Silicone hydrogel contact lens having a non-uniform morphology

Abstract

The present invention is titled "Silicone hydrogel contact lens with non-uniform morphology". The present invention describes a silicone hydrogel contact lens with non-uniform morphology. The contact lens can be made from a reactive mixture that includes: a silicone-containing component; a hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator. The contact lens has an oxygen permeability of at least about 60 Barrers, and wherein without surface treatment, the molar ratio of the polymeric non-reactive internal wetting agent to silicone in the lens is greater at the lens surface than in its bulk.

Description

[0001] Related Applications

[0002] This application claims priority to U.S. Patent Application Serial No. 16 / 875,164, filed May 15, 2020, and U.S. Provisional Patent Application Serial No. 62 / 865,586, filed Jun. 24, 2019, the disclosures of which are hereby incorporated by reference in their entireties. Field of the Invention

[0003] The present invention relates to silicone hydrogel contact lenses having non-uniform morphology. More particularly, the present invention relates to silicone hydrogel contact lenses comprising a non-reactive polymeric internal wetting agent, wherein the non-reactive polymeric internal wetting agent is more concentrated in the lens surface than in its bulk. Background of the Invention

[0004] Soft contact lenses are based on hydrogels. Many users find soft contact lenses comfortable enough to wear throughout the day. There are two main types of soft contact lens materials: namely, conventional soft contact lenses formed from hydrogels that do not contain silicone, and soft contact lenses formed from silicone hydrogels.

[0005] Silicone hydrogels are water-swellable polymer networks having a relatively high oxygen permeability. One challenge with silicone hydrogels is the inherent hydrophobicity of the lens surface, which reduces their compatibility with the eye. Many strategies have been employed to address this hydrophobic property. Some techniques rely on post-fabrication modification of the lens surface, such as by applying a hydrophilic surface coating to increase hydrophilicity. Other techniques rely on including an internal wetting agent in the lens. The advantage of the latter approach is that it does not require post-fabrication surface modification. The disadvantage is that hydrophilic wetting agents are generally not readily compatible with the hydrophobic components of the monomer mixture, such as the silicone component, and thus compatible materials are required, increasing the complexity and cost of the formulation.

[0006] The commonly used wetting agent that has been used to impart hydrophilicity to silicone hydrogel contact lenses is polyvinylpyrrolidone (PVP). In a typical manufacturing process, PVP is included in a reactive monomer mixture containing a photoinitiator and other reactive components, and then PVP is subjected to ultraviolet or visible light-initiated curing (photochemical curing). The resulting product contains PVP uniformly distributed throughout the lens.

[0007] One of the main beneficial effects of PVP is its effect on the surface properties of the lens, such as surface wettability. Thus, although PVP is uniformly distributed throughout the lens, it is typically present in a concentration sufficient to still improve the lens surface.

[0008] Silicone hydrogel contact lenses have achieved widespread success in the industry. These lenses provide high oxygen permeability and a good level of comfort for many lens wearers. However, some wearers still experience discomfort and excessive ocular deposits, resulting in reduced visual acuity when using these lenses, especially during extended wear periods such as several consecutive days (e.g., up to about 30 days). Such discomfort and deposits are caused by the hydrophobic properties discussed above and the interaction of these surfaces with the proteins, lipids, and mucins of the eye, as well as hydrophilic surfaces. Therefore, it would be advantageous in the art to develop novel silicone hydrogel contact lenses with further improved surface properties. Summary of the Invention

[0009] The present invention relates to silicone hydrogel contact lenses comprising a non-reactive polymeric internal wetting agent, wherein the wetting agent is enriched at the lens surface relative to the bulk. Such lenses provide a more efficient use of the wetting agent by positioning the wetting agent where it is needed. As a result, many beneficial effects are produced, including, for example, better surface wettability at a substantially the same overall wetting agent concentration as existing lenses. Alternatively, surface-enriched lenses can provide the option of using less wetting agent to achieve substantially the same wettability as existing lenses, which can in turn simplify the manufacturing process and / or reduce costs.

[0010] Accordingly, in one aspect, the present invention provides a silicone hydrogel contact lens that is the reaction product of a reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator, the contact lens having an oxygen permeability of at least about 60 barrers, and wherein, without surface treatment, the molar ratio of the polymeric non-reactive internal wetting agent to silicone in the lens is greater at the lens surface than in its bulk.

[0011] In another aspect, the present invention provides a method for manufacturing a contact lens. The method includes: (a) providing a reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator; and (b) polymerizing the reactive mixture to form a contact lens, wherein the method is carried out under conditions such that, without surface treatment, the contact lens has a molar ratio of the polymeric non-reactive internal wetting agent to silicone that is greater at the lens surface than in its bulk. Brief Description of the Drawings

[0012] Figure 1 Shows FTIR spectra showing the surface concentration and bulk concentration of PVP using the PVP / silicone ratio for the contact lenses of the present invention and comparative contact lenses.

[0013] Figure 2An FTIR spectrum is shown, showing the PVP surface concentration and bulk concentration using the PVP / methacrylate ratio of the contact lenses of the present invention and comparative contact lenses. Detailed Description

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

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

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

[0017] Wherever chemical structures are provided, it should be understood that the alternative options disclosed for substituents on the structure can be combined in any combination. Thus, if the structure contains substituents R* and R**, each of which contains three lists of possible groups, 9 combinations are disclosed. The same applies to combinations of properties.

[0018] When subscripts such as “n” in the general formula [***] n are used to describe the number of repeating units in the chemical formula of a polymer, the formula should be interpreted as representing the number average molecular weight of the macromolecule.

[0019] The term “individual” includes humans and vertebrates.

[0020] The term “ocular surface” includes the surfaces and glandular epithelial cells of the cornea, conjunctiva, lacrimal gland, accessory lacrimal gland, nasolacrimal duct, and meibomian gland, and their apical and basal matrices, lacrimal puncta, and adjacent or related structures, including the eyelids that are connected by epithelial cell continuity, innervation, and the endocrine and immune systems into a functional system.

[0021] The term "contact lens" refers to an ophthalmic device that can be placed on the cornea of an individual's eye. Contact lenses can provide corrective, cosmetic, or therapeutic benefits, including wound healing, drug or nutritional agent delivery, diagnostic evaluation or monitoring, ultraviolet light absorption, visible light or glare reduction, or any combination thereof. Contact lenses can be any suitable material known in the art and can be soft lenses, rigid lenses, or hybrid lenses containing at least two different parts having different physical, mechanical, or optical properties such as modulus, water content, light transmission, or any combination thereof.

[0022] "Target macromolecule" means a macromolecule synthesized from a reactive monomer mixture comprising monomers, macromonomers, prepolymers, crosslinkers, initiators, additives, diluents, etc.

[0023] The term "polymerizable compound" or "polymerizable component" means a compound containing one or more polymerizable groups. This term encompasses, for example, monomers, macromonomers, oligomers, prepolymers, crosslinkers, etc.

[0024] "Polymerizable group" is a group that can undergo chain-growth polymerization (such as free radical and / or cationic polymerization), for example, a carbon-carbon double bond that can polymerize when subjected to free radical polymerization initiation conditions. Non-limiting examples of free radical polymerizable groups include (meth)acrylate, styrene, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, and other vinyl groups. Preferably, the free radical polymerizable groups include (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, and styryl functional groups, and mixtures of any of the foregoing. More preferably, the free radical polymerizable groups include (meth)acrylate, (meth)acrylamide, and mixtures thereof. The polymerizable group can be unsubstituted or substituted. For example, the nitrogen atom in (meth)acrylamide can be bonded to hydrogen, or the hydrogen can be replaced by an alkyl or cycloalkyl group (which itself can be further substituted).

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

[0026] "Monomer" is a monofunctional molecule that is a repeating unit in a chemical structure that can undergo chain-growth polymerization (and specifically free-radical polymerization) to form a target macromolecule. Some monomers have difunctional impurities that can act as crosslinking agents. "Hydrophilic monomer" is additionally a monomer that, when mixed with deionized water at a concentration of 5 wt% at 25 °C, produces a clear single-phase solution. "Hydrophilic component" is a monomer, macromonomer, prepolymer, initiator, crosslinking agent, additive, or polymer that, when mixed with deionized water at a concentration of 5 wt% at 25 °C, produces a clear single-phase solution. "Hydrophobic component" is a monomer, macromonomer, prepolymer, initiator, crosslinking agent, additive, or polymer that is slightly soluble or insoluble in deionized water at 25 °C.

[0027] "Macromolecule" is an organic compound with a number-average molecular weight greater than 1500 and can be reactive or non-reactive.

