Contact lenses containing photochromic groups and their packaging

Abstract

The present invention provides a contact lens system, the contact lens system comprising: a contact lens containing a photosensitive chromophore and a package surrounding the contact lens. The photosensitive chromophore has at least one active wavelength between 250 nanometers and 400 nanometers and at least one active wavelength between 400 nanometers and 450 nanometers. The package has a transmittance of no more than 99% at each active wavelength.

Description

[0001] Related Applications

[0002] This application claims priority to U.S. patent application serial number 16 / 952,841 filed on November 19, 2020 and U.S. provisional patent application serial number 62 / 950,577 filed on December 19, 2019, which are incorporated herein by reference in their entirety. Technical Field

[0003] The present invention relates to a contact lens system comprising a contact lens comprising a photosensitive chromophore and a surrounding packaging for protecting the chromophore from photodegradation. Background Art

[0004] High-energy light from the sun, such as UV light and high-energy visible light, is known to cause cell damage. Although most radiation with wavelengths below 280 nm is absorbed by the Earth's atmosphere, photons with wavelengths in the range of 280 nm to 400 nm are associated with a variety of eye diseases, including corneal degenerative changes, age-related cataracts, and macular degeneration. (See "Statement on Ocular Ultraviolet Radiation Hazards in Sunlight" by the American Optometric Association, November 10, 1993). The human cornea absorbs some radiation 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 ineffective in protecting the back of the eye from radiation in the 320 to 400 nm wavelength range.

[0005] Contact lens standards define the upper UV radiation wavelength as 380 nm. The current Class I UV absorption standard defined by the American Optometric Association requires contact lenses to absorb >99% of radiation between 280 nm and 315 nm (UV B) and >90% of radiation between 316 nm and 380 nm (UV A). While this standard effectively addresses corneal protection (UV B transmittance <1%), little attention is paid to lower energy UV radiation (>380 nm and <400 nm) associated with retinal damage (Ham, WT, Mueller, HA, Sliney, DH Nature 1976; 260(5547): 153-5), or to high energy visible radiation.

[0006] High energy visible (HEV) radiation (e.g., 400nm to 450nm) can cause visual discomfort or circadian rhythm disruption. For example, computer and electronic device screens, flat-panel televisions, energy-saving lamps, and LED lamps are known to generate HEV light. Prolonged exposure to such HEV light sources can cause eye fatigue. In addition, it is assumed that viewing HEV light emitting devices at night can disrupt natural circadian rhythms, resulting in, for example, lack of sleep.

[0007] Reducing the amount of HEV light absorbed by the eye is a desired goal in the field of ophthalmology. However, it is sometimes the case that a chromophore that absorbs HEV light and is otherwise desired for use as a HEV filter in a contact lens is sensitive to ambient light, which results in its photodegradation. This photosensitivity can manifest itself in a number of undesirable ways, which can include yellowing or discoloration of the lens and / or degradation of the chromophore's ability to absorb the HEV wavelengths for which it was originally selected over time. Thus, when the chromophore in the lens is photosensitive, the shelf life, cosmetic appeal, and performance of the contact lens can all be negatively impacted.

[0008] There is a need for materials that provide targeted absorption of undesirable wavelengths of high energy radiation and that can be processed into functional products. Where such materials are photosensitive, techniques for protecting them from photodegradation are also desirable. Summary of the invention

[0009] The present invention relates to a contact lens system comprising a contact lens comprising a photosensitizing chromophore and packaging for protecting the photosensitizing chromophore from photodegradation.

[0010] The packaging used in the contact lens system of the present invention at least partially blocks wavelengths of light that would otherwise photodegrade the chromophore. Thus, the packaging is able to stabilize the photosensitive chromophore to prevent photodegradation.

[0011] Advantageously, packaging according to the present invention, while protecting the chromophore, can transmit light of other wavelengths, thereby allowing the contents of the package to be visible, for example, to the naked eye and / or to testing equipment used during the lens production process. Another 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. This allows manufacturers to specifically control the shelf life of their products. Products that do not require a long shelf life can be contained in a package that only partially blocks light that would otherwise degrade the chromophore. On the other hand, if a longer shelf life is desired, a package that provides a greater barrier can be used.

[0012] Thus, more specifically, the present invention provides a contact lens system comprising: a contact lens comprising a photosensitizing chromophore having at least one active wavelength (defined below) between 250 nanometers and 400 nanometers and at least one active wavelength between 400 nanometers and 450 nanometers; and a package surrounding the contact lens, the package having a light transmittance of no more than 99% at each active wavelength. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 is the UV / Vis transmission spectrum of the test lens according to Example 1.

[0014] Figure 2 UV / Vis transmission spectra of lenses exposed to light under ICH guideline Q1B conditions compared to unexposed lenses.

[0015] Figure 3 is the UV / Vis spectrum of the light absorbing compound used to protect the test lenses from photodegradation.

[0016] Figure 4 Schematic diagram of the equipment used in Example 2.

[0017] Figure 5 Shown are UV / Vis spectral transmittance curves for test lenses of Example 1 (including those protected against photodegradation) exposed to LED light.

[0018] Figure 6 is the UV / Vis transmission spectrum of the test lens according to Example 3.

[0019] Fig. 7A Shown are UV / Vis spectral transmittance curves for test lenses of Example 3 (including those protected against photodegradation) exposed to LED light. Figure 7B for Fig. 7A A magnified view of the graph showing the transmittance from 380 nm to 680 nm. DETAILED DESCRIPTION

[0020] It should be understood that the invention is not limited to the details of construction or process steps set forth in the following description. Using the teachings herein, the invention is capable of other embodiments and of being practiced or carried out in various ways.

[0021] With respect to terms used in this disclosure, the following definitions are provided.

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Polymer definitions are consistent with those 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, and recommended by IUPAC in 2008. All publications, patent applications, patents and other references mentioned herein are incorporated herein by reference.

[0023] As used herein, the term "(meth)" refers to optional methyl substitution. Thus, a term such as "(meth)acrylate" refers to both methacrylate and acrylate.

[0024] Wherever a chemical structure is provided, it is understood that the alternatives disclosed for substituents on the structure can be combined in any combination. Thus, if a structure contains substituents R* and R**, each of which contains three lists of possible groups, nine combinations are disclosed. The same applies to combinations of properties.

[0025] When a subscript such as a general formula [***] n When "n" is used to describe the number of repeating units in a chemical formula of a polymer, the formula should be interpreted as indicating the number average molecular weight of the macromolecule.

[0026] The term "subject" includes humans and vertebrates.

[0027] The term "ocular surface" includes the surface and glandular epithelial cells of the cornea, conjunctiva, lacrimal glands, accessory lacrimal glands, nasolacrimal ducts, and meibomian glands and their apical and basal stroma, puncta, and adjacent or related structures, including the eyelids connected as a functional system by epithelial continuity, innervation, and endocrine and immune systems.

[0028] The term "contact lens" refers to an ophthalmic device that can be placed on the cornea of ​​an individual's eye. Contact lenses can provide corrective, cosmetic, or therapeutic benefits, including wound healing, drug or nutraceutical delivery, diagnostic assessment or monitoring, ultraviolet light absorption, visible light or glare reduction, or any combination thereof. Contact lenses can be any suitable material known in the art, and can be soft lenses, hard lenses, or hybrid lenses comprising at least two different parts having different physical, mechanical or optical properties such as modulus, water content, light transmission, or a combination thereof.

[0029] The contact lenses of the present invention may include silicone hydrogels or conventional hydrogels.Silicone hydrogels generally contain at least one hydrophilic monomer and at least one silicone-containing component, which are covalently bonded to each other in a curing device.

[0030] "Target macromolecule" means a macromolecule synthesized from a reactive monomer mixture including monomers, macromonomers, prepolymers, crosslinking agents, initiators, additives, diluents, and the like.

[0031] The term "polymerizable compound" means a compound containing one or more polymerizable groups. The term encompasses, for example, monomers, macromers, oligomers, prepolymers, crosslinking agents, and the like.

[0032] "Polymerizable group" is a group in which chain growth polymerization (such as free radical and / or cationic polymerization) can occur, for example, a carbon-carbon double bond that can be polymerized when subjected to free radical polymerization initiation conditions. Non-limiting examples of free radical polymerizable groups include (methyl) acrylate, styrene, vinyl ether, (methyl) acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate and other vinyl groups. Preferably, free radical polymerizable groups include (methyl) acrylate, (methyl) acrylamide, N-vinyl lactam, N-vinyl amide and styryl functional groups and a mixture of any of the aforementioned substances. More preferably, free radical polymerizable groups include (methyl) acrylate, (methyl) acrylamide and their mixture. Polymerizable groups can be unsubstituted or substituted. For example, the nitrogen atom in (methyl) acrylamide can be bonded to hydrogen, or hydrogen can be replaced by an alkyl or cycloalkyl group (which itself can be further substituted).

[0033] Any type of free radical polymerization may be used, including but not limited to bulk, solution, suspension, and emulsion, as well as any of the controlled radical polymerization methods such as stable free radical polymerization, nitroxide-mediated living polymerization, atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization, organotellurium-mediated living radical polymerization, and the like.

[0034] "Monomers" are monofunctional molecules that can undergo chain growth polymerization (and specifically free radical polymerization) to form repeating units in the chemical structure of the target macromolecule. Certain monomers have difunctional impurities that can act as crosslinking agents. "Hydrophilic monomers" are also monomers that produce a clear single-phase solution when mixed with deionized water at a concentration of 5% by weight at 25°C. "Hydrophilic components" are monomers, macromers, prepolymers, initiators, crosslinkers, additives or polymers that produce a clear single-phase solution when mixed with deionized water at a concentration of 5% by weight at 25°C. "Hydrophobic components" are monomers, macromers, prepolymers, initiators, crosslinkers, additives or polymers that are slightly soluble or insoluble in deionized water at 25°C.

[0035] "Macromolecules" are organic compounds having a number average molecular weight greater than 1500, and may be reactive or non-reactive.

