Transition metal complexes as visible light absorbers

Abstract

Visible light absorbing ophthalmic devices are described that are readily prepared from ophthalmic device precursors, the ophthalmic device precursors comprising (a) a heterocyclic ligand of Formula I, [Formula 1] TIFF2026502754000020.tif35128 where m, n, t, R 1 , R 2 , and R 3 is as described herein; and (b) a monomer suitable for making an ophthalmic device precursor.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Patent Application No. 18 / 498,374, filed October 31, 2023, and U.S. Provisional Patent Application No. 63 / 387,561, filed December 15, 2022, both of which are incorporated herein by reference in their entireties.

[0002] FIELD OF THE INVENTION The present invention relates to a visible light-absorbing ophthalmic device. More specifically, the present invention relates to an ophthalmic device incorporating a transition metal complex that exhibits absorption of light having a wavelength within the range of, for example, about 500 to about 625 nm. [Background technology]

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

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

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

[0006] Absorbing high-energy radiation before it reaches the eye remains a desirable goal in ophthalmology. However, the degree to which certain wavelength ranges are absorbed is also important. For example, in the UV-A and UV-B ranges, it may be desirable to absorb as much radiation as possible. On the other hand, because HEV light forms part of the visible spectrum, complete absorption of HEV light may have adverse effects on vision. Therefore, partial absorption of HEV light may be more desirable.

[0007] Beyond HEV light, absorption of other portions of the visible spectrum can provide additional visual benefits (see Hammond, BR, Scientifica, 2012, 12, pp. 1-18). Indeed, because the human eye is most sensitive to green light with a wavelength of 555 nanometers under photopic or daylight conditions, a band of green-yellow light centered around 555 nanometers produces images with the highest brightness compared to other light colors. As a result, blocking green-yellow light between approximately 550 nanometers and approximately 600 nanometers can enhance contrast, improve image detail, and reduce glare and dazzle, thereby promoting visual comfort. For example, in U.S. Patent No. 7,506,977, Y. Aiiso describes eyeglass lenses containing organic dyes that absorb between 565 nanometers and 605 nanometers. In U.S. Patent No. 9,910,297, BSM McCabe et al. describe an ophthalmic lens configured to attenuate visible light in two spectral bands, one of which is green-yellow light between 550 nanometers and 590 nanometers.

[0008] Various compounds can provide visible light absorption at desired wavelengths. However, incorporating light-absorbing compounds into ophthalmic devices such as contact lenses can present difficulties. For example, transition metal complexes can provide desired light absorption, but they may exhibit lower solubility in the diluents or solvents typically used to prepare ophthalmic devices. As a result, it can be difficult to incorporate them at desired concentrations. Summary of the Invention [Problem to be solved by the invention]

[0009] There is a need for materials that provide targeted absorption of light wavelengths. Compounds that absorb or attenuate specific wavelengths, when used in ophthalmic devices, may help protect the cornea and internal cells in the ocular environment from deterioration, strain, and / or circadian rhythm disruption, and / or may provide visual benefits such as contrast enhancement, glare reduction, and treatment of color vision deficiencies. There is also a need for technology that facilitates the incorporation of light-absorbing materials into ophthalmic devices such as contact lenses. [Means for solving the problem]

[0010] The present invention relates to ophthalmic devices and their precursors that allow for the direct incorporation of transition metal complexes with desirable light absorption properties. For example, the device precursors of the present invention facilitate the incorporation of transition metal complexes in ophthalmic devices in desirable amounts.

[0011] Thus, in one aspect, the present invention provides an ophthalmic device precursor, which is a polymerization reaction product of a reactive mixture comprising: (a) a heterocyclic ligand of Formula I,

[0012] [ka] wherein m, n, and t are independently 0, 1, 2, 3, or 4; R 1 , R 2 , and R 3 is, when present, independently in each occurrence alkyl, aryl, heteroaryl, alkenyl, alkynyl, -COR 4 -COOR 4 -CONR 4 R 5 , CO(C=O)NR 4 R 5 -OR 4 , -SR 4 , -SOR 4 , -SO2R 4 , -NR 4 R 5 or -ALP g where R 4 and R5 is independently, in each occurrence, H or alkyl; A is a bond or aryl; L is a linking group; P g is a polymerizable group, and the heterocyclic ligand of formula I is at least one ALP g and (b) a monomer suitable for making an ophthalmic device precursor.

[0013] In another aspect, the present invention provides an ophthalmic device comprising an ophthalmic device precursor as described herein, wherein the ophthalmic device precursor is complexed with an iron salt.

[0014] In a further aspect, the present invention provides a process for making an ophthalmic device, the process comprising contacting an ophthalmic device precursor as described herein with a solution containing an iron salt, wherein the contacting is performed under conditions such that a complex is formed between the ophthalmic device precursor and the iron salt.

[0015] In a still further aspect, the present invention provides a compound which is 3-(4-([2,2':6',2''-terpyridin]-4'-yl)phenoxy)propyl methacrylate. [Brief explanation of the drawings]

[0016] [Figure 1] 1 shows the UV-VIS spectrum of the contact lens from Example 5. [Figure 2] 1 shows the UV-VIS spectrum of the contact lens from Example 6. [Figure 3] 1 shows the UV-VIS spectrum of the contact lens from Example 7. DETAILED DESCRIPTION OF THE INVENTION

[0017] It is to be understood that the invention is not limited to the details of construction or process steps set forth in the following description, as the invention is capable of other embodiments and of being practiced or carried out in various ways using the teachings herein.

[0018] The following definitions are provided for terms used in this disclosure.

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. The definition of polymer is consistent with the definition disclosed in Compendium of Polymer Terminology and Nomenclature, IUPAC Recommendations 2008, edited by: Richard G. Jones, Jaroslav Kahovec, Robert Stepto, Edward S. Wilks, Michael Hess, Tatsuki Kitayama, and W. Val Metanomski. All publications, patent applications, patents, and other references mentioned herein are incorporated herein by reference.

[0020] As used herein, the term "(meth)" refers to optional methyl substitution. Thus, a term such as "(meth)acrylate" refers to both methacrylate and acrylate.

[0021] Wherever a chemical structure is depicted, it should be understood that the disclosed alternatives for substituents in the structure can be combined in any combination. * and R ** and each of these contains a list of three possible groups, then nine combinations are disclosed. The same is true for combinations of properties.

[0022] General formula [ *** ] nWhen a subscript, such as "n" in {overscore (R)} is used to denote the number of repeat units in a chemical formula of a polymer, the formula should be interpreted as representing the number average molecular weight of the polymer.

[0023] The term "individual" includes humans and vertebrates.

[0024] The term "biomedical device" refers to any article designed to be used in or on mammalian tissue or fluid, preferably human tissue or fluid. Examples of these devices include, but are not limited to, wound dressings, sealants, tissue prostheses, drug delivery systems, coatings, adhesion barriers, catheters, implants, stents, and ophthalmic devices such as intraocular lenses and contact lenses. The biomedical device may be an ophthalmic device, specifically a contact lens, most specifically a contact lens made from a silicone hydrogel or a conventional hydrogel.

[0025] The term "ocular surface" includes the surface and glandular epithelium of the cornea, conjunctiva, lacrimal gland, accessory lacrimal gland, nasolacrimal duct, and meibomian gland, as well as their apical and basal matrices, puncta, and adjacent or associated structures, including the eyelids, which are connected as a functional system by both epithelial continuity through innervation and by the endocrine and immune systems.

[0026] The term "ophthalmic device" refers to any optical device that resides in or on the eye or any part of the eye (including the ocular surface). These devices can provide optical correction, appearance enhancement, vision enhancement, therapeutic effects (e.g., as a bandage), or delivery of active ingredients such as pharmaceutical and nutritional supplements, or any combination of the foregoing. Examples of ophthalmic devices include, but are not limited to, lenses, optics, and ocular inserts (including, but not limited to, punctal plugs). "Lens" includes spectacle lenses, sunglass lenses, soft contact lenses, hard contact lenses, hybrid contact lenses, intraocular lenses, and overlay lenses. Ophthalmic devices can include contact lenses.

[0027] 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, delivery of medications or nutritional supplements, diagnostic evaluation or monitoring, ultraviolet light absorption, visible light or glare reduction, or any combination thereof. Contact lenses can be of any suitable material known in the art and can be soft lenses, hard lenses, or hybrid lenses containing at least two distinct portions with different physical, mechanical, or optical properties, such as elastic modulus, water content, light transmission, or a combination thereof.

[0028] The ophthalmic devices, ophthalmic device precursors of the present invention may be composed of silicone hydrogels or conventional hydrogels. Silicone hydrogels typically contain at least one hydrophilic monomer and at least one silicone-containing component covalently bonded to each other in the cured device.

[0029] "Target polymer" means a polymer that has been synthesized from a reactive monomer mixture, including monomers, macromers, prepolymers, crosslinkers, initiators, additives, diluents, and the like.

[0030] The term "polymerizable compound" means a compound containing one or more polymerizable groups. This term includes, for example, monomers, macromers, oligomers, prepolymers, crosslinkers, and the like.

[0031] A "polymerizable group" is a group capable of undergoing chain growth polymerization, such as a carbon-carbon double bond that can polymerize when subjected to radical polymerization initiation conditions, such as free radical and / or cationic polymerization, preferably free radical polymerization. Non-limiting examples of polymerizable groups include (meth)acrylate groups, styryl groups, (meth)acrylamide groups, and vinyl groups. Preferably, the polymerizable group is selected from (meth)acrylate functional groups, (meth)acrylamide functional groups, N-vinyl lactam functional groups, N-vinylamide functional groups, vinyl carbonate functional groups, vinyl ether functional groups, vinyl carbamate functional groups, and styryl functional groups. More preferably, the polymerizable group is selected from (meth)acrylate and (meth)acrylamide. The polymerizable group can be unsubstituted or substituted. For example, the nitrogen atom in (meth)acrylamide can be bonded to hydrogen, or the hydrogen can be replaced by alkyl or cycloalkyl (which can themselves be further substituted).

[0032] Any type of free radical polymerization can be used, including but not limited to bulk, solution, suspension, and emulsion, as well as any of the controlled radical polymerization 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, etc.

[0033] A "monomer" is a monofunctional molecule that can undergo chain-growth polymerization, particularly free-radical polymerization, thereby creating repeating units within the chemical structure of a target macromolecule. Some monomers have difunctional impurities that can act as crosslinkers. A "hydrophilic monomer" is also a monomer that, when mixed with deionized water at 25°C at a concentration of 5 weight percent, yields a clear, single-phase solution. A "hydrophilic component" is a monomer, macromer, prepolymer, initiator, crosslinker, additive, or polymer that, when mixed with deionized water at 25°C at a concentration of 5 weight percent, yields a clear, single-phase solution. A "hydrophobic component" is a monomer, macromer, prepolymer, initiator, crosslinker, additive, or polymer that is slightly soluble or insoluble in deionized water at 25°C.

[0034] A "polymer" is an organic compound having a number average molecular weight greater than 1500, and can be reactive or non-reactive.