[0028] "Macromonomer (macromonomer or macromer)" is a macromolecule having a group that is a repeating unit in a chemical structure that can undergo chain-growth polymerization (and specifically free-radical polymerization) to form a target macromolecule. Generally, the chemical structure of the macromonomer is different from that of the target macromolecule, in other words, the repeating unit of the side group of the macromonomer is different from the repeating unit of the target macromolecule or its main chain. The difference between a monomer and a macromonomer is only one of chemical structure, molecular weight, and molecular weight distribution of the side group. Thus, and as used herein, patent literature occasionally defines a monomer as a polymerizable compound having a relatively low molecular weight of about 1,500 daltons or less, which essentially includes some macromonomers. Specifically, monomethacryloxypropyl-capped monon-butyl-capped polydimethylsiloxane (molecular weight = 500 - 1500 g / mol) (mPDMS) and mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether-capped monon-butyl-capped polydimethylsiloxane (molecular weight = 500 - 1500 g / mol) (OH-mPDMS) can be referred to as monomers or macromonomers. Additionally, patent literature occasionally defines a macromonomer as having one or more polymerizable groups, thereby essentially expanding the general definition of a macromonomer to include prepolymers. Thus, and as used herein, difunctional and polyfunctional macromonomers, prepolymers, and crosslinking agents can be used interchangeably.

[0029] "Silicone-containing component" is a monomer, macromonomer, prepolymer, crosslinking agent, initiator, additive, or polymer in a reactive mixture that has at least one silicon-oxygen bond, which is typically in the form of a silyloxy group, siloxanyl group, carbosiloxanyl group, and mixtures thereof.

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

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

[0032] A "homopolymer" is a polymer made from one monomer; a "copolymer" is a polymer made from two or more monomers; a "terpolymer" is a polymer made from three monomers. A "block copolymer" is composed of compositionally distinct blocks or segments. A diblock copolymer has two blocks. A triblock copolymer has three blocks. A "comb or graft copolymer" is made from at least one macromonomer.

[0033] A "repeating unit" is the smallest group of atoms in a polymer that corresponds to the polymerization of a specific monomer or macromonomer.

[0034] "Initiator" is a molecule that can decompose into free radicals, which can then react with monomers to initiate radical polymerization. Depending on the temperature, thermal initiators decompose at a certain rate; 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 perbenzoate, dicumyl peroxide and lauroyl peroxide, peracids such as peracetic acid and potassium persulfate, and various redox systems. Photoinitiators that decompose by photochemical methods; typical examples are benzil, benzoin, acetophenone, benzophenone, camphorquinone, and mixtures thereof, and derivatives of various monoacyl and diacyl phosphine oxides, and combinations thereof.

[0035] "Crosslinking agent" is a difunctional or polyfunctional monomer or macromonomer that can undergo radical polymerization at two or more positions on the molecule to form branch points and a polymer network. Common examples are ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, methylenebisacrylamide, triallyl cyanurate, etc.

[0036] "Prepolymer" is the reaction product of monomers that contains remaining polymerizable groups capable of undergoing further reaction to form a polymer.

[0037] "Polymer network" is a crosslinked macromolecule that can swell but not dissolve in a solvent. "Hydrogel" is a polymer network that swells in water or an aqueous solution and usually absorbs at least 10% by weight of water. "Silicone hydrogel" is a hydrogel made from at least one silicone-containing component and at least one hydrophilic component. The hydrophilic component may also include non-reactive polymers.

[0038] "Conventional hydrogel" refers to a polymer network made of components that do not contain any silyloxy, siloxane or carbosilane groups. Conventional hydrogels are prepared from a reactive mixture containing hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate ("HEMA"), N-vinylpyrrolidone ("NVP"), N,N-dimethylacrylamide ("DMA") or vinyl acetate. U.S. Patent Nos. 4,436,887, 4,495,313, 4,889,664, 5,006,622, 5,039459, 5,236,969, 5,270,418, 5,298,533, 5,824,719, 6,420,453, 6,423,761, 6,767,979, 7,934,830, 8,138,290 and 8,389,597 disclose the formation of conventional hydrogels. Commercially available conventional hydrogels include, but are not limited to, etafilcon, genfilcon, hilafilcon, lenefilcon, nesofilcon, omafilcon, polymacon and verofilcon, including all their variants.

[0039] "Silicone hydrogel" refers to a polymer network made from at least one hydrophilic component and at least one silicone-containing component. Examples of silicone hydrogels include acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon, including all their variants, as well as silicone hydrogels prepared as described in U.S. Patent Nos. 4,659,782, 4,659,783, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,998,498, 6,087,415, 5,760,100, 5,776,999, 5,789,461, 5,849,811, 5,965,631, 6,367,929, 6,822,016, 6,867,245, 6,943,203, 7,247,692, 7,249,848, 7,553,880, 7,666,921, 7,786,185, 7,956,131, 8,022,158, 8,273,802, 8,399,538, 8,470,906, 8,450,387, 8,487,058, 8,507,577, 8,637,621, 8,703,891, 8,937,110, 8,937,111, 8,940,812, 9,056,878, 9,057,821, 9,125,808, 9,140,825, 9156,934, 9,170,349, 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,929, and WO 03 / 22321, WO 2008 / 061992, and US 2010 / 0048847. These patents are hereby incorporated by reference in their entirety.

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

[0041] "Reactive component" means a polymerizable compound (such as a monomer, macromonomer, oligomer, prepolymer, and crosslinker) in a reactive mixture (defined below), and any other component in the reactive mixture that is intended to remain substantially in the polymer network after polymerization and all post-treatment steps (such as extraction steps) and packaging steps have been completed. The reactive component can be retained in the polymer network by covalent bonding, hydrogen bonding, electrostatic interaction, formation of an interpenetrating polymer network, or any other means. A component intended to be released from the polymer network is still considered a "reactive component" during use. For example, a drug component or nutritional component in a contact lens that is intended to be released during wearing is considered a "reactive component". A component such as a diluent that is intended to be removed from the polymer network during the manufacturing process (such as by extraction) is not a "reactive component".

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

[0043] The term "silicone hydrogel contact lens" refers to a hydrogel contact lens made from at least one silicone-containing compound. Compared to conventional hydrogels, silicone hydrogel contact lenses generally have improved oxygen permeability. Silicone hydrogel contact lenses utilize both their water and polymer contents to transport oxygen to the eye.

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

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

[0046] "Alkyl" means an optionally substituted straight-chain or branched alkyl group containing a specified number of carbon atoms. If the number is not specified, the alkyl group (including any optional substituents on the alkyl) can contain 1 to 16 carbon atoms. Preferably, the alkyl group contains 1 to 10 carbon atoms, alternatively 1 to 8 carbon atoms, alternatively 1 to 6 carbon atoms, or alternatively 1 to 4 carbon atoms. Examples of alkyl include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl, pentyl, hexyl, heptyl, 3-ethylbutyl, etc. Examples of substituents on the alkyl include 1, 2 or 3 groups independently selected from the following: hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, alkylthio, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Alkylene" means a divalent alkyl group, such as -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH(CH3)CH2- and -CH2CH2CH2CH2-.

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

[0048] "Cycloalkyl" means an optionally substituted cyclic hydrocarbon containing a specified number of ring carbon atoms. If the number is not indicated, the cycloalkyl can contain 3 to 12 ring carbon atoms. Preferred are C3-C8 cycloalkyl groups, C3-C7 cycloalkyl, more preferably C4-C7 cycloalkyl, and still more preferably C5-C6 cycloalkyl. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Examples of substituents on the cycloalkyl include 1, 2 or 3 groups independently selected from the following: alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, alkylthio, amido, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Cycloalkylene" means a divalent cycloalkyl group, such as 1,2-cyclohexylene, 1,3-cyclohexylene or 1,4-cyclohexylene.

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

[0050] "Aryl" refers to an optionally substituted aromatic hydrocarbon ring system containing at least one aromatic ring. An aryl group contains a specified number of ring carbon atoms. If no number is indicated, an aryl may contain 6 to 14 ring carbon atoms. The aromatic rings may be optionally fused or otherwise linked to other aromatic hydrocarbon rings or non-aromatic hydrocarbon rings. Examples of aryl groups include phenyl, naphthyl, and biphenyl. Preferred examples of aryl groups include phenyl. Examples of substituents on the aryl include one, two, or three groups independently selected from the following: alkyl, hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, alkylthio, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Arylene" means a divalent aryl group, such as 1,2-phenylene, 1,3-phenylene, or 1,4-phenylene.

[0051] "Heteroaryl" refers to an aryl ring or ring system as defined above in which at least one ring carbon atom has been replaced by a heteroatom selected from nitrogen, oxygen, and sulfur. Heteroaryl rings may be fused or otherwise linked 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" means a divalent heteroaryl group.