[0036] A "silicone-containing component" is a monomer, macromer, prepolymer, crosslinker, initiator, additive or polymer in a reactive mixture having at least one silicon-oxygen bond, typically in the form of a siloxy group, a siloxane group, a carbosiloxane group, and mixtures thereof.

[0037] Examples of silicone-containing components useful in the present invention can be found in U.S. Pat. Nos. 3,808,178, 4,120,570, 4,136,250, 4,153,641, 4,740,533, 5,034,461, 5,070,215, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,760,100, 5,849,81 1. 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, 7,6 66,921、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、8,937,11 0, 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. 080 539. These patents are hereby incorporated by reference in their entirety.

[0038] A "polymer" is a macromolecule of interest composed of repeating units of the monomers used during polymerization.

[0039] A "repeat unit" is the smallest grouping of atoms in a polymer that corresponds to the polymerization of a particular monomer or macromer.

[0040] An "initiator" is a molecule that decomposes into free radicals that can then react with monomers to initiate free radical polymerization. Thermal initiators decompose at a rate that depends on the temperature; typical examples are azo compounds such as 1,1'-azobisisobutyronitrile and 4,4'-azobis(4-cyanovaleric acid), peroxides such as benzoyl peroxide, tert-butyl peroxide, tert-butyl hydroperoxide, tert-butyl peroxybenzoate, dicumyl peroxide, and lauroyl peroxide, peracids such as peracetic acid and potassium persulfate, and various redox systems. Photoinitiators decompose photochemically; typical examples are derivatives of benzil, benzoin, acetophenone, benzophenone, camphorquinone, and mixtures thereof and various mono- and bis-acylphosphine oxides, and combinations thereof.

[0041] A "crosslinking agent" is a difunctional or multifunctional monomer or macromer that can undergo free radical polymerization at two or more positions on the molecule to form branching points and a polymer network. Common examples are ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, methylenebisacrylamide, triallyl cyanurate, etc.

[0042] A "prepolymer" is the reaction product of monomers which contains residual polymerizable groups capable of further reaction to form a polymer.

[0043] A "polymer network" is a cross-linked macromolecule that is swellable in a solvent but not soluble. A "hydrogel" is a polymer network that swells in water or an aqueous solution, typically absorbing at least 10% by weight of water. A "silicone hydrogel" is a hydrogel made from at least one silicone-containing component and at least one hydrophilic component. The hydrophilic component may also include a non-reactive polymer.

[0044] "Conventional hydrogel" refers to a polymer network made from components that do not contain any siloxy, siloxane, or carbosiloxane groups. Conventional hydrogels are prepared from a reactive mixture containing hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate ("HEMA"), N-vinyl pyrrolidone ("NVP"), N,N-dimethylacrylamide ("DMA"), or vinyl acetate. U.S. Patent Nos. 4,436,887, 4,495,313, 4,889,664, 5,006,622, 5,039459, 5,236,969, 5,270,418, 5,298,533, 5,824,719, 6,420,453, 6,423,761, 6,767,979, 7,934,830, 8,138,290 and 8,389,597 disclose the formation of conventional hydrogels. Conventional hydrogels may also be formed from polyvinyl alcohol. Conventional hydrogel lenses may include a coating, and the coating may be the same or different material as the substrate. Conventional hydrogels may contain additives such as polyvinyl pyrrolidone, and comonomers including phosphorylcholine, methacrylic acid, and the like. Commercially available conventional hydrogels include, but are not limited to, etafilcon, genfilcon, hilafilcon, linifilcon, nesofilcon, omafilcon, polymacon, and vifilcon, including all modifications thereof.

[0045] "Silicone hydrogel" refers to a polymer network made of at least one hydrophilic component and at least one silicone-containing component. Examples of suitable types of hydrophilic components that may be present in the reactive mixture include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl carbamates, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof. Silicone-containing components are well known and have been extensively described in the patent literature. For example, the silicone-containing component may include at least one polymerizable group (e.g., (meth)acrylates, styryls, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, O-vinyl carbamates, O-vinyl carbonates, vinyl groups, or mixtures thereof), at least one siloxane group, and one or more linking groups (which may be bonds) connecting one or more polymerizable groups to one or more siloxane groups. The silicone-containing component may, for example, include 1 to 220 siloxane repeating units. The silicone-containing component may also include at least one fluorine atom. The silicone hydrogel lens may include a coating, and the coating may be the same or a different material than the substrate.

[0046] Examples of silicone hydrogels include acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon, including all variations thereof, and as described in 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, The silicone hydrogels prepared in WO 03 / 22321, WO 2008 / 061992 and US 2010 / 0048847 are hereby incorporated by reference in their entirety.

[0047] An "interpenetrating polymer network" includes two or more networks that are at least partially interwoven on a molecular scale but are not covalently bound to each other and cannot be separated without interfering chemical bonds. A "semi-interpenetrating polymer network" includes one or more networks and one or more polymers characterized by some intermixing on a molecular level between at least one network and at least one polymer. A mixture of different polymers is a "polymer blend." Technically, a semi-interpenetrating network is a polymer blend, but in some cases the polymers are entangled so that they cannot be easily removed.

[0048] "Reactive components" are polymerizable compounds (such as monomers, macromers, oligomers, prepolymers, and crosslinkers) in a reactive mixture (defined below), and any other components in the reactive mixture, which are intended to be substantially retained in the resulting polymer network after polymerization and all post-processing steps (such as extraction steps) and packaging steps have been completed. Reactive components may be retained in the polymer network by covalent bonding, hydrogen bonding, electrostatic interactions, formation of an interpenetrating polymer network, or any other means. Components that are intended to be released from the polymer network while in use are still considered "reactive components". For example, a pharmaceutical component or nutritional component in a contact lens that is intended to be released during wear is considered a "reactive component". Components such as diluents that are intended to be removed from the polymer network during the manufacturing process (e.g., by extraction) are not "reactive components".

[0049] The terms "reactive mixture" and "reactive monomer mixture" refer to a mixture of components that are mixed together and, when subjected to polymerization conditions, result in the formation of a polymer network (such as a conventional hydrogel or a silicone hydrogel) and a contact lens made therefrom. The reactive mixture may contain reactive components such as monomers, macromers, prepolymers, crosslinkers and initiators, additives (such as wetting agents), polymers, dyes, light absorbing compounds (such as UV absorbers and / or HEV absorbers), pigments, photochromic compounds, pharmaceutical compounds and / or nutritional compounds, any of which are polymerizable or non-polymerizable, but are capable of being retained in the resulting contact lens. The reactive mixture may also contain other components, such as diluents, that are intended to be removed from the device before use. It should be understood that a wide range of additives may be added based on the contact lens being produced and its intended use. The concentrations of the components of the reactive mixture are expressed in weight percentages of all reactive components (thus excluding diluents) in the reactive mixture. When diluents are used, their concentrations are expressed in weight percentages based on the amount of all components (including diluents) in the reactive mixture.

[0050] The term "silicone hydrogel contact lens" refers to a hydrogel contact lens made from at least one silicone-containing compound. Silicone hydrogel contact lenses generally have increased oxygen permeability compared to conventional hydrogels. Silicone hydrogel contact lenses utilize both their water and polymer content to transport oxygen to the eye.

[0051] The term "multifunctional" refers to a component having two or more polymerizable groups. The term "monofunctional" refers to a component having one polymerizable group.

[0052] The term "halogen" or "halo" refers to fluorine, chlorine, bromine and iodine.

[0053] "Alkyl" refers to an optionally substituted straight or branched chain alkyl group containing a specified number of carbon atoms. If no number is specified, the alkyl group (including any optional substituents on the alkyl group) may contain 1 to 16 carbon atoms. Preferably, the alkyl group contains 1 to 10 carbon atoms, alternatively 1 to 8 carbon atoms, alternatively 1 to 6 carbon atoms, or alternatively 1 to 4 carbon atoms. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl, amyl, hexyl, heptyl, 3-ethylbutyl, etc. Examples of substituents on the alkyl group include 1, 2 or 3 groups independently selected from the following items: hydroxyl, amino, amide, oxa, carboxyl, alkylcarboxyl, carbonyl, alkoxy, alkylthio, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Alkylene" means a divalent alkyl group such as -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH(CH3)CH2-, and -CH2CH2CH2CH2-.

[0054] "Haloalkyl" refers to an alkyl group as defined above substituted with one or more halogen atoms, wherein each halogen is independently F, Cl, Br or I. Preferred halogens are F. Preferred haloalkyl groups contain 1 to 6 carbons, more preferably 1 to 4 carbons, and still more preferably 1 to 2 carbons. "Haloalkyl" includes perhaloalkyl groups, such as -CF3- or -CF2CF3-. "Haloalkylene" means a divalent haloalkyl group, such as -CH2CF2-.

[0055] "Cycloalkyl" refers to an optionally substituted cyclic hydrocarbon containing a specified number of ring carbon atoms. If the number is not indicated, the cycloalkyl may contain 3 to 12 ring carbon atoms. Preferably, a C3-C8 cycloalkyl group, a C3-C7 cycloalkyl, more preferably a C4-C7 cycloalkyl, and even more preferably a C5-C6 cycloalkyl. Examples of cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Examples of substituents on the cycloalkyl include 1, 2 or 3 groups independently selected from the following: alkyl, hydroxyl, amino, amide, oxa, carbonyl, alkoxy, alkylthio, amide, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Cycloalkylene" means a divalent cycloalkyl group, such as 1,2-cyclohexylene, 1,3-cyclohexylene or 1,4-cyclohexylene.

[0056] "Heterocycloalkyl" refers to a cycloalkyl ring or ring system as defined above in which at least one ring carbon has been replaced by a heteroatom selected from nitrogen, oxygen and sulfur. The heterocycloalkyl ring is optionally fused to or otherwise connected to other heterocycloalkyl rings and / or non-aromatic hydrocarbon rings and / or benzene rings. Preferred heterocycloalkyl groups have 5 to 7 members. More preferred heterocycloalkyl groups have 5 or 6 members. Heterocycloalkylene means a divalent heterocycloalkyl group.

