Contact lens containing a photosensitive chromophore and its package

Abstract

A contact lens system is provided that includes a contact lens containing a photochromophore having at least one active wavelength between 250 and 400 nanometers and at least one active wavelength between 400 and 450 nanometers, and a package surrounding the contact lens. The photochromophore has at least one active wavelength between 250 and 400 nanometers and at least one active wavelength between 400 and 450 nanometers. The package has a transmittance of 99 percent or less at each active wavelength.

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims priority to U.S. Patent Application No. 16 / 952,841, filed November 19, 2020, and U.S. Provisional Patent Application No. 62 / 950,577, filed December 19, 2019, the entireties of which are incorporated herein by reference.

[0002] (Field of the Invention) The present invention relates to a contact lens system including a contact lens containing a photosensitive chromophore and a surrounding package for protecting the chromophore from photodegradation.

Background Art

[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 less than 280 nm is absorbed by the earth's atmosphere, but photons having wavelengths in the range of 280 - 400 nm are associated with some eye disorders including degenerative changes in the cornea and several 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 with wavelengths up to 320 nm (30% transmittance) (Kolozsvari et al., Investigative Ophthalmology & Visual Science, July 2002, Vol. 43(7), pp. 2165 - 2168, Hoover, Applied Optics, February 1986, Vol. 25(3), pp. 359 - 368), but is not useful for protecting the back of the eye from radiation in the range of wavelengths 320 - 400 nm.

[0004] Contact lens standards define the upper side of the ultraviolet wavelength at 380 nm. The current Class I UV absorption standard defined by the American Optometric Association requires that >99% of the radiation in the range of 280 - 315 nm (UV B) and >90% of the radiation in the range of 316 - 380 nm (UV A) be absorbed by the contact lens. This standard effectively addresses the protection of the cornea (<1% UV B transmittance), but little attention has been paid to the lower energy ultraviolet rays (>380 and <400 nm) (Ham, W.T, Mueller, H.A., Sliney, D.H. Nature 1976;260(5547):153 - 5) or high - energy visible radiation related to retinal damage.

[0005] High - energy visible (HEV) radiation (e.g., 400 - 450 nm) may cause visual discomfort or disrupt the circadian rhythm. For example, computer and electronic device screens, flat - screen TVs, energy - efficient lights, and LED lights are known to emit HEV light. Long - term exposure to such HEV light sources may cause eye fatigue. In addition, viewing devices that emit HEV light at night is assumed to disrupt the natural circadian rhythm, leading to, for example, sleep deprivation.

[0006] Reducing the amount of HEV light absorbed by the eye is a desirable goal in the field of ophthalmology. However, chromophores that absorb HEV light or are desirable for use as HEV light filters in contact lenses are sometimes plagued by sensitivity to ambient light, resulting in their photodegradation. This photosensitivity can manifest itself in many undesirable ways, including yellowing or discoloration of the lens and / or a time - dependent deterioration of the ability of the originally selected chromophore to absorb the HEV wavelength. Thus, if the chromophore in the lens is photosensitive, the shelf life, aesthetic appeal, and performance of the contact lens can all be negatively affected. SUMMARY OF THE INVENTION

Problems to be Solved by the Invention

[0007] There is a need for materials that provide target absorption at undesirable wavelengths of high - energy radiation and can be processed into functional products. When such materials are photosensitive, techniques for protecting them from photodegradation are also desirable.

Means for Solving the Problems

[0008] The present invention relates to a contact lens system comprising a contact lens containing a photosensitive chromophore and a package for protecting the photosensitive chromophore from photodegradation.

[0009] The package used in the contact lens system of the present invention at least partially blocks the wavelengths of light that can photodegrade the chromophore by other means. Thus, the package can stabilize the photosensitive chromophore against photodegradation.

[0010] Advantageously, the package according to the present invention can transmit light of other wavelengths while protecting the chromophore, thus enabling the contents of the package to be visible, for example, to the naked eye and / or with test equipment used during the lens manufacturing process. A further advantage of the present invention is that the level of protection provided by the package can be adjusted by varying the amount of light it blocks. Thereby, the manufacturer can specifically control the shelf life of its product. Products that do not require a long shelf life can be housed in a package that only partially blocks the light that would otherwise decompose the chromophore. On the other hand, when a longer shelf life is desired, a package that provides a greater blockage can be used.

[0011] Accordingly, more specifically, the present invention provides a contact lens system. The contact lens system includes a contact lens containing a photosensitive chromophore, wherein the photosensitive chromophore has at least one active wavelength in the range of 250 to 400 nanometers (defined hereinafter) and at least one active wavelength in the range of 400 to 450 nanometers, and a package surrounding the contact lens, the package having a light transmittance of 99 percent or less at each active wavelength. BRIEF DESCRIPTION OF THE DRAWINGS

[0012]

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Figure 7B

[0013] It should be understood that the present invention is not limited to the details of the structures or process steps described in the following description. The present invention is capable of other embodiments and can be practiced or implemented in various ways using the teachings set forth herein.

[0014] The following definitions are provided with respect to the terms used in this disclosure.

[0015] Unless otherwise defined, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill 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 hereby incorporated by reference into this specification.

[0016] As used herein, the term “(meth)” means an optional methyl substitution. Thus, terms such as “(meth)acrylate” mean both methacrylate and acrylate.

[0017] It should be understood that wherever a chemical structure is described, the disclosed options for substituents in the structure may be combined in any combination. Thus, if a structure contains substituents R * and R ** and each of these contains a list of three possible groups, nine combinations are disclosed. The same applies to combinations of properties.

[0018] General formula *** n ​When subscripts such as "n" are used to indicate the number of repeating units in the chemical formula of a polymer, the formula should be interpreted as representing the number-average molecular weight of the polymer.

[0019] The term "individual" includes humans and vertebrates.

[0020] The term "ocular surface" includes the cornea, conjunctiva, lacrimal gland, accessory lacrimal gland, nasolacrimal duct, and the surface and glandular epithelium of the Meibomian glands, as well as their tips and basal matrices, dots, and adjacent or related structures including the eyelids that are functionally linked as a system by both innervation and the endocrine and immune systems.

[0021] 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 absorption, reduction of visible light or glare, or any combination thereof. A contact lens can be made of any suitable material known in the art and can be a soft lens, a hard lens, or a hybrid lens containing at least two distinct parts having different physical, mechanical, or optical properties such as modulus of elasticity, water content, light transmission, or combinations thereof.

[0022] The contact lens of the present invention can be made of a silicone hydrogel or a conventional hydrogel. A silicone hydrogel typically contains at least one hydrophilic monomer and at least one silicone-containing component that are covalently bonded to each other within the cured device.

[0023] "Target macromolecule" means a macromolecule synthesized from a reactive monomer mixture containing monomers, macromers, prepolymers, crosslinking agents, initiators, additives, diluents, and the like.

[0024] The term "polymerizable compound" means a compound containing one or more polymerizable groups. This term includes, for example, monomers, macromers, oligomers, prepolymers, crosslinking agents, and the like.

[0025] A "polymerizable group" is a group capable of undergoing chain-growth polymerization, such as a carbon-carbon double bond that can polymerize when subjected to free radical and / or cationic polymerization, for example, under free radical polymerization initiation conditions. Non-limiting examples of free radical polymerizable groups include (meth)acrylate, styrene, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, and other vinyl groups. Preferably, the free radical polymerizable group includes (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, and styryl functional groups, and any mixture of the foregoing. More preferably, the free radical polymerizable group includes (meth)acrylate, (meth)acrylamide, and mixtures thereof. The polymerizable group may be unsubstituted or substituted. For example, the nitrogen atom in (meth)acrylamide may be bonded to hydrogen, or hydrogen may be substituted with alkyl or cycloalkyl (which may itself be further substituted).

[0026] Any type of free radical polymerization, including but not limited to bulk, solution, suspension, and emulsion, and any of the controlled radical polymerization methods such as stable free radical polymerization, nitrogen oxide-mediated living polymerization, atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization, organotellurium-mediated living radical polymerization, etc. can be used.

[0027] A "monomer" is a monofunctional molecule that can undergo chain-growth polymerization, particularly free-radical polymerization, thereby creating repeating units within the chemical structure of a target macromolecule. Some monomers have difunctional impurities that can act as crosslinking agents. A "hydrophilic monomer" is also a monomer that, when mixed with deionized water at a concentration of 5 weight percent at 25 °C, results in a clear, single-phase solution. A "hydrophilic component" is a monomer, macromer, prepolymer, initiator, crosslinking agent, additive, or polymer that, when mixed with deionized water at a concentration of 5 weight percent at 25 °C, results in a clear, single-phase solution. A "hydrophobic component" is a monomer, macromer, prepolymer, initiator, crosslinking agent, additive, or polymer that is slightly soluble or insoluble in deionized water at 25 °C.

[0028] A "macromolecule" is an organic compound having a number-average molecular weight greater than 1500, which may be reactive or non-reactive.