[0052] "Alkoxy" refers to an alkyl group linked to the parent molecular moiety by an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy, and isopropoxy. "Alkylthio" means an alkyl group linked to the parent molecule by a sulfur bridge. Examples of alkylthio groups include, for example, methylthio, ethylthio, n-propylthio, and isopropylthio. "Aryloxy" refers to an aryl group linked to the parent molecular moiety by an oxygen bridge. Examples include phenoxy. "Cycloalkoxy" means a cycloalkyl group linked to the parent moiety by an oxygen bridge.

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

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

[0055] "Silyl" refers to a structure of the formula R3Si-, and "silyloxy" refers to a structure of the formula R3Si-O-, where each R in the silyl or silyloxy independently is selected from trimethylsilyloxy, C1-C8 alkyl (preferably C1-C3 alkyl, more preferably ethyl or methyl), and C3-C8 cycloalkyl.

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

[0057] "Oxaalkylene" refers to an alkylene group as defined above in which one or more non - adjacent CH2 groups have been replaced by oxygen atoms, such as -CH2CH2OCH(CH3)CH2-. "Thiaalkylene" refers to an alkylene group as defined above in which one or more non - adjacent CH2 groups have been replaced by sulfur atoms, such as -CH2CH2SCH(CH3)CH2-.

[0058] The term "linking group" refers to the moiety that connects the polymerizable group to the parent molecule. The linking group can be any moiety compatible with the compound, which is part of the compound and does not undesirably interfere with the polymerization of the compound and is stable under the polymerization conditions and the conditions for processing and storing the final product. For example, the linking group can be a chemical bond, or it can include one or more alkylene, haloalkylene, amide, amine, alkyleneamine, carbamate, ester (-CO2-), arylene, heteroarylene, cycloalkylene, heterocycloalkylene, alkoxy, oxaalkylene, thiaalkylene, haloalkoxy (alkoxy substituted with one or more halogen groups, such as -OCF2-, -OCF2CF2-, -OCF2CH2-), siloxanyl, alkylsiloxanyl, or combinations thereof. The linking group can be optionally substituted with one or more substituent groups. Suitable substituent groups can include those independently selected from alkyl, halogen (such as fluorine), hydroxy, HO-alkoxy, MeO-alkoxy, siloxanyl, silyloxy, silyloxy-alkoxy-, silyloxy-alkyl-alkoxy- (wherein there can be more than one alkoxy group, and each methylene in the alkyl and alkoxy is independently optionally substituted with hydroxy), ether, amine, carbonyl, carbamate, and combinations thereof. The linking group can also be substituted with a polymerizable group such as (meth)acrylate (in addition to the polymerizable group to which the linking group is attached).

[0059] Preferred linking groups include C1-C8 alkylene (preferably C2-C6 alkylene) and C1-C8 oxaalkylene (preferably C2-C6 oxaalkylene), each of which is optionally substituted with 1 or 2 groups independently selected from hydroxy and silyloxy. Preferred linking groups also include carboxylate, amide, C1-C8 alkylene-carboxylate-C1-C8 alkylene or C1-C8 alkylene-amide-C1-C8 alkylene.

[0060] When the linking group is composed of a combination of moieties (e.g., alkylene and cycloalkylene) as described above, the moieties can be present in any order. For example, if in formula A below, L is indicated as -alkylene-cycloalkylene-, then Rg-L can be Rg-alkylene-cycloalkylene- or Rg-cycloalkylene-alkylene-. Nevertheless, the listed order represents the preferred order of the moieties as they appear in the compound starting from the terminal polymerizable group (Rg or Pg) to which the linking group is attached. For example, if in formula A, L is indicated as -alkylene-cycloalkylene-, then Rg-L is preferably Rg-alkylene-cycloalkylene-.

[0061] The phrase "without surface treatment" or "untreated surface" means that the enrichment of the non-reactive polymeric internal wetting agent of the lens of the present invention at the surface and the improved surface wettability are achieved without the need for separate treatment of the outer surface of the lens to improve wettability. Surface treatment can include plasma treatment and coating. Coatings that provide properties other than improved wettability, such as antimicrobial coatings or coloring or other cosmetic enhancements, are not considered surface treatment.

[0062] When used in the context of the presence of a non-reactive polymeric wetting agent, the term "surface" means the outer region of the lens, e.g., the region that can be analyzed by ATR infrared spectroscopy. The surface can include the outer 2 microns of the lens. When used in the context of the presence of a non-reactive polymeric wetting agent in a contact lens, the term "bulk" means the entire lens, including its surface.

[0063] Unless otherwise specified, ratios, percentages, parts, etc. are by weight.

[0064] Unless otherwise specified, a numerical range (e.g., "2 to 10") includes the numbers defining the range (e.g., 2 and 10).

[0065] As described above, in one aspect, the present invention provides a silicone hydrogel contact lens that is the reaction product of a reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator, the contact lens having an oxygen permeability of at least about 60 Barrers, and wherein without surface treatment, the molar ratio of the polymeric non-reactive internal wetting agent to the silicone from the silicone-containing component in the lens is greater at the lens surface than in its bulk.

[0066] The molar ratio of the polymeric non-reactive internal wetting agent to the silicone in the silicone hydrogel contact lens of the present invention is at least 1.5 times greater at the lens surface than in its bulk. The molar ratio of the polymeric non-reactive internal wetting agent to the silicone can be at least 2 times, or at least 2.3 times, or at least 3 times, or at least 3.5 times, or at least 4 times, or at least 4.9 times, or at least 6 times, or at least 7 times, or at least 7 times, or at least 9 times greater at the lens surface than in its bulk. This ratio and other component ratios can be measured by a variety of methods. Exemplary methods are described in the examples. The method uses infrared spectroscopy in both attenuated total reflection (ATR) and transmission modes to measure the relative amounts of component molecules in the surface and bulk of the lens. According to this method, as will be understood by those skilled in the art, silicone is identified by the silicone vibration mode in the infrared spectrum of the material.

[0067] If the silicone hydrogel lens is made of a material containing (meth)acrylate groups, such groups are readily visible in the IR spectrum. Thus, when (meth)acrylate groups are present, the increased concentration of the polymer non-reactive internal wetting agent at the surface relative to the bulk can also be expressed in terms of the molar ratio of the polymer non-reactive internal wetting agent to (meth)acrylate. Thus, expressed in this way, the contact lens of the present invention can have a molar ratio of the polymer non-reactive internal wetting agent to (meth)acrylate groups in the lens that is greater in the lens surface than in its bulk without surface treatment. For example, the molar ratio of the polymer non-reactive internal wetting agent to (meth)acrylate can be at least 1.5 times, or at least 2 times, or at least 2.5 times, or at least 3 times, or at least 3.5 times, or at least 4 times, or at least 4.5 times, or at least 6 times, or at least 7 times, or at least 8 times, or at least 9 times in the lens surface as compared to its bulk.

[0068] While the concentration of the polymer non-reactive internal wetting agent is enriched at the lens surface, other constituent molecules can remain distributed substantially uniformly throughout the lens. For example, the hydrophilic portions of the polymer network other than the polymer non-reactive internal wetting agent (e.g., those introduced via the hydrophilic components of the reactive monomer mixture such as hydroxyethyl methacrylate) can be distributed substantially uniformly in the lens. By way of example, the molar ratio of the hydrophilic constituent molecules other than the polymer non-reactive internal wetting agent to silicone in the silicone hydrogel contact lens of the present invention is no more than 1.2 times, or no more than 1.1 times in the lens surface as compared to its bulk. As another example, the molar ratio of the hydrophilic constituent molecules other than the polymer non-reactive internal wetting agent to silicone in the silicone hydrogel contact lens of the present invention can be substantially the same in the lens surface as in its bulk.

[0069] As described above, the silicone hydrogel contact lens of the present invention provides many desirable properties by enriching the non-reactive polymer internal wetting agent at the lens surface. One such property is improved surface wettability (as measured by the advancing dynamic contact angle). For example, it has been found that silicone hydrogel contact lenses that are reaction products of reactive mixtures containing as little as 2 wt% or as little as 2.5 wt% of the non-reactive polymer internal wetting agent exhibit an advancing dynamic contact angle (Wilhelmy plate method) of 75° or less, or 70° or less, or 60° or less, or 50° or less, or 45° or less, or 40° or less, or 35° or less, or 30° or less, or 25° or less, or 22° or less without surface treatment. In contrast, as confirmed by the examples, lenses prepared from reactive mixtures containing the same amount of the non-reactive polymer internal wetting agent but without enrichment of the wetting agent at the surface exhibit an advancing contact angle greater than 75° (without surface treatment).