[0035] A "macromonomer" or "macromer" is a polymer having one group capable of undergoing chain-growth polymerization, particularly free-radical polymerization, thereby creating repeat units within the chemical structure of a target polymer. Generally, the chemical structure of a macromer differs from that of the target polymer; i.e., the repeat units of the pendant group of the macromer differ from the repeat units of the target polymer or its backbone. The only differences between a monomer and a macromer are the chemical structure of the pendant group, the molecular weight, and the molecular weight distribution. Consequently, and as used herein, patent literature sometimes defines a monomer as a polymerizable compound having a relatively low molecular weight of about 1,500 daltons or less, which essentially includes some macromers. Specifically, monomethacryloxypropyl-terminated, mono-n-butyl-terminated polydimethylsiloxane (molecular weight = 500-1500 g / mol) (mPDMS) and mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether-terminated, mono-n-butyl-terminated polydimethylsiloxane (molecular weight = 500-1500 g / mol) (OH-mPDMS) may be referred to as monomers or macromers. Furthermore, the patent literature sometimes defines macromers as having one or more polymerizable groups, essentially expanding the general definition of macromer to include prepolymers. Consequently, and as used herein, difunctional and multifunctional macromers, prepolymers, and crosslinkers may be used interchangeably.

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

[0037] Examples of silicone-containing components useful in the present invention are disclosed in U.S. Pat. Nos. 3,808,178, 4,120,570, 4,136,250, 4,153,641, 4,740,533, 5,034,461, 5,070,215, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,760,100, 5,849,811, 5,96 No. 2,548, No. 5,965,631, No. 5,998,498, No. 6,367,929, No. 6,822,016, No. 6,943,203, No. 6,951,894, No. 7,052,131, No. No. 7,247,692, No. 7,396,890, No. 7,461,937, No. 7,468,398, No. 7,538,146, No. 7,553,880, No. 7,572,841, No. 7,666,921 , No. 7,691,916, No. 7,786,185, No. 7,825,170, No. 7,915,323, No. 7,994,356, No. 8,022,158, No. 8,163,206, No. 8,273, No. 802, No. 8,399,538, No. 8,415,404, No. 8,420,711, No. 8,450,387, No. 8,487,058, No. 8,568,626, No. 8,937,110, No. 8,9 37,111, 8,940,812, 8,980,972, 9,056,878, 9,125,808, 9,140,825, 9,156,934, 9,170,349, 9,217,813, 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,929, and European Patent No. 080539. These patents are incorporated herein by reference in their entirety.

[0038] A "polymer" is a target macromolecule made up of repeating units of the monomers used during polymerization.

[0039] A "homopolymer" is a polymer made from one monomer; a "copolymer" is a polymer made from two or more monomers; and a "terpolymer" is a polymer made from three monomers. A "block copolymer" consists of compositionally distinct blocks or segments. A diblock copolymer has two blocks. A triblock copolymer has three blocks. A "comb or graft copolymer" is made from at least one macromer.

[0040] A "repeating unit" is the smallest group of atoms in a polymer that corresponds to the polymerization of a particular monomer or macromer.

[0041] An "initiator" is a molecule that can decompose into radicals that can subsequently react with monomers to initiate a free-radical polymerization reaction. Thermal initiators decompose at a specific rate depending on the temperature, and typical examples are azo compounds such as 1,1'-azobisisobutyronitrile and 4,4'-azobis(4-cyanovaleric acid); peroxides such as benzoyl peroxide, tert-butyl peroxide, tert-butyl hydroperoxide, tert-butyl peroxybenzoate, dicumyl peroxide, and lauroyl peroxide; peracids such as peracetic acid and potassium persulfate; and various redox systems. Photoinitiators decompose by a photochemical process, and typical examples are derivatives of benzil, benzoin, acetophenone, benzophenone, camphorquinone, and mixtures thereof, as well as various monoacyl and bisacylphosphine oxides and combinations thereof.

[0042] A "crosslinker" is a di- or polyfunctional monomer or macromer that can undergo free radical polymerization at two or more positions on the molecule, thereby creating branch points and polymer networks. Common examples are ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, methylene bisacrylamide, triallyl cyanurate, etc.

[0043] A "prepolymer" is a reaction product of monomers that contain remaining polymerizable groups that can undergo further reaction to form a polymer.

[0044] A "polymer network" is a cross-linked polymer that can swell but cannot be dissolved in a solvent. 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 together with at least one hydrophilic component. The hydrophilic component may also include a non-reactive polymer.

[0045] "Conventional hydrogel" refers to a polymer network made from components that do not have any siloxy, siloxane, or carbosiloxane groups. Conventional hydrogels are prepared from reactive mixtures that include hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate ("HEMA"), N-vinylpyrrolidone ("NVP"), N,N-dimethylacrylamide ("DMA"), or vinyl acetate. U.S. Patent Nos. 4,436,887, 4,495,313, 4,889,664, 5,006,622, 5,039459, 5,236,969, 5,270,418, 5,298,533, 5,824,719, 6,420,453, 6,423,761, 6,767,979, 7,934,830, 8,138,290, and 8,389,597 disclose the formation of conventional hydrogels. Commercially available conventional hydrogels include, but are not limited to, etafilcon, genfilcon, hilafilcon, lenefilcon, nesofilcon, omafilcon, polymacon, and vifilcon, including all variations thereof.

[0046] "Silicone hydrogel" refers to a polymer network made from at least one hydrophilic component and at least one silicone-containing component. Examples of suitable groups of hydrophilic components that can 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 widely described in 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 chemical bonds) connecting the polymerizable group to the siloxane group. The silicone-containing component can contain, for example, 1 to 220 siloxane repeating units. The silicone-containing component can also contain at least one fluorine atom. The silicone hydrogel lens can include a coating, which can be the same or a different material as the substrate.

[0047] Examples of silicone hydrogels include acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, and narafilcon. In addition to lyon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon (including all variations thereof), U.S. Patent Nos. 4,659,782, 4,659,783, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,998,498, 6,087,415, 5,760,1 No. 00, No. 5,776,999, No. 5,789,461, No. 5,849,811, No. 5,965,631, No. 6 ,367,929, 6,822,016, 6,867,245, 6,943,203, 7,247,692 No. 7,249,848, No. 7,553,880, No. 7,666,921, No. 7,786,185, No. 7,95 6,131, 8,022,158, 8,273,802, 8,399,538, 8,470,906, No. 8,450,387, No. 8,487,058, No. 8,507,577, No. 8,637,621, No. 8,703,8 No. 91, No. 8,937,110, No. 8,937,111, No. 8,940,812, No. 9,056,878, No. 9, No. 057,821, No. 9,125,808, No. 9,140,825, No. 9156,934, No. 9,170,349, Same No. 9,244,196, Same No. 9,244,197, Same No. 9,260,544, Same No. 9,297,928, Same No. 9,297,929, and silicone hydrogels such as those prepared in WO 03 / 22321, WO 2008 / 061992, and U.S. Patent Application Publication No. 2010 / 0048847, which are incorporated herein by reference in their entireties.

[0048] An "interpenetrating polymer network" comprises two or more networks that are at least partially entangled on a molecular scale but are not covalently bonded to each other and cannot be separated without interlocking chemical bonds. A "semi-interpenetrating polymer network" comprises one or more networks and one or more polymers characterized by some intermixing at the molecular level between at least one network and at least one polymer. A mixture of different polymers is a "polymer blend." Although a semi-interpenetrating network is technically a polymer blend, in some cases the polymers are entangled so that they cannot be easily removed.

[0049] "Reactive components" are polymerizable compounds (such as monomers, macromers, oligomers, prepolymers, and crosslinkers) in the reactive mixture (as defined below), as well as any other components in the reactive mixture that are intended to substantially remain in the resulting polymer network after polymerization and all workup steps (such as extraction steps) and packaging steps are complete. Reactive components may be retained within the polymer network by covalent bonds, 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 during use are still considered "reactive components." For example, a pharmaceutical or nutraceutical ingredient in a contact lens that is intended to be released during wear would be considered a "reactive component." Components that are intended to be removed from the polymer network during the manufacturing process (e.g., by extraction), such as diluents, are not "reactive components."

[0050] The terms "reactive mixture" and "reactive monomer mixture" refer to a mixture of components that, when mixed together and subjected to polymerization conditions, result in the formation of polymer networks (such as conventional or silicone hydrogels) and biomedical devices, ophthalmic devices, and contact lenses made therefrom. Reactive monomer mixtures can include reactive components such as monomers, macromers, prepolymers, crosslinkers, and initiators; wetting agents, polymers; light-absorbing compounds such as dyes and UV absorbers; pigments, dyes, and photochromic compounds; and additives such as pharmaceutical and nutraceutical compounds (all of which can be polymerizable or non-polymerizable but can be retained in the resulting biomedical device (e.g., contact lens)). The reactive mixture can also contain other components, such as diluents, that are intended to be removed from the device prior to use. It is understood that a wide range of additives can be added depending on the contact lens being manufactured and its intended use. The concentrations of the components of the reactive mixture are expressed as weight percent of all reactive components in the reactive mixture. If diluents are used, their concentrations are expressed as weight percent based on the amount of all components (including the diluent) in the reactive mixture.

[0051] The term "silicone hydrogel contact lenses" refers to hydrogel contact lenses made from at least one silicone-containing compound. Silicone hydrogel contact lenses generally have increased oxygen permeability compared to traditional hydrogels. Silicone hydrogel contact lenses utilize both their water content and polymer content to deliver oxygen to the eye.

[0052] The term "multifunctional" refers to a component having two or more polymerizable groups. The term "monofunctional" refers to a component having one polymerizable group.

[0053] The terms "halogen" or "halo" refer to fluorine, chlorine, bromine, and iodine.

[0054] "Alkyl" refers to an optionally substituted straight or branched chain alkyl group containing the indicated number of carbon atoms. If no number is indicated, the alkyl (including any optional substituents on the alkyl) can 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 include methyl, ethyl, propyl, isopropyl, butyl, iso-, sec-, and tert-butyl, pentyl, hexyl, heptyl, 3-ethylbutyl, and the like. Examples of substituents on alkyl include one, two, or three groups independently selected from hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, thioalkyl, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Alkylene" means a divalent alkyl group, for example, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH(CH3)CH2-, and -CH2CH2CH2CH2-.

[0055] "Haloalkyl" refers to an alkyl group, as defined above, substituted by one or more halogen atoms, where each halogen is independently F, Cl, Br, or I. A preferred halogen is F. Preferred haloalkyl groups contain 1 to 6 carbons, more preferably 1 to 4 carbons, and even more preferably 1 to 2 carbons. "Haloalkyl" includes perhaloalkyl groups such as -CF3- or -CF2CF3-. "Haloalkylene" refers to a divalent haloalkyl group, such as -CH2CF2-.

[0056] "Cycloalkyl" refers to an optionally substituted cyclic hydrocarbon containing the designated number of ring carbon atoms. If no number is specified, the cycloalkyl can contain 3 to 12 ring carbon atoms. C3-C8 cycloalkyl, C3-C7 cycloalkyl, more preferably C4-C7 cycloalkyl, and even more preferably C5-C6 cycloalkyl are preferred. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of substituents on cycloalkyl include one, two, or three groups independently selected from alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, thioalkyl, amido, carbamate, carbonate, halo, phenyl, benzyl, and combinations thereof. "Cycloalkylene" refers to a divalent cycloalkyl group such as 1,2-cyclohexylene, 1,3-cyclohexylene, or 1,4-cyclohexylene.

