H), 7.31(1H,t,Ar-H), 7.39(2H,m,Ar-H), 7.49(1H,d,Ar-H), 7.55(1H,m,Ar-H), 7.61(1H,d,Ar-H), 8.04(1H,m,Ar-H).

[0199] Example 2 - Synthesis of 2-(2-cyanoacetamido)ethyl methacrylate (F) and N-(2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl)methacrylamide (G) as shown in Scheme 3

[0200] [ka] Methyl cyanoacetate (22 grams, 0.22 moles) and 250 mL of dichloromethane were stirred in a three-necked 500 mL round bottom flask equipped with a reflux condenser under a nitrogen atmosphere. The solution was cooled in a water bath and 1,2-diaminoethane (12 grams, 0.2 moles, approximately 0.9 equivalents) was added to the mixture. As the reaction proceeded, the mixture appeared increasingly heterogeneous and the product crashed out of solution. After stirring at room temperature for 4 hours, the volatiles were evaporated under reduced pressure and the residue was washed with ethyl acetate on a fritted glass funnel and dried at 50° C. before further use. 1 H NMR (500MHz, D2O) δ2.74(2H,t,CH2NH2), 3.29(2H,t,CH2NH), 3.38(2H,s,CH2CN).

[0201] 2-Aminoethylcyanoacetamide (12.7 g, 0.1 moles) and 12.0 grams of sodium carbonate are stirred in 150 mL of methanol while cooling in an ice bath. Methacryloyl chloride (11.5 g, 1.1 equiv.) is added dropwise to the suspension while maintaining the reaction temperature below 30° C. at all times. Once the reaction is complete, all volatiles are evaporated under reduced pressure, the product is redissolved in acetonitrile, and the solution is filtered to remove any salts present. The acetonitrile is evaporated under reduced pressure, and the resulting solid is washed with ethyl acetate on a fritted glass funnel to give the desired 2-(2-cyanoacetamido)ethyl methacrylamide (F). 1 H NMR(500MHz,CD3OD)δ1.86(3H,s,CH3), 3.22-3.26(4H,m,NH,CH2CN), 3.29(4H,m,CH2NH), 5.31(1H,m,vinylic), 5.63(1H,m,vinylic).

[0202] A mixture of thioxanthone (4.24 g, 0.02 mol) and 8 mL of thionyl chloride (13.12 g, ca. 0.11 mol) was gently refluxed under nitrogen atmosphere with constant stirring. After heating for 2 hours, the solution was evaporated to dryness under reduced pressure to ensure removal of all unreacted thionyl chloride. 2-(2-cyanoacetamido)ethylmethacrylamide (F) (4.2 grams, ca. 1.1 eq.) and 20 mL of degassed methylene chloride were added to the flask and the mixture was gently refluxed under nitrogen atmosphere for 3 hours while monitoring the progress by TLC. Evaporate the volatiles under reduced pressure and wash the organics with ethyl acetate. A large amount of precipitate was observed, concentrating the main product. The suspension was filtered and the remaining solid was washed with ethyl acetate before drying in a vacuum oven. The UV-VIS transmission spectrum of a 0.2 mM solution of compound G in methanol is shown in Figure 2. 1 H NMR(500MHz,CDCl3)δ1.89(3H,s,CH3), 3.26(2H,m,CH2NH), 3.32(2H,m,CH2NH), 5.33(1H,m,vinylic), 5.68(1H,m,vinylic), 6.63 (1H,m,NH), 6.49(1H,m,NH), 7.25(1H,m,Ar-H), 7.33(1H,dt,Ar-H), 7.39(2H,m,Ar-H), 7.51-7.59(3H,m,Ar-H), 8.05(1H,m,Ar-H).