[0057] "Aryl" refers to an optionally substituted aromatic hydrocarbon ring system containing at least one aromatic ring. The aryl group contains a specified number of ring carbon atoms. If the number is not indicated, the aryl group may contain 6 to 14 ring carbon atoms. The aromatic ring may be optionally fused or otherwise connected to other aromatic hydrocarbon rings or non-aromatic hydrocarbon rings. Examples of aryl groups include phenyl, naphthyl and biphenyl. Preferred examples of aryl groups include phenyl. Examples of substituents on the aryl group include 1, 2 or 3 groups independently selected from the following items: alkyl, hydroxyl, amino, amide, oxa, carboxyl, alkylcarboxyl, carbonyl, alkoxy, alkylthio, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Arylene" means a divalent aryl group, such as 1,2-phenylene, 1,3-phenylene or 1,4-phenylene.

[0058] "Heteroaryl" means an aryl ring or ring system as defined above in which at least one ring carbon atom has been replaced by a heteroatom selected from nitrogen, oxygen and sulfur. The heteroaryl ring may be fused or otherwise attached to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings or heterocycloalkyl rings. Examples of heteroaryl groups include pyridyl, furanyl and thienyl. "Heteroarylene" means a divalent heteroaryl group.

[0059] "Alkoxy" means an alkyl group attached to the parent molecular moiety through an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy, and isopropoxy. "Alkylthio" means an alkyl group attached to the parent molecular moiety through a sulfur bridge. Examples of alkylthio groups include, for example, methylthio, ethylthio, n-propylthio, and isopropylthio. "Aryloxy" means an aryl group attached to the parent molecular moiety through an oxygen bridge. Examples include phenoxy. "Cycloalkoxy" means a cycloalkyl group attached to the parent moiety through an oxygen bridge.

[0060] "Alkylamine" refers to an alkyl group attached to the parent molecular moiety through an -NH bridge. Alkyleneamine means a divalent alkylamine group, such as -CH2CH2NH-.

[0061] "Siloxane" refers to a structure having at least one Si-O-Si bond. Thus, for example, a siloxane group means a group having at least one Si-O-Si group (i.e., a siloxane group), and a siloxane compound means a compound having at least one Si-O-Si group. "Siloxane" encompasses monomers (e.g., Si-O-Si) as well as oligomeric / polymeric structures (e.g., -[Si-O] n -, wherein n is 2 or greater). Each silicon atom in the siloxane group is independently selected by R A Group substitution (where R A As defined in Formula A options (b) to (i)) to complete its valency.

[0062] "Silyl" refers to a structure of the formula R3Si-, and "siloxy" refers to a structure of the formula R3Si-O-, wherein each R in the silyl or siloxy group is independently selected from trimethylsiloxy, C1-C8 alkyl (preferably C1-C3 alkyl, more preferably ethyl or methyl) and C3-C8 cycloalkyl.

[0063] "Alkyleneoxy" refers to a group having the general formula -(alkylene-O-) p -or-(O-alkylene) p -, wherein alkylene is as defined above, and p is 1 to 200, or 1 to 100, or 1 to 50, or 1 to 25, or 1 to 20, or 1 to 10, wherein each alkylene is independently optionally substituted by one or more groups, and the one or more groups are independently selected from hydroxyl, halogen (e.g., fluorine), amino, amide, ether, carbonyl, carboxyl, and combinations thereof. If p is greater than 1, each alkylene may be the same or different, and the alkyleneoxy may be a block or random configuration. When the alkyleneoxy forms a terminal group in the molecule, the terminal end of the alkyleneoxy may be, for example, a hydroxyl or alkoxy group (e.g., HO-[CH2CH2O] p - or CH3O-[CH2CH2O] p -). Examples of the alkyleneoxy group include polyethyleneoxy, polypropyleneoxy, polybutyleneoxy and poly(ethyleneoxy-co-propyleneoxy).

[0064] "Oxaalkylene" refers to an alkylene group as defined above in which one or more non-adjacent CH2 groups have been replaced by an oxygen atom, such as -CH2CH2OCH(CH3)CH2-. "Thiaalkylene" refers to an alkylene group as defined above in which one or more non-adjacent CH2 groups have been replaced by a sulfur atom, such as -CH2CH2SCH(CH3)CH2-.

[0065] The term "linking group" refers to the part by which a polymerizable group is connected to a parent molecule. A linking group can be any part compatible with a compound, which is a part of a compound and does not undesirably interfere with the polymerization of the compound, and is stable under polymerization conditions and under conditions for processing and storing the final product. For example, a linking group can be a chemical bond, or it can include one or more alkylene groups, halogenated alkylene groups, amides, amines, alkyleneamines, carbamates, esters (-CO2-), arylidenes, heteroarylidenes, cycloalkylene groups, heterocycloalkylene groups, alkyleneoxy groups, oxygen heteroalkylene groups, thio heteroalkylene groups, halogenated alkyleneoxy groups (alkyleneoxy groups substituted with one or more halogen groups, such as-OCF2-,-OCF2CF2-,-OCF2CH2-), siloxane groups, alkylenesiloxane groups or combinations thereof. A linking group can be optionally substituted with one or more substituent groups. Suitable substituent groups may include those independently selected from alkyl, halogen (e.g., fluorine), hydroxyl, HO-alkyleneoxy, MeO-alkyleneoxy, siloxane, siloxy, siloxy-alkyleneoxy-, siloxy-alkylene-alkyleneoxy- (wherein there may be more than one alkyleneoxy group, and wherein each methylene group in the alkylene and alkyleneoxy groups is independently optionally substituted with 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).

[0066] Preferred linking groups include C1-C8 alkylene (preferably C2-C6 alkylene) and C1-C8 oxoalkylene (preferably C2-C6 oxoalkylene), each of which is optionally substituted by 1 or 2 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.

[0067] When the linking group is composed of a combination of parts (e.g., alkylene and cycloalkylene) as described above, the parts can exist in any order. For example, if in the following formula A, L is indicated as -alkylene-cycloalkylene-, then Rg-L can be Rg-alkylene-cycloalkylene-or Rg-cycloalkylene-alkylene-. Nevertheless, the order of listing represents the preferred order of the parts that appear in the compound starting from the terminal polymerizable group (Rg or Pg) to which the linking group is connected. For example, if in formula A, L is indicated as -alkylene-cycloalkylene-, then Rg-L is preferably Rg-alkylene-cycloalkylene-.

[0068] The term "light absorbing compound" refers to a chemical material that absorbs light in the visible spectrum (e.g., in the range of 380 nm to 780 nm). A "high energy radiation absorber," "UV / HEV absorber," or "high energy light absorbing compound" is a chemical material that absorbs various wavelengths of ultraviolet light, high energy visible light, or both. The ability of a material to absorb certain wavelengths of light can be determined by measuring its UV / visible transmission or absorption spectrum.

[0069] 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 (e.g., in the range of 400 nm to 450 nm) through the lens. The ability of a material to absorb certain wavelengths of light can be determined by measuring its UV / Vis transmission spectrum. A material that exhibits no absorption at a particular wavelength will exhibit essentially 100% transmittance at that wavelength. Conversely, a material that completely absorbs at a particular wavelength will exhibit essentially 0% transmittance at that wavelength. As used herein, if the amount of transmission of a contact lens is expressed as a percentage of a particular wavelength range, it should be understood that the contact lens exhibits a transmission percentage at all wavelengths within that range. On the other hand, references to "average transmittance" can be calculated as the average of the transmission percentages at 1 nm increments within a determined range.

[0070] The term "photosensitive" means that the contact lenses comprising a chromophore, preferably a HEV light absorbing chromophore, exhibit photodegradation as evidenced by a change in average transmittance of at least 2% over the wavelength range of 400 nm to 450 nm. Various exposure methods can be used. Preferred methods of light exposure are those described in the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use guideline, Q1B Photostability Testing of New Drug Substances and Products, published November 1996. Preferably, under the ICH photostability guidelines, Option 2 light sources are used, preferably in a photostability chamber controlled at 25°C / Amb RH, at 1.5192×10 6 Lux hours of estimated light exposure (168.8 hours of exposure time) and 259.4Wh / m 2The samples are exposed to an estimated UV radiation exposure of 16.2 hours (16.2 hours exposure time). After exposure, the UV / visible spectrum of the sample is collected and compared with the spectrum of the sample that has been protected from exposure. By way of example, a contact lens comprising a photosensitizing chromophore according to the present invention exhibits a change of at least 2%, or at least 5%, or at least 7%, or at least 10% in its average transmittance in the wavelength range of 400 nm to 450 nm after exposure to light under the conditions of the ICH Guideline Q1B as described above (sometimes abbreviated herein as "ICH Guideline Q1B" or "Q1B conditions"). Such a change can be calculated as the absolute value of the difference between the average transmittance with and without exposure (in the indicated wavelength range). The photosensitizing chromophore according to the present invention is preferably not photochromic (photochromic materials typically reversibly darken when exposed to light of a specific intensity and wavelength).

[0071] The terms "photostable," "photostable" or similar expressions mean that a contact lens comprising a photosensitizing chromophore as described herein is protected from photodegradation such that, after exposure to the conditions of the ICH guideline Q1B as described above, it exhibits a change in average transmittance in the wavelength range of 400 nm to 450 nm that is less than the change it would exhibit in the absence of such protection.

[0072] The term "active wavelength" means a wavelength in the UV / Vis spectrum of a material where the percent transmission at that wavelength is 85% or less.

[0073] The term "primary package" refers to the package that directly contains the contact lens for use by the lens wearer. The primary package may be, for example, a vial, or it may be a blister package comprising a housing or base portion sealed with a laminated foil or cover. Typically, a primary package may contain one contact lens in a small amount of packaging solution.

[0074] A "secondary package" is typically an outer package in which a primary package is contained. For example, it may be a carton. A secondary package differs from a primary package in that the secondary package does not directly contact the contact lens packaging solution. A secondary package may typically contain multiple primary packages, although a secondary package containing one primary package is also contemplated.

[0075] Unless otherwise indicated, ratios, percentages, parts, etc. are by weight.

[0076] Unless otherwise indicated, a numerical range, such as, for example, "2 to 10" or "between 2 and 10" includes the numbers defining the range (eg, 2 and 10).