[0057] "Heterocycloalkyl" refers to a cycloalkyl ring or ring system, as defined above, in which at least one ring carbon is replaced by a heteroatom selected from nitrogen, oxygen, and sulfur. The heterocycloalkyl ring is optionally fused to or otherwise attached to other heterocycloalkyl rings and / or non-aromatic hydrocarbon rings and / or phenyl rings. Preferred heterocycloalkyl groups have 5 to 7 members. More preferred heterocycloalkyl groups have 5 or 6 members. Heterocycloalkylene refers to a divalent heterocycloalkyl group.

[0058] "Aryl" refers to an optionally substituted aromatic hydrocarbon ring system containing at least one aromatic ring. The aryl group contains the indicated number of ring carbon atoms. If no number is indicated, the aryl may contain 6 to 14 ring carbon atoms. The aromatic ring may optionally be fused to or otherwise attached to another aromatic or non-aromatic hydrocarbon ring. Examples of aryl groups include phenyl, naphthyl, and biphenyl. Preferred examples of aryl groups include phenyl. Examples of substituents on aryl groups include one, two, or three groups independently selected from alkyl, hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, thioalkyl, carbamate, carbonate, halo, phenyl, benzyl, and combinations thereof. "Arylene" refers to a divalent aryl group, such as 1,2-phenylene, 1,3-phenylene, or 1,4-phenylene.

[0059] "Heteroaryl" refers to an aryl ring or ring system, as defined above, in which at least one ring carbon atom is replaced by a heteroatom selected from nitrogen, oxygen, and sulfur. The heteroaryl ring may be fused to or otherwise bonded to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings, or heterocycloalkyl rings. Examples of heteroaryl groups include pyridyl, furyl, pyrazinyl, benzimidazolyl, and thienyl. "Heteroarylene" refers to a divalent heteroaryl group.

[0060] "Alkoxy" refers to an alkyl group attached to the parent molecular moiety through an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy, and isopropoxy. "Thioalkyl" refers to an alkyl group attached to the parent molecular moiety through a sulfur bridge. Examples of thioalkyl groups include, for example, methylthio, ethylthio, n-propylthio, and isopropylthio. "Aryloxy" refers to an aryl group attached to the parent molecular moiety through an oxygen bridge. An example is phenoxy. "Cyclicalkoxy" refers to a cycloalkyl group attached to the parent moiety through an oxygen bridge.

[0061] "Alkylamine" refers to an alkyl group attached to the parent molecular moiety through an -NH bridge. Alkyleneamine refers to a divalent alkylamine group, such as -CH2CH2NH-.

[0062] "Siloxanyl" refers to a structure having at least one Si-O-Si bond. Thus, for example, a siloxanyl group refers to a group having at least one Si-O-Si group (i.e., a siloxane group), and a siloxanyl compound refers to a compound having at least one Si-O-Si group. "Siloxanyl" refers to 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 siloxanyl group is independently selected to complete their valence. A Group(R A is replaced by (as defined in options (b) to (i) of Formula A).

[0063] "Silyl" refers to a structure of formula R3Si-, and "siloxy" refers to a structure of formula R3Si-O-, where each R in silyl or siloxy is independently selected from trimethylsiloxy, C1-C8 alkyl (preferably C1-C3 alkyl, more preferably ethyl or methyl), and C3-C8 cycloalkyl.

[0064] "Alkyleneoxy" refers to a group having the general formula -(alkylene-O) p -or -(O-alkylene) p " refers to the group -, where alkylene is as defined above, 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, and each alkylene is independently optionally substituted with one or more groups independently selected from hydroxyl, halo (e.g., fluoro), amino, amido, ether, carbonyl, carboxyl, and combinations thereof. When p is greater than 1, each alkylene can be the same or different, and the alkyleneoxy can be in a block or random configuration. When the alkyleneoxy forms a terminal group in a molecule, the terminus of the alkyleneoxy can be, for example, a hydroxy or alkoxy (e.g., HO-[CHCHO] p - or CHO-[CHCHO] p Examples of alkyleneoxy include polyethyleneoxy, polypropyleneoxy, polybutyleneoxy, and poly(ethyleneoxy-co-propyleneoxy).

[0065] "Oxaalkylene" refers to an alkylene group as defined above in which one or more non-adjacent CH groups are replaced by an oxygen atom, such as -CHCHOCH(CH)CH-. "Thiaalkylene" refers to an alkylene group as defined above in which one or more non-adjacent CH groups are replaced by a sulfur atom, such as -CHCHSCH(CH)CH-.

[0066] The term "linking group" refers to a moiety that connects a polymerizable group to a parent molecule. The linking group can be any moiety that is compatible with the compound of which it is a part, does not undesirably interfere with the polymerization of the compound, and is stable under the conditions of polymerization, as well as under the conditions of processing and storage of the final product. For example, the linking group can be a bond or can include one or more alkylene, haloalkylene, amide, amine, alkyleneamine, carbamate, ester (-CO-), arylene, heteroarylene, cycloalkylene, heterocycloalkylene, alkyleneoxy, oxaalkylene, thiaalkylene, haloalkyleneoxy (alkyleneoxy substituted with one or more halo groups, e.g., -OCF-, -OCFCF-, -OCFCH-), siloxanyl, alkylenesiloxanyl, or combinations thereof. The linking group can be optionally substituted with one or more substituents. Suitable substituents may include those independently selected from alkyl, halo (e.g., fluoro), hydroxyl, HO-alkyleneoxy, MeO-alkyleneoxy, siloxanyl, siloxy, siloxy-alkyleneoxy-, siloxy-alkylene-alkyleneoxy- (two or more alkyleneoxy groups may be present, and each methylene in the alkylene and alkyleneoxy is independently optionally replaced with hydroxyl), ether, amine, carbonyl, carbamate, and combinations thereof. The linking group may also be substituted with a polymerizable group (in addition to the polymerizable group to which it is linked), such as (meth)acrylate.

[0067] Preferred linking groups include C1-C8 alkylene (preferably C2-C6 alkylene), C1-C8 oxaalkylene (preferably C2-C6 oxaalkylene), C1-C8 thiaalkylene, C1-C8 alkylene-carboxylate-C1-C8 alkylene, C1-C8 alkylene-amido-C1-C8 alkylene, and C1-C8 alkylene-amine-C1-C8 alkylene, each of which is optionally substituted with one or two groups independently selected from hydroxyl and siloxy.

[0068] When the linking group is composed of a combination of moieties (e.g., alkylene and cycloalkylene) as described above, the moieties can be present in any order. For example, in Formula A below, when L is shown to be -alkylene-cycloalkylene-, Rg-L can be either Rg-alkylene-cycloalkylene- or Rg-cycloalkylene-alkylene-. Regardless, the listed order represents the preferred order in which the moieties appear in the compound, starting from the terminal polymerizable group (Rg or Pg) to which the linking group is attached. For example, in Formula A, when L is shown to be alkylene-cycloalkylene, Pg-L is preferably Pg-alkylene-cycloalkylene-.

[0069] The term "light-absorbing compound" refers to a chemical substance that absorbs light within the visible spectrum (e.g., in the range of 380-780 nm). The ability of a material to absorb light of a particular wavelength can be determined by measuring its UV / Vis transmission or absorption spectrum.

[0070] When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless otherwise specified, the compounds are intended to include the cis, trans, Z-, and E-configurations, as well as all tautomeric and salt forms.

[0071] The term "optional substituent" means that an underlying hydrogen atom is optionally replaced by a substituent. Any substituent that is sterically practical at the substitution site and synthetically feasible may be used. Identification of suitable optional substituents is within the ability of one of ordinary skill in the art. Examples of "optional substituents" include C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl, halo, hydroxy, amino, NR 4 R 5 , benzyl, SO3H, SO3Na, or -LP g and wherein R 4 and R5 are independently H or C1-C6 alkyl, L is a linking group, and P g is a polymerizable group. The foregoing substituents can be optionally substituted with optional substituents (which, unless otherwise indicated, are preferably not further substituted). For example, alkyl can be substituted with halo (e.g., resulting in CF).

[0072] Unless otherwise indicated, ratios, percentages, parts, etc. are by weight.

[0073] Unless otherwise indicated, numerical ranges, such as in "from 2 to 10" or "between 2 and 10," include the numbers defining the range (e.g., 2 and 10).

[0074] As noted above, in one aspect, the present invention provides an ophthalmic device precursor that is a polymerization reaction product of a reactive mixture comprising (a) a heterocyclic ligand and (b) a monomer suitable for making the ophthalmic device precursor.

[0075] The heterocyclic ligand used in the present invention is a compound of formula I:

[0076] [ka] wherein m, n, and t are independently 0, 1, 2, 3, or 4; R 1 , R 2 , and R 3 is, when present, independently in each occurrence alkyl, aryl, heteroaryl, alkenyl, alkynyl, -COR 4 , -COOR 4 , -CONR 4 R 5 , CO(C=O)NR 4 R 5 , -OR 4 , -SR 4 , -SOR 4 , -SO2R4 , -NR 4 R 5 or -ALP g where R at each occurrence 4 and R 5 are independently H or alkyl; A is a bond or an aryl; L is a linking group; P g is a polymerizable group, and the heterocyclic ligand of formula I is at least one ALP g It contains a group.

[0077] Preferred heterocyclic ligands of formula I include compounds where m or t is 0.

[0078] Preferred heterocyclic ligands of formula I include compounds where m and t are both zero.

[0079] Preferred heterocyclic ligands of formula I include compounds where n is 1.

[0080] Preferred heterocyclic ligands of formula I are R 2 Ga-ALP g The present invention includes compounds in which:

[0081] Preferred heterocyclic ligands of formula I include compounds where A is a bond.

[0082] Preferred heterocyclic ligands of formula I include compounds where A is aryl, preferably phenyl.

[0083] Preferred heterocyclic ligands of Formula I are those in which the linking group at each occurrence is independently C1-C8 alkylene, C1-C8 oxaalkylene, C1-C8 thiaalkylene, carboxylate-C1-C8 alkylene, C1-C8 alkylene-carboxylate-C1-C8 alkylene, C1-C8 alkylene-amido-C1-C8 alkylene, arylene-C1-C8 alkyleneoxy, arylene-amine-C1-C8 alkylene, or C1-C8 alkylene-amine-C1-C8 alkylene. Exemplary linking groups include -OCH2CH2- and -OCH2CH2CH2-.

[0084] Preferred heterocyclic ligands of Formula I include compounds in which the polymerizable group in each occurrence is independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, vinyl carbonate, vinyl ether, vinyl carbamate, or styryl. Preferred polymerizable groups are (meth)acrylate, more preferably methacrylate.

[0085] Specific examples of heterocyclic ligands for use in the present invention are shown in Table A.

[0086] [Table 1]

[0087] The heterocyclic ligands used in the present invention can be prepared by those skilled in the art using literature methods. Exemplary syntheses are presented in the examples below.

[0088] The heterocyclic ligands of the present invention are included in a reactive mixture to form an ophthalmic device precursor. The ligands can generally be added to the reactive mixture from which the device is made and can be present in any amount up to their solubility limits. For example, the ligands can be present in a concentration of at least 0.1 percent, or at least 2 percent, and up to 10 percent or up to 5 percent, based on the weight percent of all components in the reactive mixture excluding the diluent. Typical concentrations can range from 1 to 5 percent. The upper limit is typically determined by the solubility of the compound with other comonomers and / or diluents in the reactive monomer mixture.