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

[0030] Examples of silicone-containing components useful in the present invention can be found in U.S. Patent Nos. 3,808,178; 4,120,570; 4,136,250; 4,153,641; 4,740,533; 5,034,461; 5,070,215; 5,244,981; 5,314,960; 5,331,067; 5,371,147; 5,760,100; 5,849,811; 5,962,548; 5,965,631; 5,998,498; 6,367,929; 6,822,016; 6,943,203; 6,951,894; 7,052,131; 7,247,692; 7,396,890; 7,461,937; 7,468,398; 7,538,146; 7,553,880; 7,572,841; 7,666,921; 7,691,916; 7,786,185; 7,825,170; 7,915,323; 7,994,356; 8,022,158; 8,163,206; 8,273,802; 8,399,538; 8,415,404; 8,420,711; 8,450,387; 8,487,058; 8,568,626; 8,937,110; 8,937,111; 8,940,812; 8,980,972; 9,056,878; 9,125,808; 9,140,825; 9,156,934; 9,170,349; 9,217,813; 9,244,196; 9,244,197; 9,260,544; 9,297,928; 9,297,929; and European Patent No. 080539. These patents are hereby incorporated by reference in their entirety.

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

[0032] A "repeating unit" is the smallest group of atoms in a polymer that corresponds to the polymerization of a specific monomer or macromer.

[0033] An "initiator" is a molecule that can decompose into radicals that can subsequently react with monomers to initiate a free radical polymerization reaction. Thermal initiators decompose at a specific rate depending on 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 benzyl, benzoin, acetophenone, benzophenone, camphorquinone, and mixtures thereof, as well as various monoacyl and bisacylphosphine oxides, and combinations thereof.

[0034] A "crosslinking agent" is a bifunctional or polyfunctional monomer or macromer that can undergo free radical polymerization at two or more positions on the molecule, thereby creating branch points and a polymer network. General examples are ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, methylene bisacrylamide, triallyl cyanurate, and the like.

[0035] A "prepolymer" is a reaction product of monomers containing remaining polymerizable groups that can further react to form a polymer.

[0036] A "polymer network" is a cross-linked polymer that can swell but is insoluble in a solvent. A "hydrogel" is a polymer network that swells in water or an aqueous solution while typically absorbing at least 10 weight percent of 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.

[0037] A "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 a reactive mixture containing hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate ("HEMA"), N-vinylpyrrolidone ("NVP"), N,N-dimethylacrylamide ("DMA"), or vinyl acetate. U.S. Patent Nos. 4,436,887, 4,495,313, 4,889,664, 5,006,622, 5,039,459, 5,236,969, 5,270,418, 5,298,533, 5,824,719, 6,420,453, 6,423,761, 6,767,979, 7,934,830, 8,138,290, and 8,389,597 disclose the formation of conventional hydrogels. Conventional hydrogels may also be formed from polyvinyl alcohol. Conventional hydrogel lenses may include a coating, which may be made of the same or a different material as the substrate. Conventional hydrogels may include additives such as polyvinylpyrrolidone and comonomers including phosphorylcholine, methacrylic acid, etc. Commercially available conventional hydrogels include, but are not limited to, etafilcon, genfilcon, hilafilcon, lenefilcon, nesofilcon, omafilcon, polymacon, and vifilcon (including all variations thereof).

[0038] "Silicone hydrogel" refers to a polymer network made from at least one hydrophilic component and at least one silicone-containing component. Examples of suitable families of hydrophilic components that may be present in the reactive mixture include (meth)acrylates, styrene, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl carbamates, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof. Silicone-containing components are well-known and widely described in the patent literature. For example, the silicone-containing component may include at least one polymerizable group (e.g., (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, vinyl group, or a mixture of the foregoing), at least one siloxane group, and one or more linking groups (which may be chemical bonds) connecting the polymerizable group to the siloxane group. The silicone-containing component may contain, for example, 1 to 220 siloxane repeat units. The silicone-containing component may also contain at least one fluorine atom. The silicone hydrogel lens may include a coating, and the coating may be the same or a different material from the substrate.

[0039] Examples of silicone hydrogels include, in addition to acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon (including all variations thereof), U.S. Patent Nos. 4,659,782, 4,659,783, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,998,498, 6,087,415, 5,760,100, 5,776,999, 5,789,461, 5,849,811, 5,965,631, 6,367,929, 6,822,016, 6,867,245, 6,943,203, 7,247,692, 7,249,848, 7,553,880, 7,666,921, 7,786,185, 7,956,131, 8,022,158, 8,273,802, 8,399,538, 8,470,906, 8,450,387, 8,487,058, 8,507,577, 8,637,621, 8,703,891, 8,937,110, 8,937,111, 8,940,812, 9,056,878, 9,057,821, 9,125,808, 9,140,825, 9156,934, 9,170,349, 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,Silicone hydrogels prepared as in U.S. Pat. No. 929, and International Publications Nos. WO 03 / 22321, WO 2008 / 061992, and U.S. Patent Application Publication No. 2010 / 0048847 are included. These patents are hereby incorporated by reference in their entirety.,

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

[0041] "Reactive component" is a polymerizable compound (such as monomers, macromers, oligomers, prepolymers, and crosslinking agents, etc.) in a reactive mixture (defined below), and similarly, any other component in the reactive mixture that is intended to substantially remain within the resulting polymer network after polymerization and completion of all work-up steps (such as extraction steps) and packaging steps. Reactive components can be retained within the polymer network by covalent bonds, hydrogen bonds, electrostatic interactions, formation of interpenetrating polymer networks, or any other means. Components intended to be released from the polymer network during use are still considered "reactive components". For example, pharmaceutical or nutritional supplement components in a contact lens intended to be released during wear are considered "reactive components". Components intended to be removed from the polymer network during the manufacturing process (such as by extraction), such as diluents, are not "reactive components".

[0042] The terms "reactive mixture" and "reactive monomer mixture" refer to a mixture of components that, when mixed together and subjected to polymerization conditions, result in the formation of a polymer network (such as a conventional or silicone hydrogel) and contact lenses made therefrom. The reactive mixture may contain reactive components such as monomers, macromers, prepolymers, crosslinking agents, and initiators, wetting agents, polymers, light-absorbing compounds such as dyes, UV absorbers and / or HEV absorbers, pigments, photochromic compounds, pharmaceutical compounds, and / or additive compounds such as nutritional supplements (any of which may be polymerizable or non-polymerizable but capable of being retained within the resulting contact lens), and may also contain other components intended to be removed from the device prior to use, such as diluents. It is understood that a wide range of additives can be added depending on the contact lens to be manufactured and the intended use. The concentration of the components of the reactive mixture is thus expressed as a weight percentage of all components in the reactive mixture, excluding diluents. When diluents are used, their concentration is expressed as a weight percentage based on the amount of all components (including diluents) in the reactive mixture.

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

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

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

[0046] "Alkyl" refers to an optionally substituted straight-chain or branched-chain alkyl group containing the specified number of carbon atoms. When the number is not specified, alkyl (including any optional substituents on the alkyl) may contain 1 to 16 carbon atoms. Preferably, the alkyl group contains 1 to 10 carbon atoms, or 1 to 8 carbon atoms, or 1 to 6 carbon atoms, or 1 to 4 carbon atoms. Examples of alkyl include methyl, ethyl, propyl, isopropyl, butyl, iso-, sec- and tert-butyl, pentyl, hexyl, heptyl, 3-ethylbutyl, etc. Examples of substituents on the alkyl include one, two, or three groups independently selected from hydroxy, amino, amide, 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. The 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" means a divalent haloalkyl group such as -CH2CF2-.

[0048] "Cycloalkyl" refers to an optionally substituted cyclic hydrocarbon containing a specified number of ring carbon atoms. When no number is indicated, cycloalkyl may contain 3 to 12 ring carbon atoms. Preferably, it is a C3-C8 cycloalkyl group, C3-C7 cycloalkyl, more preferably C4-C7 cycloalkyl, and even more preferably 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, amide, oxa, carbonyl, alkoxy, thioalkyl, amide, carbamate, carbonate, halo, phenyl, benzyl, and combinations thereof. "Cycloalkylene" means 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 substituted with a heteroatom selected from nitrogen, oxygen, and sulfur. The heterocycloalkyl ring is optionally fused to or otherwise bonded to another heterocycloalkyl ring and / or a non-aromatic hydrocarbon ring and / or a phenyl ring. Preferred heterocycloalkyl groups have 5 to 7 members. More preferred heterocycloalkyl groups have 5 or 6 members. Heterocycloalkylene means 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 the indicated number of ring carbon atoms. When no number is indicated, aryl may contain 6 to 14 ring carbon atoms. The aromatic ring may optionally be fused to another aromatic hydrocarbon ring or non-aromatic hydrocarbon ring, or otherwise bonded. Examples of aryl groups include phenyl, naphthyl, and biphenyl. A preferred example of an aryl group is phenyl. Examples of substituents on aryl include one, two, or three groups independently selected from alkyl, hydroxy, amino, amide, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, thioalkyl, carbamate, carbonate, halo, phenyl, benzyl, and combinations thereof. "Arylene" means a divalent aryl group, such as 1,2-phenylene, 1,3-phenylene, or 1,4-phenylene.