[0203] Example 3 - Synthesis of 2-(2-cyanoacetoxy)ethyl methacrylate (K) and 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetoxy)ethyl methacrylate (L) as shown in Scheme 4

[0204] [ka] 2-(2-cyanoacetoxy)ethyl methacrylate (K) was prepared by coupling cyanoacetic acid with 2-hydroxyethyl methacrylate as follows: Cyanoacetic acid (9 g, 0.106 mol) and 13 g of 2-hydroxyethyl methacrylate (HEMA) are stirred in 250 mL of dichloromethane and ethyl dimethylaminopropylcarbodiimide hydrochloride (EDC) is added to the suspension in four batches of 5 grams each (20 g, 0.104 mol). The mixture gradually becomes more homogeneous as less polar derivatives are formed and after completion of the reaction the volatiles are evaporated under reduced pressure. The product is redissolved in a 25:75 (by weight) mixture of ethyl acetate and hexane and extracted several times with deionized water to remove any residual salts and unreacted HEMA. A small amount of 4-methoxyhydroquinone (<20 mg) is added to the organic layer and the pure product is obtained after evaporation of the solvent under reduced pressure. 1 H NMR (500MHz, CDCl3) δ1.92(3H,m,CH3), 3.47(2H,S,NCCH2), 4.36(2H,m,OCH2), 4.44(2H,m,OCH2), 4.59(1H,m,vinylic), 6.10(1H,m,vinylic).

[0205] A mixture of thioxanthone (4.24 g, 0.02 mol) and 8 mL of thionyl chloride (13.12 g, ca. 0.11 mol) was gently refluxed under nitrogen atmosphere with constant stirring. After heating for 2 hours, the solution was evaporated to dryness under reduced pressure to ensure removal of all unreacted thionyl chloride. A solution of 2-(2-cyanoacetoxy)ethyl methacrylate (K) (4.33 grams, ca. 1.1 equiv.) in 20 mL of degassed methylene chloride was added to the flask and the mixture was gently refluxed under nitrogen atmosphere for 3 hours while monitoring the progress by TLC. The residue was washed with methanol to remove most of the unreacted starting thioxanthone, reconcentrated, and the crude product was purified by chromatography on a silica gel plug and dried in vacuum overnight. The UV-VIS transmission spectrum of a 0.2 mM solution of compound L in dichloromethane is shown in Figure 2. 1H NMR(500MHz,CDCl3)δ1.92(3H,s,CH3), 4.36(2H,m,CH2), 4.44(2H,m,CH2), 5.59( 1H,m,vinylic), 6.10(1H,m,vinylic), 7.24-7.62(7H,m,Ar-H), 8.1(1H,m,Ar-H).

[0206] Example 4 - Silicone hydrogel formulation containing compound (B) Reactive monomer mixtures were prepared consisting of 77 weight percent of the formulations listed in Table 4 and 23 weight percent diluent D3O. The reactive monomer mixtures were individually filtered under pressure through 3 μm filters using stainless steel syringes.

[0207] [Table 4]

[0208] Formulations 4A-4D were degassed at ambient temperature by applying vacuum (40 Torr) for 45 minutes. Approximately 75 μL of the reactive mixture was then dispensed onto a FC made of 90:10 (w / w) Zeonor / TT blend using an Eppendorf pipette at room temperature in a glove box containing a nitrogen gas atmosphere and less than about 0.1-0.2 percent oxygen gas. A BC made of a 90:10 Z:TT blend was then placed onto the FC. The molds were allowed to equilibrate in the glove box for a minimum of 12 hours before dispensing. The pallets containing the eight mold assemblies were each transferred to an adjacent glove box maintained at 65° C. and tuned to approximately 2 mW / cm at the tray position. 2 The coating was cured from the top and bottom for 15 minutes using a 435 nm LED light with an intensity of 1000 Hz.

[0209] With most of the lenses attached to the FC, the lenses were removed from the molds by hand and demolded by floating the lenses in about 1 liter of 70 percent IPA for about 1 hour, followed by immersion in fresh 70 percent IPA twice for 30 minutes, then fresh DIW twice for 15 minutes, then packing solution twice for 30 minutes. The lenses were equilibrated and stored in the borate buffered packing solution. Those skilled in the art will appreciate that the exact lens demolding process can vary depending on the lens formulation and mold material in terms of the concentration of the aqueous isopropanol, the number of washes with each solvent, and the duration of each step. The objective of the lens demolding process is to demold all of the lenses without damage and transition from a diluent swollen network to a packaging solution swollen hydrogel. The average center thickness of each lens set was measured: 4A=87.7 microns, 4B=85.3 microns, 4C=87.3 microns, and 4D=85.7 microns.