[0077] As described above, the present invention provides a contact lens system, which includes: a contact lens containing a photosensitizing chromophore having at least one active wavelength between 250 nanometers and 400 nanometers and at least one active wavelength between 400 nanometers and 450 nanometers; and a package surrounding the contact lens, the package having a transmittance of no more than 99% at each active wavelength.

[0078] Any type of contact lens can be used in the contact lens system of the present invention, including soft contact lenses, hard contact lenses, rigid gas permeable (RGP) contact lenses and hybrid contact lenses. Preferably, the contact lens is a soft hydrogel contact lens (conventional hydrogel or silicone hydrogel).

[0079] The contact lens comprises a photosensitizing chromophore having at least one active wavelength between 250 nm and 400 nm (as defined above) and at least one active wavelength between 400 nm and 450 nm. Preferably, the at least one active wavelength between 400 nm and 450 nm comprises at least one active wavelength between 400 nm and 425 nm, or between 400 nm and 420 nm, or between 400 nm and 415 nm, or between 400 nm and 410 nm. More preferably, the at least one active wavelength between 400 nm and 450 nm is between 400 nm and 410 nm. More preferably, the transmittance at all wavelengths in the range of 400 nm to 410 nm is 50% or less, or 30% or less, or 20% or less, or 18% or less, or 15% or less.

[0080] Contact lenses containing photosensitizing chromophores can generally be prepared by free radical polymerization of a reactive mixture comprising one or more monomers suitable for making the desired contact lens (also referred to herein as device-forming monomers or hydrogel-forming monomers) and optional components. The reactive mixture may contain the photosensitizing chromophore as a polymerizable monomer, thereby resulting in its covalent incorporation into the lens, or it may be present as a non-polymerizable additive. Other methods of introducing photosensitizing chromophores into lenses may be used, including, for example, by applying the chromophore to the lens as part of a coating (in which case the chromophore may be polymerizable or non-polymerizable).

[0081] Preferably, the photosensitive chromophore is introduced into the reactive mixture as a polymerizable monomer. Such polymerizable chromophores typically contain polymerizable substituents that allow the monomer to be covalently integrated into 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 serial number 16 / 398,722 filed on April 30, 2019, which is incorporated herein by reference. Specific examples of such compounds are: 2-(4-acetyl-3-amino-2,6-dimethoxyphenoxy)ethyl methacrylate. Additional exemplary photosensitive chromophores include, for example, tetrahydronaphthyl derivatives, such as those described in U.S. patent application serial number 16 / 548,204 filed on August 22, 2019, which is incorporated herein by reference. A specific example of such a compound: 2-((1-amino-8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)oxy)ethyl methacrylate.

[0082] As described above, the reactive mixture used to form the contact lens comprises one or more device-forming monomers (and optionally a photosensitizing chromophore when incorporated at this stage). Examples of suitable device-forming monomers for soft contact lenses include one or more of the following: 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 (e.g., polyamides), crosslinking agents, UV absorbing compounds, and other components (e.g., diluents and initiators).

[0083] Examples of suitable types of hydrophilic monomers that may be present in the reactive mixture include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl urethanes, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof.

[0084] 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.

[0085] Hydrophilic monomers may also be ionic, including anions, cations, zwitterions, betaines, and mixtures thereof. Non-limiting examples of such charged monomers include (meth) acrylic acid, N-[(vinyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropionic acid (ACA1), 5-acrylamidopropionic acid (ACA2), 3-acrylamido-3-methylbutyric acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-1-propaneammonium inner salt (CBT), N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-1-propaneammonium inner salt (SBT), 4-hydroxy-N , N,N-trimethyl-9-oxo-4-oxide 3,5-dioxa-8-aza-4-phosphaundec-10-en-1-ammonium inner salt (9CI) (PBT), 2-methacryloyloxyethyl phosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS) and 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

[0086] Non-limiting examples of hydrophilic N-vinyl lactam and N-vinyl amide monomers include: N-vinyl pyrrolidone (NVP), N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-caprolactam, N-vinyl-3-methyl-2-piperidone, N-vinyl-4-methyl-2-piperidone, N-vinyl-4-methyl-2-caprolactam, N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone, N-vinyl acetamide (NVA), N-vinyl-N-methylacetamide (VMA), N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N-vinylformamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N-vinyl 1-ethyl-5-methylene-2-pyrrolidone, N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-N-propyl-3-methylene-2-pyrrolidone, 1-N-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N-vinylformamide, N-vinylisopropylamide, N-vinylcaprolactam, N-vinylimidazole, and mixtures thereof.

[0087] Non-limiting examples of hydrophilic O-vinyl carbamate and O-vinyl carbonate monomers include N-2-hydroxyethyl vinyl carbamate and N-carboxy-β-alanine N-vinyl ester. Other examples of hydrophilic vinyl carbonate or vinyl carbamate monomers are disclosed in U.S. Pat. No. 5,070,215. Hydrophilic oxazolone monomers are disclosed in U.S. Pat. No. 4,910,277.

[0088] Other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, and 2-ethyloxazoline.

[0089] The hydrophilic monomer may also be a linear or branched macromonomer or prepolymer of poly(ethylene glycol), poly(propylene glycol) or a statistically random or block copolymer of ethylene oxide and propylene oxide with a polymerizable moiety such as (meth)acrylate, styrene, vinyl ether, (meth)acrylamide, N-vinylamide, etc. The macromonomers of these polyethers have one polymerizable group; the prepolymers may have two or more polymerizable groups.

[0090] Preferred hydrophilic monomers of the present invention are DMA, NVP, HEMA, VMA, NVA, and mixtures thereof. Preferred hydrophilic monomers include mixtures of DMA and HEMA. Other suitable hydrophilic monomers will be apparent to those skilled in the art.

[0091] Generally speaking, there is no particular limit on the amount of hydrophilic monomer present in the reactive monomer mixture. The amount of hydrophilic monomer can be selected based on the desired characteristics of the resulting hydrogel, including water content, light transmittance, wettability, protein absorption rate, etc. Wettability can be measured by contact angle, and the required contact angle is less than about 100°, less than about 80°, and less than about 60°. Based on the total weight of the reactive components in the reactive monomer mixture, the hydrophilic monomer can be, for example, in the range of about 0.1 wt % to about 100 wt %, alternatively in the range of about 1 wt % to about 80 wt %, alternatively in the range of about 5 wt % to about 65 wt %, alternatively in the range of about 40 to about 60 wt %, or alternatively in the range of about 55 wt % to about 60 wt %.

[0092] The silicone-containing component that may be present in the reactive mixture typically comprises one or more polymerizable compounds, wherein each compound independently comprises at least one polymerizable group, at least one siloxane group, and one or more linking groups linking the one or more polymerizable groups to the one or more siloxane groups. The silicone-containing component may, for example, contain from 1 to 220 siloxane repeating units, such as the groups defined below. The silicone-containing component may also contain at least one fluorine atom.

[0093] The silicone-containing component may comprise: one or more polymerizable groups as defined above; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units. The silicone-containing component may comprise: one or more polymerizable groups, the one or more polymerizable groups being independently (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, vinyl group, or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.

[0094] The silicone-containing component may include: one or more polymerizable groups that are independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinylamide, styryl, or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups that connect the polymerizable group to the siloxane unit.

[0095] The silicone-containing component may include: one or more polymerizable groups that are independently (meth)acrylates, (meth)acrylamides, or mixtures of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups that connect the polymerizable groups to the siloxane units.

[0096] The silicone-containing component may comprise one or more polymerizable compounds of formula A:

[0097]

[0098] in:

[0099] At least one R A Formula R g -L-, where R g is a polymerizable group and L is a linking group, and the remaining R A Each independently is:

[0100] (a)R g -L-,

[0101] (b) C1-C2 optionally substituted with one or more hydroxyl, amino, amide, oxa, carboxyl, alkylcarboxyl, carbonyl, alkoxy, amide, carbamate, carbonate, halogen, phenyl, benzyl, or a combination thereof 16 alkyl,

[0102] (c) C3-C4 optionally substituted with one or more alkyl, hydroxy, amino, amide, oxa, carbonyl, alkoxy, amido, carbamate, carbonate, halogen, phenyl, benzyl or a combination thereof 12 Cycloalkyl,

[0103] (d) C6-C6 optionally substituted with one or more alkyl, hydroxy, amino, amido, oxa, carboxyl, alkylcarboxyl, carbonyl, alkoxy, amido, carbamate, carbonate, halogen, phenyl, benzyl, or a combination thereof 14 Aryl groups,

[0104] (e) halogen,

[0105] (f) an alkoxy group, a cycloalkoxy group or an aryloxy group,

[0106] (g) silyloxy,

[0107] (h) an alkyleneoxy-alkyl or alkoxy-alkyleneoxy-alkyl, such as polyethyleneoxyalkyl, polypropyleneoxyalkyl or poly(ethyleneoxy-co-propyleneoxyalkyl), or

[0108] (i) a monovalent siloxane chain comprising 1 to 100 siloxane repeating units, the siloxane repeating units optionally substituted with alkyl, alkoxy, hydroxy, amino, oxa, carboxyl, alkylcarboxyl, alkoxy, amido, carbamate, halogen, or combinations thereof; and

[0109] n is 0 to 500, or 0 to 200, or 0 to 100, or 0 to 20, wherein it is understood that when n is not 0, n is a distribution with a mode equal to the specified value. When n is 2 or greater, the SiO units may have the same or different R A substituents, and if different R A Substituents, the n groups can be in random or block configuration.

[0110] In formula A, the three R A may each contain a polymerizable group, alternatively two R A may each contain a polymerizable group, or alternatively an R A A polymerizable group may be included.

[0111] Examples of silicone-containing components suitable for use in the present invention include, but are not limited to, the compounds listed in Table A. Where 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.

[0112] Table A

[0113]

[0114]

[0115] Additional non-limiting examples of suitable silicone-containing components are listed in Table B. Unless otherwise specified, where applicable, j2 is preferably 1 to 100, more preferably 3 to 40, or even more preferably 3 to 15. In compounds containing j1 and j2, the sum of j1 and j2 is preferably 2 to 100, more preferably 3 to 40, or even more preferably 3 to 15.