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

[0052] "Alkoxy" refers to an alkyl group bonded to the parent molecular moiety via an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy, and isopropoxy. "Thioalkyl" means an alkyl group bonded to the parent molecule via a sulfur bridge. Examples of thioalkyl groups include, for example, methylthio, ethylthio, n-propylthio, and isopropylthio. "Aryloxy" refers to an aryl group bonded to the parent molecular moiety via an oxygen bridge. An example is phenoxy. "Cyclic alkoxy" means a cycloalkyl group bonded to the parent moiety via an oxygen bridge.

[0053] "Alkylamine" refers to an alkyl group bonded to the parent molecular moiety via an -NH bridge. Alkyleneamine means a divalent alkylamine group such as -CH2CH2NH-.

[0054] "Siloxanyl" refers to a structure having at least one Si-O-Si bond. Thus, for example, a siloxanyl group means a group having at least one Si-O-Si group (i.e., a siloxane group), and a siloxanyl compound means a compound having at least one Si-O-Si group. "Siloxanyl" encompasses monomers (e.g., Si-O-Si) as well as oligomer / polymer structures (e.g., -[Si-O] n -, where n is 2 or greater than or equal to 3). Each silicon atom in the siloxanyl group is independently substituted with an R A group (where R A is as defined in options (b) to (i) of formula A).

[0055] "Silyl" refers to a structure of the formula R3Si-, and "siloxy" refers to a structure of the formula R3Si-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 of the general formula -(alkylene - O) p - or -(O - alkylene) p - where alkylene is as defined above, and p is 1 to 200, or 1 to 100, or 1 to 50, or 1 to 25, or 1 to 20, or 1 to 10. Each alkylene is independently optionally substituted with one or more groups independently selected from hydroxyl, halo (e.g., fluoro), amino, amide, 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 the molecule, the terminal of the alkyleneoxy may be, for example, hydroxy or alkoxy (e.g., HO - [CH2CH2O] 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 CH2 groups are substituted with oxygen atoms such as -CH2CH2OCH(CH3)CH2-. "Thiaalkylene" refers to an alkylene group as defined above in which one or more non - adjacent CH2 groups are substituted with sulfur atoms such as -CH2CH2SCH(CH3)CH2-.

[0058] The term "linking group" refers to the moiety that links the polymerizable group to the parent molecule. The 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 and further under the conditions of processing and storage of the final product. For example, the linking group may be a bond, or may include one or more of alkylene, haloalkylene, amide, amine, alkyleneamine, carbamate, ester (-CO2-), arylene, heteroarylene, cycloalkylene, heterocycloalkylene, alkyleneoxy, oxaalkylene, thiaalkylene, haloalkyleneoxy (alkyleneoxy substituted with one or more halo groups, e.g., -OCF2-, -OCF2CF2-, -OCF2CH2-), siloxanyl, alkylenesiloxanyl, or combinations thereof. The linking group may optionally be substituted with one or more substituents. Suitable substituents may be independently selected from alkyl, halo (e.g., fluoro), hydroxyl, HO-alkyleneoxy, MeO-alkyleneoxy, siloxanyl, siloxy, siloxy-alkyleneoxy-, siloxy-alkylene-alkyleneoxy- (more than one alkyleneoxy group may 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 may also be substituted with a polymerizable group such as (meth)acrylate (in addition to the polymerizable group to which the linking group is attached).

[0059] Preferred linking groups include C1-C8 alkylene (preferably C2-C6 alkylene) and C1-C8 oxaalkylene (preferably C2-C6 oxaalkylene), each 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 consists of a combination of the above-described moieties (e.g., alkylene and cycloalkylene), the moieties may be present in any order. For example, in the following formula A, when L is shown to be -alkylene-cycloalkylene-, Rg-L may be either Rg-alkylene-cycloalkylene- or Rg-cycloalkylene-alkylene-. Nevertheless, the listed order 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 A, when L is shown to be alkylene-cycloalkylene, Rg-L is preferably Rg-alkylene-cycloalkylene-.

[0061] The term "light-absorbing compound" means a chemical substance that absorbs light within the visible spectrum (e.g., in the range of 380 to 780 nm). "High-energy radiation absorber", "UV / HEV absorber" or "high-energy light-absorbing compound" is a chemical substance that absorbs ultraviolet rays, high-energy visible light, or both at various wavelengths. The ability of a material to absorb light at a specific wavelength can be determined by measuring its UV / Vis transmission spectrum or absorption spectrum.

[0062] The terms "high-energy visible light absorption", "HEV light absorption", or similar terms refer to contact lenses that limit the transmission of one or more wavelengths of high-energy visible light through the lens, e.g., in the range of 400 to 450 nm. The ability of a material to absorb light at a specific wavelength can be determined by measuring its UV / Vis transmission spectrum. A material that does not exhibit absorption at a specific wavelength exhibits a transmittance of substantially 100 percent at that wavelength. Conversely, a material that completely absorbs at a specific wavelength exhibits a transmittance of substantially 0% at that wavelength. As used herein, when the amount of transmission of a contact lens is expressed as a percentage over a specific wavelength range, it should be understood that the contact lens exhibits that transmission percentage at all wavelengths over that range. On the other hand, a reference to "average transmittance" can be calculated as the average of the transmittance percentages at 1 nm intervals over the specified range.

[0063] The term "photosensitive" means that a contact lens containing a chromophore (preferably an HEV light-absorbing chromophore) exhibits photodegradation as exemplified by a change in average transmittance of at least two percent over a wavelength range of 400 to 450 nm. Various exposure methods can be used. A preferred exposure method is that described by the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Guidelines, Q1B Photostability Testing of New Drug Substances and Products (published November 1996). Preferably, the exposure is 1.5192×10 6 lux hours of estimated irradiance exposure (168.8 hours of exposure time) and 259.4 watt-hours / m 2 of estimated ultraviolet irradiation exposure (16.2 hours of exposure time) using an Option 2 light source, preferably in a photostability chamber controlled at 25°C / Amb RH, and is carried out under the ICH photostability guidelines. After exposure, the UV / Vis spectrum of the sample is collected and compared to the spectrum of an unexposed sample. By way of example, a contact lens containing a photosensitive chromophore according to the present invention, after exposure under the ICH guideline Q1B conditions (which may also be abbreviated herein as "ICH guideline Q1B" or "Q1B conditions") as described above, exhibits a change in their average transmittance of at least two percent, or at least five percent, or at least seven percent, or at least ten percent over a wavelength range of 400 to 450 nm. Such a change can be calculated as the absolute value of the difference between the average transmittance with exposure (over the wavelength range shown) and the average transmittance without exposure. The photosensitive chromophores according to the present invention are preferably not photochromic (photochromic materials generally darken reversibly when exposed to specific intensities and wavelengths of light).

[0064] The terms "photo-stabilized" and "photo-stabilizing", or similar expressions, mean that a contact lens containing a photosensitive chromophore as described herein is protected against photodegradation such that, after exposure under the ICH guideline Q1B conditions as described above, the change in the average transmittance exhibited over the wavelength range of 400 - 450 nm is less than that exhibited in the absence of protection.

[0065] The term "active wavelength" means a wavelength in the UV / Vis spectrum of a material at which the percent transmittance is 85 percent or less.

[0066] The term "primary package" refers to a package that directly houses a contact lens for use by a lens wearer. The primary package may be, for example, a vial, or a blister package including a shell or base portion sealed with a laminated foil or cover. Typically, the primary package can contain one contact lens in a small amount of packaging solution.

[0067] The "secondary package" is typically the outer package that houses the primary package. The secondary package may be, for example, a carton. The secondary package differs from the primary package in that the secondary package does not come into direct contact with the contact lens packaging solution. The secondary package can typically contain a plurality of primary packages, although a secondary package containing one primary package is also contemplated.

[0068] Unless otherwise specified, ratios, percentages, parts, etc. are by weight.

[0069] Unless otherwise specified, a numerical range such as, for example, "2 - 10 (from 2 to 10)" or "2 - 10 (between 2 and 10)" includes the numbers defining the range (e.g., 2 and 10).

[0070] As described above, the present invention provides a contact lens containing a photosensitive chromophore, the photosensitive chromophore having at least one active wavelength in the range of 250 to 400 nanometers and at least one active wavelength in the range of 400 to 450 nanometers, a contact lens, and a package surrounding the contact lens, the package having a transmittance of 99 percent or less at each active wavelength, a contact lens system.

[0071] Any type of contact lens, including soft contact lenses, hard contact lenses, rigid gas permeable (RGP) contact lenses, and hybrid contact lenses, can be used in the contact lens system of the present invention. Preferably, the contact lens is a soft hydrogel contact lens (either a conventional hydrogel or a silicone hydrogel).

[0072] The contact lens contains a photosensitive chromophore having at least one active wavelength in the range of 250 to 400 nanometers (as defined above) and at least one active wavelength in the range of 400 to 450 nm. Preferably, at least one active wavelength in the range of 400 to 450 nm includes at least one active wavelength in the range of 400 to 425 nm, or 400 to 420 nm, or 400 to 415 nm, or 400 to 410 nm. More preferably, at least one active wavelength in the range of 400 to 450 nm is 400 to 410 nm. Even more preferably, the transmittance at all wavelengths over the range of 400 to 410 nm is 50 percent or less, or 30 percent or less, or 20 percent or less, or 18 percent or less, or 15 percent or less.