[0210] Figures 1-3 show the UV-VIS spectra of lenses made from Formulations 4A-4D, demonstrating that Compound (B) or a combination of Compound (B) and Norbloc® can provide complete or near complete absorption from 300 nm to 400 nm, while providing some absorption in the high energy visible region from 400 nm to 450 nm.

[0211] Example 5 - Light Stability Silicone hydrogel contact lenses made from reactive mixtures containing compound (B) were subjected to photostability testing as described above. The spectral transmission from 380 to 450 nm of lenses containing compound (B) exposed under ICH-Q1b conditions relative to contact lenses containing compound (B) but without exposure is shown in Table 5. The data demonstrate that lenses containing the HEV light absorbing compounds described herein are photostable.

[0212] [Table 5]

[0213] Example 6 - Clinical Trials Test lenses, which were silicone hydrogel contact lenses made from a reactive mixture containing 3 weight percent of compound (B), were evaluated in various clinical studies described below. The purpose of the study was to assess the visual effects of wearing test lenses that absorb HEV light, including the wavelength range of 400-409 nm, in direct comparison with lenses that do not contain a compound that absorbs in that range. The control lenses were Acuvue® OASYS lenses available from Johnson & Johnson Vision Care, Inc.

[0214] This study shows that the lenses of the present invention may provide improved visual performance in contact lens wearers by improving one or more desirable attributes, such as, for example, reduced light scattering, starburst, halos, glare discomfort, or by improving the wearer's glare attenuation threshold and / or heterochromatic contrast, or photostress recovery time, relative to control lenses. The data should be understood as presented herein for illustrative purposes, and should not be construed as limiting the scope of the disclosed technology in any way or excluding any alternative or additional embodiments.

[0215] This study was a single-site, single-session, contralateral, non-administered, randomized, controlled, and single-masked study. At one time, subjects were randomly assigned to one of two lens-wearing arms (left: test, right: control or left: control, right: test) and underwent psychophysical testing as described below. Approximately 60 subjects were involved in this study.

[0216] Glare Discomfort (GDC). GDC may be assessed by the strabismus response to a light stressor. The strabismus response may be captured by using a high-resolution camera on each subject's eye. The resulting footage may then be analyzed as still frames. The strabismus response may be quantified as a calculated ratio (in mm) of the palpebral fissure height under normal light conditions compared to the maximum strabismus produced during light stress exposure. More specifically, glare discomfort (GDC) is quantified using strabismus response and a questionnaire. Discomfort associated with exposure to light beyond an individual's adaptive state is accompanied by contraction of the extraocular muscles (strabismus). The strabismus response has been shown to be a valid objective indicator of glare discomfort. The degree of strabismus may be calculated as the ratio of the palpebral fissure height under normal light conditions compared to the maximum strabismus produced during light stress exposure. A high-resolution camera (AmScope MU300 digital camera, Irvine, CA) is used and calibrated against a spatial standard prior to the start of each test day. The resulting images are analyzed as still frames using AmScope measurement software (Irvine, CA). To determine the subjective rating of GDC, subjects are asked to rate the degree of discomfort of the light stressor using a single-item questionnaire OD (right eye) and OS (left eye): How bothersome is the glare you just experienced? Subjects have the response options of extremely bothersome, very bothersome, slightly bothersome, a little bothersome, and not bothersome at all.

[0217] Glare Disability (GD) threshold. GD threshold is assessed by exposing subjects to various intensities of a white light annulus (approximately 10 degree diameter) and can be quantified by the log-relative energy level required to obscure a central target. More specifically, the target stimulus is presented for 2 seconds on and 1 second off to reduce the opportunity for the subject to habituate to the stimulus. A second channel provides an annulus with an inner diameter of approximately 11 degrees and an outer diameter of 12 degrees. Before each trial, the annulus is set to a level well below which the target stimulus can be obscured. The experimenter then adjusts the intensity of the annulus, via a neutral density wedge, until the target stimulus is no longer visible. The participant indicates that the target has been obscured by pressing a buzzer. Effectively, in this task, the experimenter increases the intensity of light scattering in the subject's test eye until the subject can no longer effectively see. Unlike standard light stress bleaching, which is set on the subject, in this test the intensity is varied and thus the dependent variable aversion is also varied.