[0070] The silicone hydrogel contact lens of the present invention comprises the reaction product of a reactive mixture, the reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator.

[0071] The silicone-containing component suitable for the present invention comprises one or more polymerizable compounds, each of which independently comprises at least one polymerizable group, at least one siloxane group, and one or more linking groups connecting one or more polymerizable groups to one or more siloxane groups. The silicone-containing component may contain, for example, 1 to 220 siloxane repeating units, such as the groups defined below. The silicone-containing component may also contain at least one fluorine atom.

[0072] 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, which are independently (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl carbamate, O-vinyl carbonate, vinyl group, or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.

[0073] The silicone-containing component may comprise: one or more polymerizable groups, which are independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, styryl or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.

[0074] The silicone-containing component may comprise: one or more polymerizable groups, which are independently (meth)acrylate, (meth)acrylamide or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.

[0075] The silicone-containing component may comprise one or more polymerizable compounds of formula A:

[0076]

[0077] Wherein:

[0078] At least one R A Is a group of formula R g -L-, where Rg is a polymerizable group and L is a linking group, and the remaining R A are each independently:

[0079] (a) R g -L-,

[0080] (b) C1-C 16 alkyl, optionally substituted with one or more hydroxyl groups, amino groups, amide groups, oxa groups, carboxyl groups, alkylcarboxyl groups, carbonyl groups, alkoxy groups, amide groups, carbamate groups, carbonate groups, halogens, phenyl groups, benzyl groups, or combinations thereof;

[0081] (c) C3-C 12 cycloalkyl, optionally substituted with one or more alkyl groups, hydroxyl groups, amino groups, amide groups, oxa groups, carbonyl groups, alkoxy groups, amide groups, carbamate groups, carbonate groups, halogens, phenyl groups, benzyl groups, or combinations thereof;

[0082] (d) C6-C 14 aryl group, optionally substituted with one or more alkyl groups, hydroxyl groups, amino groups, amide groups, oxa groups, carboxyl groups, alkylcarboxyl groups, carbonyl groups, alkoxy groups, amide groups, carbamate groups, carbonate groups, halogens, phenyl groups, benzyl groups, or combinations thereof;

[0083] (e) halogen;

[0084] (f) alkoxy group, cyclic alkoxy group, or aryloxy group;

[0085] (g) silyloxy group;

[0086] (h) alkyleneoxy-alkyl or alkoxy-alkyleneoxy-alkyl, such as poly(ethyleneoxy)alkyl, poly(propyleneoxy)alkyl, or poly(ethyleneoxy-co-propyleneoxy)alkyl; or

[0087] (i) a monovalent siloxane chain containing 1 to 100 siloxane repeating units, the siloxane repeating units optionally substituted with alkyl groups, alkoxy groups, hydroxyl groups, amino groups, oxa groups, carboxyl groups, alkylcarboxyl groups, alkoxy groups, amide groups, carbamate groups, halogens, or combinations thereof; and

[0088] n is from 0 to 500, or from 0 to 200, or from 0 to 100, or from 0 to 20, it being understood that when n is not 0, n has a distribution with a mode equal to the specified value. When n is 2 or greater, the SiO units may carry the same or different R A substituents, and if different R A substituents are present, the n groups may be in a random or block configuration.

[0089] In formula A, three R A may each contain a polymerizable group, alternatively two RA may each contain a polymerizable group, or alternatively one R A may contain a polymerizable group.

[0090] Examples of the silicone-containing components suitable for the present invention include, but are not limited to, the compounds listed in Table A. If the compounds in Table A contain polysiloxane groups, unless otherwise specified, the number of SiO repeating units in such compounds is preferably from 3 to 100, more preferably from 3 to 40, or still more preferably from 3 to 20.

[0091] Table A

[0092]

[0093]

[0094] Further non-limiting examples of suitable silicone-containing components are listed in Table B. Unless otherwise specified, where applicable, j2 is preferably from 1 to 100, more preferably from 3 to 40, or still more preferably from 3 to 15. In the compounds containing j1 and j2, the sum of j1 and j2 is preferably from 2 to 100, more preferably from 3 to 40, or still more preferably from 3 to 15.

[0095] Table B

[0096]

[0097]

[0098]

[0099] The silicone-containing component can be a component containing a hydroxy-functionalized silicone. Mixtures of silicone-containing components can be used. For example, suitable mixtures can include a component containing a hydroxy-functionalized silicone and a component containing a non-hydroxy-functionalized silicone. Another example is that suitable mixtures can include, but are not limited to: mixtures of mono-(2-hydroxy-3-methacryloyloxypropoxy)-propyl-capped mono-n-butyl-capped polydimethylsiloxanes (OH-mPDMS) having different molecular weights, such as mixtures of OH-mPDMS containing 4 and 15 SiO repeating units; mixtures of OH-mPDMS having different molecular weights (e.g., containing 4 and 15 repeating SiO repeating units) and a silicone-based crosslinker such as bis-3-acryloyloxy-2-hydroxypropoxypropyl polydimethylsiloxane (ac-PDMS); mixtures of 2-hydroxy-3-[3-methyl-3,3-bis(trimethylsilyloxy)silylpropoxy]-propyl methacrylate (SiMAA) and mono-methacryloyloxypropyl-capped mono-n-butyl-capped polydimethylsiloxane (mPDMS) such as mPDMS 1000.

[0100] The silicone-containing component used in the present invention can have an average molecular weight of about 400 daltons to about 4000 daltons.

[0101] Based on all the reactive components of the reactive mixture (i.e., excluding diluents), the silicone-containing component can be present in an amount of at most about 95% by weight, or about 10% to about 80% by weight, or about 20% to about 70% by weight.

[0102] Examples of suitable types of hydrophilic monomers that can be used in the reactive mixture include (meth)acrylates, styrene, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl carbamates, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof.

[0103] Non-limiting examples of hydrophilic (meth)acrylate and (meth)acrylamide monomers include: acrylamide, N-isopropylacrylamide, N,N-dimethylaminopropyl (meth)acrylamide, N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2,3-dihydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, N-(2-hydroxyethyl) (meth)acrylamide, N,N-bis(2-hydroxyethyl) (meth)acrylamide, N-(2-hydroxypropyl) (meth)acrylamide, N,N-bis(2-hydroxypropyl) (meth)acrylamide, N-(3-hydroxypropyl) (meth)acrylamide, N-(2-hydroxybutyl) (meth)acrylamide, N-(3-hydroxybutyl) (meth)acrylamide, N-(4-hydroxybutyl) (meth)acrylamide, 2-aminoethyl (meth)acrylate, 3-aminopropyl (meth)acrylate, 2-aminopropyl (meth)acrylate, N-2-aminoethyl (meth)acrylamide, N-3-aminopropyl (meth)acrylamide, N-2-aminopropyl (meth)acrylamide, N,N-bis-2-aminoethyl (meth)acrylamide, N,N-bis-3-aminopropyl (meth)acrylamide, N,N-bis-2-aminopropyl (meth)acrylamide, glycerol methacrylate, polyethylene glycol monomethacrylate, (meth)acrylic acid, vinyl acetate, acrylonitrile, and mixtures thereof.

[0104] The hydrophilic monomer can also be ionic, including anionic, cationic, zwitterionic, betaine, and mixtures thereof. Non-limiting examples of such charged monomers include (meth)acrylic acid, N-[(vinyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropionic acid (ACA1), 5-acrylamidovaleric acid (ACA2), 3-acrylamido-3-methylbutyric acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-1-propanaminium inner salt (CBT), N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-1-propanaminium inner salt (SBT), 4-hydroxy-N,N,N-trimethyl-9-oxo-4-oxide 3,5-dioxa-8-aza-4-phosphaundec-10-en-1-aminium inner salt (9CI) (PBT), 2-methacryloyloxyethylphosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS), and 3-((3-(methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

[0105] Non-limiting examples of hydrophilic N-vinyl lactam and N-vinyl amide monomers include: N-vinyl pyrrolidone (NVP), N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-caprolactam, N-vinyl-3-methyl-2-piperidone, N-vinyl-4-methyl-2-piperidone, N-vinyl-4-methyl-2-caprolactam, N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone, N-vinyl acetamide (NVA), N-vinyl-N-methyl acetamide (VMA), N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, N-vinyl-N-methyl propionamide, N-vinyl-N-methyl-2-methyl propionamide, N-vinyl-2-methyl propionamide, N-vinyl-N,N'-dimethyl urea, 1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone; 1-ethyl-5-methylene-2-pyrrolidone, N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-N-propyl-3-methylene-2-pyrrolidone, 1-N-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, N-vinyl isopropyl amide, N-vinyl caprolactam, N-vinyl imidazole, and mixtures thereof.