[0089] Heterocyclic ligands can be used in combination with other light-absorbing compounds to provide desirable absorption properties. For example, preferred compositions can include heterocyclic ligands as described above in conjunction with UV-absorbing compounds and / or visible light, such as high-energy visible (HEV) light, absorbing compounds. Suitable UV-absorbing compounds are well 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, dipnone derivatives, crotonic acid derivatives, or any mixture thereof. A preferred class of UV-absorbing compounds are benzotriazoles, such as Norbloc (2-(2'-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole). Non-limiting examples of visible light-absorbing compounds are provided in the examples below.

[0090] The reactive mixtures from which the ophthalmic device precursors and ophthalmic devices of the present invention are made contain, in addition to the heterocyclic ligands described above, one or more monomers and optional components suitable for making the desired ophthalmic device or precursor. Thus, the reactive mixtures may contain, for example, hydrophilic components, hydrophobic components, silicone-containing components, wetting agents such as polyamides, crosslinkers, and additional components such as diluents and initiators.

[0091] hydrophilic component Examples of suitable families of hydrophilic monomers that may be present in the reactive mixture include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl carbamates, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof.

[0092] 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-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.

[0093] The hydrophilic monomers can also be ionic, such as anionic, cationic, zwitterionic, betaine, and mixtures thereof. Non-limiting examples of such charged monomers include (meth)acrylic acid, N-[(ethenyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropanoic acid (ACA1), 5-acrylamidopentanoic acid (ACA2), 3-acrylamido-3-methylbutanoic acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, inner salt (CBT), 1-propanaminium, N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-, inner salt (SBT), 3,5-dioxa- Examples include 8-aza-4-phosphanundec-10-en-1-aminium, 4-hydroxy-N,N,N-trimethyl-9-oxo-, inner salt, 4-oxide (9CI) (PBT), 2-methacryloyloxyethyl phosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS), and methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

[0094] Non-limiting examples of hydrophilic N-vinyl lactam and N-vinyl amide monomers include N-vinylpyrrolidone (NVP), N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-caprolactam, N-vinyl-3-methyl-2-piperidone, N-vinyl-4-methyl-2-piperidone, N-vinyl-4-methyl-2-caprolactam, N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone, N-vinylacetamide (NVA), N-vinyl-N-methylacetamide (VMA), N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N-vinylformamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N-vinyl ... N-methylpropionamide, N-vinyl-N,N'-dimethylurea, 1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-N-propyl-3-methylene-2-pyrrolidone, 1-N-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N-vinylformamide, N-vinylisopropylamide, N-vinylcaprolactam, N-vinylimidazole, and mixtures thereof.

[0095] Non-limiting examples of hydrophilic O-vinyl carbamate and O-vinyl carbonate monomers include N-2-hydroxyethyl vinyl carbamate and N-carboxy-β-alanine N-vinyl ester. Further examples of hydrophilic vinyl carbonate or vinyl carbamate monomers are disclosed in U.S. Patent No. 5,070,215. Hydrophilic oxazolone monomers are disclosed in U.S. Patent No. 4,910,277.

[0096] Other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, and 2-ethyloxazoline.

[0097] The hydrophilic monomer may also be a macromer or prepolymer of linear or branched poly(ethylene glycol), poly(propylene glycol), or statistical random or block copolymers of ethylene oxide and propylene oxide, having polymerizable moieties such as (meth)acrylate, styrene, vinyl ether, (meth)acrylamide, N-vinylamide, etc. Macromers of these polyethers have one polymerizable group, and prepolymers may have two or more polymerizable groups.

[0098] 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.

[0099] Generally, there are no particular limitations regarding the amount of hydrophilic monomer present in the reactive monomer mixture. The amount of hydrophilic monomer can be selected based on the desired properties of the resulting hydrogel, including water content, transparency, wettability, protein uptake, etc. Wettability can be measured by contact angle, with desirable contact angles being less than about 100°, less than about 80°, and less than about 60°. The hydrophilic monomer can be present in an amount ranging from about 0.1 to about 100 weight percent, alternatively from about 1 to about 80 weight percent, alternatively from about 5 to about 65 weight percent, alternatively from about 40 to about 60 weight percent, or alternatively from about 55 to about 60 weight percent, based on the total weight of the reactive components in the reactive monomer mixture.

[0100] Silicone-containing ingredients Silicone-containing components suitable for use in the present invention include one or more polymerizable compounds, each compound independently including at least one polymerizable group, at least one siloxane group, and one or more linking groups connecting the polymerizable group to the siloxane group. The silicone-containing component may contain, for example, 1 to 220 siloxane repeating units, such as those defined below. The silicone-containing component may also contain at least one fluorine atom.

[0101] 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 that are independently (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, vinyl groups, or mixtures thereof, one or more optionally repeating siloxane units, and one or more linking groups connecting the polymerizable groups to the siloxane units.

[0102] The silicone-containing component may independently comprise one or more polymerizable groups that are (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, styryl, or mixtures of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.

[0103] The silicone-containing component may independently comprise one or more polymerizable groups that are (meth)acrylate, (meth)acrylamide, 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.

[0104] The silicone-containing component can include one or more polymerizable compounds of Formula A:

[0105] [ka] where: At least one R A is the formula R g -L- group, where R g is a polymerizable group, L is a linking group, and the remaining R A are each independently (a)R g -L-, (b) C1-C optionally substituted with one or more hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof. 16 Alkyl, (c) C3-C optionally substituted with one or more alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof. 12 cycloalkyl, (d) C6-C optionally substituted with one or more alkyl, hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof. 14 aryl groups, (e) halo, (f) alkoxy, cyclic alkoxy, or aryloxy; (g) siloxy, (h) alkyleneoxy-alkyl or alkoxy-alkyleneoxy-alkyl, such as, for example, polyethyleneoxyalkyl, polypropyleneoxyalkyl, or poly(ethyleneoxy-co-propyleneoxyalkyl), or (i) a monovalent siloxane chain comprising 1 to 100 siloxane repeat units optionally substituted with alkyl, alkoxy, hydroxy, amino, oxa, carboxy, alkylcarboxy, alkoxy, amido, carbamate, halo, or combinations thereof; n is 0 to 500, or 0 to 200, or 0 to 100, or 0 to 20. When n is other than 0, it is understood that n is a distribution having a mode equivalent to the indicated value. When n is 2 or 3 or more, the SiO units may be the same or different R A may carry substituents, and different R A When substituents are present, the n groups may be in a random or block configuration.

[0106] In formula A, three R A may each contain a polymerizable group, alternatively two R A may each contain a polymerizable group, or alternatively one R A may contain polymerizable groups.

[0107] Examples of silicone-containing components suitable for use in the present invention include, but are not limited to, the compounds listed in Table B. When the compounds of Table B contain polysiloxane groups, the number of SiO repeat units in such compounds is preferably 3 to 100, more preferably 3 to 40, or even more preferably 3 to 20, unless otherwise specified.

[0108] [Table 2-1]

[0109] [Table 2-2]

[0110] Additional non-limiting examples of suitable silicone-containing components are listed in Table C. Unless otherwise indicated, where applicable, j2 is preferably 1 to 100, more preferably 3 to 40, or even more preferably 3 to 15. In compounds containing j1 and j2, the sum of j1 and j2 is preferably 2 to 100, more preferably 3 to 40, or even more preferably 3 to 15.

[0111] [Table 3-1]

[0112] [Table 3-2]

[0113] Mixtures of multiple components containing silicone can be used.For example, suitable mixtures include, but are not limited to, mixtures of mono-(2-hydroxy-3-methacryloxypropyloxy)-propyl-terminated mono-n-butyl-terminated polydimethylsiloxanes (OH-mPDMS) with different molecular weights, such as mixtures of OH-mPDMS containing 4 and 15 SiO repeat units; mixtures of OH-mPDMS (for example, containing 4 and 15 repeat SiO repeat units) with silicone-based crosslinkers, such as bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (ac-PDMS); mixtures of 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA) with mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxanes (mPDMS), such as mPDMS1000.

[0114] The silicone-containing component used in the present invention can have an average molecular weight of from about 400 to about 4000 daltons.

[0115] The silicone-containing component may be present in an amount of up to about 95% by weight, or from about 10 to about 80% by weight, or from about 20 to about 70% by weight of the reactive mixture (excluding diluent), based on all reactive components.

[0116] polyamide The reactive mixture may include at least one polyamide. As used herein, the term "polyamide" refers to polymers and copolymers containing repeating units containing amide groups. The polyamide may include cyclic amide groups, acyclic amide groups, and combinations thereof, and may be any polyamide known to those skilled in the art. Acyclic polyamides include pendant acyclic amide groups that are capable of association with hydroxyl groups. Cyclic polyamides include cyclic amide groups that are capable of association with hydroxyl groups.

[0117] Examples of suitable acyclic polyamides include polymers and copolymers comprising repeat units of formulae G1 and G2,

[0118] [ka] In the formula, X is a direct bond, —(CO)—, or —(CONHR 44 )- and R 44 is a C1-C3 alkyl group, and R 40 is selected from H, a straight or branched chain, substituted or unsubstituted C1-C4 alkyl group, and R 41 is selected from H, straight or branched chain, substituted or unsubstituted C1-C4 alkyl groups, amino groups having up to 2 carbon atoms, amido groups having up to 4 carbon atoms, and alkoxy groups having up to 2 carbon atoms; R 42 is selected from H, straight or branched, substituted or unsubstituted C1-C4 alkyl groups, or selected from methyl, ethoxy, hydroxyethyl, and hydroxymethyl; R 43 is selected from H, straight or branched, substituted or unsubstituted C1-C4 alkyl groups, or selected from methyl, ethoxy, hydroxyethyl, and hydroxymethyl; R 40 and R 41the total number of carbon atoms in R is 8 or less, including 7, 6, 5, 4, 3, or less; 42 and R 43 The total number of carbon atoms in R is 8 or less, including 7, 6, 5, 4, 3, or less. 40 and R 41 The total number of carbon atoms in R may be 6 or less, or 4 or less. 42 and R 43 The total number of carbon atoms in the alkyl group may be up to 6. As used herein, a substituted alkyl group includes an alkyl group substituted with an amine group, an amide group, an ether group, a hydroxyl group, a carbonyl group, or a carboxyl group, or a combination thereof.

[0119] R 40 and R 41 can be independently selected from H, a substituted or unsubstituted C1-C2 alkyl group, X can be a direct bond, and R 40 and R 41 may be independently selected from H, substituted or unsubstituted C1-C2 alkyl groups. 42 and R 43 may be independently selected from H, substituted or unsubstituted C1-C2 alkyl groups, methyl, ethoxy, hydroxyethyl, and hydroxymethyl.

[0120] The acyclic polyamides of the present invention may comprise a majority of repeat units of Formula LV or Formula LVI, or the acyclic polyamides may comprise at least 50 mole percent, such as at least about 70 mole percent and at least 80 mole percent, of repeat units of Formula G or Formula G1. Specific examples of repeat units of Formula G and Formula G1 include repeat units derived from N-vinyl-N-methylacetamide, N-vinylacetamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N-vinyl-2-methyl-propionamide, N-vinyl-N,N'-dimethylurea, N,N-dimethylacrylamide, methacrylamide, and acrylamide of Formulas G2 and G3.

