Imidazolium Zwitterionic Polymerizable Compounds and Ophthalmic Devices Incorporating Them

Abstract

Imidazolium zwitterionic polymerizable compounds and their use in ophthalmic devices and packaging solutions are provided. The zwitterionic polymerizable compounds are compounds of Formula I: [Formula 1] TIFF2023530377000024.tif32128 in formula, R 1 , R 2 , R 3 , L 1 , L 2 , and R g is as described herein.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Patent Application No. 17 / 317,259 (filed May 11, 2021) and U.S. Provisional Patent Application No. 63 / 039,485 (filed June 16, 2020), both of which are incorporated herein by reference in their entireties.

[0002] FIELD OF THE INVENTION The present invention relates to imidazolium zwitterionic polymerizable compounds, polymers made therefrom, and their use in ophthalmic devices and / or packaging solutions for ophthalmic devices. [Background technology]

[0003] Contact lenses have been used commercially to improve vision since the 1950s. The first contact lenses were made from hard materials. While these lenses are still in use today, they are not suitable for all patients due to their poor initial comfort and relatively low permeability to oxygen. A later development in this field was the hydrogel-based soft contact lens, which is now extremely common. Many soft contact lens users find that soft lenses are more comfortable, and the increased comfort level allows them to wear the lenses for longer periods of time than hard contact lens users. Summary of the Invention [Problem to be solved by the invention]

[0004] Many users rely on contact lenses for their vision care needs, and therefore there is a continuing effort in the industry to further improve the properties of contact lenses and other ophthalmic devices, for example, to increase hydrophilicity or equilibrium water content and / or to provide non-staining or antimicrobial activity. [Means for solving the problem]

[0005] The present invention relates to new zwitterionic polymerizable compounds suitable for use in ophthalmic devices such as contact lenses. The compounds can be incorporated, for example, into the covalent structure of the ophthalmic device, or they can be polymerized and used as coatings or non-covalent additives to the ophthalmic device. Polymers derived from the zwitterionic polymerizable compounds can also be used as additives in packaging solutions for ophthalmic devices. The resulting ophthalmic devices exhibit favorable properties, including increased water content, which is particularly desirable in hydrogel contact lenses.

[0006] Thus, in one aspect, the present invention provides zwitterionic polymerizable compounds of formula I:

[0007] [ka] In the formula, R 1 , R 2 , and R 3 are independently H, alkyl, cycloalkyl, phenyl, or benzyl; L 1 and L 2 are each independently a linking group, and R g is a polymerizable group.

[0008] In another aspect, the present invention provides an ophthalmic device comprising a polymer derived from the zwitterionic polymerizable compounds described herein.

[0009] In a further aspect, the present invention provides a blister pack comprising an ophthalmic device and a packaging solution, wherein the packaging solution comprises a polymer derived from a zwitterionic polymerizable ionic compound as described herein. DETAILED DESCRIPTION OF THE INVENTION

[0010] 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.

[0011] The following definitions are provided for terms used in this disclosure.

[0012] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The definition of polymer is consistent with the definition disclosed in Compendium of Polymer Terminology and Nomenclature, IUPAC Recommendations 2008, edited by: Richard G. Jones, Jaroslav Kahovec, Robert Stepto, Edward S. Wilks, Michael Hess, Tatsuki Kitayama, and W. Val Metanomski. All publications, patent applications, patents, and other references mentioned herein are incorporated herein by reference.

[0013] As used herein, the term "(meth)" refers to optional methyl substitution. Thus, a term such as "(meth)acrylate" refers to both methacrylate and acrylate.

[0014] Wherever a chemical structure is depicted, it should be understood that the disclosed options for substituents in the structure may 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.

[0015] General formula [ *** ] nWhen a subscript, such as "n" in {circle around (a)} is used to indicate 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.

[0016] The term "individual" includes humans and vertebrates.

[0017] The term "ophthalmic device" refers to any 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 soft contact lenses, hard contact lenses, hybrid contact lenses, intraocular lenses, and overlay lenses. Ophthalmic devices can include contact lenses.

[0018] 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 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 modulus of elasticity, water content, light transmission, or a combination thereof.

[0019] The ophthalmic devices of the present invention may be composed of silicone hydrogels or conventional hydrogels, which typically contain at least one hydrophilic monomer and at least one silicone-containing component covalently bonded to each other within the cured device.

[0020] "Target macromolecule" means a macromolecule that has been synthesized from a reactive monomer mixture, including monomers, macromers, prepolymers, crosslinkers, initiators, additives, diluents, and the like.

[0021] 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.

[0022] A "polymerizable group" is a group capable of undergoing chain growth polymerization, such as a carbon-carbon double bond that can polymerize when subjected to free radical and / or cationic polymerization, e.g., radical polymerization initiation conditions. Non-limiting examples of free radical polymerizable groups include (meth)acrylate, styrene, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, and other vinyl groups. Preferably, the free radical polymerizable group comprises (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, and styryl functional groups, as well as mixtures of any of the foregoing. More preferably, the free radical polymerizable group comprises (meth)acrylate, (meth)acrylamide, and mixtures thereof. The polymerizable group may be optionally substituted. For example, the nitrogen atom in (meth)acrylamide may be bonded to hydrogen, or the hydrogen may be substituted with alkyl or cycloalkyl (which may themselves be further substituted).

[0023] Any type of free radical polymerization can be used, including but not limited to bulk, solution, suspension, and emulsion, as well as any controlled radical polymerization method, 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.

[0024] 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 a concentration of 5 weight percent at 25°C, 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 a concentration of 5 weight percent at 25°C, 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.

[0025] A "macromolecule" is an organic compound having a number average molecular weight greater than 1500, and may be reactive or non-reactive.

[0026] A "macromonomer" or "macromer" is a macromolecule having one group capable of undergoing chain-growth polymerization, particularly free-radical polymerization, thereby creating repeat units within the chemical structure of a target macromolecule. Generally, the chemical structure of a macromer differs from that of a target macromolecule; i.e., the repeat units of the pendant group of the macromer differ from the repeat units of the target macromolecule 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.

[0027] A "silicone-containing component" is a monomer, macromer, prepolymer, crosslinker, initiator, additive, or polymer in a reactive mixture that has at least one silicon-oxygen bond, usually in the form of a siloxy group, a siloxane group, a carbosiloxane group, and mixtures thereof.

[0028] 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.

[0029] A "polymer" is a target macromolecule made up of repeating units of the monomers used during polymerization.

[0030] 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.

[0031] A "repeating unit" is the smallest group of atoms in a polymer that corresponds to the polymerization of a particular monomer or macromer.

[0032] 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.

[0033] 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.

[0034] A "prepolymer" is a reaction product of monomers that contain remaining polymerizable groups that can undergo further reaction to form a polymer.

[0035] A "polymer network" is a cross-linked macromolecule 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 weight percent of water. A "silicone hydrogel" is a hydrogel made from at least one silicone-containing component together with at least one hydrophilic component. The hydrophilic component may also include a non-reactive polymer.

[0036] "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, 5,039,459, 5,236,969, 5,270,418, 5,298,533, 5,824,719, 6,420,453, 6,423,761, 6,767,979, 7,934,830, 8,138,290, and 8,389,597 disclose the formation of conventional hydrogels. Conventional hydrogels may also be formed from polyvinyl alcohol. Conventional hydrogel lenses may also include a coating, which may be the same or different material as the substrate. Conventional hydrogels may include additives such as polyvinylpyrrolidone and comonomers including phosphorylcholine, polymerizable derivatives of methacrylic acid, etc. Commercially available conventional hydrogels include, but are not limited to, etafilcon, genfilcon, hilafilcon, lenefilcon, nesofilcon, omafilcon, polymacon, and vifilcon, including all variations thereof.

[0037] "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 the patent literature. For example, the silicone-containing component may contain 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 may contain, for example, 1 to 220 siloxane repeating units. The silicone-containing component may also contain at least one fluorine atom. The silicone hydrogel lens may include a coating, which may be the same or a different material as the substrate.

[0038] 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.

[0039] 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.