[0218] Hetero Chromatic Contrast (HCC) Threshold. HCC threshold can be assessed using a variable wavelength central target presented on a shortwave (460 nm) skylight background and quantified by the amount of light absorbed by the macula.

[0219] Halo. Halo is quantified by the diameter (mm) of the outer edge of the halo image and may be measured using the same micrometer as starburst and light scattering. More specifically, subjects have the nature of the halo described using visual aids prior to the experiment. Halo measurements utilize the same light source as starburst and two-point measurements to generate the halo. The same calibrated micrometer as the starburst test is used to define the outer edge of the halo image (the researcher adjusts based on subject feedback). The threshold rise and fall method may be used. This measurement takes approximately 10-15 minutes. Record the values ​​OD (right eye) and OS (left eye) in mm (2 decimal places). Subjects respond to a single item halo questionnaire OD and OS: What is the severity / intensity of the halo experienced? Subjects have response options of severe, moderate, mild, and none at all.

[0220] Starbursts. Starbursts may be quantified by the diameter of the lateral spread of light. A calibrated micrometer (two sides with inverted threads) is used to spread two posts from the central midpoint. These posts can then be used to define the outer boundary (i.e., diameter) of the starburst image. More specifically, the subject has the nature of the starburst described using a visual aid prior to the experiment. The researcher adjusts the micrometer to spread two posts from the central midpoint. These posts are used to define the outer boundary of the starburst image. A method of raising and lowering thresholds may be used based on subject feedback. This measurement takes approximately 10-15 minutes. Record the values ​​OD (right eye) and OS (left eye) in mm (two decimal places). Subjects respond to a single-item starburst questionnaire OD and OS: What is the degree of severity / intensity of the starburst experienced? Subjects have the response options of severe, moderate, mild, and none at all.

[0221] Light Scattering. Light scatter (two-point light spread function) is defined as the minimum distance (mm) at which two points of light are completely separate. These two-point thresholds can be measured with and without the addition of an interference filter, which changes the wavelength of the light and thus the appearance of the scatter. More specifically, the threshold is defined as the minimum distance at which two points of light are completely separate. A threshold ascending method is used. Tests are performed with and without the presence of a 403 nm interference filter in the light path. Briefly, the researcher starts with two points of light at 0 mm from each other. At the distance at which the subject is positioned, this initial position appears as a single point of light. The researcher slowly increases the distance between the two points until the participant sees two separate points of light separated by a black space. The distance between the two points is then recorded as the subject's two-point threshold.

[0222] Photostress Recovery Time (PRT). PRT is assessed by exposing the subject to an intense light source (10 degree circular broadband white with approximately 4.5 log Tds) and can be quantified as the time required to reacquire the site of the grating after exposure to the photostressor. More specifically, to measure PRT, participants are exposed to the same target used in each of the other visual function tests. Once the participant comfortably views the target, the experimenter exposes the target to a bright, bleaching light for 5 seconds. Exposure to the light causes the participant to momentarily lose sight of the target, and the target becomes obscured by an afterimage. As the afterimage clears, the participant is able to gradually recover vision of the target. PRT is recorded as the time it takes to recover vision of the target after exposure to the bleaching light.

[0223] Psychophysical measurements of GD, HCC, PRT, and GDC are recorded in the presence of a light source containing HEV light using an optical bench setup.

[0224] Statistical analysis: All data summaries and statistical analyses were performed using SAS software version 9.4 (SAS Institute, Cary, NC). Throughout the analysis of the data, results for each subject / eye were used when available for summaries and statistical analyses.

[0225] Light scatter (mm). The two-point light spread function was assessed under two filter conditions, with and without distance filter. In this study, there were many high order outliers, which caused the distribution of the two-point light spread function to be skewed to the right. Therefore, the planned analysis of the linear model could not be performed because the distribution did not meet the normality assumption of the linear mixed model. Instead, a logarithmic transformation was used for the two-point light spread function in both conditions (with and without distance filter). Therefore, the transformed data were analyzed separately using a linear mixed model with a normal distribution.