[0116] Table B

[0117]

[0118]

[0119] Mixtures of silicone-containing components may be used. By way of example, suitable mixtures may include, but are not limited to, mixtures of mono-(2-hydroxy-3-methacryloxypropoxy)-propyl terminated mono-n-butyl terminated polydimethylsiloxane (OH-mPDMS) having different molecular weights, such as mixtures of OH-mPDMS containing 4 and 15 SiO repeating units; mixtures of OH-mPDMS having different molecular weights (e.g., containing 4 and 15 repeating SiO repeating units) with silicone-based crosslinkers such as bis-3-acryloxy-2-hydroxypropoxypropyl polydimethylsiloxane (ac-PDMS); mixtures of 2-hydroxy-3-[3-methyl-3,3-bis(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA) and mono-methacryloxypropyl terminated mono-n-butyl terminated polydimethylsiloxane (mPDMS) such as mPDMS1000.

[0120] The silicone-containing components useful in the present invention may have an average molecular weight of from about 400 Daltons to about 4000 Daltons.

[0121] The one or more silicone-containing components may be present in an amount up to about 95 wt %, or about 10 wt % to about 80 wt %, or about 20 wt % to about 70 wt %, based on all reactive components of the reactive mixture (excluding diluent).

[0122] The reactive mixture may include at least one polyamide as a wetting agent. As used herein, the term "polyamide" refers to polymers and copolymers comprising repeating units containing amide groups. Polyamides may include cyclic amide groups, acyclic amide groups, and combinations thereof, and may be any polyamide known to those skilled in the art. Acyclic polyamides include acyclic amide pendant groups and are capable of combining with hydroxyl groups. Cyclic polyamides include cyclic amide groups and are capable of combining with hydroxyl groups.

[0123] Examples of suitable acyclic polyamides include polymers and copolymers comprising repeating units of formula G1 and G2:

[0124]

[0125]

[0126] Where X is a direct bond, -(CO)- or –(CONHR 44 )-, where R 44 is a C1 to C3 alkyl group; R 40 R is selected from H, linear or branched substituted or unsubstituted C1 to C4 alkyl groups; 41R is selected from H, a linear or branched substituted or unsubstituted C1 to C4 alkyl group, an amino group having up to two carbon atoms, an amide group having up to four carbon atoms and an alkoxy group having up to two carbon atoms; 42 R is selected from H, a linear or branched substituted or unsubstituted C1 to C4 alkyl group; or methyl, ethoxy, hydroxyethyl and hydroxymethyl; 43 is selected from H, a linear or branched substituted or unsubstituted C1 to C4 alkyl group; or methyl, ethoxy, hydroxyethyl and hydroxymethyl; wherein R 40 and R 41 The total number of carbon atoms in is 8 or less, including 7, 6, 5, 4, 3 or less; and wherein R 42 and R 43 The total number of carbon atoms in R is 8 or less, including 7, 6, 5, 4, 3 or less. 40 and R 41 The total number of carbon atoms in R may be 6 or less or 4 or less. 42 and R 43 The number of carbon atoms in the sum of may be 6 or less. As used herein, substituted alkyl groups include alkyl groups substituted with amine, amide, ether, hydroxyl, carbonyl or carboxyl groups, or combinations thereof.

[0127] R 40 and R 41 may be independently selected from H, substituted or unsubstituted C1 to C2 alkyl groups. X may be a direct bond, and R 40 and R 41 R may be independently selected from H, substituted or unsubstituted C1 to C2 alkyl groups. 42 and R 43 The groups may be independently selected from H, substituted or unsubstituted C1 to C2 alkyl groups, methyl, ethoxy, hydroxyethyl and hydroxymethyl.

[0128] The acyclic polyamide of the present invention may contain a majority of repeating units of formula LV or formula LVI, or the acyclic polyamide may contain at least 50 mol % (including at least 70 mol % and at least 80 mol %) of repeating units of formula G or formula G1. Specific examples of repeating units of formula G and formula G1 include repeating units derived from N-vinyl-N-methylacetamide, N-vinylacetamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N-vinyl-2-methyl-propionamide, N-vinyl-N,N'-dimethylurea, N,N-dimethylacrylamide, methacrylamide, and acyclic amides of formula G2 and G3:

[0129]

[0130]

[0131] Examples of suitable cyclic amides that can be used to form cyclic polyamides include α-lactams, β-lactams, γ-lactams, δ-lactams, and ε-lactams. Examples of suitable cyclic polyamides include polymers and copolymers comprising repeating units of formula G4:

[0132]

[0133] Where R 45 is a hydrogen atom or a methyl group; wherein f is a number from 1 to 10; wherein X is a direct bond, -(CO)- or -(CONHR 46 )-, where R 46 is a C1 to C3 alkyl group. In Formula LIX, f may be 8 or less, including 7, 6, 5, 4, 3, 2 or 1. In Formula G4, f may be 6 or less, including 5, 4, 3, 2 or 1. In Formula G4, f may be 2 to 8, including 2, 3, 4, 5, 6, 7 or 8. In Formula LIX, f may be 2 or 3. When X is a direct bond, f may be 2. In such cases, the cyclic polyamide may be polyvinylpyrrolidone (PVP).

[0134] The cyclic polyamide of the present invention may contain 50 mol% or more of the repeating unit of formula G4, or the cyclic polyamide may contain at least 50 mol% (including at least 70 mol% and at least 80 mol%) of the repeating unit of formula G4.

[0135] The polyamide may also be a copolymer comprising repeating units of both cyclic amides and acyclic amides. Additional repeating units may be formed from monomers selected from hydroxyalkyl (meth)acrylates, alkyl (meth)acrylates, other hydrophilic monomers, and siloxane-substituted (meth)acrylates. Any of the monomers (listed as suitable hydrophilic monomers) may be used as a co-monomer to form additional repeating units. Specific examples of additional monomers that can be used to form polyamides include 2-hydroxyethyl (meth)acrylate, vinyl acetate, acrylonitrile, hydroxypropyl (meth)acrylate, methyl (meth)acrylate, and hydroxybutyl (meth)acrylate, dihydroxypropyl (meth)acrylate, polyethylene glycol mono(meth)acrylate, and the like, and mixtures thereof. Ionic monomers may also be included. Examples of "ionic monomers" include (meth)acrylic acid, N-[(vinyloxy)carbonyl]-β-alanine (VINAL, CAS#148969-96-4), 3-acrylamidopropionic acid (ACA1), 5-acrylamidopropionic acid (ACA2), 3-acrylamido-3-methylbutyric acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-1-propaneammonium inner salt (CBT, carboxybetaine; CAS 79704-35-1), N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-1-propaneammonium inner salt (SBT, sulfobetaine, CAS 80293-60-3), 3,5-dioxa-8-aza-4-phosphaundec-10-en-1-ammonium, 4-hydroxy-N,N,N-trimethyl-9-oxo-4-oxide inner salt (9CI) (PBT, phosphobetaine, CAS163674-35-9), 2-methacryloyloxyethyl phosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS), methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

[0136] The reactive monomer mixture may include both acyclic polyamide and cyclic polyamide or their copolymers. Acyclic polyamide may be any of those acyclic polyamides described herein or their copolymers, and cyclic polyamide may be any of those cyclic polyamides described herein or their copolymers. Polyamide may be selected from polyvinyl pyrrolidone (PVP), polyvinyl methyl acetamide (PVMA), polydimethyl acrylamide (PDMA), polyvinyl acetamide (PNVA), poly (hydroxyethyl (methyl) acrylamide), polyacrylamide, and their copolymers and mixtures. Polyamide may be PVP (e.g., PVP K90) and PVMA (e.g., having an M of about 570 KDa). w ).

[0137] In all cases, the total amount of all polyamides in the reactive mixture can range from 1 wt % to about 35 wt %, including from about 1 wt % to about 15 wt % and from about 5 wt % to about 15 wt %, based on the total weight of the reactive components in the reactive monomer mixture.

[0138] Without intending to be bound by theory, the polyamide acts as an internal wetting agent when used with a silicone hydrogel. The polyamide of the present invention may be non-polymerizable, and in this case is incorporated into the silicone hydrogel as a semi-interpenetrating network. The polyamide is entrapped or physically retained within the silicone hydrogel. Alternatively, the polyamide of the present invention is polymerizable, for example as a polyamide macromer or prepolymer, and in this case is covalently incorporated into the silicone hydrogel. Mixtures of polymerizable and non-polymerizable polyamides may also be used.

[0139] When the polyamides are incorporated into the reactive monomer mixture, they may have a weight average molecular weight of at least 100,000 Daltons; greater than about 150,000 Daltons; about 150,000 Daltons to about 2,000,000 Daltons; about 300,000 Daltons to about 1,800,000 Daltons. Higher molecular weight polyamides may be used if they are compatible with the reactive monomer mixture.

[0140] It is generally desirable to add one or more crosslinking agents (also referred to as crosslinking monomers, multifunctional macromonomers, and prepolymers) to the reactive mixture. The crosslinking agent may be selected from a difunctional crosslinking agent, a trifunctional crosslinking agent, a tetrafunctional crosslinking agent, and mixtures thereof, including silicone-containing and silicone-free crosslinking agents. Silicone-free crosslinking agents include ethylene glycol dimethacrylate (EGDMA), tetraethylene glycol dimethacrylate (TEGDMA), trimethylolpropane trimethacrylate (TMPTMA), triallyl cyanurate (TAC), glycerol trimethacrylate, methacrylate oxyethyl vinyl carbonate (HEMAVc), allyl methacrylate, methylene bisacrylamide (MBA), and polyethylene glycol dimethacrylate (wherein the polyethylene glycol has a molecular weight of up to about 5000 Daltons). The crosslinking agent is used in the reactive mixture in conventional amounts (e.g., about 0.000415 moles to about 0.0156 moles per 100 grams of reactive formulation). Alternatively, if the hydrophilic monomers and / or silicone-containing components are multifunctional by molecular design or due to impurities, the addition of a crosslinker to the reactive mixture is optional. Examples of hydrophilic monomers and macromers that can act as crosslinkers and (when present) do not require the addition of an additional crosslinker to the reactive mixture include (meth)acrylates and (meth)acrylamide terminated polyethers. Other crosslinkers will be known to those skilled in the art and can be used to prepare the silicone hydrogels of the present invention.