[0040] The terms "reactive mixture" and "reactive monomer mixture" refer to a mixture of components (both reactive and non-reactive) that, when mixed together and subjected to polymerization conditions, form the polymer network of the present invention, as well as the ophthalmic devices and contact lenses made therefrom. The reactive monomer mixture may include reactive components such as monomers, macromers, prepolymers, crosslinkers, and initiators; additives such as wetting agents, polymers, dyes; light-absorbing compounds such as UV absorbers, pigments, dyes, and photochromic compounds (all of which may be reactive or non-reactive but can be retained in the resulting contact lenses, as well as pharmaceutical and nutraceutical compounds); and optional diluents. It will be understood that various additives may be added depending on the ophthalmic device being made and its intended use. The concentrations of the components of the reactive mixture are expressed as weight percentages of all components in the reactive mixture, excluding the diluent. If a diluent is used, their concentration is expressed as weight percentages based on the amount of all components and diluent in the reactive mixture.

[0041] A "reactive component" is a component of the reactive mixture that becomes part of the chemical structure of the polymer network of the resulting hydrogel through covalent bonding, hydrogen bonding, electrostatic interactions, formation of an interpenetrating polymer network, or any other means.

[0042] The term "silicone hydrogel contact lenses" refers to hydrogel contact lenses made from at least one silicone-containing component. Silicone hydrogel contact lenses generally have increased oxygen permeability compared to traditional hydrogels. Silicone hydrogel contact lenses use both their water content and polymer content to deliver oxygen to the eye.

[0043] The term "multifunctional" refers to a component having two or more polymerizable groups. The term "monofunctional" refers to a component having one polymerizable group.

[0044] The terms "halogen" or "halo" refer to fluorine, chlorine, bromine, and iodine.

[0045] "Alkyl" refers to an optionally substituted straight- or branched-chain alkyl group containing the specified number of carbon atoms. If no number is specified, the alkyl (including any optional substituents on the alkyl) may contain 1 to 16 carbon atoms. Preferably, the alkyl group contains 1 to 10 carbon atoms, alternatively 1 to 8 carbon atoms, alternatively 1 to 6 carbon atoms, or alternatively 1 to 4 carbon atoms. Examples of alkyl 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, alkoxyalkyl, oxo ((=O)), carboxy, alkylcarboxy, carbonyl, alkoxy, thioalkyl, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. Preferred substituents include hydroxy, alkoxy, halo, alkoxyalkyl, or oxo groups. "Alkylene" means a divalent alkyl group such as -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH(CH3)CH2-, and -CH2CH2CH2CH2-.

[0046] "Haloalkyl" refers to an alkyl group, as defined above, substituted with 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-.

[0047] "Cycloalkyl" refers to an optionally substituted cyclic hydrocarbon containing the specified number of ring carbon atoms. If no number is specified, the cycloalkyl may contain 3 to 12 ring carbon atoms. Preferred are C3-C8 cycloalkyl groups, C3-C7 cycloalkyl, more preferably C4-C7 cycloalkyl, and even more preferably C5-C6 cycloalkyl. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of substituents on cycloalkyl include one, two, or three groups independently selected from alkyl, hydroxy, amino, amido, alkoxyalkyl, carbonyl, alkoxy, thioalkyl, amido, carbamate, carbonate, halo, phenyl, benzyl, and combinations thereof. Preferred substituents include hydroxy, alkoxy, halo, alkoxyalkyl, or oxo groups. "Cycloalkylene" means a divalent cycloalkyl group such as 1,2-cyclohexylene, 1,3-cyclohexylene, or 1,4-cyclohexylene.

[0048] "Heterocycloalkyl" refers to a cycloalkyl ring or ring system, as defined above, in which at least one ring carbon is replaced with a heteroatom selected from nitrogen, oxygen, and sulfur. The heterocycloalkyl ring is optionally fused or otherwise attached to other heterocycloalkyl rings and / or non-aromatic hydrocarbon rings and / or phenyl rings. Preferred heterocycloalkyl groups have 5 to 7 members. More preferred heterocycloalkyl groups have 5 or 6 members. Heterocycloalkylene refers to a divalent heterocycloalkyl group.

[0049] "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 other aromatic or non-aromatic hydrocarbon rings. Examples of aryl groups include phenyl, naphthyl, and biphenyl. Preferred examples of aryl groups include phenyl. Examples of substituents on aryl groups include one, two, or three groups independently selected from alkyl, hydroxy, amino, amido, alkoxyalkyl, 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.

[0050] "Heteroaryl" refers to an aryl ring or ring system, as defined above, in which at least one ring carbon atom is replaced with a heteroatom selected from nitrogen, oxygen, and sulfur. The heteroaryl ring may be fused or otherwise bonded to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings, or heterocycloalkyl rings. Examples of heteroaryl groups include pyridyl, furyl, and thienyl. "Heteroarylene" refers to a divalent heteroaryl group.

[0051] "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.

[0052] "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-.

[0053] "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 3 or greater. Each silicon atom in the siloxanyl group is independently selected to complete their valence. A group (where R A is as defined in options (b) to (i) of Formula A).

[0054] "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.

[0055] "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 may be the same or different, and the alkyleneoxy may be in a block or random configuration. When alkyleneoxy forms a terminal group in a molecule, the terminus of the alkyleneoxy may be, for example, hydroxy or alkoxy (e.g., HO-[CHCHO] p - or CHO-[CHCHO] p Examples of alkyleneoxy include polyethyleneoxy, polypropyleneoxy, polybutyleneoxy, and poly(ethyleneoxy-co-propyleneoxy).

[0056] "Oxaalkylene" refers to an alkylene group as defined above in which one or more non-adjacent CH groups are replaced with an oxygen atom, such as -CHCHOCH(CH)CH-. "Thiaalkylene" refers to an alkylene group as defined above in which one or more non-adjacent CH groups are replaced with a sulfur atom, such as -CHCHSCH(CH)CH-.

[0057] The term "linking group" refers to a moiety that connects a polymerizable group to a parent molecule. The linking group may be any moiety that is compatible with the compound of which it is a part, does not undesirably interfere with the polymerization of the compound, and is stable under the conditions of polymerization, as well as the processing and storage of the final product. For example, the linking group may be a bond or may contain 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 may be optionally substituted with one or more substituents. Suitable substituents can include those independently selected from alkyl, halo (e.g., fluoro), hydroxyl, HO-alkyleneoxy, MeO-alkyleneoxy, siloxanyl, siloxy, siloxy-alkyleneoxy-, siloxy-alkylene-alkyleneoxy- (more than one alkyleneoxy group can be present, and each methylene in the alkylene and alkyleneoxy is independently optionally substituted with hydroxyl), ether, amine, carbonyl, carbamate, and combinations thereof. The linking group can also be substituted with a polymerizable group (in addition to the polymerizable group to which it is linked), such as (meth)acrylate.

[0058] Preferred linking groups include alkylene, cycloalkylene, heterocycloalkylene, arylene (e.g., phenylene), heteroarylene, oxaalkylene, alkylene-amido-alkylene, alkylene-amine-alkylene, or a combination of any of the foregoing groups. Preferred linking groups also include C1-C8 alkylene (preferably a C2-C6 alkylene such as ethylene or propylene), C1-C8 oxaalkylene (preferably a C2-C6 oxaalkylene), 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. Preferred linking groups further include carboxylate, amide, C1-C8 alkylene-carboxylate-C1-C8 alkylene, or C1-C8 alkylene-amide C1-C8 alkylene.

[0059] When the linking group is composed of a combination of moieties (e.g., alkylene-cycloalkylene), the moieties may be present in any order. Regardless, the order listed represents the preferred order in which the moieties appear in the compound, starting from the terminal polymerizable group to which the linking group is attached.

[0060] "Optionally substituted" means that a moiety may contain one or more optional substituents. The term "optionally substituted" 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, but are not limited to, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl, halo, hydroxy, amino, NR 4 R 5 , benzyl, SO3H, SO3Na, or -YP g In the formula, R 4 and R 5are independently H or C1-C6 alkyl, Y is a linking group, and P g is a polymerizable group. The foregoing substituents may be optionally substituted with optional substituents (which, unless otherwise indicated, are preferably not further substituted). For example, alkyl may be substituted with halo (e.g., to give CF).

[0061] Unless otherwise stated, ratios, percentages, parts, etc. are by weight.