[0226] Each model included the study lens, dominant eye, age group, all possible interactions between the study lens and age group, and interactions between the study lens and dominant eye as fixed effects. The Kenward and Roger method was used for the denominator degrees of freedom. An unstructured (UN) covariance structure was used to model the residual error between eyes within the same subject. The unstructured (UN) covariance structure was chosen because this structure returned the lowest Akaike's Information Criterion Corrected (AICC).

[0227] Halo. Halo (mm) was analyzed using a linear mixed model. The model included lens type, dominant eye, age group, and two-way interactions (lens type by age group and lens type by dominant eye) as fixed effects. The Kenward and Roger method was used for the denominator degrees of freedom. A compound symmetric (CS) covariance structure was used to model residual error between eyes within the same subject. The compound symmetric covariance structure was chosen because this structure returned the lowest Akaike's Information Criterion Corrected (AICC).

[0228] Starburst. Starburst (mm) was analyzed using a linear mixed model. The model included lens type, dominant eye, age group, and two-way interactions (lens type by age group and lens type by dominant eye) as fixed effects. The Kenward and Roger method was used for the denominator degrees of freedom. A compound symmetric (CS) covariance structure was used to model residual error between eyes within the same subject. The compound symmetric covariance structure was chosen because this structure returned the lowest Akaike's Information Criterion Corrected (AICC).

[0229] Photostress Recovery (PR) time (sec). In this study, there were many high outliers (long PR times), which caused the distribution of PR times to be skewed to the right. Thus, planned analyses of linear models could not be performed because the distribution of PR times no longer met the normality assumptions of linear mixed models. Instead, PR times were analyzed using generalized linear mixed models with log-normal distribution. Study lens, age group, dominant eye, and the interaction between study lens and age group were included in the model as fixed effects. A compound symmetric (CS) covariance structure was used to model residual error between eyes within the same subject. The Kenward and Roger method () for denominator degrees of freedom was used.

[0230] Glare attenuation thresholds. Glare attenuation thresholds were analyzed using mixed models. Study lens, age group, the interaction between study lens and age group, and the interaction between study lens and dominant eye were included as fixed effects. A compound symmetric (CS) covariance structure was used to model residual error between eyes within the same subject. The Kenward and Roger method was used for the denominator degrees of freedom.

[0231] Glare discomfort (change in palpebral fissure height). Glare discomfort was analyzed using a mixed model. Study lens, age group, and the interaction between study lens and age group were included as fixed effects. A compound symmetric (CS) covariance structure was used to model residual error between eyes within the same subject. The Kenward and Roger method was used for the denominator degrees of freedom. Heterochromatic contrast thresholds

[0232] Heterochromatic contrast thresholds. HCC was analyzed using a mixed model. Lens type, age group, and the interaction between lens type and age group were included as fixed effects. A compound symmetry (CS) covariance structure was used to model residual error between eyes within the same subject. The Kenward and Roger method () was used for the denominator degrees of freedom.

[0233] Test results The results of the studies on glare discomfort, glare desensitization threshold, heterochromatic contrast threshold, halos, starbursts, and light scattering, as well as light stress recovery time, are shown in Figures 4-10, respectively. In each case, the data demonstrated improvement, and in some cases clinically significant improvement, with the test lenses compared to the control lenses. Thus, Figure 4 shows that patients were less strabismus-prone with the test lenses compared to the control lenses. Figure 5 shows that patients wearing the test lenses were able to be exposed to higher light intensities before the target disappeared than with the control lenses. Figure 6 shows that patients wearing the test lenses were able to be exposed to higher light intensities before the green target disappeared from the blue background. Figure 7 shows that patients wearing the test lenses experienced less halo than when wearing the control lenses. Figure 8 shows that patients wearing the test lenses experienced less starburst than when wearing the control lenses. Figure 9 shows that patients wearing the test lenses experienced less light scattering than when wearing the control lenses. Figure 10 shows a trend towards improved photostress recovery time. Clinically significant improvements were observed for glare discomfort, glare impairment threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering.