[0121] [ka]

[0122] Examples of suitable cyclic amides that can be used to form the cyclic polyamides include α-lactams, β-lactams, γ-lactams, δ-lactams, and ε-lactams. Examples of suitable cyclic polyamides include polymers and copolymers comprising repeat units of formula G4:

[0123] [ka] In the formula, R 45 is a hydrogen atom or a methyl group, f is a number from 1 to 10, and X is a direct bond, —(CO)—, or —(CONHR 46 )- and R 46 is a C1-C3 alkyl group. In Formula LIX, f can be 8 or less, including 7, 6, 5, 4, 3, 2, or 1. In Formula G4, f can be 6 or less, including 5, 4, 3, 2, or 1. In Formula G4, f can be 2 to 8, including 2, 3, 4, 5, 6, 7, or 8. In Formula LIX, f can be 2 or 3. When X is a direct bond, f can be 2. In such cases, the cyclic polyamide can be polyvinylpyrrolidone (PVP).

[0124] The cyclic polyamides of the present invention may comprise 50 mole percent or more of repeat units of formula G4, or the cyclic polyamides may comprise at least 50 mole percent of repeat units of formula G4, such as at least 70 mole percent, and at least 80 mole percent.

[0125] Polyamides can also be copolymers containing both cyclic and non-cyclic amide repeat units. The additional repeat units can 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 can be used as comonomers to form the additional repeat 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 mixtures thereof. Ionic monomers can also be included.Examples of ionic monomers include (meth)acrylic acid, N-[(ethenyloxy)carbonyl]-β-alanine (VINAL, CAS# 148969-96-4), 3-acrylamidopropanoic acid (ACA1), 5-acrylamidopentanoic acid (ACA2), 3-acrylamido-3-methylbutanoic acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, inner salt (CBT, carboxybetaine, CAS 79704-35-1), 1-propanaminium, N,N-dimethyl-N-[3-[(-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-, inner salt (SBT, sulfobetaine, CAS 80293-60-3), 3,5-dioxa-8-aza-4-phosphanundec-10-ene-1-aminium, 4-hydroxy-N,N,N-trimethyl-9-oxo-, inner salt, 4-oxide(9CI) (PBT, phosphobetaine, CAS 163674-35-9), 2-methacryloyloxyethyl phosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS), methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

[0126] The reactive monomer mixture may include both acyclic polyamides and cyclic polyamides or copolymers thereof. The acyclic polyamide may be any of the acyclic polyamides described herein or copolymers thereof, while the cyclic polyamide may be any of the cyclic polyamides described herein or copolymers thereof. The polyamide may be selected from the group consisting of polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof. The polyamide may be a mixture of PVP (e.g., PVP K90) and PVMA (e.g., a hydroxyethyl (meth)acrylamide copolymer having an M of about 570 KDa). w It may be a mixture with

[0127] The total amount of all polyamides in the reactive mixture can be in the range of 1% to about 35% by weight, such as in the range of 1% to about 15% by weight, and in the range of about 5% to about 15% by weight, in all cases based on the total weight of the reactive components of the reactive monomer mixture.

[0128] Without intending to be bound by theory, when used with silicone hydrogels, polyamides function as internal wetting agents. The polyamides of the present invention can be non-polymeric, in which case they are incorporated into the silicone hydrogel as a semi-interpenetrating network. The polyamides are encapsulated or physically held within the silicone hydrogel. Alternatively, the polyamides of the present invention can be polymeric, for example, as polyamide macromers or prepolymers, in which case they are covalently incorporated into the silicone hydrogel. Mixtures of polymeric and non-polymeric polyamides can also be used.

[0129] When a polyamide is incorporated into the reactive monomer mixture, the polyamide may have a weight average molecular weight of at least 100,000 daltons, greater than about 150,000, from about 150,000 to about 2,000,000 daltons, or from about 300,000 to about 1,800,000 daltons. High molecular weight polyamides may be used if compatible with the reactive monomer mixture.

[0130] Crosslinking agent It is generally desirable to add one or more crosslinking agents, also referred to as crosslinking monomers, multifunctional macromers, and prepolymers, to the reactive mixture. The crosslinking agent can be selected from difunctional, trifunctional, tetrafunctional crosslinkers, and mixtures thereof, including silicone-containing and non-silicone-containing crosslinkers. Non-silicone-containing crosslinkers include ethylene glycol dimethacrylate (EGDMA), tetraethylene glycol dimethacrylate (TEGDMA), trimethylolpropane trimethacrylate (TMPTMA), triallyl cyanurate (TAC), glycerol trimethacrylate, methacryloxyethyl vinyl carbonate (HEMAVc), allyl methacrylate, methylenebisacrylamide (MBA), and polyethylene glycol dimethacrylate, where 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, for example, from about 0.000415 to about 0.0156 moles per 100 grams of reactive formulation. Alternatively, if the hydrophilic monomer and / or silicone-containing component is multifunctional due to molecular design or impurities, adding a crosslinker to the reactive mixture is optional. Examples of hydrophilic monomers and macromers that can act as crosslinkers and, if present, do not require the addition of additional crosslinkers to the reactive mixture include (meth)acrylate and (meth)acrylamide end-capped polyethers. Other crosslinkers will be known to those skilled in the art and can be used to prepare the silicone hydrogels of the present invention.

[0131] It may be desirable to select a crosslinker that has similar reactivity with one or more of the other reactive components in the formulation. In some cases, it may be desirable to select a mixture of crosslinkers with different reactivities to control some of the physical, mechanical, or biological properties of the resulting silicone hydrogel. The structure and morphology of the silicone hydrogel can also be affected by the diluent and curing conditions used.

[0132] To further increase the modulus and maintain tensile strength, multifunctional silicone-containing components, including macromers, crosslinkers, and prepolymers, may also be included. Silicone-containing crosslinkers may be used alone or in combination with other crosslinkers. An example of a silicone-containing component that can act as a crosslinker and, when present, does not require the addition of a crosslinking monomer to the reactive mixture, is α,ω-bismethacryloylpropyl polydimethylsiloxane. Another example is bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (ac-PDMS).

[0133] Crosslinkers with rigid chemical structures and polymerizable groups capable of undergoing free radical polymerization can also be used. Non-limiting examples of suitable rigid structures include crosslinkers containing phenyl and benzyl rings, such as 1,4-phenylenediacrylate, 1,4-phenylenedimethacrylate, 2,2-bis(4-methacryloxyphenyl)-propane, 2,2-bis[4-(2-acryloxyethoxy)phenyl]propane, 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl]propane, and 4-vinylbenzyl methacrylate, and combinations thereof. Rigid crosslinkers can be included in amounts of about 0.5 to about 15, or about 2 to 10, or 3 to 7, based on the total weight of all reactive components. The physical and mechanical properties of the silicone hydrogels of the present invention can be optimized for specific applications by adjusting the components in the reactive mixture.

[0134] Non-limiting examples of silicone crosslinkers also include the multifunctional silicone-containing components set forth in Table C above.

[0135] Further components The reactive mixture may contain additional components such as, but not limited to, diluents, initiators, UV absorbers, visible light absorbers, photochromic compounds, pharmaceuticals, nutritional supplements, antimicrobial substances, colorants, pigments, copolymerizable dyes, non-polymerizable dyes, mold release agents, and combinations thereof.

[0136] Suitable classes of diluents for silicone hydrogel reactive mixtures include alcohols having 2 to 20 carbon atoms, amides derived from primary amines having 10 to 20 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. The diluents can be primary, secondary, and tertiary alcohols.

[0137] Generally, the reactive components are mixed in a diluent to form a reactive mixture. Suitable diluents are known in the art. For silicone hydrogels, suitable diluents are disclosed in WO 03 / 022321 and U.S. Pat. No. 6,020,445, the disclosures of which are incorporated herein by reference. Suitable diluent classes for silicone hydrogel reactive mixtures include alcohols having 2 to 20 carbon atoms, amides having 10 to 20 carbon atoms derived from primary amines, and carboxylic acids having 8 to 20 carbon atoms. Primary and tertiary alcohols can be used. Preferred classes include alcohols having 5 to 20 carbon atoms and carboxylic acids having 10 to 20 carbon atoms. Specific diluents that can be used include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropanol, 3,7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-octanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, tert-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2 ... Examples of suitable diluents include ethanol, 2-propanol, 1-propanol, ethanol, 2-ethyl-1-butanol, (3-acetoxy-2-hydroxypropyloxy)-propylbis(trimethylsiloxy)methylsilane, 1-tert-butoxy-2-propanol, 3,3-dimethyl-2-butanol, tert-butoxyethanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, 2-(diisopropylamino)ethanol, and mixtures thereof. Examples of amide diluents include N,N-dimethylpropionamide and dimethylacetamide.

[0138] Preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, 2-pentanol, t-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, mixtures thereof, and the like.

[0139] More preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 1-dodecanol, 3-methyl-3-pentanol, 1-pentanol, 2-pentanol, t-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, mixtures thereof, and the like. When a diluent is present, there are generally no particular limitations on the amount of diluent present. When a diluent is used, the diluent may be present in an amount ranging from about 2 to about 70 weight percent, such as from about 5 to about 50 weight percent and from about 15 to about 40 weight percent, based on the total weight of the reactive mixture (including reactive and non-reactive compounds). A mixture of diluents may be used.

[0140] A polymerization initiator may be used in the reactive mixture. The polymerization initiator may include at least one of those that generate free radicals at moderately high temperatures, such as lauryl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, and photoinitiator systems such as aromatic α-hydroxyketones, alkoxyoxybenzoins, acetophenones, acylphosphine oxides, bisacylphosphine oxides, and tertiary amines plus diketones, and mixtures thereof. Illustrative examples of photoinitiators are 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenyl-propan-1-one, bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentylphosphine oxide (DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure 819), 2,4,6-trimethylbenzyldiphenylphosphine oxide and 2,4,6-trimethylbenzoyldiphenylphosphine oxide, benzoin methyl ester, and a combination of camphorquinone and ethyl 4-(N,N-dimethylamino)benzoate.

[0141] Commercially available visible light initiator systems (manufactured by IGM Resins BV, The Netherlands) include Irgacure® 819, Irgacure® 1700, Irgacure® 1800, Irgacure® 819, Irgacure® 1850, and Lucrin® TPO initiators. Commercially available UV photoinitiators (manufactured by IGM Resins BV) include Darocur® 1173 and Darocur® 2959. These and other photoinitiators that can be used are disclosed in Volume III, Photoinitiators for Free Radical Cationic & Anionic Photopolymerization, 2nd Edition by JV Crivello & K. Dietliker; edited by G. Bradley; John Wiley and Sons; New York; 1998. The initiator is used in the reactive mixture in an amount effective to initiate photopolymerization of the reactive mixture, for example, from about 0.1 to about 2 parts by weight per 100 parts of the reactive monomer mixture. Polymerization of the reactive mixture can be initiated using heat, visible or ultraviolet light, or other means, depending on the polymerization initiator used. Alternatively, initiation can be carried out using an electron beam without a photoinitiator. However, when a photoinitiator is used, preferred initiators are bisacylphosphine oxides, such as bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure® 819) or a combination of 1-hydroxycyclohexyl phenyl ketone and bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentylphosphine oxide (DMBAPO).

[0142] The reactive mixture for making the ophthalmic device precursors of the present invention may include, in addition to the heterocyclic ligand of Formula I, any of the polymerizable compounds and optional ingredients described above.

[0143] The reactive mixture can include a heterocyclic ligand of Formula I and a hydrophilic component.