[0106] Non-limiting examples of hydrophilic O-vinyl carbamate and O-vinyl carbonate monomers include N-2-hydroxyethyl vinyl carbamate and N-carboxy-β-alanine N-vinyl ester. Other examples of hydrophilic ethylene carbonate or vinyl carbamate monomers are disclosed in U.S. Patent 5,070,215. Hydrophilic oxazolone monomers are disclosed in U.S. Patent 4,910,277.

[0107] Other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, and 2-ethyl oxazoline.

[0108] The hydrophilic monomer can also be a linear or branched macromonomer or prepolymer of poly(ethylene glycol), poly(propylene glycol), or a statistical random or block copolymer of ethylene oxide and propylene oxide, which has polymerizable moieties such as (meth)acrylate, styrene, vinyl ether, (meth)acrylamide, N-vinyl amide, etc. These macromonomers of polyethers have one polymerizable group; the prepolymers can have two or more polymerizable groups.

[0109] Preferred hydrophilic monomers of the present invention are DMA, NVP, HEMA, VMA, NVA, and mixtures thereof. Preferred hydrophilic monomers include NVP, DMA, and HEMA, or mixtures thereof. Preferred hydrophilic monomers also include a mixture of DMA and HEMA. Other suitable hydrophilic monomers will be apparent to those skilled in the art.

[0110] Generally speaking, there is no particular limitation on the amount of hydrophilic monomers present in the reactive monomer mixture. The amount of hydrophilic monomers can be selected based on the desired characteristics of the resulting hydrogel, including water content, light transmittance, wettability, protein absorption rate, etc. Wettability can be measured by contact angle, and the required contact angle is less than about 100°, less than about 80°, and less than about 60°. Based on the total weight of the reactive components in the reactive monomer mixture, the hydrophilic monomers can be present, for example, in the range of about 0.1 wt% to about 100 wt%, alternatively in the range of about 1 wt% to about 80 wt%, alternatively in the range of about 5 wt% to about 65 wt%, alternatively in the range of about 40 to about 60 wt%, or alternatively in the range of about 55 wt% to about 60 wt%.

[0111] The reaction mixture of the present invention contains a non-reactive polymer internal wetting agent. The non-reactive polymer internal wetting agent can be a hydrophilic polymer. The non-reactive polymer internal wetting agent can have a weight average molecular weight of at least about 50,000 Daltons, or at least about 100,000 Daltons, or at least about 150,000 Daltons; or from about 150,000 Daltons to about 2,000,000 Daltons; or from about 300,000 Daltons to about 1,800,000 Daltons. If higher molecular weight polymers are compatible with the reactive monomer mixture, higher molecular weight polymers can be used.

[0112] Alternatively, based on kinematic viscosity measurements, the molecular weight of the non-reactive polymer internal wetting agent can be represented by a K value as described in the following document: Encyclopedia of Polymer Science and Engineering, N-VinylAmide Polymers, 2nd Edition, Volume 17, pages 198 - 257, John Wiley & Sons Inc. When represented in this way, non-reactive polymer internal wetting agents with a K value greater than about 46 and, in one embodiment, between about 46 and about 150 are preferred. K values of about K60 to K120, or about K80 to K100, or about K90 are also preferred.

[0113] The amount of non-reactive polymer internal wetting agent that can be added to the reactive monomer mixture of the present invention can vary depending on the other components used and the desired properties of the resulting product. For example, the non-reactive polymer internal wetting agent can be included in an amount of about 0.5 wt% to about 35 wt%, about 1 wt% to about 20 wt%, about 1 wt% to about 15 wt%, about 2 wt% to about 15%, or about 2% to about 12%, based on the total weight of all reactive components. Based on the total weight of all reactive components, the amount of non-reactive polymer internal wetting agent can range from about 1 wt% to about 10 wt%.

[0114] Non-reactive polymer internal wetting agents useful in the present invention include, but are not limited to, homopolymers, statistical random copolymers, diblock copolymers, triblock copolymers, segmented block copolymers, graft copolymers, and mixtures thereof. Non-limiting examples of non-reactive polymer internal wetting agents are polyamides, polyesters, poly(lactones), polyimides, poly(lactams), polyethers, homopolymers of polyacids, and copolymers prepared by free radical polymerization of suitable monomers, which monomers include acrylates, methacrylates, styrene, vinyl ethers, acrylamides, methacrylamides, N-vinyl lactams, N-vinyl amides, O-vinyl carbamates, O-vinyl carbonates, and other vinyl compounds. Non-reactive polymer internal wetting agents can be made from any hydrophilic monomer, including those listed herein.

[0115] Suitable non-reactive polymer internal wetting agents include, but are not limited to, polyamides. As used herein, the term "polyamide" refers to polymers and copolymers that include repeating units containing amide groups. Polyamides can include cyclic amide groups, acyclic amide groups, and combinations thereof, and can be any polyamide known to those skilled in the art. Acyclic polyamides contain acyclic amide side groups and are capable of binding to hydroxyl groups. Cyclic polyamides contain cyclic amide groups and are capable of binding to hydroxyl groups.

[0116] Examples of suitable acyclic polyamides include polymers and copolymers containing repeating units of formula G1 and G2:

[0117]

[0118] wherein X is a direct bond, -(CO)-, or -(CONHR 44 )-, wherein R 44 is a C1 to C3 alkyl group; R 40 is selected from H, straight or branched chain substituted or unsubstituted C1 to C4 alkyl groups; R 41 is selected from H, straight or branched chain substituted or unsubstituted C1 to C4 alkyl groups, amino groups having at most two carbon atoms, amide groups having at most four carbon atoms, and alkoxy groups having at most two carbon groups; R42 Selected from H, straight-chain or branched-chain substituted or unsubstituted C1 to C4 alkyl groups; or methyl, ethoxy, hydroxyethyl, and hydroxymethyl; R 43 Selected from H, straight-chain or branched-chain substituted or unsubstituted C1 to C4 alkyl groups; or methyl, ethoxy, hydroxyethyl, and hydroxymethyl; wherein R 40 and R 41 The number of carbon atoms in together is 8 or less, including 7, 6, 5, 4, 3 or less; and wherein R 42 and R 43 The number of carbon atoms in together is 8 or less, including 7, 6, 5, 4, 3 or less. R 40 and R 41 The number of carbon atoms in together can be 6 or less or 4 or less. R 42 and R 43 The number of carbon atoms in together can be 6 or less. As used herein, substituted alkyl groups include alkyl groups substituted with amine, amide, ether, hydroxy, carbonyl, or carboxyl groups or combinations thereof.

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

[0120] The acyclic polyamide can comprise a majority of repeating units of formula LV or formula LVI, or the acyclic polyamide can comprise at least 50 mol% (including at least 70 mol% and at least 80 mol%) of repeating units of formula G or formula G1. Specific examples of repeating units of formula G and formula G1 include repeating units derived from the following: N-vinyl-N-methylacetamide, N-vinylacetamide, N-vinyl-N-methylpropanamide, N-vinyl-N-methyl-2-methylpropanamide, N-vinyl-2-methyl-propanamide, N-vinyl-N,N'-dimethylurea, N,N-dimethylacrylamide, methacrylamide, and acyclic amides of formula G2 and G3:

[0121]

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

[0123]

[0124] wherein R 45 is a hydrogen atom or a methyl group; wherein f is a number from 1 to 10; wherein X is a direct bond, -(CO)- or -(CONHR 46 ), wherein R 46 is a C1 to C3 alkyl group. In formula LIX, f can be 8 or less, including 7, 6, 5, 4, 3, 2 or 1. In formula G4, f can be 6 or less, including 5, 4, 3, 2 or 1. In formula G4, f can be from 2 to 8, including 2, 3, 4, 5, 6, 7 or 8. In formula LIX, f can be 2 or 3. When X is a direct bond, f can be 2. In such cases, the cyclic polyamide can be polyvinylpyrrolidone (PVP).

[0125] The cyclic polyamide can comprise 50 mol% or more of the repeating units of formula G4, or the cyclic polyamide can comprise at least 50 mol% (including at least 70 mol% and at least 80 mol%) of the repeating units of formula G4.