[0062] Unless otherwise stated, a numerical range such as, for example, "2 to 10" is inclusive of the numbers defining the range (eg, 2 and 10).

[0063] As noted above, the present invention provides a zwitterionic polymerizable compound, the compound having formula (I):

[0064] [ka] In the formula, R 1 , R 2 , and R 3 are independently H, alkyl, cycloalkyl, phenyl, or benzyl; L 1 and L 2 are each independently a linking group, and R g is a polymerizable group.

[0065] R in compounds of formula I 1 is H. R in compounds of formula I 1 may be C1 to C6 alkyl, preferably C1 to C3 alkyl, more preferably methyl.

[0066] R in compounds of formula I 2 can be H.

[0067] R in compounds of formula I 3 can be H.

[0068] L in compounds of formula I 1 and L2 can independently be alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amido-alkylene, alkylene-amine-alkylene, or combinations thereof.

[0069] L 1 and L 2 may be independently alkylene, preferably independently C2-C6 alkylene. Each alkylene is optionally substituted with, for example, one or two groups independently selected from hydroxy, alkoxy, halo, alkoxyalkyl, and oxo.

[0070] P in the compound of formula I g can be a styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide.

[0071] P g may be a (meth)acrylate or a (meth)acrylamide.

[0072] P g can be a methacrylate.

[0073] Exemplary compounds of Formula I are shown in Table 1.

[0074] [Table 1]

[0075] The zwitterionic polymerizable compounds of the present invention can be formed into polymers for incorporation into ophthalmic devices by a variety of techniques. For example, the compounds may be homopolymerized or copolymerized into polymers that are then coated onto ophthalmic devices or added to the reactive monomer mixture from which the ophthalmic device is made (e.g., forming a semi-interpenetrating network with other components of the reactive monomer mixture).

[0076] Zwitterionic polymerizable compounds according to the present invention may also be incorporated into ophthalmic devices via grafting, as further demonstrated by the examples. Exemplary grafting techniques are described in U.S. Pregrant Publication No. 2018 / 0037690, the entire contents of which are incorporated herein by reference.

[0077] In addition, the zwitterionic polymerizable compound according to the present invention can be added to a reactive monomer mixture containing other monomers suitable for preparing ophthalmic devices, and react therewith under free radical polymerization conditions to form a polymer capable of preparing the ophthalmic device. Such a reactive mixture can contain, in addition to the zwitterionic polymerizable compound, one or more monomers suitable for preparing the desired ophthalmic device, as well as optional components. Thus, the reactive mixture can contain additional components, such as, for example, a hydrophilic component, a hydrophobic component, a silicone-containing component, a wetting agent such as a polyamide, a crosslinking agent, and a diluent and an initiator.

[0078] hydrophilic component Examples of suitable families of hydrophilic monomers include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl carbamates, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof.

[0079] 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.

[0080] The hydrophilic monomers may also be ionic, such as anionic, cationic, zwitterionic, betaine, and mixtures thereof. Non-limiting examples of such charged monomers include (meth)acrylic acid, N-[(ethenyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropanoic acid (ACA1), 5-acrylamidopropanoic acid (ACA2), 3-acrylamido-3-methylbutanoic acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, inner salt (CBT), 1-propanaminium, N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-, inner salt (SBT), 3,5-dioxa- Examples include 8-aza-4-phosphanundec-10-ene-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).

[0081] 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.

[0082] 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.

[0083] Other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, and 2-ethyloxazoline.

[0084] 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.

[0085] 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.

[0086] Generally, there are no particular limitations regarding the amount of hydrophilic monomer that can be 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.

[0087] 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.

[0088] The silicone-containing component may comprise one or more polymerizable groups, as defined above, one or more optionally repeating siloxane units, and one or more linking groups connecting the polymerizable groups to the siloxane units. The silicone-containing component may comprise one or more polymerizable groups, one or more optionally repeating siloxane units, and one or more linking groups connecting the polymerizable groups to the siloxane units, which are independently (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, vinyl groups, or mixtures thereof.

[0089] 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.

[0090] The silicone-containing component may independently comprise one or more polymerizable groups that are (meth)acrylate, (meth)acrylamide, or mixtures of the foregoing, one or more optionally repeating siloxane units, and one or more linking groups connecting the polymerizable groups to the siloxane units.

[0091] Formula A. The silicone-containing component may include one or more polymerizable compounds of Formula A:

[0092] [ka] During the ceremony, At least one R A is the formula R g -L- group, where R g is a polymerizable group, L is a linking group, and the remaining R A are each independently (a)R g -L-, (b) C1-C optionally substituted with one or more hydroxy, amino, amido, alkoxyalkyl, 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, alkoxyalkyl, 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, alkoxyalkyl, carboxy, alkylcarboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof. 14 aryl groups, (e) halo, (f) alkoxy, cyclic alkoxy, or aryloxy; (g) siloxy, (h) alkyleneoxy-alkyl or alkoxy-alkyleneoxy-alkyl, such as polyethyleneoxyalkyl, polypropyleneoxyalkyl, or poly(ethyleneoxy-co-propyleneoxyalkyl); or (i) a monovalent siloxane chain comprising 1 to 100 siloxane repeat units optionally substituted with alkyl, alkoxy, hydroxy, amino, alkoxyalkyl, 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 more, the SiO units may be the same or different R A may carry substituents, different R A When substituents are present, the n groups may be in a random or block configuration.

[0093] In formula A, three R A may each contain a polymerizable group, alternatively two R A may each contain a polymerizable group, or alternatively one R A may contain a polymerizable group.

[0094] Examples of silicone-containing components suitable for use in the present invention include, but are not limited to, the compounds listed in Table A. When a compound in Table A contains a polysiloxane group, the number of SiO repeat units in such a compound is preferably 3 to 100, more preferably 3 to 40, or even more preferably 3 to 20, unless otherwise specified.

[0095] [Table 2-1]

[0096] [Table 2-2]

[0097] Further non-limiting examples of suitable silicone-containing components are listed in Table B. Unless otherwise specified, where applicable, j2 is preferably 1 to 100, more preferably 3 to 40, or even more preferably 3 to 15. In compounds containing j1 or j2, the sum of j1 and j2 is preferably 2 to 100, more preferably 3 to 40, or even more preferably 3 to 15.

[0098] [Table 3-1]

[0099] [Table 3-2]

[0100] Mixtures of silicone-containing components may also 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 a mixture of OH-mPDMS containing 4 and 15 SiO repeat units; mixtures of OH-mPDMS (e.g., containing 4 and 15 repeat SiO repeat units) with silicone-based crosslinkers, such as bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (ac-PDMS); and 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 mPDMS 1000.

[0101] The silicone-containing component used in the present invention can have an average molecular weight of from about 400 to about 4000 daltons.

[0102] 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.

[0103] 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. Polyamides may include cyclic amide groups, non-cyclic amide groups, and combinations thereof, and may be any polyamide known to those skilled in the art. Non-cyclic polyamides include pendant non-cyclic amide groups capable of association with hydroxyl groups. Cyclic polyamides include cyclic amide groups capable of association with hydroxyl groups.

[0104] Examples of suitable acyclic polyamides include polymers and copolymers comprising repeat units of formulae G and G1,

[0105] [ka] In the formula, X is a direct bond, —(CO)—, or —(CONHR 44 )-, wherein R 44 is a C1-C3 alkyl group, and R 40 is H, a linear or branched chain substituted or unsubstituted C1-C4 alkyl group, 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, a linear or branched, substituted or unsubstituted C1-C4 alkyl group, or methyl, ethoxy, hydroxyethyl, and hydroxymethyl; R 43 is selected from H, a linear or branched, substituted or unsubstituted C1-C4 alkyl group, or methyl, ethoxy, hydroxyethyl, and hydroxymethyl; R 40 and 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.

[0106] R 40 and R 41 may be independently selected from H, a substituted or unsubstituted C1-C2 alkyl group, X may be a direct bond, and R 40 and R 41 R may be independently selected from H, a substituted or unsubstituted C1-C2 alkyl group. 42 and R 43 may be independently selected from H, substituted or unsubstituted C1-C2 alkyl groups, methyl, ethoxy, hydroxyethyl, and hydroxymethyl.