[0141] It may be desirable to select a cross-linking agent that has a similar reactivity to one or more of the other reactive components in the formulation. In some cases, it may be desirable to select a mixture of cross-linking agents with different reactivities to control some physical, mechanical, or biological properties of the resulting silicone hydrogel. The structure and morphology of the silicone hydrogel may also be affected by the diluent or diluents used and the curing conditions.

[0142] Multifunctional silicone-containing components (including macromers, crosslinkers, and prepolymers) may also be included to further increase modulus and maintain tensile strength. Silicone-containing crosslinkers may be used alone or in combination with other crosslinkers. Examples of silicone-containing components that can act as crosslinkers and (when present) do not require the addition of crosslinking monomers to the reactive mixture include α,ω-bismethacryloxypropyl polydimethylsiloxane. Another example is bis-3-acryloxy-2-hydroxypropoxypropyl polydimethylsiloxane (ac-PDMS).

[0143] Crosslinkers having a rigid chemical structure and a polymerizable group that undergoes free radical polymerization may also be used. Non-limiting examples of suitable rigid structures include crosslinkers containing phenyl rings and benzyl rings, such as 1,4-phenylene diacrylate, 1,4-phenylene dimethacrylate, 2,2-bis(4-methacryloyloxyphenyl)-propane, 2,2-bis[4-(2-acryloyloxyethoxy)phenyl]propane, 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)-phenyl]propane and 4-vinylbenzyl methacrylate, and combinations thereof. The rigid crosslinker can be included in an amount between about 0.5 and about 15, or 2 to 10, 3 to 7, based on the total weight of all reactive components. By adjusting the components in the reactive mixture, the physical and mechanical properties of the silicone hydrogel of the present invention can be optimized for specific uses.

[0144] As described above, the reactive mixture may include additional components such as, but not limited to, diluents, initiators, UV absorbers, visible light absorbers, photochromic compounds, drugs, nutraceuticals, antimicrobial substances, toners, pigments, copolymerizable dyes, non-polymerizable dyes, release agents, and combinations thereof. Preferably, the reactive mixture may include a compound that imparts UV absorbing properties to the lens. Suitable UV absorbing compounds are known in the art and fall into several categories, including, but not limited to, benzophenones, benzotriazoles, triazines, substituted acrylonitriles, salicylic acid derivatives, benzoic acid derivatives, cinnamic acid derivatives, chalcone derivatives, acetophenone derivatives, crotonic acid derivatives, or any mixture thereof. One preferred class of UV absorbing compounds is benzotriazole, such as Norbloc (2-(2'-hydroxy-5-methacryloyloxyethylphenyl)-2H-benzotriazole).

[0145] Suitable classes of diluents for the silicone hydrogel reactive mixture include alcohols having 2 to 20 carbon atoms, amides derived from primary amines having 10 to 20 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. The diluents can be primary, secondary, and tertiary alcohols.

[0146] Generally, the reactive components are mixed in a diluent to form a reactive mixture. Suitable diluents are known in the art. Diluents suitable for silicone hydrogels are disclosed in WO 03 / 022321 and US6020445, the disclosures of which are incorporated herein by reference.

[0147] Suitable diluent classes for the silicone hydrogel reactive mixture include alcohols having 2 to 20 carbons, amides derived from primary amines having 10 to 20 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. Both primary and tertiary alcohols can be used. Preferred classes include alcohols having 5 to 20 carbons and carboxylic acids having 10 to 20 carbon atoms.

[0148] Specific diluents that can be used include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropyl alcohol, 3,7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-octanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, t-pentanol, t-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-propanol, 1-propanol, ethanol, 2-ethyl-1-butanol, (3-acetoxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methylsilane, 1-t-butoxy-2-propanol, 3,3-dimethyl-2-butanol, t-butoxyethanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, 2-(diisopropylamino)ethanol, mixtures thereof, and the like. Examples of amide diluents include N,N-dimethylpropionamide and dimethylacetamide.

[0149] Preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, 2-pentanol, tert-pentanol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, mixtures thereof, and the like.

[0150] More preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 1-dodecanol, 3-methyl-3-pentanol, 1-pentanol, 2-pentanol, tert-pentanol, 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.

[0151] If a diluent is present, there is generally no particular limitation on the amount of diluent present. When a diluent is used, the diluent may be present in an amount ranging from about 2 wt % to about 70 wt % (including in a range of about 5 wt % to about 50 wt % and in a range of about 15 wt % to about 40 wt %) based on the total weight of the reactive mixture (including reactive and non-reactive formulations). Mixtures of diluents may be used.

[0152] A polymerization initiator may be used in the reactive mixture. The polymerization initiator may include, for example, at least one of lauroyl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, etc., which generate free radicals at moderately elevated temperatures; and a photoinitiator system such as aromatic α-hydroxy ketones, alkoxyoxybenzoin, acetophenone, acylphosphine oxide, diacylphosphine oxide, and tertiary amine plus diketone, mixtures thereof, and the like. Illustrative examples of photoinitiators are 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenylpropane-1-one, bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentylphosphine oxide (DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure 819), 2,4,6-trimethylbenzyldiphenylphosphine oxide and 2,4,6-trimethylbenzoyldiphenylphosphine oxide, benzoin methyl ester, and a combination of camphorquinone and ethyl 4-(N,N-dimethylamino)benzoate.

[0153] Commercially available visible light initiator systems (from IGM Resins BV, The Netherlands) include 819, 1700, 1800, 819, 1850 and TPO initiator. Commercially available UV photoinitiators (from IGM Resins BV) include 1173 and 2959. These and other photoinitiators that may be used are disclosed in Volume III, Photoinitiators for Free Radical Cationic & Anionic Photopolymerization, 2nd Edition, by JV Crivello & K. Dietliker; edited by G. Bradley; John Wiley and Sons; New York; 1998. The initiator is used in the reactive mixture in an effective amount to initiate photopolymerization of the reactive mixture (e.g., from about 0.1 parts by weight to about 2 parts by weight per 100 parts of reactive monomer mixture). Polymerization of the reactive mixture may be initiated using appropriately selected heat or visible or ultraviolet light or other means, depending on the polymerization initiator used. Alternatively, initiation may be carried out using an electron beam in the absence of a photoinitiator. However, when a photoinitiator is used, the preferred initiator is a diacylphosphine oxide, such as bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide ( 819) or a combination of 1-hydroxycyclohexyl phenyl ketone and bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentylphosphine oxide (DMBAPO).

[0154] The contact lenses of the present invention containing photosensitizing chromophores preferably limit the transmission of HEV light. Thus, the contact lenses containing photosensitizing chromophores may, for example, transmit: 0% to 70% of light in the wavelength range of 400nm to 409nm. The transmittance of the contact lenses within 400nm to 409nm is at least 1%, or at least 2%, or at least 3%. The transmittance of the contact lenses at 400nm to 409nm may be 60% or less, or 50% or less, or 40% or less, or 30% or less, or 25% or less.

[0155] The contact lens containing the photosensitizing chromophore can transmit 10% to 95% of light in the wavelength range of 410 to 424 nm. The transmittance of the contact lens at 410 nm to 424 nm is at least 30%. The transmittance of the contact lens within 410 nm to 424 nm can be up to 85% or up to 75%.

[0156] The contact lens comprising the photosensitizing chromophore may transmit at least 40% of light in the wavelength range of 425 nm to 449 nm. The contact lens may have a transmittance of at least 50% in the range of 425 nm to 449 nm.

[0157] The contact lens comprising the photosensitizing chromophore may transmit at least 80% of light in the wavelength range of 450 nm to 800 nm. The contact lens may have a transmittance of at least 90% in the wavelength range of 450 nm to 800 nm.

[0158] Contact lenses containing photosensitizing chromophores may transmit 45% or less of light in the wavelength range of 280 nm to 399 nm. The contact lenses may have a transmittance of 35% or less, or 25% or less, or 20% or less, or 10% or less, or 5% or less in the range of 280 nm to 399 nm. Transmittance in the UV range of the spectrum may be achieved by including a UV filtering compound in the lens (e.g., a benzotriazole compound such as Norbloc).

[0159] Preferably, the photosensitizing chromophore in the contact lens is non-photochromic.

[0160] In addition to the contact lens containing the photosensitizing chromophore, the contact lens system of the present invention also includes a package surrounding the contact lens. The package has a transmittance of no more than 99% at each active wavelength exhibited by the photosensitizing chromophore. The package can be a primary package or a secondary package.

[0161] The packaging used in the lens system of the present invention protects the photosensitizing chromophore in the contact lens from photodegradation. The protection provided by the packaging may be complete (so the photosensitizing chromophore exhibits no photodegradation or very limited photodegradation while in the packaging), or it may be partial (the photosensitizing chromophore may partially photodegrade, but not to the same extent as would occur in the absence of the packaging). Thus, the contact lens containing the photosensitizing chromophore is photostabilized by the packaging.

[0162] The packaging of the present invention protects the photosensitive chromophore by at least partially blocking light at each active wavelength of the photosensitive chromophore. The blocking of the packaging can be described in terms of the percentage of transmittance of the packaging at the active wavelength. The packaging of the present invention has a percentage of transmittance of no more than 99%, or no more than 80%, or no more than 50% at each active wavelength. Preferably, the percentage of transmittance of the packaging at each active wavelength is equal to or less than the percentage of transmittance of the photosensitive chromophore at the same active wavelength.

[0163] Various techniques can be used to provide a package that exhibits a desired transmittance percentage at an active wavelength. For example, the package may contain its own light absorbing compound. The light absorbing compound may, for example, have a chromophore chemical structure identical to that of a photosensitive chromophore of a contact lens. However, preferably, the photosensitivity of the chromophore utilized by the package is less than that of the contact lens. Exemplary classes of chromophore compounds for packaging include thioxanthene derivatives, such as described in pre-grant publication number US20190271798, which is incorporated herein by reference. A specific example of such a light absorbing compound is: 2-(2-cyano-2-(9H-thioxanthene-9-ylidene) acetamido) ethyl methacrylate. The light absorbing compound can be incorporated into the package in a variety of ways, such as by copolymerizing or compounding it with other materials used to prepare the package, or including it in a coating applied to one or both surfaces of the package.