[0126] The polyamide may also be a copolymer comprising repeating units of both cyclic and acyclic amides. The additional repeating units may be formed from monomers selected from: hydroxyalkyl (meth)acrylates, alkyl (meth)acrylates, other hydrophilic monomers, and siloxane-substituted (meth)acrylates. Any of the monomers (listed as suitable hydrophilic monomers) may be used as a comonomer to form the additional repeating units. Specific examples of additional monomers that can be used to form the polyamide include 2-hydroxyethyl (meth)acrylate, vinyl acetate, acrylonitrile, hydroxypropyl (meth)acrylate, methyl (meth)acrylate and hydroxybutyl (meth)acrylate, dipropylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, etc., and mixtures thereof. It may also contain ionic monomers. Examples of ionic monomers include (meth)acrylic acid, N-[(vinyloxy)carbonyl]-β-alanine (VINAL, CAS#148969-96-4), 3-acrylamidopropionic acid (ACA1), 5-acrylamidovaleric acid (ACA2), 3-acrylamido-3-methylbutyric acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-1-propanaminium inner salt (CBT, carboxybetaine; CAS 79704-35-1), N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-1-propanaminium inner salt (SBT, sulfobetaine, CAS 80293-60-3), 4-hydroxy-N,N,N-trimethyl-9-oxo-4-oxide 3,5-dioxa-8-aza-4-phosphaundec-10-en-1-aminium inner salt (9CI) (PBT, phosphobetaine, CAS 163674-35-9), 2-methacryloyloxyethylphosphorylcholine, 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).

[0127] The reactive monomer mixture can contain both acyclic polyamides and cyclic polyamides or their copolymers. The acyclic polyamides can be any of those acyclic polyamides described herein or their copolymers, and the cyclic polyamides can be any of those cyclic polyamides described herein or their copolymers. The polyamide can be selected from the group consisting of polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and their copolymers and mixtures. The polyamide can be a mixture of PVP (e.g., PVP K90) and PVMA (e.g., having an M w ) of about 570KDa).

[0128] Preferred non-reactive polymer internal wetting agents include polyamides such as those selected from the group consisting of polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and their copolymers and mixtures. A particularly preferred non-reactive polymer internal wetting agent is PVP, more preferably PVP K90. Another preferred wetting agent is PVMA.

[0129] Non-reactive polymer internal wetting agents such as polyamides for use in the present invention are non-polymerizable and are thus introduced into the silicone hydrogel as a semi-interpenetrating network. The polyamide is entrapped or physically retained within the silicone hydrogel. The silicone hydrogel can also contain polymerizable internal wetting agents such as polymerizable polyamides, e.g., polyamide macromonomers or prepolymers, and in such cases, they are covalently incorporated into the silicone hydrogel. Mixtures of polymerizable and non-polymerizable polymer wetting agents can also be used.

[0130] The reactive mixture of the present invention contains a polymerization initiator. Preferably, the polymerization initiator is a thermal initiator. The thermal initiator decomposes at an elevated temperature to generate free radicals. Typical examples are azo compounds such as 1,1'-azobisisobutyronitrile and 4,4'-azobis(4-cyanovaleric acid). The amount of the polymerization initiator is not critical and can be in the range of, for example, about 0.1 wt% to about 2.0 wt% based on the total weight of all reactive components in the reactive mixture.

[0131] The reactive mixture can contain additional components such as, but not limited to, crosslinkers, diluents, initiators, UV absorbers, visible light absorbers, photochromic compounds, drugs, nutritional agents, antibacterial substances, toners, pigments, copolymerizable dyes, non-polymerizable dyes, and combinations thereof.

[0132] As described, one or more crosslinking agents (also referred to as crosslinking monomers, polyfunctional macromonomers, and prepolymers) can be included in the reactive mixture. The crosslinking agents can be selected from bifunctional crosslinking agents, trifunctional crosslinking agents, tetrafunctional crosslinking agents, and mixtures thereof, including silicone-containing and non-silicone-containing crosslinking agents. Non-silicone-containing crosslinking agents include ethylene glycol dimethacrylate (EGDMA), tetraethylene glycol dimethacrylate (TEGDMA), trimethylolpropane trimethacrylate (TMPTMA), triallyl cyanurate (TAC), glycerol trimethacrylate, hydroxyethyl vinyl carbonate methacrylate (HEMAVc), allyl methacrylate, methylene bisacrylamide (MBA), and polyethylene glycol dimethacrylate (wherein the polyethylene glycol has a molecular weight of up to about 5000 Daltons). The crosslinking agents can be used in the reaction mixture in an amount that varies, for example, from about 0.000415 moles to about 0.0156 moles per 100 grams of reactive components. Examples of hydrophilic monomers and macromonomers that can act as crosslinking agents and that (when present) obviate the need to add additional crosslinking agents to the reactive mixture include (meth)acrylate- and (meth)acrylamide-terminated polyethers. Other crosslinking agents will be known to those skilled in the art and can be used to prepare the silicone hydrogels of the present invention.

[0133] It may be desirable to select crosslinking agents that have a similar reactivity to one or more of the other reactive components in the formulation. In some cases, it may be desirable to select a mixture of crosslinking agents having 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 one or more diluents and curing conditions used.

[0134] Polyfunctional silicone-containing components (including macromonomers, crosslinking agents, and prepolymers) can also be included to further increase the modulus and maintain the tensile strength. The silicone-containing crosslinking agents can be used alone or in combination with other crosslinking agents. Examples of silicone-containing components that can act as crosslinking agents and that (when present) obviate the need to add crosslinking monomers to the reactive mixture include α,ω-bis(methacryloyloxypropyl)polydimethylsiloxane. Another example is bis-3-acryloyloxy-2-hydroxypropoxypropyl polydimethylsiloxane (ac-PDMS).

[0135] Crosslinkers having a rigid chemical structure and polymerizable groups capable of undergoing free radical polymerization can also be used. Non-limiting examples of suitable rigid structures include crosslinkers containing phenyl rings and benzyl rings, such as 1,4-phenylene diacrylate, 1,4-phenylene dimethacrylate, 2,2-bis(4-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. Based on the total weight of all reactive components, the rigid crosslinker can be included in an amount between about 0.5% and about 15%, or 2% to 10%, or 3% to 7%. By adjusting the components in the reactive mixture, the physical and mechanical properties of the silicone hydrogel of the present invention can be optimized for specific applications.

[0136] Non-limiting examples of silicone crosslinkers also include the polyfunctional silicone-containing components described in Table A above.

[0137] Classes of diluents suitable for the silicone hydrogel reactive mixture include alcohols having 2 to 20 carbon atoms, amides derived from primary amines having 10 to 20 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. The diluent can be a primary alcohol, secondary alcohol, and tertiary alcohol.

[0138] Generally, the reactive components are mixed in a diluent to form a reactive mixture. Suitable diluents are known in the art. Diluents suitable for silicone hydrogels are disclosed in WO03 / 022321 and US6020445, the disclosures of which are incorporated herein by reference.

[0139] Classes of diluents suitable for the silicone hydrogel reactive mixture include alcohols having 2 to 20 carbons, amides derived from primary amines having 10 to 20 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. Primary alcohols and tertiary alcohols can be used. Preferred classes include alcohols having 5 to 20 carbons and carboxylic acids having 10 to 20 carbon atoms.

[0140] Specific diluents that can be used include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropanol, 3,7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-octanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, tert-amyl alcohol, tert-butyl alcohol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-propanol, 1-propanol, ethanol, 2-ethyl-1-butanol, (3-acetoxy-2-hydroxypropoxy)propylbis(trimethylsilyloxy)methylsilane, 1-tert-butoxy-2-propanol, 3,3-dimethyl-2-butanol, tert-butoxyethanol, 2-octyl-1-dodecanol, capric acid, octanoic acid, dodecanoic acid, 2-(diisopropylamino)ethanol, mixtures thereof, and the like. Examples of amide diluents include N,N-dimethylpropanamide and dimethylacetamide.

[0141] Preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, 2-pentanol, tert-amyl alcohol, tert-butyl alcohol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, capric acid, octanoic acid, dodecanoic acid, mixtures thereof, and the like.

[0142] More preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 1-dodecanol, 3-methyl-3-pentanol, 1-pentanol, 2-pentanol, tert-amyl alcohol, tert-butyl alcohol, 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.

[0143] If a diluent is present, there is generally no particular limitation on the amount of the diluent present. When a diluent is used, based on the total weight of the reactive mixture (including reactive and non-reactive formulations), the diluent can be present in an amount in the range of about 2 wt% to about 70 wt% (including in the range of about 5 wt% to about 50 wt% and in the range of about 15 wt% to about 40 wt%). Mixtures of diluents can be used.

[0144] The reactive mixture of the present invention can comprise: a hydrophilic component selected from DMA, NVP, HEMA, VMA, NVA, and mixtures thereof; a silicone-containing component comprising a compound of formula A; a non-reactive polymeric internal wetting agent (preferably a polyamide, more preferably PVP or PVMA); and a polymerization initiator.