[0073] Contact lenses containing a photosensitive chromophore can generally be prepared by free radical polymerization of a reactive mixture containing one or more monomers (also referred to herein as device-forming monomers or hydrogel-forming monomers) suitable for making the contact lens, and optional components. The reactive mixture can contain the photosensitive chromophore either as a polymerizable monomer, thus effecting its covalent incorporation into the lens, or the photosensitive chromophore can be present as a non-polymerizable additive. Other methods of incorporating a photosensitive chromophore into the lens can also be used, including, for example, applying the chromophore as part of a coating on the lens, where the chromophore can be either polymerizable or non-polymerizable.

[0074] Preferably, the photosensitive chromophore is introduced as a polymerizable monomer into the reactive mixture. Such polymerizable chromophores typically contain polymerizable substituents that enable the monomer to be covalently incorporated within the contact lens. Any photosensitive chromophore that meets the photosensitivity and active wavelength requirements of the present invention can be used. Exemplary compounds include alkoxyaniline derivatives containing polymerizable groups, such as those described in co-pending U.S. Patent Application No. 16 / 398,722, filed April 30, 2019, which is incorporated herein by reference. A specific example of such a compound is 2-(4-acetyl-3-amino-2,6-dimethoxyphenoxy)ethyl methacrylate. Further exemplary photosensitive chromophores include, for example, tetrahydronaphthalenyl derivatives, such as those described in U.S. Patent Application No. 16 / 548,204, filed August 22, 2019, which is incorporated herein by reference. A specific example of such a compound is 2-((1-amino-8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)oxy)ethyl methacrylate.

[0075] As described above, the reactive mixture for forming the contact lens contains one or more device-forming monomers (and optionally a photosensitive chromophore if incorporated at this stage). Examples of suitable devices for forming monomers for soft contact lenses include one or more of a hydrophilic component, a hydrophobic component, and / or a silicone-containing component. The reactive mixture may contain other materials including, but not limited to, wetting agents such as polyamides, crosslinking agents, UV-absorbing compounds, and further components such as diluents and initiators.

[0076] Examples of suitable families of hydrophilic monomers that may be present in the reactive mixture include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl carbamates, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof.

[0077] Non-limiting examples of hydrophilic (meth)acrylate and (meth)acrylamide monomers include acrylamide, N-isopropylacrylamide, N,N-dimethylaminopropyl (meth)acrylamide, N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2,3-dihydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, N-(2-hydroxyethyl) (meth)acrylamide, N,N-bis(2-hydroxyethyl) (meth)acrylamide, N-(2-hydroxypropyl) (meth)acrylamide, N,N-bis(2-hydroxypropyl) (meth)acrylamide, N-(3-hydroxypropyl) (meth)acrylamide, N-(2-hydroxybutyl) (meth)acrylamide, N-(3-hydroxybutyl) (meth)acrylamide, N-(4-hydroxybutyl) (meth)acrylamide, 2-aminoethyl (meth)acrylate, 3-aminopropyl (meth)acrylate, 2-aminopropyl (meth)acrylate, N-2-aminoethyl (meth)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.

[0078] The hydrophilic monomer may also be ionic, such as 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-phosphaundec-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).

[0079] Non-limiting examples of hydrophilic N-vinyl lactam monomers 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-2-methyl propionamide, N-vinyl-N,N'-dimethyl urea, 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-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, N-vinyl isopropylamide, N-vinyl caprolactam, N-vinyl imidazole, and mixtures thereof.

[0080] Non-limiting examples of hydrophilic O-vinyl carbamate monomers 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 monomers 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.

[0081] Examples of other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, and 2-ethyloxazoline.

[0082] The hydrophilic monomer may also be a macromer or prepolymer of linear or branched poly(ethylene glycol), poly(propylene glycol), or a statistical random or block copolymer of ethylene oxide and propylene oxide having a polymerizable moiety such as (meth)acrylate, styrene, vinyl ether, (meth)acrylamide, N-vinylamide, etc. These polyether macromers have one polymerizable group, and the prepolymers may have two or more polymerizable groups.

[0083] Preferred hydrophilic monomers of the present invention are DMA, NVP, HEMA, VMA, NVA, and mixtures thereof. A preferred hydrophilic monomer is a mixture of DMA and HEMA. Other suitable hydrophilic monomers will be apparent to those skilled in the art.

[0084] Generally, there is no particular limitation on the amount of hydrophilic monomer present in the reactive monomer mixture. The amount of hydrophilic monomer can be selected based on the desired properties of the resulting hydrogel, including water content, transparency, wettability, protein uptake, etc. Wettability can be measured by the contact angle, and the desired contact angle is less than about 100°, less than about 80°, and less than about 60°. The hydrophilic monomer can be present in an amount, for example, in the range of about 0.1 to about 100 weight percent, or in the range of about 1 to about 80 weight percent, or in the range of about 5 to about 65 weight percent, or in the range of about 40 to about 60 weight percent, or in the range of about 55 to about 60 weight percent, based on the total weight of the reactive components in the reactive monomer mixture.

[0085] The silicone-containing components that may be present in the reactive mixture typically include one or more polymerizable compounds, each of which independently contains at least one polymerizable group, at least one siloxane group, and one or more linking groups connecting the polymerizable group to the siloxane group. The silicone-containing component may contain, for example, 1 to 220 siloxane repeating units such as the groups defined below. The silicone-containing component may also contain at least one fluorine atom.

[0086] The silicone-containing component may include one or more polymerizable groups as defined above, one or more optional repeating siloxane units, and one or more linking groups connecting the polymerizable group to the siloxane unit. The silicone-containing component may independently include one or more polymerizable groups that are (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, vinyl group, or a mixture thereof, one or more optional repeating siloxane units, and one or more linking groups connecting the polymerizable group to the siloxane unit.

[0087] The silicone-containing component may independently include one or more polymerizable groups that are (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, styryl, or a mixture of the foregoing, one or more optional repeating siloxane units, and one or more linking groups connecting the polymerizable group to the siloxane unit.

[0088] The silicone-containing component may independently include one or more polymerizable groups that are (meth)acrylate, (meth)acrylamide, or a mixture of the foregoing, one or more optional repeating siloxane units, and one or more linking groups connecting the polymerizable group to the siloxane unit.

[0089] The silicone-containing component may include one or more polymerizable compounds of Formula A.

[0090] [Chemical formula] In the formula, at least one R A is a group of the formula R g -L-, where R g is a polymerizable group and L is a linking group, and the remaining Rs A are each independently (a) R g -L-, (b) C1-C 16 alkyl optionally substituted with one or more hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof, (c) C3-C 12 cycloalkyl optionally substituted with one or more alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof, (d) C6-C 14 aryl group optionally substituted with one or more alkyl, hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof, (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 containing 1 to 100 siloxane repeating units optionally substituted with alkyl, alkoxy, hydroxy, amino, oxa, carboxy, alkylcarboxy, alkoxy, amido, carbamate, halo, or combinations thereof, n is from 0 to 500, or from 0 to 200, or from 0 to 100, or from 0 to 20, and when n is other than 0, it is understood that n has a distribution in a mode equivalent to the displayed value. When n is 2 or more, the SiO units may carry the same or different R A substituents, and when different R A substituents are present, the n groups may be in a random or block configuration.

[0091] In formula A, the three Rs A may each contain a polymerizable group, or alternatively two Rs A may each contain a polymerizable group, or alternatively one R A may contain a polymerizable group.

[0092] Examples of silicone-containing components suitable for use in the present invention include, but are not limited to, the compounds listed in Table A. When the compounds in Table A contain polysiloxane groups, the number of SiO repeating units in such compounds is preferably 3 to 100, more preferably 3 to 40, or even more preferably 3 to 20, unless otherwise specified.

[0093]

Table 1-1

[0094]

Table 1-2

[0095] Further non-limiting examples of suitable silicone-containing components are listed in Table B. Unless otherwise specified, applicable j2 is preferably 1 to 100, more preferably 3 to 40, or even more preferably 3 to 15. In compounds containing j1 or j2, the sum of j1 and j2 is preferably 2 to 100, more preferably 3 to 40, or even more preferably 3 to 15.

[0096]

Table 2-1

[0097]

Table 2-2

[0098] Mixtures of silicone-containing components may be used. By way of example, suitable mixtures include mixtures of mono-(2-hydroxy-3-methacryloxypropyloxy)-propyl-terminated mono-n-butyl-terminated polydimethylsiloxane (OH-MPDMS) having different molecular weights, such as mixtures of OH-MPDMS containing 4 and 15 SiO repeating units; mixtures of OH-MPDMS having different molecular weights (e.g., containing 4 and 15 repeating SiO repeating units) and silicone-based crosslinking agents such as bis-3-acryloxy-2-hydroxypropyl-oxypropylpolydimethylsiloxane (ac-PDMS); mixtures of 2-hydroxy-3-[3-methyl-3,3-bis(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA) and mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxane (mPDMS) such as mPDMS 1000, but are not limited thereto.