[0107] The acyclic polyamides of the present invention may comprise a majority of repeat units of Formula G or Formula G1, or the acyclic polyamides may comprise at least 50 mole percent of repeat units of Formula G or Formula G1, such as at least about 70 mole percent, and at least 80 mole percent. Specific examples of repeat units of Formula G and Formula G1 include repeat units derived from N-vinyl-N-methylacetamide, N-vinylacetamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N-vinyl-2-methyl-propionamide, N-vinyl-N,N'-dimethylurea, N,N-dimethylacrylamide, methacrylamide, and acyclic amides of Formulas G2 and G3.

[0108] [ka]

[0109] 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:

[0110] [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 )-, where R 46 is a C1-C3 alkyl group. In Formula G4, 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 G4, 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).

[0111] 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.

[0112] Polyamides may also be copolymers containing both cyclic and non-cyclic amide repeat units. The additional repeat units may be formed from monomers selected from hydroxyalkyl (meth)acrylates, alkyl (meth)acrylates, other hydrophilic monomers, and siloxane-substituted (meth)acrylates. Any of the monomers listed as suitable hydrophilic monomers may be used as comonomers to form the additional repeat units. Specific examples of additional monomers that 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 may also be included.Examples of ionic monomers include (meth)acrylic acid, N-[(ethenyloxy)carbonyl]-β-alanine (VINAL, CAS# 148969-96-4), 3-acrylamidopropanoic acid (ACA1), 5-acrylamidopentanoic acid (ACA2), 3-acrylamido-3-methylbutanoic acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, inner salt (CBT, carboxybetaine, CAS 79704-35-1), 1-propanaminium, N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-, inner salt (SBT, sulfobetaine, CAS 80293-60-3), 3,5-dioxa-8-aza-4-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).

[0113] 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 or copolymers thereof described herein, and the cyclic polyamide may be any of the cyclic polyamides or copolymers thereof described herein. 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 cyclic polyamide having an M of about 570 KDa). w The compound may be a mixture of

[0114] The total amount of all polyamides in the reactive mixture can be in the range of 1 weight percent to about 35 weight percent, such as in the range of 1 weight percent to about 15 weight percent, and in the range of about 5 weight percent to about 15 weight percent, in all cases based on the total weight of the reactive components of the reactive monomer mixture.

[0115] Without being bound by theory, when used with silicone hydrogels, polyamides function as internal wetting agents. The polyamides of the present invention may be non-polymeric, in which case they are incorporated into the silicone hydrogel as a semi-interpenetrating network. The polyamides are encapsulated or physically held within the silicone hydrogel. Alternatively, the polyamides of the present invention may be polymeric, for example, as polyamide macromers or prepolymers, in which case they are covalently incorporated into the silicone hydrogel. Mixtures of polymeric and non-polymeric polyamides may also be used.

[0116] 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 can be used if they are compatible with the reactive monomer mixture.

[0117] 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 may 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 5,000 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.

[0118] 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.

[0119] 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).

[0120] 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. The rigid crosslinkers can be present in an amount 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.

[0121] Non-limiting examples of silicone crosslinkers also include the multifunctional silicone-containing components described above, such as the multifunctional compounds shown in Table B.

[0122] 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, copolymeric dyes, non-polymeric dyes, mold release agents, and combinations thereof.

[0123] Suitable types 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. Diluents can be primary, secondary, and tertiary alcohols.

[0124] 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.

[0125] Suitable diluent classes 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. 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.

[0126] Specific diluents that may be used include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropanol, 3,7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-octanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, tert-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2 ... Examples of suitable diluents include alcohol, 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.

[0127] 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.

[0128] 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.

[0129] When a diluent is present, there is generally no particular limit as to 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 the reactive and non-reactive compounds). Mixtures of diluents may also be used.

[0130] A polymerization initiator may be used in the reactive mixture, and 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 alpha-hydroxyketones, alkoxyoxybenzoins, acetophenones, acylphosphine oxides, bisacylphosphine oxides, and tertiary amines plus diketones, and mixtures thereof. Specific examples of photoinitiators include 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenyl-propan-1-one, bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentylphosphine oxide (DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure 819), 2,4,6-trimethylbenzyldiphenylphosphine oxide and 2,4,6-trimethylbenzoyldiphenylphosphine oxide, benzoin methyl ester, and a combination of camphorquinone and ethyl 4-(N,N-dimethylamino)benzoate.

[0131] 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 described 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, appropriately selected depending on the polymerization initiator used. Alternatively, initiation can be carried out using an electron beam without a photoinitiator. However, when a photoinitiator is used, the preferred initiator is a bisacylphosphine oxide, such as bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure® 819), or a combination of 1-hydroxycyclohexyl phenyl ketone and bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentylphosphine oxide (DMBAPO).

[0132] The reactive mixture for making the ophthalmic devices of the present invention may include, in addition to the zwitterionic polymerizable compound of Formula I, any of the other polymerizable compounds and optional ingredients described above.

[0133] A preferred reactive mixture can include a zwitterionic polymerizable compound of Formula I and a hydrophilic component.

[0134] A preferred reactive mixture may comprise a zwitterionic polymerizable compound of Formula I and a hydrophilic component selected from DMA, NVP, HEMA, VMA, NVA, methacrylic acid, and mixtures thereof. A mixture of HEMA and methacrylic acid is preferred.

[0135] A preferred reactive mixture can include a zwitterionic polymerizable compound of Formula I, a hydrophilic component, and a silicone-containing component.

[0136] A preferred reactive mixture may include a zwitterionic polymerizable compound of Formula I, a hydrophilic component, and a silicone-containing component that includes a compound of Formula A.

[0137] A preferred reactive mixture may include a zwitterionic polymerizable compound of Formula I, and a hydrophilic component selected from DMA, NVP, HEMA, VMA, NVA, and mixtures thereof, a silicone-containing component such as a compound of Formula A, and an internal wetting agent.

[0138] A preferred reactive mixture may include a hydrophilic component selected from the zwitterionic polymerizable compound of Formula I, 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). A mixture of DMA and HEMA is preferred for the hydrophilic component. A mixture of SiMAA and mPDMS is preferred for the silicone-containing component.

[0139] A preferred reactive mixture may include a hydrophilic component comprising a mixture of a zwitterionic polymerizable compound of Formula I, DMA, and HEMA, and a silicone-containing component comprising a mixture of OH-mPDMS having 2 to 20 repeating units (preferably a mixture of 4 and 15 repeating units). Preferably, the reactive mixture 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).

[0140] A preferred reactive mixture comprises a zwitterionic polymerizable compound 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) that is a monofunctional hydroxyl-substituted poly(disubstituted siloxane) having 10 to 200, or 10 to 100, or 10 to 50, or 10 to 20 siloxane repeat units (e.g., OH-mPDMS, where n is 10 to 200, or wherein n is 10 to 100, or 10 to 50, or 10 to 20, preferably n is 15), about 5 to about 35 weight percent of at least one hydrophilic monomer, and optionally a multifunctional hydroxyl-substituted poly(disubstituted siloxane) (e.g., ac-PDMS) having 10 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 to provide a ratio of weight percent of the first monofunctional hydroxyl-substituted poly(disubstituted siloxane) to weight percent of the second hydroxyl-substituted poly(disubstituted siloxane) of 0.4 to 1.3 or 0.4 to 1.0.

[0141] The reactive mixture may contain optional ingredients such as, but not limited to, one or more initiators, internal wetting agents, crosslinkers, UV or high energy visible light absorbers, and diluents.

[0142] Curing of Hydrogels and Lens Fabrication The reactive mixture can 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, either with or without a diluent, to form the reactive mixture.

[0143] For example, an ophthalmic device can 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 can be placed in a mold and then cured to form a suitable article.

[0144] A method of making a molded ophthalmic device such as a silicone hydrogel contact lens may include preparing a reactive monomer mixture, transferring the reactive monomer mixture to a first mold, placing a second mold over the first mold filled with the reactive monomer mixture, and curing the reactive monomer mixture by free radical copolymerization to form a silicone hydrogel in the shape of a contact lens.

[0145] The reactive mixture may 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 of the present invention may also be formed by direct molding of silicone hydrogels, which is economical and allows for precise control of the final shape of the hydrated lens. In this method, the reactive mixture is placed into a mold having the shape of the desired final silicone hydrogel, and the reactive mixture is subjected to conditions that polymerize the monomers, thereby producing a polymer of the approximate shape of the desired final product.