[0234] [Embodiment] (1) A contact lens, one or more polymerizable compounds suitable for making said contact lenses; a high energy visible (HEV) light absorbing compound; and a free radical reaction product of a reactive mixture comprising: The contact lens transmits between 0 percent and 70 percent of light over the wavelength range of 400 to 409 nm. (2) The contact lens of claim 1, wherein the contact lens transmits no more than 45 percent of light over the wavelength range of 280 to 399 nm. (3) The contact lens of embodiment 1 or 2, which transmits at least 80 percent of light over the wavelength range of 450 to 800 nm. (4) The contact lens of any one of embodiments 1 to 3, which is photostable. (5) The contact lens of any one of the preceding claims, wherein the high energy visible light absorbing compound is a static compound.

[0235] (6) The high energy visible light absorbing compound comprises a compound of formula I, [ka] During the ceremony, m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR; Y is a linking group; P g is a polymerizable group, R, at each occurrence, is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP g and R 1 and R 2 when present, independently at each occurrence is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halo), halo, hydroxy, amino, NR 3 R 4 or benzyl, R 3 and R 4 are independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The contact lens of any one of the preceding embodiments, wherein the groups, together with the carbon atom to which they are attached, are linked to form a cycloalkyl or aryl ring. (7) The contact lens of embodiment 6, wherein m and n are each independently 0 or 1. (8) The contact lens of embodiment 6 or 7, wherein Y, at each occurrence, is independently alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or combinations thereof. (9) P g The contact lens of any one of embodiments 6 to 8, wherein comprises styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide. (10) The contact lens of any one of embodiments 1 to 9, further comprising a UV absorbing compound.

[0236] 11. The contact lens of claim 10, wherein the UV absorbing compound comprises a compound of Formula I, a benzophenone, a benzotriazole, a triazine, a substituted acrylonitrile, a salicylic acid derivative, a benzoic acid derivative, a cinnamic acid derivative, a chalcone derivative, a dipnone derivative, a crotonic acid derivative, or a mixture thereof. (12) The contact lens of any one of the preceding claims, wherein the polymerizable compound suitable for making the contact lens comprises a hydrophilic component, a silicone-containing component, or a mixture thereof. (13) A method for improving a visual attribute in a contact lens wearer, comprising providing to the contact lens wearer a contact lens according to any one of embodiments 1 to 12, wherein the visual attribute is selected from one or more of photostress recovery time, glare discomfort, glare impairment threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering. (14) Use of a contact lens according to any one of embodiments 1 to 12 for improving at least one visual attribute selected from photostress recovery time, glare discomfort, glare attenuation threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering. (15) A method for improving a visual attribute in a contact lens wearer, comprising: The contact lens wearer is one or more polymerizable compounds suitable for making said contact lenses; a high energy visible (HEV) light absorbing compound; The method, wherein the visual attribute is selected from one or more of photostress recovery time, glare discomfort, glare impairment threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering.

[0237] (16) Use of a contact lens to improve at least one visual attribute selected from photostress recovery time, glare discomfort, glare attenuation threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering, wherein the contact lens is a free radical reaction product of a reactive mixture comprising one or more polymerizable compounds suitable for making the contact lens and a high energy visible light absorbing compound. (17) The method or use of any of embodiments 13 to 16, wherein improving a vision attribute comprises an improvement in said vision attribute observed by a contact lens wearer when compared to a contact lens that transmits at least 90 percent of light over the wavelength range of 400 to 409 nm. (18) A contact lens according to any one of embodiments 1 to 12, which is imported into a country. (19) The contact lens of embodiment 18, wherein the country is the United States of America. (20) The HEV light absorbing compound is selected from the group consisting of 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)ethyl 20. The contact lens, method, or use of any of the preceding claims, comprising (E)-2-(2-cyano-2-(2,4-dichloro-9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate, (E)-2-(2-(2-chloro-9H-thioxanthen-9-ylidene)-2-cyanoacetamido)ethyl methacrylate, (E)-2-(2-cyano-2-(2-isopropyl-9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate, (E)-2-(2-cyano-2-(4-isopropyl-9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate, 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetoxy)ethyl methacrylate, or a mixture thereof.