[0099] The silicone-containing component used in the present invention may have an average molecular weight of about 400 to about 4000 Daltons.

[0100] The silicone-containing component may be present in an amount of up to about 95% by weight, or about 10 to about 80% by weight, or about 20 to about 70% by weight, based on all the reactive components of the reactive mixture (excluding diluents).

[0101] The reactive mixture may include at least one polyamide as a wetting agent. As used herein, the term "polyamide" refers to polymers and copolymers containing repeating units containing amide groups. The polyamide may include cyclic amide groups, acyclic amide groups, and combinations thereof, and may be any polyamide known to those skilled in the art. The acyclic polyamide includes pendant acyclic amide groups and is capable of associating with hydroxyl groups. The cyclic polyamide includes cyclic amide groups and is capable of associating with hydroxyl groups.

[0102] Examples of suitable acyclic polyamides include polymers and copolymers containing repeating units of formulas G1 and G2,

[0103]

Chemical formula

[0104] R 40 and R 41 may independently be selected from H, a substituted or unsubstituted C1-C2 alkyl group. X may be a direct bond, and R 40 and R 41 may independently be selected from H, a substituted or unsubstituted C1-C2 alkyl group. R 42 and R 43 may independently be selected from H, a substituted or unsubstituted C1-C2 alkyl group, methyl, ethoxy, hydroxyethyl, and hydroxymethyl.

[0105] The acyclic polyamide of the present invention may contain most of the repeating units of formula LV or formula LVI, or the acyclic polyamide may contain at least about 70 mole percent, and at least 80 mole percent, etc., of at least 50 mole percent of the repeating units of formula G or formula G1. Specific examples of the repeating units of formula G and formula G1 include 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 repeating units derived from the acyclic amides of formula G2 and G3.

[0106]

Chemical formula

[0107] Examples of suitable cyclic amides that can be used to form cyclic polyamides include α-lactam, β-lactam, γ-lactam, δ-lactam, and ε-lactam. Examples of suitable cyclic polyamides include polymers and copolymers containing repeating units of formula G4

[0108] [Chemical formula] wherein R 45 is a hydrogen atom or a methyl group, f is a number from 1 to 10, X is a direct bond, -(CO)-, or -(CONHR 46 )-, where 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 from 2 to 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).

[0109] The cyclic polyamide of the present invention may contain 50 mole percent or more of the repeating units of formula G4, or the cyclic polyamide may contain at least 50 mole percent of the repeating units of formula G4, such as at least 70 mole percent and at least 80 mole percent.

[0110] The polyamide may also be a copolymer containing repeating units of both cyclic amides and acyclic amides. The additional repeating units may be formed from monomers selected from hydroxyalkyl (meth)acrylates, alkyl (meth)acrylates, other hydrophilic monomers, and siloxane-substituted (meth)acrylates. Any of the monomers listed as suitable hydrophilic monomers may be used as comonomers to form the additional repeating units. Specific examples of additional monomers that may be used to form the polyamide include 2-hydroxyethyl (meth)acrylate, vinyl acetate, acrylonitrile, hydroxypropyl (meth)acrylate, methyl (meth)acrylate, and hydroxybutyl (meth)acrylate, dihydroxypropyl (meth)acrylate, polyethylene glycol mono(meth)acrylate, etc., as well as mixtures thereof. Ionic monomers may also be included.Examples of ionic monomers include (meth)acrylic acid, N-[(vinyloxy)carbonyl]-β-alanine (VINAL, CAS#148969-96-4), 3-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, 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 80293-60-3), 3,5-dioxa-8-aza-4-phosphaundec-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-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS), (methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

[0111] The reactive monomer mixture may include both acyclic polyamides and cyclic polyamides or copolymers thereof. The acyclic polyamide can be any of the acyclic polyamides or copolymers thereof described herein, and the cyclic polyamide can be any of the cyclic polyamides or copolymers thereof described herein. The polyamide can be selected from the group consisting of polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl (meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof. The polyamide can be a mixture of PVP (e.g., PVP K90) and PVMA (e.g., having an M w of about 570KDa).

[0112] The total amount of all polyamides in the reactive mixture can be in the range of 1 weight percent to about 35 weight percent, such as in the range of 1 weight percent to about 15 weight percent, in the range of about 5 weight percent to about 15 weight percent, etc., based on the total weight of the reactive components of the reactive monomer mixture in all cases.

[0113] Without being bound by theory, when used with a silicone hydrogel, the polyamide functions as an internal wetting agent. The polyamide of the present invention may be non-polymerizable, in which case it is incorporated into the silicone hydrogel as a semi-interpenetrating network. The polyamide is encapsulated or physically retained within the silicone hydrogel. Alternatively, the polyamide of the present invention can be polymerizable, for example, as a polyamide macromer or prepolymer, in which case it is covalently incorporated into the silicone hydrogel. Mixtures of polymerizable and non-polymerizable polyamides can also be used.

[0114] When the polyamide is incorporated into the reactive monomer mixture, the polyamide can 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, or from about 300,000 Daltons to about 1,800,000 Daltons. High molecular weight polyamides can be used if they are compatible with the reactive monomer mixture.

[0115] Generally, it is desirable to add one or more crosslinking agents, also generally referred to as crosslinking monomers, polyfunctional macromers, and prepolymers, to the reactive mixture. The crosslinking agent may be selected from difunctional crosslinking agents, trifunctional crosslinking agents, tetrafunctional crosslinking agents, and mixtures thereof, including silicone-containing crosslinking agents and non-silicone-containing crosslinking agents. Examples of non-silicone-containing crosslinking agents 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 agent is typically used in the reactive mixture in an amount of, for example, from about 0.000415 to about 0.0156 moles per 100 grams of the reactive formulation. Alternatively, the addition of a crosslinking agent to the reactive mixture is optional if the hydrophilic monomer and / or silicone-containing component is polyfunctional by molecular design or due to impurities. Examples of hydrophilic monomers and macromers that can act as crosslinking agents and do not require the addition of an additional crosslinking agent to the reactive mixture when present include polyethers end-capped with (meth)acrylate and (meth)acrylamide. Other crosslinking agents are known to those skilled in the art and can be used to make the silicone hydrogels of the present invention.

[0116] It may be desirable to select a crosslinking agent having similar reactivity to one or more of the other reactive components in the complex. In some cases, it may be desirable to select a mixture of crosslinking agents having different reactivities in order to control some of the physical, mechanical, or biological properties of the resulting silicone hydrogel. The structure and morphology of the silicone hydrogel can also be affected by the diluent and curing conditions used.

[0117] To further increase the elastic modulus and maintain the tensile strength, a multifunctional silicone-containing component including a macromer, a crosslinking agent, and a prepolymer may also be included. The silicone-containing crosslinking agent can be used alone or in combination with other crosslinking agents. Examples of silicone-containing components that can act as crosslinking agents and do not require the addition of crosslinking monomers to the reactive mixture when present include α,ω-bismethacryloxypropyl polydimethylsiloxane. Another example is bis-3-acryloxy-2-hydroxypropyl oxypropyl polydimethylsiloxane (ac-PDMS).

[0118] Crosslinking agents having a hard chemical structure and polymerizable groups that undergo free radical polymerization can also be used. Non-limiting examples of suitable hard structures include crosslinking agents 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. The hard crosslinking agent can be included in an amount of about 0.5 to about 15, or 2 to 10, 3 to 7 based on the total weight of all reactive components. The physical and mechanical properties of the silicone hydrogel of the present invention can be optimized for specific applications by adjusting the components in the reactive mixture.

[0119] As described above, the reactive mixture can contain additional components such as, but not limited to, diluents, initiators, UV absorbers, visible light absorbers, photochromic compounds, pharmaceuticals, nutritional supplements, antibacterial substances, colorants, pigments, copolymerizable dyes, non-polymerizable dyes, release agents, and combinations thereof. Preferably, the reactive mixture can contain a compound that imparts UV absorption characteristics to the lens. Suitable UV absorbing compounds are known in the art and include, but are 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, and are classified into several categories. A preferred class of UV absorbing compounds is benzotriazoles such as Norbloc (2-(2'-hydroxy-5-methacryloyloxyethylphenyl)-2H-benzotriazole).

[0120] Suitable types of diluents for the silicone hydrogel reactive mixture include alcohols having 2 to 20 carbon atoms, amides having 10 to 20 carbon atoms derived from primary amines, and carboxylic acids having 8 to 20 carbon atoms. The diluent can be primary, secondary, and tertiary alcohols.

[0121] Generally, the 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 US Patent No. 6,020,445, the disclosures of which are incorporated herein by reference.

[0122] Suitable types of diluents for the silicone hydrogel reactive mixture include alcohols having 2 to 20 carbons, amides having 10 to 20 carbon atoms derived from primary amines, and carboxylic acids having 8 to 20 carbon atoms. Primary and tertiary alcohols can be used. Preferred types include alcohols having 5 to 20 carbons and carboxylic acids having 10 to 20 carbon atoms.