[0146] After curing, the lens may be subjected to extraction to remove unreacted components and remove the lens from the lens mold. Extraction may be performed using conventional extraction fluids, such as organic solvents such as alcohols, or may be extracted using aqueous solutions.

[0147] 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.

[0148] Extraction can be accomplished, for example, by immersing the lens in an aqueous solution or by exposing the lens to a stream of aqueous solution. Extraction can 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 filter aid or extraction aid into the aqueous solution to a concentration sufficient to facilitate adequate removal of unreacted components from the lens. The foregoing, with or without the addition of heat, vibration, or both, can be carried out in a batch or continuous process.

[0149] 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.

[0150] The lenses may be sterilized by known means, including but not limited to, autoclaving.

[0151] Silicone hydrogel ophthalmic devices (e.g., contact lenses) according to the present invention preferably exhibit the following properties. All values ​​are preceded by "about," and the device can have any combination of the listed properties. Properties can be determined by methods known to those skilled in the art, for example, as described in U.S. Pregrant Publication No. 2018 / 0037690, which is incorporated herein by reference.

[0152] Equilibrium moisture content %: at least 20%, or at least 25% and up to 80%, or up to 70% Haze: 30% or less, or 10% or less Advancing dynamic contact angle (Wilhelmy plate method): 100° or less, or 80° or less, or 50° or less Tensile modulus (psi): 150 or less, or 135 or less, or 120 or less, or 80 to 135 Oxygen permeability (Dk, Barrer): at least 60 Barrer, or at least 80, or at least 100, or at least 150, or at least 200 Elongation at break: at least 100 With regard to ionic silicone hydrogels, the following properties (in addition to those mentioned above) may also be desirable: 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.

[0153] In addition to being incorporated into ophthalmic devices via the methodologies described above, the zwitterionic polymerizable compounds may alternatively (or additionally) be used in the packaging solution of a blister pack. Thus, according to this embodiment, a blister pack may be provided that includes an ophthalmic device and a packaging solution, where the packaging solution includes a polymer derived from a zwitterionic polymerizable compound as described above.

[0154] Blister packages generally include a bowl portion and a foil top. These packages contain soft contact lenses and their aqueous packaging solution. The bowl portion can be made of any suitable material. Typically, the bowl portion is made of a hydrophobic material such as polypropylene. Polypropylene is a material commonly used for contact lens packaging. Polypropylene is sufficiently elastic to withstand the sterilization process in contact lens manufacturing and can be injection molded into several suitable shapes and sizes. Non-limiting examples of such packages are described in U.S. Patent Nos. 4,691,820, 5,054,610, 5,337,888, 5,375,698, 5,409,104, 5,467,868, 5,515,964, 5,609,246, 5,695,049, 5,697,495, and 5,704, See Nos. 468, 5,711,416, 5,722,536, 5,573,108, 5,823,327, 5,704,468, 5,983,608, 6,029,808, 6,044,966, and 6,401,915, all of which are incorporated herein by reference in their entireties.

[0155] Packing solutions for use with ophthalmic devices such as contact lenses are well known. Suitable solutions include, but are not limited to, saline, other buffer solutions, and deionized water. For example, the packing solution may be a saline solution containing salts, such as, but not limited to, sodium chloride, sodium borate, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, or the corresponding potassium salts of the same acids. These components are generally combined to form a buffer solution containing the acid and its conjugate base, so that the addition of the acid and base causes only a relatively small change in pH. The buffer may also include 2-(N-morpholino)ethanesulfonic acid (MES), sodium hydroxide, 2,2-bis(hydroxymethyl)-2,2',2"-nitrilotriethanol, n-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid, citric acid, sodium citrate, sodium carbonate, sodium bicarbonate, acetic acid, sodium acetate, ethylenediaminetetraacetic acid, and the like, and combinations thereof. Preferably, the solution is a borate buffered aqueous solution or a phosphate buffered saline solution.

[0156] Some embodiments of the present invention will now be described in detail in the following examples. [Example]

[0157] The test methods used to characterize the contact lenses are described below. Some abbreviations are used in the tables as headings and some standard deviations are reported in the tables in parentheses.

[0158] Water content was measured gravimetrically. The lenses were equilibrated in the packing solution for 24 hours. Three test lenses were each removed from the packing solution using a sponge-tipped swab and placed on a blotting wipe moistened with packing solution. Both sides of the lens were contacted with the wipe. Using tweezers, the test lenses were placed in a tared weighing dish and weighed. Two more sets of samples were then prepared and weighed. All weight measurements were performed in triplicate, and the average of these values ​​was used in the calculations. The wet weight was defined as the combined weight of the weighing dish and wet lens minus the weight of the weighing dish alone.

[0159] Dry weight was measured by placing the sample pan in a vacuum oven preheated to 60°C for 30 minutes. Vacuum was applied until a pressure of at least 1 inch Hg was reached; lower pressures are acceptable. The vacuum valve and pump were turned off, and the lenses were allowed to dry for at least 12 hours (usually overnight). The purge valve was opened to admit dry air or dry nitrogen gas. The oven was allowed to reach atmospheric pressure. The weighing pan was removed and weighed. Dry weight was defined as the combined weight of the weighing pan and dry lens minus the weight of the weighing pan alone. The water content of the test lenses was calculated as follows: % Water Content (% WC) = (Wet Weight - Dry Weight) / Wet Weight x 100. The average water content and its standard deviation were calculated, and the average value was reported as the percent water content of the test lenses. The standard deviation is listed in parentheses in the tables.

[0160] The grafting weight gain (%GWG) was calculated as follows: (dry weight of grafted lens - dry weight of substrate lens) / dry weight of substrate lens x 100. Both the grafted and substrate lenses were equilibrated in deionized water for several hours to remove any residual salts before vacuum drying. Typically, at least three lenses for each sample were weighed and averaged.

[0161] The refractive index (RI) of contact lenses was measured using a Leica ARIAS 500 Abbe refractometer in manual mode or a Reichert ARIAS 500 Abbe refractometer in automatic mode with a prism gap distance of 100 micrometers. The instrument was calibrated at 20°C (±0.2°C) using deionized water. The prism assembly was opened and the test lens was placed on top of the lower prism between the magnetic dots closest to the light source. If the prism was dry, a few drops of saline were applied to the bottom prism. The front curve of the lens was brought into contact with the bottom prism. The prism assembly was then closed. The refractive index was measured after adjusting the contrast so that a shadow line appeared in the reticle field. RI measurements were performed on five test lenses. The average RI calculated from the five measurements was recorded as the refractive index along with its standard deviation.

[0162] The present invention will now be described with reference to the following examples. Before describing certain example embodiments of the present invention, 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. The invention is capable of other embodiments and of being practiced or carried out in various ways.

[0163] The following abbreviations are used throughout the examples and have the following meanings: DMA: N,N-dimethylacrylamide (Jarchem) HEMA: 2-hydroxyethyl methacrylate (Bimax) CBT: 1-Propanaminium, N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, inner salt, carboxybetaine, CAS 79704-35-1

[0164] [ka] Norbloc: 2-(2'-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole (Janssen) Blue HEMA: 1-amino-4-[3-(4-(2-methacryloyloxy-ethoxy)-6-chlorotriazin-2-ylamino)-4-sulfophenylamino]anthraquinone-2-sulfonic acid (described in U.S. Pat. No. 5,944,853) PVP K90: Poly(N-vinylpyrrolidone) (ISP Ashland) EGDMA: Ethylene glycol dimethacrylate (Esstech) TEGDMA: Tetraethylene glycol dimethacrylate (Esstech) AIBN: Azobisisobutyronitrile Omnirad 403: Bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide Omnirad 819: Bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (IGM resin) Omnirad 1173: 2-Hydroxy-2-methyl-1-phenylpropanone Omnirad 1700: a mixture of 25% by weight of Omnirad 403 and 75% by weight of Omnirad 1173 TEMPO: (2,2,6,6-tetramethylpiperidin-1-yl)oxyl or (2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl HO-mPDMS: mono-n-butyl terminated mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether terminated polydimethylsiloxane (M n =400-1500g / mol) (Ortec or DSM-Polymer Technology Group) HO-mPDMS (n=4):

[0165] [ka] HO-mPDMS (n=15):

[0166] [ka] nBu: n-butyl PP: Polypropylene, a homopolymer of propylene Z: Zeonor (Nippon Zeon Co Ltd), a polycycloolefin thermoplastic polymer DO: 3,7-dimethyl-3-octanol (Vigon) BAGE: boric acid glycerol ester (the molar ratio of boric acid to glycerol was 1:2), 299.3 grams (mol) of glycerol and 99.8 grams (mol) of boric acid were dissolved in 1247.4 grams of 5% (wt / wt) aqueous ethylenediaminetetraacetic acid solution in a suitable reactor, then heated to 90-94°C with stirring under moderate vacuum (2-6 torr) for 4-5 hours and cooled to room temperature.