[0144] The reactive mixture may comprise a heterocyclic ligand of Formula I and a hydrophilic component selected from DMA, NVP, HEMA, VMA, NVA, methacrylic acid, and mixtures thereof. Mixtures of HEMA and methacrylic acid are preferred.

[0145] The reactive mixture can include a heterocyclic ligand of Formula I, a hydrophilic component, and a silicone-containing component.

[0146] The reactive mixture may include a heterocyclic ligand of Formula I, a hydrophilic component selected from DMA, HEMA, and mixtures thereof, a silicone-containing component selected from 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA), mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxane (mPDMS), mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether-terminated mono-n-butyl-terminated polydimethylsiloxane (OH-mPDMS), and mixtures thereof, and a wetting agent (preferably PVP or PVMA). For the hydrophilic component, a mixture of DMA and HEMA is preferred. For the silicone-containing component, a mixture of SiMAA and mPDMS is preferred.

[0147] The reactive mixture can include a hydrophilic component comprising a mixture of the heterocyclic ligand of Formula I, DMA, and HEMA, and a silicone-containing component comprising a mixture of OH-mPDMS having 2-20 repeating units (preferably a mixture of 4 and 15 repeating units). Preferably, the reactive mixture further comprises a silicone-containing crosslinker such as ac-PDMS. Also preferably, the reactive mixture contains a wetting agent (preferably DMA, PVP, PVMA, or a mixture thereof).

[0148] The reactive mixture comprises a heterocyclic ligand of Formula I, from about 1 to about 15 weight percent of at least one polyamide (e.g., an acyclic polyamide, a cyclic polyamide, or a mixture thereof), at least one first monofunctional hydroxyl-substituted poly(disubstituted siloxane) having 4 to 8 siloxane repeat units (e.g., OH-mPDMS, where n is 4 to 8, preferably n is 4), and at least one second hydroxyl-substituted poly(disubstituted siloxane) having 10 to 200, or 10 to 100, or 10 to 50, or 10 to 20 siloxane repeat units (e.g., OH-mPDMS, where n is 10 to 200, or 10 to 50, or 10 to 20). The composition may comprise a first monofunctional hydroxyl-substituted poly(disubstituted siloxane) having 10 to 200 or 10 to 100 siloxane repeat units (where n is 15), about 5 to about 35 weight percent of at least one hydrophilic monomer, and, optionally, a polyfunctional hydroxyl-substituted poly(disubstituted siloxane) (e.g., ac-PDMS) having 10 to 200 or 10 to 100 siloxane repeat units. Preferably, the first monofunctional hydroxyl-substituted poly(disubstituted siloxane) and the second hydroxyl-substituted poly(disubstituted siloxane) are present in concentrations such that the ratio of the weight percent of the first monofunctional hydroxyl-substituted poly(disubstituted siloxane) to the weight percent of the second hydroxyl-substituted poly(disubstituted siloxane) is 0.4 to 1.3 or 0.4 to 1.0.

[0149] The reactive mixture can include a hydrophilic component such as a heterocyclic ligand of Formula I, DMA, a silicone-containing component such as, for example, compound 8 (TRIS) of Table B, and a silicone macromer such as, for example, compound 42 of Table C.

[0150] The reactive mixture can include a heterocyclic ligand of Formula I, a hydrophilic component such as DMA and / or NVP, a silicone-containing component such as compound 14 (TRIS-Am) of Table B, and a silicone macromer such as compound 43 (IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM) of Table C.

[0151] The reactive mixture can include a heterocyclic ligand of Formula I, a hydrophilic component such as VMA, and a silicone macromer such as compound 35 of Table C.

[0152] The reactive mixture can include a heterocyclic ligand of Formula I, a hydrophilic component such as VMA and / or NVP, a silicone-containing component such as compound 28 of Table C (e.g., when j2 is about 16), and a silicone macromer such as compound 35 of Table C.

[0153] The reactive mixture can include a heterocyclic ligand of Formula I, a hydrophilic component such as VMA and / or NVP, a silicone-containing component such as compound 18 of Table B (e.g., when j2 is about 4), and a silicone macromer such as compound 41 of Table C.

[0154] The reactive mixture may contain optional components such as, but not limited to, one or more initiators, internal wetting agents, crosslinkers, other UV or HEV absorbers, and diluents. Additionally, the ophthalmic device precursors, as well as the ophthalmic devices, made from the reactive mixture may undergo further processing, including, but not limited to, plasma treatment, application of coatings (such as in-package coatings (IPC) as described in U.S. Pat. No. 8,480,227), and the like.

[0155] Curing the Hydrogel and Fabricating Ophthalmic Device Precursors (e.g., Contact Lens Precursors) The reactive mixture may be formed by any method known in the art, such as by shaking or stirring, 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 the reactive mixture.

[0156] For example, an ophthalmic device precursor may be prepared by mixing the reactive components and optionally a diluent with a polymerization initiator and curing under appropriate conditions to form a product that can later be formed into a suitable shape by lathing, cutting, etc. Alternatively, the reactive mixture may be placed in a mold and then cured into a suitable article.

[0157] A method of making a molded ophthalmic device precursor, such as a silicone hydrogel contact lens precursor, may include preparing a reactive monomer mixture, transferring the reactive monomer mixture to a first mold, placing a second mold over the first mold filled with the reactive monomer mixture, and curing the reactive monomer mixture by free radical copolymerization to form a silicone hydrogel in the shape of the contact lens precursor.

[0158] The reactive mixture can be cured via any known process for shaping reactive mixtures in the production of contact lenses, including rotational molding and static molding. Rotational molding processes are disclosed in U.S. Patent Nos. 3,408,429 and 3,660,545, and static molding processes are disclosed in U.S. Patent Nos. 4,113,224 and 4,197,266. The contact lenses and precursors of the present invention can be formed by direct molding of silicone hydrogels, which is economical and allows precise control over the final shape of the hydrated lens. In this method, the reactive mixture is placed into a mold having the shape of the desired final silicone hydrogel, and the reactive mixture is subjected to conditions that polymerize the monomers, thereby producing a polymer of the approximate shape of the desired final product.

[0159] After curing, the Lens Precursor may be subjected to extraction to remove unreacted components and remove the Lens Precursor from the Lens Precursor Mold. Extraction may be performed using conventional extraction fluids, such as organic solvents such as alcohols, or may be extracted using aqueous solutions.

[0160] An aqueous solution is a solution containing water. The aqueous solution of the present invention may contain at least about 20 weight percent water, or at least about 50 weight percent water, or at least about 70 weight percent water, or at least about 95 weight percent water. The aqueous solution may also contain additional water-soluble ingredients, such as inorganic salts or release agents, wetting agents, slip agents, pharmaceutical ingredients, and nutritional supplements, or combinations thereof. A release agent is a compound or mixture of compounds that, when combined with water, reduces the time required to remove a contact lens from a mold compared to the time required to remove a contact lens using an aqueous solution without the release agent. The aqueous solution may not require special handling, such as purification, recycling, or special disposal.

[0161] Extraction may be accomplished, for example, by immersing the lens in an aqueous solution or by exposing the lens to a stream of aqueous solution. Extraction may also include, for example, one or more of: heating the aqueous solution; agitating the aqueous solution; increasing the concentration of a release agent in the aqueous solution to a level sufficient to cause lens release; mechanically or ultrasonically agitating the lens; and incorporating at least one leaching or extraction aid into the aqueous solution to a concentration sufficient to facilitate adequate removal of unreacted components from the lens. The foregoing steps, with or without the addition of heat, vibration, or both, may be carried out in a batch or continuous process.

[0162] To facilitate leaching and demolding, it may be desirable to apply physical agitation. For example, the lens mold part to which the lens is attached can be vibrated or moved back and forth in the aqueous solution. Other methods may include passing ultrasound through the aqueous solution.

[0163] The Lens Precursor may be sterilized by known means, such as, but not limited to, high pressure steam treatment.

[0164] The ophthalmic device precursors described herein contain a heterocyclic ligand (a residue of a heterocyclic ligand of Formula I). ​​The presence of the ligand allows the ophthalmic device precursor to be complexed with a transition metal salt, resulting in the formation of an ophthalmic device, such as a contact lens, containing the complexed transition metal salt.

[0165] The heterocyclic ligand can be complexed with a transition metal salt by contacting an ophthalmic device precursor with a solution containing the transition metal salt. This approach provides a simple method for introducing a transition metal into an ophthalmic device precursor. For example, the process can simply involve contacting an ophthalmic device precursor (containing a residue of a heterocyclic ligand of Formula 1) with a solution containing a transition metal salt ion. This approach is demonstrated by the examples. The transition metal in the present invention can be iron, preferably iron(II). The metal can be used as an ion (e.g., iron(II) ion) in an aqueous solution. Preferably, the iron salt is a ferrous salt. Preferably, the solution does not contain a reagent that can substantially compete with the heterocyclic ligand for complexing with the salt, such as a chelating agent (e.g., EDTA). Preferably, the solution does not contain borate and / or phosphate.

[0166] After complexation, the resulting ophthalmic device may exhibit optical absorbance between 500 and 625 nm.

[0167] A preferred ophthalmic device is a contact lens, more preferably a soft hydrogel contact lens. The transmission wavelengths described herein can be measured on lenses of various thicknesses. For example, a preferred center thickness for measuring the transmission spectrum of a soft contact lens can be 80-100 microns, or 90-100 microns, or 90-95 microns. Typically, measurements can be taken at the center of the lens using, for example, an instrument slit width of 4 nm.

[0168] Silicone hydrogel ophthalmic devices (e.g., contact lenses) according to the present invention preferably exhibit the following properties. All values ​​are preceded by "about," and the device may have any combination of the listed properties. Properties may be determined by methods known to those skilled in the art, for example, as described in U.S. Patent Application Publication No. 20180037690, which is incorporated herein by reference.

[0169] Water concentration: at least 20%, or at least 25%, and at most 80%, or at most 70% Haze: 30% or less, or 10% or less Advancing dynamic contact angle (Wilhelmy plate method): 100° or less, 80° or less, or 50° or less Tensile modulus (psi): 120 or less, or 80 to 120 Oxygen permeability (Dk, Barrer): at least 80, or at least 100, or at least 150, or at least 200 Elongation at break: at least 100

[0170] With regard to ionic silicone hydrogels, the following properties (in addition to those described above) may also be preferred: Lysozyme uptake (μg / lens): at least 100, or at least 150, or at least 500, or at least 700 Polyquaternium 1 (PQ1) uptake (%): 15 or less, or 10 or less, or 5 or less

[0171] The compounds of the present invention can be used with other products in addition to ophthalmic devices.For example, the compounds can be used in windows (for example, vehicle or building windows), or optical instruments such as binoculars and cameras.In such uses, the compounds can be coated on the surface of the device, for example.To facilitate coating, the compounds can be dissolved in a solvent.

[0172] Some embodiments of the present invention are described in detail in the following examples. [Example]

[0173] Test Method The UV-visible spectra of compounds in solution were measured on a Perkin Elmer Lambda 45 or Agilent Cary 6000i UV / VIS scanning spectrometer. The instruments were allowed to thermally equilibrate for at least 30 minutes before use. For the Perkin Elmer instrument, the scan range was 200–800 nm, the scan speed was 960 nm / min, the slit width was 4 nm, the mode was set to transmittance or absorbance, and baseline correction was selected. For the Cary instrument, the scan range was 200–800 nm, the scan speed was 600 nm / min, the slit width was 2 nm, the mode was set to transmittance or absorbance, and baseline correction was selected. Baseline correction was performed before analyzing samples using the auto-zero function.