[0123] Specific diluents that can be used include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropanol, 3,7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-octanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, tert-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-propanol, 1-propanol, ethanol, 2-ethyl-1-butanol, (3-acetoxy-2-hydroxypropyl oxy)-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.

[0124] 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.

[0125] 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.

[0126] When a diluent is present, generally there are no specific restrictions regarding the amount of diluent present. When using a diluent, the diluent can be present in an amount in the range of about 2 to about 70 weight percent, such as in the range of about 5 to about 50 weight percent and in the range of about 15 to about 40 weight percent, based on the total weight of the reactive mixture (including the reactive formulation and the non-reactive formulation). Mixtures of diluents may also be used.

[0127] The polymerization initiator may be used in the reactive mixture. Examples of the polymerization initiator include those that generate free radicals at a moderate high temperature, such as lauryl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, etc., and at least one of photoinitiator systems such as aromatic alpha-hydroxy ketone, alkoxy oxybenzoin, acetophenone, acylphosphine oxide, bisacylphosphine oxide, and tertiary amine + diketone, and mixtures thereof. Specific examples of the photoinitiator 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-trimethylbenzyl diphenylphosphine oxide and 2,4,6-trimethylbenzoyl diphenylphosphine oxide, benzoin methyl ester, and a combination of camphorquinone and ethyl 4-(N,N-dimethylamino)benzoate.

[0128] Examples of commercially available visible light initiator systems (manufactured by IGM Resins B.V. (The Netherlands)) include Irgacure® 819, Irgacure® 1700, Irgacure® 1800, Irgacure® 819, Irgacure® 1850, and Lucrin® TPO initiator. Examples of commercially available UV light initiators (manufactured by IGM Resins B.V.) include Darocur® 1173 and Darocur® 2959. These and other photoinitiators that can be used are disclosed in Volume III, Photoinitiators for Free Radical Cationic & Anionic Photopolymerization, 2nd Edition by J.V. Crivello & K. Dietliker; edited by G. Bradley; John Wiley and Sons; New York; 1998. The initiator is used in the reactive mixture in an amount effective to initiate photopolymerization of the reactive mixture, for example, in an amount of 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 by appropriately selecting and using heat or visible light or ultraviolet light or other means 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, preferred initiators are bisacylphosphine oxides 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).

[0129] The contact lens containing the photosensitive chromophore of the present invention preferably limits the transmission of HEV light. Therefore, the contact lens containing the photosensitive chromophore can transmit, for example, 0 percent to 70 percent of light over the wavelength range of 400 to 409 nm. The transmittance of the contact lens at 400 to 409 nm can be at least 1 percent, or at least 2 percent, or at least 3 percent. The transmittance of the contact lens at 400 to 409 nm can be 60 percent or less, or 50 percent or less, or 40 percent or less, or 30 percent or less, or 25 percent or less.

[0130] The contact lens containing the photosensitive chromophore can transmit 10 percent to 95 percent of light over the wavelength range of 410 to 424 nm. The transmittance of the contact lens at 410 to 424 nm can be at least 30 percent. The transmittance of the contact lens at 410 to 424 nm can be at most 85 percent, or at most 75 percent.

[0131] The contact lens containing the photosensitive chromophore can transmit at least 40 percent of light over the wavelength range of 425 to 449 nm. The transmittance of the contact lens at 425 to 449 nm can be at least 50 percent.

[0132] The contact lens containing the photosensitive chromophore can transmit at least 80 percent of light over the wavelength range of 450 to 800 nm. The transmittance of the contact lens at 450 to 800 nm can be at least 90 percent.

[0133] Contact lenses containing a photosensitive chromophore can transmit 45 percent or less of the light over a wavelength range of 280 to 399 nm. The transmittance of the contact lens at 280 to 399 nm can 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. The transmittance in the UV range of the spectrum can be achieved by including a UV filtering compound, such as a benzotriazole compound like norblock, within the lens.

[0134] Preferably, the photosensitive chromophore within the contact lens is non-photochromic.

[0135] In addition to the contact lens containing a photosensitive chromophore, the contact lens system of the present invention also includes a package surrounding the contact lens. The package has a transmittance of 99 percent or less at each active wavelength presented by the photosensitive chromophore. The package can be a primary package or a secondary package.

[0136] The package for use in the lens system of the present invention protects the photosensitive chromophore within the contact lens from photodegradation. The protection provided by the package can be complete (thus, the photosensitive chromophore exhibits no photodegradation or very limited photodegradation while within the package) or partial (the photosensitive chromophore can be partially photodegraded, but not to the same extent as would occur in the absence of the package). Thus, the contact lens containing the photosensitive chromophore is photo-stabilized by the package.

[0137] The package of the present invention protects the photosensitive chromophore by at least partially blocking light for each active wavelength of the photosensitive chromophore. The blocking by the package can be explained in terms of the percentage transmittance of the package at the active wavelength. The package of the present invention has a percentage transmittance of 99 percent or less, or 80 percent or less, or 50 percent or less at each active wavelength. Preferably, the percentage transmittance of the package at each active wavelength is less than or equal to the percentage transmittance of the photosensitive chromophore at the same active wavelength.

[0138] To provide a package that exhibits a desired percentage transmittance at the active wavelength, various techniques can be used. For example, the package may contain its own light-absorbing compound. The light-absorbing compound can have, for example, a chromophore with the same chemical structure as the photosensitive chromophore of the contact lens. However, preferably, the package utilizes a chromophore that is less photosensitive than the chromophore of the contact lens. Exemplary classes of chromophore compounds for use in the package include thioxanthene derivatives as described in U.S. Patent Application Publication No. 2019 / 0271798, which is incorporated herein by reference. A specific example of such a light-absorbing compound is 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate. The light-absorbing compound can be incorporated into the package, for example, by copolymerizing or blending it with other materials used to make the package, or by including the light-absorbing compound in a coating applied to one or both surfaces of the package.

[0139] Hydrogel hardening and lens manufacturing The reactive mixture is formed by any of the methods known in the art, such as shaking or stirring, and can be used to form polymer articles or devices by known methods. The reactive components are mixed together either with or without a diluent to form the reactive mixture.

[0140] For example, a contact lens can be prepared by mixing a reactive component and optionally a diluent with a polymerization initiator and curing under suitable conditions to form a product that can later be formed into a suitable shape by turning, cutting, etc. Alternatively, the reactive mixture can be cured after being placed in a mold to make a suitable article.

[0141] A method of making a shaped contact lens, such as a silicone hydrogel contact lens, can 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 hydrogel in the shape of a contact lens.

[0142] 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. The method of rotational molding is disclosed in U.S. Patent Nos. 3,408,429 and 3,660,545, and the method of static molding is disclosed in U.S. Patent Nos. 4,113,224 and 4,197,266. The contact lens of the present invention may be formed by direct molding of a hydrogel, which is economical and can accurately control the final shape of the water-containing lens. In this method, the reactive mixture is placed in a mold having the final desired hydrogel shape, and the reactive mixture is subjected to conditions under which the monomers polymerize, thereby producing a polymer of approximately the shape of the final desired product.

[0143] After curing, the lens may be subjected to extraction to remove unreacted components and removed from the lens mold. Extraction may be performed using a conventional extraction fluid, such as an organic solvent such as alcohol, or extraction may be performed using an aqueous solution.

[0144] An aqueous solution is a solution containing water. The aqueous solution of the present invention can contain at least about 20 weight percent water, or at least about 50 weight percent water, or at least about 70 weight percent water, or at least about 95 weight percent water. The aqueous solution may also contain additional water-soluble formulations such as inorganic salts or mold release agents, wetting agents, slip agents, pharmaceutical ingredients and nutritional supplements, combinations thereof, etc. The mold release agent is a compound or a mixture of compounds which, when combined with water, reduces the time required to remove a contact lens from a mold as compared to the time required to remove a contact lens using an aqueous solution without the mold release agent. The aqueous solution may not require special handling such as purification, reuse or special waste treatment.

[0145] Extraction can be carried out, for example, by immersing the lens in the aqueous solution or exposing the lens to the flow of the aqueous solution. Extraction can also include, for example, heating the aqueous solution, stirring the aqueous solution, increasing the concentration of the mold release agent in the aqueous solution to a level sufficient for the release of the lens, mechanical or ultrasonic agitation of the lens, and incorporating at least one filter aid or extraction aid into the aqueous solution at a concentration sufficient to facilitate the proper removal of unreacted components from the lens. With or without the addition of heat, vibration or both, the foregoing may be carried out in a batch process or a continuous process.

[0146] The application of physical agitation may be desirable to promote leaching and release. For example, the portion of the lens mold to which the lens is attached can be vibrated or moved back and forth in the aqueous solution. Other methods may include passing ultrasonic waves through the aqueous solution.

[0147] The lens may be placed and sealed within the primary package by known methods. The lens may be sterilized by known means such as, but not limited to, high-pressure steam treatment. The completed lens within the primary package may then be placed within a secondary package. A group of lenses within the primary package may be placed within the same secondary package.