[0167] Borate Buffer Packing Solution: 18.52 grams (300 mmol) of boric acid, 3.7 grams (9.7 mmol) of sodium borate decahydrate, and 28 grams (197 mmol) of sodium sulfate were dissolved in enough deionized water to fill a 2-liter volumetric flask. mL: milliliter nm: nanometer LED: Light-emitting diode TL03 Light: Phillips TLK 40W / 03 bulb NMR: nuclear magnetic resonance spectroscopy DO: Deuterium oxide

[0168] Example 1 Synthesis of 3-(1-(3-methacrylamidopropyl)-1H-imidazol-3-ium-3-yl)propanoate (A)

[0169] [ka]

[0170] A solution of 1-(3-methacrylamidopropyl)-1H-imidazole (19.3 grams, 0.1 mole) and ethyl 3-bromopropionate (19.0 grams, 0.105 mole) in 10 mL of ethanol was heated to 80°C with constant stirring. After 8 hours, the mixture was cooled to room temperature and the ethyl alcohol was evaporated under reduced pressure. The residual material was dissolved in 150 mL of water and washed three times with 100 mL of ethyl acetate. After adding 0.1 grams of butylated hydroxytoluene, the volatile organic components were evaporated at 50 mmHg pressure while maintaining the temperature below 20°C. Sodium carbonate (15 g, approximately 1.4 equivalents) was added to the aqueous solution and stirred at room temperature for 24 hours. After rotary evaporation of the water, the residual solid was washed with warm acetonitrile (2 x 150 mL) and the liquid was decanted. The crude product was redissolved in (5:95) ethyl alcohol and the acetonitrile mixture was filtered. After adding 150 mg of butylated hydroxytoluene to the filtrate, the solvent was evaporated under reduced pressure, and the resulting solid was washed with ethyl acetate and further dried in a rotary evaporator to obtain the desired product (compound (A)), which is 3-(1-(3-methacrylamidopropyl)-1H-imidazol-3-ium-3-yl)propanoate. 1 H NMR(500MHz,D2O)δ(ppm):1.93(3H,s,CH3),2.18(2H,dddd,J=6.5Hz,CH2),2.77(2H,t,J=7Hz,CH2),3.35(2H,t,J=6.5Hz,CH2),4.28(2H,t, J=7Hz,CH2),4.43(2H,t,J=6.5Hz),5.48(1H,bs,vinylic),5.70(1H,bs,vinylic),7.54-7.55(2H,dd,J=5,2Hz,Ar-H),8.83(1H,bs,Ar-H).

[0171] Example 2 Synthesis of 3-(1-(3-methacrylamidopropyl)-2-methyl-1H-imidazol-3-ium-3-yl)propanoate (B)

[0172] [ka]

[0173] Methacrylic anhydride (34 grams, 0.22 moles) was added dropwise to a cooled, stirred suspension of 2-methyl-1-(3-aminopropyl)-1H-imidazole (27.8 grams, 0.2 moles) and 23.32 grams of sodium carbonate (0.22 moles) in water, maintaining the temperature below 10°C. The solution was warmed to room temperature and stirred for an additional 3 hours. After adding 0.05 grams of butylated hydroxytoluene to the reaction mixture, the volatile components were evaporated under reduced pressure at a temperature below 20°C. The product was redissolved in a 75:25 (volume / volume) mixture of ethyl acetate and hexane and filtered through a short silica gel plug. The solvent was then evaporated under reduced pressure, and the product was used "as is" for the subsequent alkylation reaction to form the desired zwitterion. 2-Methyl-1-(3-acrylamidopropyl)-1H-imidazole (10.4 grams, 0.05 moles) and β-lactone (3.6 grams, 0.06 moles) were dissolved in 50 mL of ethyl alcohol containing 100 milligrams of suspended sodium carbonate. After stirring the mixture at room temperature for 20 hours, the solution appeared to contain a single major product by thin-layer chromatography. 100 mL of ethyl acetate was added, and the mixture was vacuum filtered through a fritted glass funnel to remove the sodium carbonate. All volatile components were evaporated under reduced pressure, maintaining the temperature below 20°C. The residue was washed twice with warm ethyl acetate and vacuum filtered through a fritted glass funnel. The filtrate was dried under reduced pressure to give the desired product (Compound (B)). 1 H NMR(500MHz,D2O)δ(ppm):1.93(3H,s,CH3),2.11(2H,m,CH2),2.64(3H,s,CH3),2.65-2.69(2H,m,CH2),3.35(2H,t,J= 6.75Hz,CH2),4.17(2H,m,CH2),4.33(2H,m,CH2),5.48(1H,s,vinylic),5.70(1H,s,vinylic),7.42(2H,s,vinylic).

[0174] Example 3 Synthesis of 4-(1-(3-methacrylamidopropyl)-2-methyl-1H-imidazol-3-ium-3-yl)butanoate (C)

[0175] [ka]

[0176] A solution of 2-methyl-1-(3-acrylamidopropyl)-1H-imidazole (10 grams, 0.048 moles) and 10.3 grams of ethyl 4-bromobutyrate (1.1 equivalents) in 20 mL of ethanol was heated with stirring at 80°C, and the reaction was monitored by thin-layer chromatography. After stirring overnight, the mixture was cooled to room temperature. 0.100 grams of BHT was added, and the volatile components were evaporated under reduced pressure while maintaining the temperature below 20°C. The product was dissolved in water, and the mixture was extracted three times with 100 mL of ethyl acetate to remove unreacted 4-bromobutyrate. 0.100 grams of butylated hydroxytoluene and 6.0 grams of sodium carbonate (0.056 moles) were added to the aqueous portion. The aqueous portion was then stirred at room temperature to produce the desired zwitterion. Upon completion of the reaction, the volatile components were evaporated under reduced pressure while maintaining the temperature below 20°C. The product was redissolved in 10% (v / v) ethyl alcohol in acetonitrile, and the resulting suspension was filtered to remove residual sodium carbonate. Volatile solvents were removed from the filtrate under reduced pressure, maintaining the temperature below 20°C. The product (compound (C)) was washed with warm acetonitrile on a fritted glass funnel to give the desired zwitterion. 1 H NMR(500MHz,D2O)δ(ppm):1.94(3H,s,CH3),2.07(1H,m,CH2),2.14(1H,m,CH2),2.24(2H,t,J=7.5Hz,CH2),2.63(3H,s,CH3),3.37(2H,t,J =7.25Hz,CH2),4.15(2H,t,J=7.25Hz,CH2),4.20(2H,t,J=7.25Hz),CH2),5.48(1H,s,vinylic),5.70(1H,s,vinylic),7.44(2H,s,Ar-H).

[0177] Example 4 - Grafted Silicone Hydrogel Contact Lenses A reactive monomer mixture composed of 75 weight percent of the formulation listed in Table 2 and 25 weight percent of diluent DO was prepared. The reactive monomer mixture was filtered under pressure through a 3 μm filter using a stainless steel syringe and subsequently degassed under vacuum for approximately 30 minutes. In a glove box with a nitrogen gas atmosphere and less than 0.2 percent oxygen gas (volume / volume), approximately 75-100 μL of the reactive mixture was dispensed into a front curve mold made of Zeonor at room temperature using an Eppendorf pipette. A base curve mold made from a 55:45 (wt / wt) blend of Zeonor and polypropylene was then placed on top of the front curve mold. The mold was allowed to equilibrate in the glove box for a minimum of 12 hours before dispensing. A plate containing approximately four pallets, each containing eight lens mold assemblies, was transferred to an adjacent glove box maintained at approximately 62°C and irradiated with 4 mW / cm. 2 The lenses were cured from above for 12 minutes using a 435 nm LED light with an intensity of 1.0000.