[0145] The reactive mixture may comprise: a hydrophilic component selected from DMA, HEMA, and mixtures thereof; a silicone-containing component selected from 2-hydroxy-3-[3-methyl-3,3-bis(trimethylsilyloxy)silylpropoxy]-propyl methacrylate (SiMAA), mono-methacryloxypropyl-capped mono-n-butyl-capped polydimethylsiloxane (mPDMS), mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether-capped mono-n-butyl-capped polydimethylsiloxane (OH-mPDMS), and mixtures thereof; a non-reactive polymeric internal wetting agent (preferably a polyamide, more preferably PVP or PVMA); and a polymerization initiator. For the hydrophilic component, a mixture of DMA and HEMA is preferred. For the silicone-containing component, a mixture of SiMAA and mPDMS is preferred.

[0146] The reactive mixture may comprise: a hydrophilic component comprising a mixture of DMA and HEMA; 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). A non-reactive polymeric internal wetting agent (preferably a polyamide, more preferably PVP or PVMA); and a polymerization initiator. Preferably, the reactive mixture further comprises a silicone-containing crosslinker such as ac-PDMS.

[0147] The reactive mixture may comprise: a non-reactive polymeric internal wetting agent (preferably a polyamide, such as an acyclic polyamide, a cyclic polyamide, or a mixture thereof) between about 1 wt% and about 15 wt%; a polymerization initiator; at least one first monofunctional hydroxy-substituted poly(disubstituted siloxane) having 4 to 8 siloxane repeating units (e.g., OH-mPDMS, where n is 4 to 8, preferably n is 4); at least one second hydroxy-substituted poly(disubstituted siloxane) which is a monofunctional hydroxy-substituted poly(disubstituted siloxane) having 10 to 200, or 10 to 100, or 10 to 50, or 10 to 20 siloxane repeating units (e.g., OH-mPDMS, where n is 10 to 200, or 10 to 100, or 10 to 50, or 10 to 20, preferably n is 15); at least one hydrophilic monomer from about 5 wt% to about 35 wt%; and optionally a polyfunctional hydroxy-substituted poly(disubstituted siloxane) having 10 to 200 or 10 to 100 siloxane repeating units (e.g., ac-PDMS). Preferably, the first monofunctional hydroxy-substituted poly(disubstituted siloxane) and the second hydroxy-substituted poly(disubstituted siloxane) are present at a concentration such that the ratio of the weight percentage of the first monofunctional hydroxy-substituted poly(disubstituted siloxane) to the weight percentage of the second hydroxy-substituted poly(disubstituted siloxane) is from 0.4 to 1.3 or from 0.4 to 1.0.

[0148] The reactive mixture can be cured within a lens mold to form a silicone hydrogel contact lens. As described above, the lenses of the present invention contain an enriched concentration of a non-reactive polymeric internal wetting agent at the lens surface. To achieve this enrichment, the curing of the reactive mixture to form the silicone hydrogel contact lens is preferably carried out under thermosetting conditions. Specifically, it has been found that by selecting a specific thermosetting temperature range, the silicone hydrogel contact lenses of the present invention can be prepared. As described above, such lenses provide a more efficient use of the wetting agent by positioning the wetting agent where it is needed, thereby resulting in, for example, improved surface wettability at an overall wetting agent concentration substantially the same as that of existing lenses. Alternatively, surface-enriched lenses can provide the option of using less wetting agent to achieve substantially the same wettability as existing lenses, which in turn can simplify the manufacturing process and / or reduce costs.

[0149] The selected thermosetting conditions of the present invention also result in a more efficient curing process. Specifically, it has also been found that under the thermosetting conditions described herein, the total conversion of the polymerizable components in the reactive mixture to polymer is greatly improved. For example, after polymerization of the reactive mixture but before extraction, contact lenses prepared by the method of the present invention can contain less unpolymerized polymerizable components than lenses prepared by other methods (including by other thermosetting methods). For example, the lenses can contain no more than 0.3 wt% of unpolymerized polymerizable components (after curing but before extraction).

[0150] According to the present invention, there is provided a method for manufacturing a contact lens. The method comprises: (a) providing a reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator; and (b) polymerizing the reactive mixture to form a contact lens; wherein the method is carried out under conditions such that, without surface treatment, the contact lens has a molar ratio of the polymeric non-reactive internal wetting agent to silicone that is greater at the lens surface than in its bulk. Preferably, the polymerization conditions can be thermosetting conditions. Preferred methods include: (a) providing a reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator; (b) polymerizing the reactive mixture under thermosetting conditions to form a contact lens; and (c) extracting the contact lens to remove unreacted components, wherein the thermosetting conditions of step (b) include curing at a temperature of from 60 degrees Celsius to 120 degrees Celsius.

[0151] A reactive mixture (including optional components such as diluents) can be placed in a mold having the shape of the final desired contact lens. After placement, as described above, the reactive mixture is polymerized under thermosetting conditions at a temperature of 60 degrees Celsius to 120 degrees Celsius. The thermosetting temperature can be at least 65 degrees Celsius, or at least 70 degrees Celsius, or at least 75 degrees Celsius, or at least 80 degrees Celsius, or at least 85 degrees Celsius, or at least 86 degrees Celsius, or at least 87 degrees Celsius. The thermosetting temperature can be at most 115 degrees Celsius, or at most 110 degrees Celsius, or at most 105 degrees Celsius, or at most 100 degrees Celsius, or at most 95 degrees Celsius, or at most 94 degrees Celsius, or at most 93 degrees Celsius. The thermosetting temperature can be 85 degrees Celsius to 95 degrees Celsius, or 87 degrees Celsius to 93 degrees Celsius. The thermosetting temperature can be 90 degrees Celsius.

[0152] The reaction mixture can be cured for a sufficient time to reach the desired level of conversion. Preferably, the reactive mixture is cured for a long enough time to achieve at least 90 mole percent conversion, or at least 95 mole percent conversion, or at least 98 mole percent conversion, or at least 99 mole percent conversion, or at least 99.8 mole percent conversion of the polymerizable components in the reactive mixture to the polymer. By way of example, the curing time can be 20 minutes to 90 minutes, or 30 minutes to 70 minutes. Preferably, the curing time is at least 30 minutes, or at least 45 minutes, or at least 60 minutes.

[0153] After curing, the lens can be extracted to remove unreacted components and release the lens from the lens mold. The extraction can be carried out using a conventional extraction liquid (such as an organic solvent like alcohol), or an aqueous solution extraction can be used.

[0154] An aqueous solution is a solution containing water. The aqueous solution of the present invention can contain at least about 20% by weight of water, or at least about 50% by weight of water, or at least about 70% by weight of water, or at least about 95% by weight of water. The aqueous solution can also contain additional water-soluble formulations such as inorganic salts or release agents, wetting agents, slip agents, drug and nutritional formulations, combinations thereof, etc. A release agent is a compound or mixture of compounds that, when mixed with water, will shorten the time required to release the contact lens from the mold compared to using an aqueous solution without a release agent. The aqueous solution may not require special treatment such as purification, recycling, or special disposal procedures.

[0155] Extraction can be achieved, for example, by immersing the lens in an aqueous solution or exposing it to a flowing aqueous solution. Extraction can also include, for example, one or more of the following: heating the aqueous solution; stirring the aqueous solution; increasing the content of the demolding aid in the aqueous solution to a content sufficient to release the lens; mechanically or ultrasonically agitating the lens; and incorporating at least one filtering or extraction aid into the aqueous solution until a level sufficient to promote the sufficient removal of unreacted components from the lens is reached. The above operations can be carried out in a batch or continuous process, with heating, stirring, or both, or without.

[0156] It may be desirable to apply physical agitation to facilitate leaching and demolding. For example, the lens mold part adhered with the lens can be vibrated or moved back and forth in an aqueous solution. Other methods can include ultrasonic waves through the aqueous solution.

[0157] The lens can be sterilized by known means including but not limited to autoclaving.

[0158] The silicone hydrogel contact lens according to the present invention preferably exhibits the following properties. There is a "about" before all values, and the device can have any combination of the listed properties. The properties can be determined by methods known to those skilled in the art, for example, as described in US Pre-Grant Publication US20180037690, which is incorporated herein by reference.