[0148] As shown above, a preferred contact lens is a soft hydrogel contact lens. The transmission wavelengths and percentages described herein can be measured for lenses of various thicknesses using, for example, known methodologies. By way of example, a preferred central thickness for measuring the transmission spectrum in a soft contact lens can be from 70 to 100 micrometers. Typically, the transmission measurement can be made through the center of the lens using, for example, an instrument slit width of 4 nm.

[0149] As described above, the present invention provides a contact lens system including a contact lens containing a photosensitive chromophore and a package surrounding the contact lens. The package at least partially blocks wavelengths of light that can photolyze the chromophore by other means. Thus, the package can stabilize the photosensitive chromophore against photolysis. Advantageously, the package can transmit light of other wavelengths while protecting the chromophore, thus allowing the contents of the package to be visible, for example, to the naked eye and / or to test equipment used during the lens manufacturing process.

[0150] A further advantage of the present invention is that the level of protection provided by the package can be adjusted by varying the amount of light blocked by the package. Thereby, the manufacturer can better control or regulate the shelf life of its product. Products that do not require a long shelf life can be housed in packages that only partially block light that can photodegrade the chromophore in other ways. On the other hand, if a longer shelf life is desired, a package can be used that provides a greater blockage of wavelengths that can photodegrade the chromophore in other ways. A longer shelf life can, for example, result in a reduction in product waste.

[0151] Preferably, the use of the package in the present invention protects a contact lens containing a photosensitive chromophore, such that after exposure to light under ICH guideline Q1B, the lens exhibits a change in average transmittance of less than 40 percent, or 35 percent or less, or 30 percent or less, or 10 percent or less, or 7 percent or less, or 5 percent or less, or 2 percent or less, or 0.5 percent or less over the wavelength range of 400 - 450 nm. Such a change can be calculated as the absolute value of the difference in the average transmittance (over the wavelength range of 400 - 450 nm) of the lens protected from light exposure versus the exposed lens under ICH guideline Q1B.

[0152] The contact lens according to the present invention also exhibits the following characteristics. Before all values is the word "about", and this device can have any combination of the recited properties. The characteristics can be determined by methods known to those skilled in the art, as described, for example, in U.S. Patent Application 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): 120 or less or 80 - 120 Oxygen permeability (Dk, Barrers): at least 80, or at least 100, or at least 150, or at least 200 Elongation at break: at least 100

[0153] For ionomeric silicone hydrogels, the following properties (in addition to those described above) may also be preferred: 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 less, or 10 or less, or 5 or less

[0154] Here, some embodiments of the present invention will be described in detail in the following examples.

Examples

[0155] Example 1: Preparation of Test Lenses In addition to other devices forming the monomers and additives, based on the total of all reactive components in the reactive mixture, a test contact lens based on senofilcon A (without UV absorbing components) was prepared by polymerization / molding of a reactive mixture containing 2 weight percent of 2-(4-acetyl-3-amino-2,6-dimethoxyphenoxy)ethyl methacrylate. The resulting test lenses were released from the lens mold at room temperature in 70:30 isopropyl alcohol: water and hydrated in 70:30 isopropyl alcohol: water before transferring to a standard boric acid buffered packing solution. Then, they were autoclaved in the packing solution for 30 minutes before long-term storage in a heat-sealed contact lens blister with the standard packing solution.

[0156] The light transmittance of the contact lenses was characterized using a Cary 6000 Agilent Technologies UV-VIS-NIR spectrometer. A standard borate buffered packing solution was filtered to remove any particles that could adversely affect spectral collection. After mounting the lens in a lens holder having an aperture dimension of approximately 6 mm x 12 mm, the assembly was mounted in a quartz spectrophotometer cuvette with an aperture dimension of 45 mm x 12.2 mm and a path length of 10 mm. A reference cell was prepared for the reference assembly without the contact lens in the lens holder. The UV / Vis spectrum of the test lens of Example 1 is shown in FIG. 1.

[0157] The long-term exposure of the lenses containing the above chromophores to light illustrates the photosensitivity of the chromophores. Accordingly, Senofilcon A type lenses containing 2 wt% 2-(4-acetyl-3-amino-2,6-dimethoxyphenoxy)ethyl methacrylate (these lenses also contained a UV absorbing compound, unlike the test lenses of FIG. 1) were tested. The lenses may be prepared as described in U.S. Patent Application No. 16 / 398,722. After packaging the lenses in clear blister packs, they were subjected to the above ICH guideline Q1B conditions. These were compared to lenses not exposed to Q1B light conditions. The UV-visible transmittance spectra are shown in FIG. 2.

[0158] FIG. 2 reveals the photosensitivity of the lenses after light exposure. As can be seen, the ability of the lenses to maintain their high-energy visible light filtering characteristics changed unnecessarily upon exposure. The average transmittance of the non-exposed and Q1B-exposed lenses over the range of 400 - 450 nm was approximately 53 percent and approximately 64 percent, respectively. Accordingly, the contact lenses of FIG. 2 exhibit a change of approximately 11 percent in their average transmittance over the wavelength range of 400 - 450 nm after exposure to light under ICH guideline Q1B conditions.

[0159] Example 2: Light Stress Study In this example, the effectiveness of at least partially blocking light absorbed by a photosensitive chromophore in reducing photodegradation by other means is illustrated.

[0160] In this example, protection is provided by the light-absorbing compound 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate (“LAC1”). The UV-Vis transmission spectrum of a 0.2 mM solution of LAC1 in methanol is shown in FIG. 3. As can be seen, the LAC absorbs at each of the active wavelengths of the chromophore used in the test lenses of Example 1.

[0161] To simulate the package, a solution of 2 mM LAC1 was prepared by adding an appropriate weighed powder to propylene glycol as the solvent. The glass bottle was rotated overnight to completely dissolve the LAC1. Each experimental test concentration of LAC1: 2 mM, 0.5 mM, and 0.1 mM solutions required a volume of 30 milliliters and was prepared by the serial dilution method. Before use, the solutions were protected from light.

[0162] Glass Petri dish sets (60×15 mm and 100×10 mm) were purchased from Avantor. However, only the bottom dish was used for the experiment. The smaller 60×15 mm dish for the housing test contact lens was covered with aluminum foil (Reynolds Consumer Products, LLC), and the foil covered the lip of the dish. The bottom 100×10 mm dish was used as a reservoir for the LAC1 solution and was equilibrated on the smaller dish. Thus, this stacked assembly allows the LAC1 solution to pass through the dish containing it but does not pass through the sides of the smaller dish containing the test lens. The dish was then illuminated with a 435 nm LED as the light source. A schematic of the assembly is shown in FIG. 4.

[0163] The platform was positioned 7.5 inches from the LED panel. The LED intensity was on average 20 mW / cm in the platform 2It was adjusted to have. An assembly with four test solutions was arranged on the platform, and the LED was turned on for a total of 52 hours at room temperature. It should be noted that the lighting conditions in this example are stronger than the above Q1B conditions and bring about a faster and / or more significant effect on the photosensitive chromophore.

[0164] After exposure, the UV / Vis spectrum of the test contact lens was collected using the Cary 6000 Agilent Technologies UV-VIS-NIR spectrometer described above. The UV / Vis spectra of the test lenses exposed through various concentrations of LAC1 or PG without LAC1 (control) are shown in Figure 5. Figure 5 includes the spectral curve of the non-exposed test lens.

[0165] In Figure 5, curve 1 is the reference blank. Curve 2 is the non-exposed test lens. Curve 3 is the test lens exposed through a 2 mM LAC1 solution overlay. Curve 4 is the test lens exposed through a 0.5 mM LAC1 solution overlay. Curve 5 is the test lens exposed through a 0.1 mM LAC1 solution overlay. And curve 6 is the test lens exposed through a 0 mM LAC1 solution overlay (i.e., propylene glycol solvent only).

[0166] As can be seen from Figure 5, it is observed that as the concentration of LAC1 increases, the photodegradation of the lens with respect to the non-exposed lens (curve 2) decreases. The difference in the average transmittance over the wavelength range of 400 - 450 nm between the exposed and non-exposed lenses is shown in Table 1. The average transmittance of the non-exposed lens over 400 - 450 nm is approximately 52%.

[0167]

Table 3

[0168] As illustrated in Table 1, the LAC1 compound that at least partially blocks the transmission of light at all wavelengths absorbed by the photosensitive chromophore of the test lens protects the compound from photodegradation. The greater the blockage by LAC1 (resulting from an increase in its concentration in solution), the greater the protection provided. The data suggest that an increase in protection can be brought about by further increasing the level of blockage provided by the LAC1 compound (e.g., by increasing its concentration).

[0169] Example 3: Preparation of Test Lenses In addition to monomers and other devices forming additives, based on the total of all reactive components in the reactive mixture, a test contact lens based on senofilcon A (without UV-absorbing components) was prepared by polymerization / molding of a reactive mixture containing 2 weight percent of 2-((1-amino-8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)oxy)ethyl methacrylate. The resulting test lenses were released from the lens mold at room temperature in 70:30 isopropyl alcohol: water and hydrated in 70:30 isopropyl alcohol: water before being transferred to a standard boric acid buffered packing solution. They were then autoclaved in the packing solution for 30 minutes before long-term storage in a heat-sealed contact lens blister with the standard packing solution.