[0178] By working under yellow light and limiting general exposure to further light (e.g., by wrapping the container in aluminum foil), the lenses were manually removed from the molds while most of the lenses were still attached to the front curve mold, and then stripped by suspending them in 70 percent isopropanol for about 1 or 2 hours (approximately 1 lens per 15 mL), optionally overnight. Subsequently, they were washed twice with 70 percent isopropanol and twice with deionized water, and finally stored in a container covered with aluminum foil in deionized water and refrigerated. These lenses (4A) contained covalently bound monoacylphosphine oxide groups upon which chemical grafting reactions could be initiated. Each washing step lasted approximately 30 minutes. Those skilled in the art will appreciate that the exact lens stripping 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 stripping process is to achieve defect-free release of all lenses from the diluent-swollen network into deionized water or the packaging solution-swollen hydrogel.

[0179] Twenty-five lenses (4A) were suspended in 50 mL of a 10% (wt / vol) CBT solution in 50:50 (v / v) 1,2-propylene glycol water solution in a 100 mL glass jar, degassed under vacuum (approximately 40 mmHg) for 15 minutes, and purged with nitrogen gas. The jar was capped and transferred to a glove box containing less than 0.2 percent oxygen gas (v / v) in a nitrogen atmosphere at 55°C and equilibrated on a shaker (180 rpm) for 90 minutes. The temperature of the suspension was then 55°C. The cap was replaced with a clear plastic cover, and the suspension was shaken while being heated to 1.2 mW / cm. 2 The lenses were irradiated from above for 20 minutes using a 420 LED with an intensity of 1000 ohms. After irradiation, the lenses were removed and washed twice with deionized water and twice with borate buffered packing solution. The lenses were stored in vials. After equilibrating for one day, the lenses were inspected and sterilized by autoclaving at 122°C for 30 minutes. Lenses (4B) were allowed to equilibrate for 3-4 days after sterilization, after which the physical properties of the sterilized lenses were measured as listed in Table 3.

[0180] Twenty-five lenses (4A) were suspended in 50 mL of a 10% (wt / vol) solution of Compound (B) in 50:50 (v / v) 1,2-propylene glycol in water in a 100 mL glass jar, degassed under vacuum (approximately 40 mmHg) for 15 minutes, and purged with nitrogen gas. The jar was capped and transferred to a glove box containing less than 0.2 percent oxygen gas (v / v) in a nitrogen atmosphere at 55°C and equilibrated on a shaker (180 rpm) for 90 minutes. The temperature of the suspension was then 55°C. The cap was replaced with a clear plastic cover, and the suspension was shaken while being heated to 1.2 mW / cm. 2 The lenses were irradiated from above for 20 minutes using a 420 LED with an intensity of 1000 ohms. After irradiation, the lenses were removed and washed twice with deionized water and twice with borate buffered packing solution. The lenses were stored in vials. After equilibrating for one day, the lenses were inspected and sterilized by autoclaving at 122°C for 30 minutes. The lenses (4C) were allowed to equilibrate for 3-4 days after sterilization, after which the physical properties of the sterilized lenses were measured as listed in Table 3.

[0181] Twenty-five lenses (4A) were suspended in 50 mL of a 10% (wt / vol) solution of Compound (C) in 50:50 (v / v) 1,2-propylene glycol in water in a 100 mL glass jar, degassed under vacuum (approximately 40 mmHg) for 15 minutes, and purged with nitrogen gas. The jar was capped and transferred to a glove box containing less than 0.2 percent oxygen gas (v / v) in a nitrogen atmosphere at 55°C and equilibrated on a shaker (180 rpm) for 90 minutes. The temperature of the suspension was then 55°C. The cap was replaced with a clear plastic cover, and the suspension was shaken while being heated to 1.2 mW / cm. 2The lenses were irradiated from above for 20 minutes using a 420 LED with an intensity of 1000 ohms. After irradiation, the lenses were removed and washed twice with deionized water and twice with borate buffered packing solution. The lenses were stored in vials. After equilibration for one day, the lenses were inspected and sterilized by autoclaving at 122°C for 30 minutes. The lenses (4D) were allowed to equilibrate for 3-4 days after sterilization, after which the physical properties of the sterilized lenses were measured as listed in Table 3.

[0182] [Table 4]

[0183] [Table 5]

[0184] Grafted Lens 4D was round with acceptable circularity. Grafted Lens 4C was slightly out of round but acceptable. Grafted Lens 4B was completely distorted with scalloped edges.

[0185] Example 5 - Polymer Preparation 1 50.0 grams (39.2 mmol) of tellurium powder was reacted with 14.4 mL of a 3.0 M methyllithium solution (43.1 mmol) in anhydrous tetrahydrofuran to form a tellurolate intermediate, which was then reacted with 8.82 grams (45.1 mmol) of ethyl α-bromoisobutyrate to form the organotellurium-mediated living radical polymerization mediator, ethyl 2-methyl-2-methyltellanyl-propanoate (Te-Me). The reaction was carried out in an ice bath for the transmetalation step. After the addition of ethyl α-bromoisobutyrate, the reaction mixture was warmed and maintained at room temperature until the reaction was complete (approximately 2 hours). The tetrahydrofuran was then removed under reduced pressure on a rotary evaporator. The crude product was vacuum distilled at 50-55°C (1-2 mbar) to yield the organotellurium-mediated living radical polymerization mediator, Te-Me, which was characterized by proton nuclear magnetic resonance spectroscopy.

[0186] The following Examples 5A-5D, and 6 are prophetic and serve to further illustrate the present invention.

[0187] Example 5A 26.5 grams (100 mmol) of Compound (A) and 578 milligrams (3.5 mmol) of AIBN were added to a 1-liter reactor and dissolved in approximately 250 mL of 50:50 (volume / volume) aqueous methanol. The solution was degassed by bubbling nitrogen gas through the system at room temperature for approximately 15 minutes. The reaction mixture was heated at 60-62°C for approximately 12 hours under a nitrogen atmosphere and then cooled to room temperature. The solvent was evaporated under reduced pressure. Acetone was added to the residue. The resulting mixture was heated to 62°C for 12 hours with constant stirring. The mixture was then cooled to room temperature. After 2 hours at room temperature, an insoluble solid precipitated. The acetone was decanted and discarded. The crude product was rinsed in acetone at room temperature with stirring for an additional 2 hours. The acetone was decanted and discarded. The homopolymer was then vacuum dried at 60-65°C to a constant weight.

[0188] Example 5B 13.3 grams (50 mmol) of Compound (A), 5.0 grams (50 mmol) of DMA, and 578 milligrams (3.5 mmol) of AIBN were added to a 1-liter reactor and dissolved in approximately 250 mL of 50:50 (volume / volume) aqueous methanol. The solution was degassed by bubbling nitrogen gas through the system at room temperature for approximately 15 minutes. The reaction mixture was heated at 60-62°C for approximately 12 hours under a nitrogen atmosphere and then cooled to room temperature. The solvent was evaporated under reduced pressure. Acetone was added to the residue. The resulting mixture was heated to 62°C for 12 hours with constant stirring. The mixture was then cooled to room temperature. After 2 hours at room temperature, an insoluble solid precipitated. The acetone was decanted and discarded. The crude product was rinsed in acetone at room temperature with stirring for an additional 2 hours. The acetone was decanted and discarded. The copolymer is then vacuum dried at 60-65°C to a constant weight.

[0189] Example 5C 13.3 grams (50 mmol) of Compound (A), 5.0 grams (50 mmol) of DMA, 907 milligrams (3.5 mmol) of Te-Me, and 578 milligrams (3.5 mmol) of AIBN were added to a 1-liter reactor and dissolved in approximately 250 mL of 50:50 (volume / volume) aqueous methanol. The solution was degassed by bubbling nitrogen gas through the system at room temperature for approximately 15 minutes. The reaction mixture was heated at 60-62°C for approximately 12 hours under a nitrogen atmosphere and then cooled to room temperature. The solvent was evaporated under reduced pressure. Acetone was added to the residue. The resulting mixture was heated to 62°C for 12 hours with constant stirring. The mixture was then cooled to room temperature. After 2 hours at room temperature, an insoluble solid precipitated. The acetone was decanted and discarded. The crude product was rinsed in acetone at room temperature with stirring for an additional 2 hours. The acetone was decanted and discarded. The copolymer is then vacuum dried at 60-65°C to a constant weight.