[0174] The UV-visible spectra of contact lenses partially formed from the claimed compositions were measured using packing solutions on a Perkin Elmer Lambda 45 UV / VIS or Agilent Cary 6000i UV / VIS scanning spectrometer. The instruments were allowed to thermally equilibrate for at least 30 minutes before use. The Perkin Elmer instrument had a scan range of 200-800 nm, a scan speed of 960 nm per minute, a slit width of 4 nm, and the mode set to transmission. Baseline correction was performed using a plastic two-piece lens holder and a cuvette containing the same solvent. These two-piece contact lens holders were designed to hold the sample in the quartz cuvette at a position traversed by the incident light beam. A reference cuvette also housed the two-piece holder. To ensure consistent sample thickness, all lenses were fabricated using the same mold. The central thickness of the contact lenses was measured using an electronic thickness gauge. The reported central thickness and transmittance spectra are obtained by averaging data from three individual lenses.

[0175] It is important to ensure that the exterior of the cuvette is completely clean and dry and that there are no air bubbles within the cuvette. Measurement reproducibility is improved when the reference cuvette and its lens holder remain constant and all samples use the same sample cuvette and its lens holder, ensuring that both cuvettes are properly inserted into the instrument.

[0176] The following abbreviations are used throughout the examples and figures and have the following meanings: DMA: N,N-dimethylacrylamide (Jarchem) HEMA: 2-hydroxyethyl methacrylate (Bimax) PVP K90: Poly(N-vinylpyrrolidone) (ISP Ashland) TEGDMA: Tetraethylene glycol dimethacrylate (Esstech) mPDMS: mono-n-butyl terminated monomethacryloxypropyl terminated polydimethylsiloxane, (M n = 800-1500 g / mol) (Gelest) SiMAA: 2-propenoic acid, 2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl ester (Toray), or 3-(3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy)-2-hydroxypropyl methacrylate Norbloc: 2-(2'-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole (Janssen) Dye 1: 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate

[0177] [ka] Dye 2: 2-(2-(10-butyl-2-methoxyacridin-9(10H)-ylidene)-2-cyanoacetamido)ethyl methacrylate

[0178] [ka] Omnirad 403: Bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide (IGM Resins) Omnirad 1173: 2-hydroxy-2-methyl-1-phenylpropanone (IGM Resins) Omnirad 1870: a mixture of 70% by weight of Omnirad 403 and 30% by weight of Omnirad 1173 (IGM Resins) DO: 3,7-dimethyl-3-octanol (Vigon) DIW: Deionized water IPA: Isopropanol or 2-propanol HCl: Hydrochloric acid DMSO: dimethyl sulfoxide DMF: dimethylformamide Cs2CO3: Cesium carbonate BC: Back or base curve plastic mold FC: Front curve plastic molding mold PP: Polypropylene, a homopolymer of propylene TT: Tuftec (Asahi Kasei Chemicals), a hydrogenated styrene butadiene block copolymer Z: Zeonor (Nippon Zeon Co Ltd), a polycycloolefin thermoplastic polymer LED: Light-emitting diode 1 N NMR: Proton nuclear magnetic resonance spectroscopy UV-VIS: Ultraviolet-visible spectroscopy TLC: Thin Layer Chromatography L: Liter mL: milliliter Equiv. or eq.: equivalent weight kg: kilogram g: grams mol: mole mmol: millimolar min:minutes nm: nanometer M: moles (moles / L)

[0179] Example 1 - Synthesis of 3-([2,2':6',2''-terpyridin]-4'-yloxy)propyl methacrylate [Compound (B)] as shown in Scheme 1.

[0180] [ka]

[0181] Synthesis of 3-([2,2':6',2''-terpyridin]-4'-yloxy)propan-1-ol [Compound (A)] 1,3-Propanediol (0.09 mol), potassium hydroxide (0.09 mol), and DMSO (45 mL) were added sequentially to a three-necked round-bottom flask equipped with a reflux condenser and a nitrogen gas inlet. The reaction mixture was heated to 60°C for 10 minutes, after which 4'-chloro-2,2':6',2''-terpyridine was added. The reaction mixture was cooled to room temperature and poured into ice water. The pH was adjusted to approximately 6 using 1 M HCl. The resulting precipitate was filtered through a glass frit filter and washed with excess cold water to give a white solid [compound (A)]. 1 H NMR (CDCl3, 500MHz): δ2.11 (2H, dt, J=6.0Hz, ArCH2CH2CH2OH), 3.88 (2H, dd, J=6.0Hz, ArC H2CH2CH2OH), 4.38(2H, dd, J=6.0Hz, ArCH2CH2CH2OH), 7.32(2H, ddd, J=1.2, 4.7, 7.6Hz, 5 ,5'-H-pyridyl), 7.83 (2H, ddd, J = 1.7, 7.6, 7.7 Hz, 4,4'-H-pyridyl), 8.0 (2H, s, 3',5'-H-pyridyl), 8.59 (2H, dd, J = 1.1, 7.7 Hz, 6,6'-H-pyridyl), 8.59 (2H, dd, J = 1.2, 4.7 Hz, 3,3'-H-pyridyl).

[0182] Synthesis of 3-([2,2':6',2''-terpyridin]-4'-yloxy)propyl methacrylate [Compound (B)] Compound (A) (8.1 mmol), 300 mL of dichloromethane, and triethylamine (13.8 mmol) were sequentially added to a 500 mL three-neck round-bottom flask equipped with a stir bar, a reflux condenser with a nitrogen gas inlet, and methacryloyl chloride (13.8 mmol) was slowly added to the reaction mixture via syringe. The reaction was monitored by neutral alumina TLC (20% (v / v) ethyl acetate / hexane). When the reaction was determined to be complete by TLC, the reaction mixture was washed with 1X DIW, 2X aqueous sodium carbonate, and 1X DIW. The organic layer was separated, and the volatile components were removed by rotary evaporation to give a white solid. The white solid was dissolved in a minimum amount of dichloromethane and subsequently loaded onto and flushed through a basic alumina plug (0-20% (v / v) ethyl acetate / hexane) to give compound (B). 1 H NMR (CDCl3, 500MHz): δ1.95(3H, m, OC(O)C(=CH2)CH3), 2.24(2H, dt, J=6.2Hz, ArCH2CH2CH2O ), 4.34(2H, dd, J=6.2Hz, ArCH2CH2CH2O), 4.38(2H, dd, J=6.2Hz, arCH2CH2CH2O), 5.56(1H, br s, vinyl), 6.12(1H, br s, vinyl), 7.32 (2H, ddd, J = 1.2, 4.7, 7.5 Hz, 5,5"-H-pyridyl), 7.84 (2H, ddd, J = 1.8, 7.7, 7.8 Hz, 4,4'-H-pyridyl), 8.02 (2H, s, 3', 5'-H-pyridyl), 8.61 (2H, dt, J = 1.2, 1.8, 7.8 Hz, 6,6"-H-pyridyl), 8.68 (2H, dd, J = 1.2, 4.7 Hz, 3,3"-H-pyridyl). Compound (B) can be stabilized for storage using butylated hydroxytoluene, also known as dibutylhydroxytoluene.

[0183] Example 2 - Synthesis of 3-(4-([2,2':6',2''-terpyridin]-4'-yl)phenoxy)propyl methacrylate [Compound (D)] as shown in Scheme 2.

[0184] [ka] Synthesis of 3-(4-([2,2':6',2''-terpyridin]-4'-yl)phenoxy)propan-1-ol [Compound (C)] 4-([2,2':6',2''-terpyridin]-4'-yl)phenol (15.3 mmol), 3-bromopropyl acetate (16.9 mmol), and potassium carbonate (18.4 mmol) were added to a 500 mL three-neck round-bottom flask containing 250 mL of DMF, fitted with a stir bar, a reflux condenser, and a nitrogen gas inlet. The reaction mixture was heated at 60°C for 12 hours. The reaction was monitored by neutral alumina TLC (25% (v / v) ethyl acetate / hexane). Once the reaction was complete as determined by TLC, DIW was added to the reaction mixture, followed by extraction three times with ethyl acetate. The organic phase was collected and then washed with 1X DIW, 2X aqueous sodium carbonate, and 1X DIW. The organic layer was separated, and the volatile components were removed by rotary evaporation to give a white solid. The white solid was dry packed and purified on a basic alumina plug (0-25% (v / v) ethyl acetate / hexanes). Fractions were collected and the volatile components were removed by rotary evaporation to give a white fluffy solid.

[0185] The acetate-protected compound was dissolved in methanol with a minimal amount of dichloromethane (4:1 (v / v)), and cesium carbonate (15.3 mmol) was added. The deprotection reaction was complete within 4 hours, as judged by basic alumina TLC (25% (v / v) ethyl acetate / hexane), but the reaction mixture was stirred overnight (approximately 12 hours). The volatile components were removed by rotary evaporation to give a white solid, Compound (C). Compound (C) was collected on a glass frit filter and washed with excess DIW. 1H NMR (DMSO-d6, 500MHz): δ1.91 (2H, dt, J=6.4Hz, ArCH2CH2CH2OH), 3.59 (2H, dd, J=6.4Hz, ArCH2CH2CH2OH), 4. 12 (2H, dd, J=6.4Hz, arCH2CH2CH2OH), 4.61 (1H, t, J=5.2Hz, ArCH2CH2CH2OH), 7.08~7.16 (2H, m, 2,6-aryl), 7. 51 (2H, ddd, J = 1.2, 4.7, 7.6 Hz, pyridyl), 7.83-7.90 (2H, m, 3,5-aryl), 8.02 (2H, ddd, J = 1.8, 7.6 Hz, pyridyl), 8.62-8.66 (2H, dt, J = 1.2, 7.6 Hz, pyridyl), 8.66 (2H, s, 3',5'-H-pyridyl), 8.73-8.78 (2H, dd, J = 1.2, 1.8, 4.7 Hz, pyridyl).

[0186] Synthesis of 3-(4-([2,2':6',2''-terpyridin]-4'-yl)phenoxy)propyl methacrylate [Compound (D)] Compound (C) (3.9 mmol), 250 mL of dichloromethane, and triethylamine (7.8 mmol) were sequentially added to a 500 mL three-neck round-bottom flask equipped with a stir bar, a reflux condenser with a nitrogen gas inlet, and methacryloyl chloride (6.6 mmol) was slowly added to the reaction mixture via syringe. The reaction was monitored by neutral alumina TLC (25% (v / v) ethyl acetate / hexane). When the reaction was determined to be complete by TLC, the reaction mixture was washed with 1X DIW, 2X aqueous sodium carbonate, and 1X DIW. The organic layer was separated, and the volatile components were removed by rotary evaporation to give a white solid. The white solid was dissolved in a minimum amount of dichloromethane and subsequently loaded onto and flushed through a basic alumina plug (0-25% (v / v) ethyl acetate / hexane) to give compound (D). 1H NMR (DMSO-d6, 500 MHz): δ 1.89-1.93 (2H, m, methyl), 2.13 (2H, dt, J = 6.2 Hz, ArCH2CH2CH2OH), 4.16 (2H, dd, J = 6.2 Hz, ArCH2CH2CH2O), 4.29 (2H, dd, J = 6.2 Hz, arCH2CH2CH2O), 5.65-5.71 (1H, m, vinyl), 6.06 (1H, s, vinyl), 7. 10-7.16 (2H, m, 2,6-aryl), 7.52 (2H, ddd, J = 1.2, 4.7, 7.6 Hz, pyridyl), 7.84-7.91 (2H, m, 3,5-aryl), 8.03 (2H, ddd, J = 1.8, 7.7 Hz, pyridyl), 8.64-8.66 (2H, m, pyridyl), 8.67 (2H, s, 3',5'-H-pyridyl), 8.74-8.77 (2H, m, pyridyl). Compound (D) can be stabilized for storage using butylated hydroxytoluene, also known as dibutylhydroxytoluene.