Claims

1. A contact lens, one or more polymerizable compounds suitable for preparing the contact lens; a high energy visible (HEV) light absorbing compound; and a free radical reaction product of a reactive mixture comprising: the contact lens transmits between 0 percent and 70 percent of light over the wavelength range of 400 to 409 nm; The high energy visible light absorbing compound comprises a compound of formula I, 【Chemistry 1】 During the ceremony, m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR; Y is a linking group; P g comprises styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide; R, at each occurrence, is independently H, C 1 -C 6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or Y-P g ; A contact lens wherein R 1 and R 2 , when present, at each occurrence are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 thioalkyl, C 3 -C 7 cycloalkyl, aryl, halo, hydroxy, amino, NR 3 R 4 , or benzyl, and R 3 and R 4 are independently H or C 1 -C 6 alkyl, or two adjacent R 1 or R 2 groups, together with the carbon atom to which they are attached, are joined to form a cycloalkyl or aryl ring.

2. 10. The contact lens of claim 1, wherein the contact lens transmits no more than 45 percent of light over the wavelength range of 280 to 399 nm.

3. 3. The contact lens of claim 1, which transmits at least 80 percent of light over the wavelength range of 450 to 800 nm.

4. The contact lens of any one of claims 1 to 3, wherein the high energy visible light absorbing compound is a static compound.

5. The contact lens of any one of claims 1 to 4, wherein m and n are each independently 0 or 1.

6. 6. The contact lens of any one of claims 1 to 5, wherein Y, at each occurrence, is independently alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or combinations thereof.

7. The contact lens of any one of claims 1 to 6, further comprising a UV absorbing compound.

8. 8. The contact lens of claim 7, wherein the UV absorbing compound comprises a compound of Formula I, a benzophenone, a benzotriazole, a triazine, a substituted acrylonitrile, a salicylic acid derivative, a benzoic acid derivative, a cinnamic acid derivative, a chalcone derivative, a dipnone derivative, a crotonic acid derivative, or a mixture thereof.

9. The contact lens of any one of claims 1 to 8, wherein the polymerizable compound suitable for making the contact lens comprises a hydrophilic component, a silicone-containing component, or a mixture thereof.

10. 10. A method for improving a visual attribute in a contact lens wearer, comprising providing to the contact lens wearer a contact lens according to any one of claims 1 to 9, wherein the visual attribute is selected from one or more of the following: photostress recovery time, glare discomfort, glare impairment threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering.

11. Use of a contact lens according to any one of claims 1 to 9 for improving at least one visual attribute selected from photostress recovery time, glare discomfort, glare attenuation threshold, heterochromatic contrast threshold, halo size, starburst size and light scattering.

12. 1. A method for improving a visual attribute in a contact lens wearer, comprising: The contact lens wearer is Providing a contact lens according to any one of claims 1 to 9, The method, wherein the visual attributes are selected from one or more of photostress recovery time, glare discomfort, glare impairment threshold, heterochromatic contrast threshold, halo size, starburst size, and light scattering.

13. 13. The method or use of any one of claims 10 to 12, wherein improving a vision attribute comprises improving said vision attribute as observed by a contact lens wearer when compared to a contact lens that transmits at least 90 percent of light over the wavelength range of 400 to 409 nm.

14. A contact lens according to any one of claims 1 to 9, which is imported into a country.

15. The contact lens of claim 14, wherein the country is the United States of America.

16. The HEV light absorbing compound is 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)ethyl 16. The contact lens, method or use of any one of claims 1 to 15, comprising (E)-2-(2-(2-cyano-2-(2,4-dichloro-9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate, (E)-2-(2-(2-chloro-9H-thioxanthen-9-ylidene)-2-cyanoacetamido)ethyl methacrylate, (E)-2-(2-cyano-2-(2-isopropyl-9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate, (E)-2-(2-cyano-2-(4-isopropyl-9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate, 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetoxy)ethyl methacrylate, or mixtures thereof.

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