[0190] Example 5D 13.3 grams (50 mmol) of compound (A), 907 milligrams (3.5 mmol) of Te-Me, and 578 milligrams (3.5 mmol) of AIBN were added to a 1-liter reactor and dissolved in approximately 250 mL of 1-propanol. The solution was degassed by bubbling nitrogen gas through the system at room temperature for approximately 15 minutes. The reaction mixture was heated at 60-62°C under a nitrogen atmosphere for approximately 3 hours. 13.0 grams (100 mmol) of HEMA was dissolved in 30 mL of 1-propanol, degassed by bubbling nitrogen gas through the system at room temperature for 15 minutes, charged into the reactor, and heated at 70-72°C with continuous stirring for approximately 6 hours. Finally, 13.3 grams (50 mmol) of compound (A) was dissolved in 30 mL of 1-propanol, degassed by bubbling nitrogen gas through the system at room temperature for 15 minutes, charged into a reaction vessel, and heated at 60-62°C with continuous stirring for approximately 4 hours.

[0191] The volatile components of the reaction mixture were removed under reduced pressure on a rotary evaporator. The crude product was redissolved in 400 mL of toluene at 60 °C and cooled to room temperature. The mixed solvent system was removed by rotary evaporation to yield a crude product free of 1-propanol. The crude product contained methyltellurium end groups. To remove these organometallic end groups, the crude product was dissolved in 250 mL of toluene containing TEMPO in an amount representing 3.5 times the theoretical molar amount of methyltellurium. This solution was heated at 88 °C for 4 hours. The reaction mixture was cooled to room temperature, and then the volatile components were evaporated on a rotary evaporator at 60-65 °C. The residue was dissolved in 1000 mL of acetonitrile at 72 °C for 30 minutes to form a cloudy solution. This cloudy solution was cooled to room temperature. After standing for a period of time, the insoluble solids were allowed to settle, and the solvent was decanted. The triblock copolymer was isolated by evaporation from the acetonitrile and dried under vacuum at 60-65 °C to constant weight. The triblock copolymer can be further purified by precipitation or extraction.

[0192] Example 6 - Hydrogel Contact Lenses A reactive monomer mixture consisting of 50 weight percent of the formulation listed in Table 4 and 50 weight percent of the diluent BAGE is prepared. The reactive monomer mixture is filtered under pressure through a 3 μm filter using a stainless steel syringe, followed by degassing under reduced pressure for approximately 30 minutes. In a glove box with a nitrogen gas atmosphere and less than 0.2 percent oxygen gas (volume / volume), approximately 75-100 μL of the reactive mixture is dispensed into a front curve mold made of Zeonor at room temperature using an Eppendorf pipette. A base curve mold made from a 55:45 (wt / wt) blend of Zeonor and polypropylene is then placed on top of the front curve mold. The mold is allowed to equilibrate in the glove box for a minimum of 12 hours before dispensing. A plate containing approximately four pallets, each containing eight lens mold assemblies, is transferred to an adjacent glove box maintained at approximately 62°C and 4.5 mW / cm. 2 Cure the lens from above for 5 min using a TL03 light with an intensity of 10 ...

[0193] The lenses are manually removed from the molds, with most of the lenses adhering to the front curve mold, and stripped by suspending the lenses in 80 percent isopropanol for about 1 or 2 hours (about 1 lens per 15 mL), or optionally overnight, followed by washing twice with 80 percent isopropanol, twice with deionized water, and twice with borate buffered packing solution, and finally stored in borate buffered packing solution in vials. After equilibrating for 1 day, the lenses are inspected and sterilized by autoclaving at 122°C for 30 minutes.

[0194] [Table 6]

[0195] [Embodiment] (1) A zwitterionic polymerizable compound of formula I,

[0196] [ka] In the formula, R 1 , R 2 , and R 3 is independently H, alkyl, cycloalkyl, phenyl, or benzyl; L 1 and L 2 are each independently a linking group, R g is a polymerizable group. (2) R 1 is H or C1-C6 alkyl. (3) R 2 The compound of any one of embodiments 1-2, wherein is H. (4) R 3 is H. (5) L 1 and L 2is independently alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, oxaalkylene, alkylene-amido-alkylene, alkylene-amine-alkylene, or a combination thereof.

[0197] (6) L 1 and L 2 is independently alkylene. (7) P g comprises a styryl, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinyl amide, (meth)acrylate, or (meth)acrylamide. (8) 3-(1-(3-methacrylamidopropyl)-1H-imidazol-3-ium-3-yl)propanoate, 3-(1-(3-methacrylamidopropyl)-2-methyl-1H-imidazol-3-ium-3-yl)propanoate, or The compound according to embodiment 1, which is 4-(1-(3-methacrylamidopropyl)-2-methyl-1H-imidazol-3-ium-3-yl)butanoate. (9) An ophthalmic device comprising a polymer derived from the zwitterionic polymerizable compound according to any one of embodiments 1 to 8. (10) The ophthalmic device of embodiment 9, wherein the polymer is contained within the device or coated on the device.

[0198] (11) The ophthalmic device of embodiment 9, wherein the polymer comprises a free radical reaction product of the compound and one or more monomers suitable for fabricating the ophthalmic device. (12) The ophthalmic device of embodiment 11, wherein the monomer suitable for preparing the ophthalmic device is selected from a hydrophilic component, a hydrophobic component, a silicone-containing component, and a mixture of two or more thereof. (13) The ophthalmic device according to any one of embodiments 9 to 12, which is an intraocular lens or a soft contact lens. (14) The ophthalmic device of embodiment 13, which is a hydrogel contact lens. (15) A blister package comprising an ophthalmic device and a packaging solution, wherein the packaging solution comprises a polymer derived from the zwitterionic polymerizable compound according to any one of embodiments 1 to 8.

Claims

1. Zwitterionic polymerizable compounds of formula I, 【Chemical 1】 During the ceremony, R 1 is H or C 1 -C 6 alkyl; R 2 is H; R 3 is H; L 1 and L 2 are independently —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH(CH 3 )CH 2 —, or —CH 2 CH 2 CH 2 CH 2 —; The compound wherein R g is (meth)acrylamide.

2. The compound of claim 1, wherein R g is methacrylamide.

3. The compound of claim 1, wherein R 1 is H or methyl, L 1 is propylene, and L 2 is ethylene or propylene.

4. The compound of claim 1, wherein R 1 is H or methyl, L 1 is propylene, L 2 is ethylene or propylene, and R g is methacrylamide.

5. 3-(1-(3-methacrylamidopropyl)-1H-imidazol-3-ium-3-yl)propanoate, 3-(1-(3-methacrylamidopropyl)-2-methyl-1H-imidazol-3-ium-3-yl)propanoate, or The compound of claim 1 which is 4-(1-(3-methacrylamidopropyl)-2-methyl-1H-imidazol-3-ium-3-yl)butanoate.

6. An ophthalmic device comprising a polymer derived from the zwitterionic polymerizable compound of any one of claims 1 to 5.

7. The ophthalmic device of claim 6 , wherein the polymer is contained within or coated on the ophthalmic device.

8. The ophthalmic device of claim 6 , wherein the polymer comprises a free radical reaction product of the compound and one or more monomers suitable for fabricating the ophthalmic device.

9. The ophthalmic device of claim 8 , wherein the monomers suitable for making the ophthalmic device are selected from hydrophilic components, hydrophobic components, silicone-containing components, and mixtures of two or more thereof.

10. The ophthalmic device according to any one of claims 6 to 9, which is an intraocular lens or a soft contact lens.

11. The ophthalmic device of claim 10 which is a hydrogel contact lens.

12. 10. A blister package comprising an ophthalmic device and a packaging solution, wherein the packaging solution comprises a polymer derived from the zwitterionic polymerizable compound of any one of claims 1 to 5.

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