[0187] Examples 3 to 7 A reactive monomer mixture (RMM) consisting of 77 weight percent of the formulation listed in Table 1 and 23 weight percent of diluent DO was prepared. The RMM was filtered under pressure through a 0.3 μm stainless steel filter. The RMM was degassed at ambient temperature by applying a static vacuum (650 mmHg) for 30 minutes. Approximately 75 μL of the reactive mixture was then dispensed into a FC made with a 90:10 (w / w) Zeonor / TT blend using an Eppendorf pipette at room temperature in a glove box containing a nitrogen gas atmosphere and approximately 0.1 to 0.2 percent oxygen gas. A BC made with a 90:10 (w / w) Zeonor / TT blend was then placed on the FC. The molds were allowed to equilibrate in the glove box for a minimum of 12 hours before dispensing. Each pallet containing eight mold assemblies was transferred into an adjacent glove box maintained at 65°C, with a luminous intensity of approximately 2 mW / cm at the tray position. 2 The adhesive was cured from the top and bottom for 20 minutes using a 435 nm LED light with an intensity of 1000 kJ / min.

[0188] [Table 4] 1 Prophetic Example

[0189] With most of the lens still attached to the FC, the lens was manually removed from the mold and released by floating it in approximately 1 liter of 70% IPA for approximately 1 hour, followed by two 30-minute soaks in fresh 70% IPA and two 15-minute soaks in fresh DIW. The lens was equilibrated and stored in DIW. Those skilled in the art will appreciate that the exact lens release process, with respect to the concentration of the aqueous isopropanol, the number of washes with each solvent, and the duration of each step, can vary depending on the lens formulation and mold material. The goal of the lens release process is to release all of the lens without damage and transition from a diluent-swollen network to a packaging solution-swollen hydrogel. The average center thickness of the lenses in Examples 5-7 was approximately 100 micrometers.

[0190] The lenses of Example 5 and Example 6 were placed overnight (approximately 12 hours) in an 8.4 weight percent aqueous solution of ferrous tetrafluoroborate [Fe(BF4)2], and an iron bis-terpyridine complex was formed, as determined by UV-VIS spectroscopy and the appearance of an absorption band at approximately 562 nanometers. The UV-VIS spectra of these lenses before and after equilibration in the ferrous tetrafluoroborate solution are shown in Figures 1 and 2. The lenses containing the iron bis-terpyridine complex are labeled Iron Example 5 Lens and Iron Example 6 Lens in the figures.

[0191] The lenses of Example 7 were placed overnight (approximately 12 hours) in a 0.037 weight percent aqueous solution of ferrous sulfate heptahydrate [FeSO4·7H2O], resulting in the formation of an iron bis-terpyridine complex, as determined by UV-VIS spectroscopy and the appearance of an absorption band at approximately 573 nanometers. The UV-VIS spectra of these lenses before and after equilibration in the ferrous sulfate heptahydrate solution are shown in Figure 3. The lenses containing the iron bis-terpyridine complex are labeled iron Example 7 lenses in the figure.

[0192] [Embodiment] (1) An ophthalmic device precursor that is a polymerization reaction product of a reactive mixture, comprising: (a) a heterocyclic ligand of formula I, [ka] wherein m, n, and t are independently 0, 1, 2, 3, or 4; R 1 , R 2 , and R 3 is, when present, independently in each occurrence alkyl, aryl, heteroaryl, alkenyl, alkynyl, -COR 4 , -COOR 4 , -CONR 4 R 5 , CO(C=O)NR 4 R 5 , -OR 4 , -SR 4 , -SOR 4 , -SO2R 4 , -NR 4 R 5 or -ALP g where R at each occurrence 4 and R 5 are independently H or alkyl, A is a bond or aryl, L is a linking group, and P g is a polymerizable group, and said heterocyclic ligand of formula I is at least one ALP g a heterocyclic ligand containing a group; (b) a monomer suitable for making said ophthalmic device precursor. (2) An ophthalmic device precursor according to embodiment 1, which is a contact lens precursor or an intraocular lens precursor. (3) The ophthalmic device precursor of any one of claims 1 to 2, wherein the monomer suitable for making the ophthalmic device comprises a hydrophilic component, a hydrophobic component, a silicone-containing component, or a mixture of two or more thereof. (4) The ophthalmic device precursor according to any one of embodiments 1 to 3, wherein m or t is 0. (5) The ophthalmic device precursor of any one of embodiments 1 to 4, wherein m and t are both 0.

[0193] (6) The ophthalmic device precursor according to any one of embodiments 1 to 4, wherein n is 1. (7) R 2 But, -ALP g 7. The ophthalmic device precursor of any one of embodiments 1 to 6, wherein (8) The ophthalmic device precursor of embodiment 7, wherein A is a bond. (9) The ophthalmic device precursor of embodiment 7, wherein A is aryl, preferably phenyl. (10) The ophthalmic device precursor of any of embodiments 1-9, wherein the linking group at each occurrence is independently C1-C8 alkylene, C1-C8 oxaalkylene, C1-C8 thiaalkylene, carboxylate-C1-C8 alkylene, C1-C8 alkylene-carboxylate-C1-C8 alkylene, C1-C8 alkylene-amido-C1-C8 alkylene, arylene-C1-C8 alkyleneoxy, arylene-amine-C1-C8 alkylene, or C1-C8 alkylene-amine-C1-C8 alkylene.

[0194] (11) The ophthalmic device precursor of any one of embodiments 1 to 9, wherein the polymerizable group in each occurrence is independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, vinyl carbonate, vinyl ether, vinyl carbamate, or styryl. (12) The ophthalmic device precursor of embodiment 1, wherein the heterocyclic ligand of Formula I comprises 3-([2,2':6',2''-terpyridin]-4'-yloxy)propyl methacrylate or 3-(4-([2,2':6',2''-terpyridin]-4'-yl)phenoxy)propyl methacrylate. (13) An ophthalmic device comprising the ophthalmic device precursor of any one of embodiments 1 to 12 complexed with an iron salt. (14) The ophthalmic device of embodiment 13, wherein the iron salt is a ferrous salt. (15) The ophthalmic device of embodiment 13 or 14, wherein the device exhibits light absorption in the range of 500 to 625 nm.

[0195] (16) A process for making the ophthalmic device of any one of embodiments 13 to 15, comprising contacting the ophthalmic device precursor with a solution containing an iron salt, wherein the contacting is performed under conditions such that a complex is formed between the ophthalmic device precursor and the iron salt. 17. The process of claim 16, wherein the iron salt is a ferrous salt. 18. The process of claim 16 or 17, wherein the solution does not contain borate or phosphate. 19. The process of any one of claims 16 to 18, wherein the solution does not contain a chelating agent. (20) A compound which is 3-(4-([2,2':6',2''-terpyridin]-4'-yl)phenoxy)propyl methacrylate.

Claims

1. An ophthalmic device precursor that is a polymerization reaction product of a reactive mixture comprising: (a) a heterocyclic ligand of formula I, 【Chemistry 1】 wherein m, n, and t are independently 0, 1, 2, 3, or 4; R １ , R ２ , and R ３ is, when present, independently in each occurrence alkyl, aryl, heteroaryl, alkenyl, alkynyl, -COR ４ , -COOR ４ , -CONR ４ R ５ , CO(C=O)NR ４ R ５ , -OR ４ , -SR ４ , -SOR ４ , -SO ２ R ４ , -NR ４ R ５ or -AL-P ｇ where R at each occurrence ４ and R ５ are independently H or alkyl; A is a bond or an aryl; L is a linking group; P ｇ is a polymerizable group, and said heterocyclic ligand of formula I is at least one A-L-P ｇ a heterocyclic ligand containing a group; (b) a monomer suitable for making said ophthalmic device precursor.

2. 10. The ophthalmic device precursor of claim 1, which is a contact lens precursor or an intraocular lens precursor.

3. 3. The ophthalmic device precursor of claim 1 or 2, wherein the monomer suitable for making the ophthalmic device comprises a hydrophilic component, a hydrophobic component, a silicone-containing component, or a mixture of two or more thereof.

4. The ophthalmic device precursor of claim 1 , wherein m or t is 0.

5. The ophthalmic device precursor of claim 1 , wherein m and t are both 0.

6. The ophthalmic device precursor of claim 1 , wherein n is 1.

7. R ２ But, -AL-P ｇ 2. The ophthalmic device precursor of claim 1 , wherein:

8. The ophthalmic device precursor of claim 7 , wherein A is a bond.

9. 8. The ophthalmic device precursor of claim 7, wherein A is aryl, preferably phenyl.

10. said linking group in each occurrence independently being C １ ~C ８ Alkylene, C １ ~C ８ Oxaalkylene, C １ ~C ８ Thiaalkylene, carboxylate-C １ ~C ８ Alkylene, C １ ~C ８ Alkylene-carboxylate-C １ ~C ８ Alkylene, C １ ~C ８ Alkylene-amide-C １ ~C ８ Alkylene, arylene-C １ ~C ８ Alkyleneoxy, arylene-amine-C １ ~C ８ Alkylene, or C １ ~C ８ Alkylene-amine-C １ ~C ８ The ophthalmic device precursor of claim 1 , wherein the alkylene is alkylene.

11. 10. The ophthalmic device precursor of claim 1, wherein the polymerizable group in each occurrence is independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, vinyl carbonate, vinyl ether, vinyl carbamate, or styryl.

12. 2. The ophthalmic device precursor of claim 1, wherein the heterocyclic ligand of Formula I comprises 3-([2,2':6',2''-terpyridin]-4'-yloxy)propyl methacrylate or 3-(4-([2,2':6',2''-terpyridin]-4'-yl)phenoxy)propyl methacrylate.

13. An ophthalmic device comprising the ophthalmic device precursor of claim 1 complexed with an iron salt.

14. The ophthalmic device of claim 13 , wherein the iron salt is a ferrous salt.

15. The ophthalmic device of claim 13, wherein the device exhibits light absorption between 500 and 625 nm.

16. 14. A process for making the ophthalmic device of claim 13, the process comprising contacting the ophthalmic device precursor with a solution containing an iron salt, the contacting being carried out under conditions such that a complex is formed between the ophthalmic device precursor and the iron salt.

17. 17. The process of claim 16, wherein the iron salt is a ferrous salt.

18. 17. The process of claim 16, wherein the solution does not contain borate or phosphate.

19. 17. The process of claim 16, wherein the solution is free of chelating agents.

20. The compound is 3-(4-([2,2':6',2''-terpyridin]-4'-yl)phenoxy)propyl methacrylate.

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