[0164] Curing of hydrogels and lens fabrication

[0165] The reactive mixture can be formed by any of the methods known in the art, such as shaking or agitation, and used to form a polymeric article or device by known methods.The reactive components are mixed together with or without a diluent to form a reactive mixture.

[0166] For example, contact lenses may be prepared by mixing the reactive components and optionally one or more diluents with a polymerization initiator and curing by appropriate conditions to form a product which may then be formed into an appropriate shape by lathing, cutting, etc. Alternatively, the reactive mixture may be placed in a mold and then cured into an appropriate article.

[0167] A method for making a molded contact lens such as a conventional or silicone hydrogel contact lens may include: preparing a reactive monomer mixture; transferring the reactive monomer mixture to a first mold; placing a second mold on top of the first mold filled with the reactive monomer mixture; and curing the reactive monomer mixture by free radical copolymerization to form a hydrogel in the shape of a contact lens.

[0168] The reactive mixture may be cured via any known process for molding reactive mixtures in the production of contact lenses, including spin casting and static casting. Spin molding is disclosed in U.S. Pat. Nos. 3,408,429 and 3,660,545, while static casting is disclosed in U.S. Pat. Nos. 4,113,224 and 4,197,266. The contact lenses of the present invention may be formed by direct molding of the hydrogel, which is both economical and allows precise control of the final shape of the hydrated lens. For this method, the reactive mixture is placed in a mold having the shape of the final desired hydrogel, and the reactive mixture is subjected to conditions that polymerize the monomers, thereby producing a polymer having the approximate shape of the final desired product.

[0169] After curing, the lens can be extracted to remove unreacted components and release the lens from the lens mold. The extraction can be performed using a conventional extraction liquid (eg, an organic solvent such as alcohol), or an aqueous solution can be used.

[0170] An aqueous solution is a solution comprising water. The aqueous solution of the present invention may comprise at least about 20% by weight of water, or at least about 50% by weight of water, or at least about 70% by weight of water, or at least about 95% by weight of water. The aqueous solution may also comprise additional water-soluble formulations, such as inorganic salts or release agents, wetting agents, lubricants, pharmaceutical and nutritional formulations, combinations thereof, and the like. A release agent is a compound or mixture of compounds that, when combined with water, reduces the time required to release a contact lens from a mold compared to the time required to release a contact lens from a mold using an aqueous solution without the release agent. The aqueous solution may not require specialized treatment, such as purification, recycling, or special disposal procedures.

[0171] Extraction can be achieved, for example, by immersing the lens in an aqueous solution or exposing it to a flowing aqueous solution. Extraction can also include, for example, one or more of the following: heating the aqueous solution; stirring the aqueous solution; increasing the level of a release aid in the aqueous solution to a level sufficient to release the lens; mechanically or ultrasonically agitating the lens; and incorporating at least one filtration or extraction aid into the aqueous solution to a level sufficient to promote adequate removal of unreacted components from the lens. The above operations can be performed in a batch or continuous process, with or without heating, stirring, or both.

[0172] It may be desirable to apply physical agitation to facilitate leaching and demolding. For example, the lens mold part to which the lens is adhered may be vibrated or moved back and forth in the aqueous solution. Other methods may include passing ultrasound through the aqueous solution.

[0173] The lens may be placed and sealed in a primary package by known methods. The lens may be sterilized by known means, including but not limited to autoclaving. The finished lens in its primary package may then be placed in a secondary package. A group of lenses in a primary package may be placed in the same secondary package.

[0174] As noted above, preferred contact lenses are soft hydrogel contact lenses. The transmission wavelengths and percentages described herein can be measured for lenses of various thicknesses using known methods. By way of example, the preferred center thickness for measuring the transmission spectrum in soft contact lenses can be 70 microns to 100 microns. Typically, transmittance measurements can be made through the center of the lens using an instrument slit width of, for example, 4 nm.

[0175] As discussed above, the present invention provides a contact lens system comprising a contact lens comprising a photosensitive chromophore and a package surrounding the contact lens. The package at least partially blocks wavelengths of light that would otherwise photodegrade the chromophore. Thus, the package is capable of stabilizing the photosensitive chromophore to prevent photodegradation. Advantageously, the package, while protecting the chromophore, can transmit light of other wavelengths, thereby allowing the contents of the package to be visible, for example, to the naked eye and / or to testing equipment used during the lens production process.

[0176] Another advantage of the present invention is that the level of protection provided by the packaging can be adjusted by changing the amount of light it blocks. This allows manufacturers to better control or adjust the shelf life of their products. Products that do not require a long shelf life can be contained in a package that only partially blocks the light of the otherwise photodegradable chromophore. On the other hand, if a longer shelf life is desired, a package that provides greater blocking of the wavelengths of the otherwise photodegradable chromophore can be used. A longer shelf life can result in, for example, reduced product waste.

[0177] Preferably, the contact lens containing the photosensitizing chromophore is protected using packaging in the present invention so that after exposure to light under ICH Guideline Q1B, the lens exhibits a change in its average transmittance in the wavelength range of 400nm to 450nm of less than 40%, or 35% or less, or 30% or less, or 10% or less, or 7% or less, or 5% or less, or 2% or less, or 0.5% or less. Such a change can be calculated as the absolute value of the difference between the average transmittance (in the wavelength range of 400nm to 450nm) of the lens protected from light exposure and the lens exposed under ICH Guideline Q1B.

[0178] The contact lenses according to the present invention may also exhibit the following properties. All values ​​are preceded by "about", and the device may have any combination of the listed properties. The properties may be determined by methods known to those skilled in the art, for example, as described in U.S. Pre-grant Publication US20180037690, which is incorporated herein by reference.

[0179] Water concentration %: at least 20% or at least 25% and at most 80% or at most 70%

[0180] Haze: 30% or less, or 10% or less

[0181] Advancing dynamic contact angle (Wilhelmy plate method): 100° or less, or 80° or less, or 50° or less

[0182] Tensile modulus (psi): 120 or less, or 80 to 120

[0183] Oxygen permeability (Dk, Baler): at least 80, or at least 100, or at least 150, or at least 200

[0184] Elongation at break: at least 100

[0185] For ionic silicone hydrogels, the following properties (in addition to those described above) may also be preferred:

[0186] Lysozyme absorption rate (μg / lens): at least 100, or at least 150, or at least 500, or at least 700

[0187] Polyquaternium 1 (PQ1) intake (%): 15 or less, or 10 or less, or 5 or less

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

[0189] Example

[0190] Example 1: Test lens preparation

[0191] Test contact lenses based on senofilcon A (without UV absorbing compounds) were prepared by polymerization / molding of a reactive mixture that contained, in addition to other device-forming monomers and additives, 2 wt % of 2-(4-acetyl-3-amino-2,6-dimethoxyphenoxy)ethyl methacrylate based on the total amount of all reactive components in the reactive mixture. The resulting test lenses were stripped from the lens molds in 70:30 isopropanol:water at room temperature and hydrated in 70:30 isopropanol:water before being transferred to standard borate buffered packaging solution. The test lenses were then autoclaved in the packaging solution for 30 minutes before long-term storage in heat-sealed contact lens blisters with standard packaging solution.

[0192] Contact lenses were characterized for light transmittance using a Cary 6000 Agilent Technologies UV-VIS-NIR spectrometer. Standard borate buffered packing solutions were filtered to remove any particles that could adversely affect spectral collection. The lenses were mounted in a lens holder with a hole size of approximately 6 mm x 12 mm and the assembly was then inserted into a 45 mm x 12.2 mm quartz spectrophotometer cuvette with a 10 mm path length. A matching assembly was prepared for a reference unit without a contact lens in the lens holder. Figure 1 The UV / Vis spectra of the test lenses of Example 1 are shown in FIG.

[0193] The lenses containing the chromophores described above exhibit photosensitivity to long-term exposure to light. Therefore, senofilcon A lenses containing 2 wt. % 2-(4-acetyl-3-amino-2,6-dimethoxyphenoxy)ethyl methacrylate were tested (these lenses are similar to Figure 1 The lenses can be prepared as described in U.S. Patent Application Serial No. 16 / 398,722. The lenses are packaged in transparent blister packs and then subjected to the ICH guideline Q1B conditions described above. These lenses are compared to lenses that were not exposed to the Q1B light conditions. The UV-visible light transmission spectrum is Figure 2 Shown in.

[0194] Figure 2 The photosensitivity of the lens after light exposure is shown. It can be seen that the ability of the lens to maintain its high energy visible light filtering properties is adversely altered with exposure. The average transmission in the 400nm-450nm range for the unexposed lens and the Q1B exposed lens is about 53% and about 64%, respectively. Therefore, Figure 2 The contact lens exhibited a change of about 11% in its average transmittance in the wavelength range of 400 nm to 450 nm after exposure to light under the conditions of ICH guideline Q1B.

[0195] Example 2: Light stress study

[0196] In this example, the effect of at least partially blocking light that would otherwise be absorbed by the photosensitizing chromophore, thereby reducing its photodegradation, is demonstrated.

[0197] 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 Figure 3 As can be seen, LAC absorbs at each of the active wavelengths of the chromophores used in the test lenses of Example 1.

[0198] To simulate packaging, prepare a 2mM solution of LAC1 by adding the appropriately weighed powder to propylene glycol as solvent; roll the glass bottle overnight to completely dissolve the LAC1. Each experimental test concentration of LAC1 requires a 30 ml volume: prepare 2mM, 0.5mM, and 0.1mM solutions by serial dilution. Protect the solution from light before use.