[0170] The light transmittance of the contact lenses was characterized using a Cary 6000 Agilent Technologies UV-VIS-NIR spectrometer. The standard boric acid buffered packing solution was filtered to remove any particles that could adversely affect spectrum collection. After mounting the lens in a lens holder with an aperture dimension of approximately 6 mm × 12 mm, the assembly was mounted in a quartz spectrophotometer cuvette with an aperture dimension of 45 mm × 12.2 mm and a path length of 10 mm. A reference cell was prepared for alignment of the assembly without the contact lens in the lens holder. The UV / Vis spectrum of the test lens of Example 3 is shown in Figure 6.

[0171] Example 4: Light Stress Study In this example, the effectiveness of at least partially blocking light absorbed by the photosensitive chromophore in reducing photodegradation by other means is illustrated.

[0172] In this example, protection is provided by the light-absorbing compound 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate (“LAC1”). The UV-Vis transmission spectrum of a 0.2 mM solution of LAC1 in methanol is shown in FIG. 3. As can be seen, the LAC absorbs at each of the active wavelengths of the chromophore used in the test lenses of Example 3.

[0173] To simulate the package, a solution of 2 mM LAC1 was prepared by adding an appropriate weighed powder to propylene glycol as a solvent. The glass bottle was rotated overnight to completely dissolve the LAC1. Each experimental test concentration of LAC1: 2 mM, 0.5 mM, and 0.1 mM solutions required a volume of 30 milliliters and was prepared by serial dilution. Before use, the solutions were protected from light.

[0174] Glass petri dish sets (60×15 mm and 100×10 mm) were purchased from Avantor. However, only the bottom dish was used for the experiment. The smaller 60×15 mm dish for the housing test contact lens was covered with aluminum foil (Reynolds Consumer Products, LLC), and the foil covered the lip of the dish. The bottom 100×10 mm dish was used as a reservoir for the LAC1 solution and was equilibrated on the smaller dish. Thus, this laminated assembly allows the LAC1 solution to pass through the dish containing it but does not pass through the sides of the smaller dish containing the test lens. The dish was then illuminated with a 435 nm LED as a light source. A schematic of the assembly is shown in FIG. 4.

[0175] The platform was positioned 7.5 inches from the LED panel. The LED intensity was on average 20 mW / cm in the platform 2Adjusted to have. An assembly with four test solutions was arranged on the platform, and the LED was turned on for a total of 5 hours at room temperature.

[0176] After exposure, the UV / Vis spectrum of the test contact lens was collected using the Cary 6000 Agilent Technologies UV-VIS-NIR spectrometer described above. The UV / Vis spectra of the test lenses exposed through various concentrations of LAC1 or PG without LAC1 (control) are shown in Figure 7. Figure 7 includes the spectral curve of the non-exposed test lens.

[0177] In Figure 7A, curve 1 is the reference blank. Curve 2 is the non-exposed test lens of Example 3. Curve 3 is the test lens exposed through a 2 mM LAC1 solution overlay. Curve 4 is the test lens exposed through a 0.5 mM LAC1 solution overlay. Curve 5 is the test lens exposed through a 0.1 mM LAC1 solution overlay. And curve 6 is the test lens exposed through a 0 mM LAC1 solution overlay (i.e., propylene glycol solvent only). Figure 7B is an enlarged view of Figure 7A showing the transmittance at 380 - 680 nm.

[0178] As can be seen from Figures 7A and 7B, it is observed that as the concentration of LAC1 increases, the photodegradation of the lens with respect to the non-exposed lens (curve 2) decreases. The difference in the average transmittance over the wavelength range of 400 - 450 nm between the exposed lenses and the non-exposed lens is shown in Table 2. The average transmittance of the non-exposed lens over 400 - 450 nm is approximately 48%.

[0179]

Table 4

[0180] As illustrated in Table 2, the LAC1 compound that at least partially blocks the transmission of light at all wavelengths absorbed by the photosensitive chromophore of the test lens of Example 3 protects the compound from photolysis. The greater the blocking by LAC1 (resulting from an increase in its concentration in solution), the greater the protection provided. The data suggest that a 2 mM LAC1 solution provides sufficient protection to preserve the average transmission level of 400 - 450 nanometers as a non-exposed test lens.

[0181] 〔Embodiments〕 (1) A contact lens system, comprising: A contact lens containing a photosensitive chromophore, wherein the photosensitive chromophore has at least one active wavelength in the range of 250 - 400 nanometers and at least one active wavelength in the range of 400 - 450 nanometers, and a contact lens; A package surrounding the contact lens, wherein the package has a light transmittance of 99 percent or less at each active wavelength, and a package. (2) The contact lens system according to Embodiment 1, wherein at each active wavelength, the transmittance of the package is 80 percent or less. (3) The contact lens system according to Embodiment 1 or 2, wherein at each active wavelength, the transmittance of the package is less than or equal to the transmittance of the photosensitive chromophore. (4) The contact lens system according to any one of Embodiments 1 - 3, wherein the contact lens containing the photosensitive chromophore transmits 0 percent to 70 percent over a wavelength range of 400 - 409 nm. (5) The contact lens containing the photosensitive chromophore transmits 10 percent to 95 percent over a wavelength range of 410 to 424 nm, at least 40 percent over a wavelength range of 425 to 449 nm, and at least 80 percent over a wavelength of 450 to 800 nm, the contact lens system according to any one of Embodiments 1 to 4.

[0182] (6) The contact lens containing the photosensitive chromophore transmits 45 percent or less over a wavelength range of 280 to 399 nm, the contact lens system according to any one of Embodiments 1 to 5. (7) The photosensitive chromophore is non-photochromic, the contact lens system according to any one of Embodiments 1 to 6. (8) The package is a primary package, the contact lens system according to any one of Embodiments 1 to 7. (9) The package is a secondary package, the contact lens system according to any one of Embodiments 1 to 7. (10) After the contact lens containing the photosensitive chromophore is exposed to light under ICH guideline Q1B conditions, it exhibits a change of at least 2 percent in the average transmittance of the contact lens over a wavelength range of 400 to 450 nm, the contact lens system according to any one of Embodiments 1 to 9.

[0183] (11) The photosensitive chromophore includes an alkoxy aniline derivative containing a polymerizable group or a tetrahydro-naphthalenyl derivative containing a polymerizable group, the contact lens according to any one of Embodiments 1 to 10. (12) The contact lens system according to any one of Embodiments 1 to 11, which is imported into a certain country. (13) The country is the United States of America, the contact lens system according to Embodiment 12.

Claims

1. A contact lens system, comprising: A contact lens containing a photosensitive chromophore, wherein the photosensitive chromophore has at least one active wavelength between 250 and 400 nanometers and at least one active wavelength between 400 and 450 nanometers; and A package surrounding the contact lens, wherein the package has a light transmittance of 99% or less, which is lower than other visible light wavelengths, at each active wavelength, and the package contains a light-absorbing compound containing a thioxanthene derivative.

2. The contact lens system according to claim 1, wherein the light-absorbing compound contains 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate.

3. The contact lens system according to claim 1 or 2, wherein the photosensitive chromophore contains an alkoxyaniline derivative containing a polymerizable group.

4. The contact lens system according to claim 1 or 2, wherein the photosensitive chromophore contains a tetrahydro-naphthalenyl derivative containing a polymerizable group.

5. The contact lens system according to claim 2, wherein the photosensitive chromophore contains 2-((1-amino-8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)oxy)ethyl methacrylate.

6. The contact lens system according to claim 2 or 5, wherein the light transmittance of the package is 80% or less at each active wavelength.

7. The contact lens system according to claim 6, wherein the light transmittance of the package is not higher than that of the photosensitive chromophore at each active wavelength.

8. The contact lens system according to any one of claims 1 to 7, wherein the contact lens containing the photosensitive chromophore transmits 0 percent to 70 percent over a wavelength range of 400 to 409 nm.

9. The contact lens system according to claim 8, wherein the contact lens containing the photosensitive chromophore transmits 10 percent to 95 percent over a wavelength range of 410 to 424 nm, at least 40 percent over a wavelength range of 425 to 449 nm, and at least 80 percent over a wavelength range of 450 to 800 nm.

10. The contact lens system according to claim 9, wherein the contact lens containing the photosensitive chromophore transmits 45 percent or less over a wavelength range of 280 to 399 nm.

11. The contact lens system according to any one of claims 1 to 10, wherein the photosensitive chromophore is non-photochromic.

12. The contact lens system according to any one of claims 1 to 11, wherein the package is a primary package.

13. The contact lens system according to claim 12, further comprising a secondary package.

14. The contact lens system according to any one of claims 1 to 13, wherein the contact lens containing the photosensitive chromophore exhibits a change of at least 2 percent in the average transmittance of the contact lens over a wavelength range of 400 to 450 nm after being exposed to light under ICH guideline Q1B conditions.

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