[0199] A set of glass covered petri dishes (60×15 mm and 100×10 mm) was purchased from Avantor; however, only the bottom petri dishes were used for the experiments. The smaller 60 mm×15 mm petri dishes used to hold the test contact lenses were covered with aluminum foil (Reynolds Consumer Products, LLC), with the foil covering the lip of the petri dish. The bottom 100×10 mm petri dish served as a reservoir for the LAC1 solution and should be balanced on the smaller petri dish. Therefore, this stacked assembly allows light to pass through the petri dish containing the LAC1 solution, but not through the sides of the smaller petri dish containing the test lens. The petri dishes were then illuminated with a 435 nm LED as the light source. A schematic diagram of this assembly is shown in Figure 4 Shown in.

[0200] The platform was set 7.5 inches from the LED panel. The LED intensity was adjusted to have 20 mW / cm across the platform. 2 The assembly with the four test solutions was assembled on the platform and the LEDs were illuminated for a total of 52 hours at room temperature. It should be noted that the lighting conditions of this example are more intense than the Q1B conditions discussed above and result in faster and / or more significant effects on the photosensitizing chromophores.

[0201] After exposure, UV / Vis spectra of the test contact lenses were collected using a Cary 6000 Agilent Technologies UV-VIS-NIR spectrometer as discussed above. UV / Vis spectra of test lenses exposed by various concentrations of LAC1 or by PG without LAC1 (control) were Figure 5 Shown in. Figure 5 Included are spectral curves for unexposed test lenses.

[0202] exist Figure 5 , Curve 1 is a reference blank control. Curve 2 is an unexposed test lens. Curve 3 is a test lens exposed through a 2 mM LAC1 solution cover layer. Curve 4 is a test lens exposed through a 0.5 mM LAC1 solution cover layer. Curve 5 is a test lens exposed through a 0.1 mM LAC1 solution cover layer. And Curve 6 is a test lens exposed through a 0 mM LAC1 solution cover layer (i.e., propylene glycol solvent only).

[0203] from Figure 5 As can be seen in Table 1, as the concentration of LAC1 increases, less photodegradation of the lens is observed relative to the unexposed lens (curve 2). The difference in average transmittance between the exposed lens and the unexposed lens in the wavelength range of 400nm to 450nm is shown in Table 1. The average transmittance of the unexposed lens in the range of 400nm-450nm is about 52%.

[0204] Table 1

[0205] Covering solution 400nm-450nm average transmittance Average transmittance: Difference from unexposed lens 2mM LAC1 77％ 25％ 0.5mM LAC1 89％ 37％ 0.1mM LAC1 87％ 35％ 0mM LAC1 92％ 40％

[0206] As shown in Table 1, LAC1 compounds that at least partially block the transmission of all wavelengths of light absorbed by the photosensitive chromophores of the test lenses protect the compound from photodegradation. The greater the degree of LAC1 blocking (due to its increased concentration in solution), the greater the degree of protection provided. The data suggest that increased protection can be provided by further increasing the level of blocking provided by the LAC1 compound (e.g., by increasing its concentration).

[0207] Example 3: Test lens preparation

[0208] Test contact lenses based on senofilcon A (without UV absorbing compounds) were prepared by polymerization / molding of a reactive mixture that contained, in addition to other device-forming monomers and additives, 2% by weight of 2-(1-amino-8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)oxy)ethyl methacrylate based on the total amount of all reactive components in the reactive mixture. The resulting test lenses were stripped from the lens molds in 70:30 isopropanol:water at room temperature and hydrated in 70:30 isopropanol:water before being transferred to a standard borate buffered packaging solution. The test lenses were then autoclaved in the packaging solution for 30 minutes before long-term storage in heat-sealed contact lens blisters with a standard packaging solution.

[0209] Contact lenses were characterized for light transmittance using a Cary 6000 Agilent Technologies UV-VIS-NIR spectrometer. Standard borate buffered packing solutions were filtered to remove any particles that could adversely affect spectral collection. The lenses were mounted in a lens holder with a hole size of approximately 6 mm x 12 mm and the assembly was then inserted into a 45 mm x 12.2 mm quartz spectrophotometer cuvette with a 10 mm path length. A matching assembly was prepared for a reference unit without a contact lens in the lens holder. Figure 6 The UV / Vis spectra of the test lenses of Example 3 are shown in FIG.

[0210] Example 4: Light stress study

[0211] In this example, the effect of at least partially blocking light that would otherwise be absorbed by the photosensitizing chromophore, thereby reducing its photodegradation, is demonstrated.

[0212] 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 Figure 3 As can be seen, LAC absorbs at each of the active wavelengths of the chromophores used in the test lenses of Example 3.

[0213] To simulate packaging, prepare a 2mM solution of LAC1 by adding the appropriately weighed powder to propylene glycol as solvent; roll the glass bottle overnight to completely dissolve the LAC1. Each experimental test concentration of LAC1 requires a 30 ml volume: prepare 2mM, 0.5mM, and 0.1mM solutions by serial dilution. Protect the solution from light before use.

[0214] A set of glass covered petri dishes (60×15 mm and 100×10 mm) was purchased from Avantor; however, only the bottom petri dish was used for the experiments. The smaller 60 mm×15 mm petri dishes used to hold the test contact lenses were covered with aluminum foil (Reynolds Consumer Products, LLC), where the foil covered the lip of the petri dish. The bottom 100×10 mm petri dish served as a reservoir for the LAC1 solution and should be balanced on the smaller petri dish. Therefore, this stacked assembly allows light to pass through the petri dish containing the LAC1 solution, but not through the sides of the smaller petri dish containing the test lens. The petri dishes were then illuminated with a 435 nm LED as the light source. A schematic diagram of this assembly is shown in Figure 4 Shown in.

[0215] The platform was set 7.5 inches from the LED panel. The LED intensity was adjusted to have 20 mW / cm across the platform. 2 The assemblies with the four test solutions were assembled on the platform, and the LEDs were lit for a total of 5 hours at room temperature.

[0216] After exposure, UV / Vis spectra of the test contact lenses were collected using a Cary 6000 Agilent Technologies UV-VIS-NIR spectrometer as discussed above. The UV / Vis spectra of the test lenses exposed by various concentrations of LAC1 or by PG without LAC1 (control) are shown in Figure 7. Figure 7 includes the spectrum curves of the unexposed test lenses.

[0217] exist Fig. 7A In the figure, Curve 1 is a reference blank control. Curve 2 is an unexposed test lens of Example 3. Curve 3 is a test lens exposed through a 2 mM LAC1 solution cover layer. Curve 4 is a test lens exposed through a 0.5 mM LAC1 solution cover layer. Curve 5 is a test lens exposed through a 0.1 mM LAC1 solution cover layer. And Curve 6 is a test lens exposed through a 0 mM LAC1 solution cover layer (i.e., propylene glycol solvent only). Figure 7B for Fig. 7A A magnified view of the graph showing the transmittance from 380 nm to 680 nm.

[0218] from Fig. 7A and Figure 7B As can be seen in Table 2, as the concentration of LAC1 increases, less photodegradation of the lens is observed relative to the unexposed lens (curve 2). The difference in average transmittance between the exposed lens and the unexposed lens in the wavelength range of 400nm to 450nm is shown in Table 2. The average transmittance of the unexposed lens in the range of 400nm-450nm is about 48%.

[0219] Table 2

[0220] Covering solution 400nm-450nm average transmittance Average transmittance: Difference from unexposed lens 2mM LAC1 48％ 0％ 0.5mM LAC1 56％ 8％ 0.1mM LAC1 56％ 8％ 0mM LAC1* 53％ 5％

[0221] *Note: The dish containing the propylene glycol solution above the lens had some condensation on the top surface which may have scattered some light and resulted in some degree of protection, which may explain why the 0 mM propylene glycol solution provided more protection than the diluted LAC1 solution. 2 The test method light intensity may be too high for the more photosensitive compound 2-((1-amino-8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)oxy)ethyl methacrylate, which in turn may affect the sensitivity of the test method.

[0222] As shown in Table 2, the LAC1 compound, which at least partially blocks the transmission of all wavelengths of light absorbed by the photosensitizing chromophore of the test lens of Example 3, protects the compound from photodegradation. The greater the degree of LAC1 blocking (due to its increased concentration in the solution), the greater the degree of protection provided. The data indicate that the 2 mM LAC1 solution provides sufficient protection to maintain an average transmission level between 400 nanometers and 450 nanometers as the unexposed test lens.

Claims

1. A contact lens system comprising: A contact lens comprising a photosensitizing chromophore having at least one active wavelength between 250 nanometers and 400 nanometers and at least one active wavelength between 400 nanometers and 450 nanometers; and A package surrounding the contact lens, the package having a light transmittance of no more than 80% at each active wavelength, wherein the active wavelength is a wavelength in the UV / Vis spectrum of the material where the percent transmission is 85% or less at that wavelength.

2. The contact lens system of claim 1, wherein the transmittance of the package is equal to or less than the transmittance of the photosensitizing chromophore at each active wavelength.

3. The contact lens system of claim 1 or 2, wherein the contact lens comprising the photosensitizing chromophore transmits: 0% to 70% of light in the wavelength range of 400 nm to 409 nm.

4. The contact lens system of claim 1 or 2, wherein the contact lens comprising the photosensitizing chromophore transmits: 10% to 95% of light within the wavelength range of 410 nm to 424 nm; at least 40% of light within the wavelength range of 425 nm to 449 nm; and at least 80% of light within the wavelength range of 450 nm to 800 nm.

5. The contact lens system of claim 1 or 2, wherein the contact lens comprising the photosensitizing chromophore transmits: 45% or less of light within the wavelength range of 280 nm to 399 nm.

6. The contact lens system of claim 1 or 2, wherein the photosensitizing chromophore is non-photochromic.

7. The contact lens system of claim 1 or 2, wherein the package is a primary package.

8. The contact lens system of claim 1 or 2, wherein the packaging is a secondary packaging.

9. The contact lens system of claim 1 or 2, wherein the contact lens comprising the photosensitizing chromophore exhibits a change of at least 2% in its average transmittance in the wavelength range of 400 nm to 450 nm after exposure to light under the conditions of ICH guideline Q1B.

10. The contact lens system of claim 1 or 2, wherein the photosensitive chromophore comprises an alkoxyaniline derivative containing a polymerizable group or a tetrahydronaphthyl derivative containing a polymerizable group.

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