[0159] Water concentration %: at least 20% or at least 25% and at most 80% or at most 70%

[0160] Haze: 30% or lower, or 10% or lower

[0161] Advancing dynamic contact angle (Wilhelmy plate method): 80° or smaller, or 75° or smaller, or 50° or smaller

[0162] Tensile modulus (psi): 120 or lower, or 80 to 120

[0163] Oxygen permeability (Dk, Barrers): at least 60, or at least 80, or at least 100, or at least 150, or at least 200

[0164] Elongation at break: at least 100

[0165] For ionic silicone hydrogels, the following properties (in addition to the above) can also be preferred:

[0166] Lysozyme absorption rate (μg / lens): at least 100, or at least 150, or at least 500, or at least 700

[0167] Polyquaternium 1 (PQ1) uptake (%): 15 or less, or 10 or less, or 5 or less

[0168] As described herein, a silicone hydrogel contact lens made by thermal curing can exhibit a molar ratio of a polymeric non-reactive internal wetting agent to silicone in the lens surface that is greater than that in a contact lens of similar composition made by photochemical curing. For example, a lens made by thermal curing as described herein can have a molar ratio of a polymeric non-reactive internal wetting agent to silicone in the surface that is at least 2.5 times, or at least 3 times, or at least 3.5 times, or at least 4 times that in a contact lens of similar composition made by photochemical curing. By "similar composition" is meant that the components of the reactive mixture are the same except for the free radical initiator, which can be a photochemical free radical initiator in the case of a photochemically cured lens and a thermal free radical initiator in the case of a thermally cured lens.

[0169] As described herein, a silicone hydrogel contact lens made by thermal curing can exhibit a molar ratio of a polymeric non-reactive internal wetting agent to silicone in the bulk that is substantially the same as that in a contact lens of similar composition made by photochemical curing. By "substantially the same" is meant that the molar ratio of the polymeric non-reactive internal wetting agent to silicone in the bulk of the thermally cured lens is no more than 1.1 times that in the bulk of the photochemically cured lens. The molar ratio of the polymeric non-reactive internal wetting agent to silicone in the bulk of the thermally cured lens can be the same as that in the bulk of the photochemically cured lens.

[0170] The following clauses set forth non-limiting embodiments of the present disclosure:

[0171] 1. A silicone hydrogel contact lens that is a reaction product of a reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator, the contact lens having an oxygen permeability of at least about 60 Barrers, and wherein, in a lens that is a reaction product of a reactive mixture comprising as low as 2.0 wt% or as low as 2.5 wt% of the non-reactive polymeric internal wetting agent (based on the total weight of the reactive components in the reactive mixture), without surface treatment, the lens has an advancing contact angle of 75° or less.

[0172] 2. The contact lens according to clause 1, wherein the advancing contact angle is 70° or less, or 60° or less, or 50° or less, or 45° or less, or 40° or less, or 35° or less, or 30° or less, or 25° or less, or 22° or less.

[0173] 3. The contact lens according to clause 1 or 2, wherein without surface treatment, the molar ratio of the polymer non-reactive internal wetting agent to silicone in the lens is greater at the lens surface than in its bulk.

[0174] 4. The silicone hydrogel contact lens according to clause 3, wherein the molar ratio of the polymer non-reactive internal wetting agent to silicone in the lens surface is at least 1.5 times, or at least 2 times, or at least 2.3 times, or at least 3 times, or at least 3.5 times, or at least 4 times, or at least 4.9 times, or at least 6 times, or at least 7 times, or at least 7 times, or at least 9 times that in its bulk.

[0175] 5. The silicone hydrogel contact lens according to any one of clauses 1 to 4, wherein the non-reactive polymer internal wetting agent is polyamide.

[0176] 6. The silicone hydrogel contact lens according to any one of clauses 1 to 5, wherein the non-reactive polymer internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl (meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof.

[0177] 7. A method for manufacturing a contact lens, the method comprising:

[0178] (a) providing a reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymer internal wetting agent; and a polymerization initiator; and

[0179] (b) polymerizing the reactive mixture to form a contact lens;

[0180] wherein the method is carried out under conditions such that in a lens which is a reaction product of a reactive mixture comprising as low as 2.0 wt% or as low as 2.5 wt% of the non-reactive polymer internal wetting agent (based on the total weight of the reactive components in the reactive mixture), without surface treatment, the lens has an advancing contact angle of 75° or less.

[0181] 8. The method according to clause 7, wherein the advancing contact angle is 70° or less, or 60° or less, or 50° or less, or 45° or less, or 40° or less, or 35° or less, or 30° or less, or 25° or less, or 22° or less.

[0182] 9. The method according to clause 7 or 8, wherein without surface treatment, the molar ratio of the polymer non-reactive internal wetting agent to silicone in the lens is greater at the lens surface than in its bulk.

[0183] 10. The method according to clause 9, wherein the molar ratio of the polymeric non-reactive internal wetting agent to the silicone in the lens surface is at least 1.5 times, or at least 2 times, or at least 2.3 times, or at least 3 times, or at least 3.5 times, or at least 4 times, or at least 4.9 times, or at least 6 times, or at least 7 times, or at least 7 times, or at least 9 times that in its bulk.

[0184] 11. The method according to any one of clauses 7 to 10, wherein the non-reactive polymeric internal wetting agent is a polyamide.

[0185] 12. The method according to any one of clauses 7 to 11, wherein the non-reactive polymeric internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl (meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof.

[0186] 13. A silicone hydrogel contact lens, which is a thermally cured reaction product of a reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator, the contact lens having an oxygen permeability of at least about 60 Barrers, and wherein the molar ratio of the polymeric non-reactive internal wetting agent to the silicone in the surface of the lens is greater than that in the surface of a contact lens having a similar composition but made by photochemical curing.

[0187] 14. The silicone hydrogel contact lens according to clause 13, wherein the molar ratio of the polymeric non-reactive internal wetting agent to the silicone in the surface of the thermally cured lens is at least 2.5 times, or at least 3 times, or at least 3.5 times, or at least 4 times that in the surface of a contact lens having a similar composition but made by photochemical curing.

[0188] 15. The silicone hydrogel contact lens according to any one of clauses 13 to 14, wherein the molar ratio of the polymeric non-reactive internal wetting agent to the silicone in the bulk of the thermally cured lens is substantially the same as that in the bulk of a contact lens having a similar composition but made by photochemical curing.

[0189] 16. The silicone hydrogel contact lens according to any one of clauses 13 to 15, wherein the non-reactive polymeric internal wetting agent is a polyamide.

[0190] 17. The silicone hydrogel contact lens according to any one of clauses 13 to 16, wherein the non-reactive polymer internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl (meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof.

[0191] 18. A method for manufacturing a contact lens, the method comprising:

[0192] (a) providing a reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymer internal wetting agent; and a polymerization initiator;

[0193] (b) thermally curing the reactive mixture to form a contact lens; and

[0194] (c) extracting the contact lens to remove unpolymerized components,

[0195] wherein the method is carried out under conditions such that the molar ratio of the polymer non-reactive internal wetting agent to silicone in the surface of the contact lens is greater than that in the surface of a contact lens having a similar composition but made by photochemical curing.

[0196] 19. The method according to clause 18, wherein the molar ratio of the polymer non-reactive internal wetting agent to silicone in the surface of the thermally cured lens is at least 2.5 times, or at least 3 times, or at least 3.5 times, or at least 4 times that in the surface of a contact lens having a similar composition but made by photochemical curing.

[0197] 20. The method according to any one of clauses 18 to 19, wherein the molar ratio of the polymer non-reactive internal wetting agent to silicone in the body of the thermally cured lens is substantially the same as that in the body of a contact lens having a similar composition but made by photochemical curing.

[0198] 21. A silicone hydrogel contact lens, which is a reaction product of a reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymer internal wetting agent; and a polymerization initiator, the contact lens having an oxygen permeability of at least about 60 Barrers, and wherein without surface treatment, the molar ratio of the polymer non-reactive internal wetting agent to silicone in the lens is greater in the lens surface than in its body.

[0199] 22. The silicone hydrogel contact lens according to clause 21, wherein the molar ratio of the polymer non-reactive internal wetting agent to silicone in the lens surface is at least 1.5 times that in its body.

[0200] 23. The silicone hydrogel contact lens according to any one of clauses 21 to 22, wherein the molar ratio of the polymeric non-reactive internal wetting agent to the silicone is at least 2.3 times in the lens surface than in its bulk.

[0201] 24. The silicone hydrogel contact lens according to any one of clauses 21 to 23, wherein the non-reactive polymeric internal wetting agent is a polyamide.

[0202] 25. The silicone hydrogel contact lens according to any one of clauses 21 to 24, wherein the non-reactive polymeric internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof.

[0203] 26. The silicone hydrogel contact lens according to any one of clauses 21 to 25, wherein in the lens which is a reaction product of a reactive mixture containing 2.5 wt% of the non-reactive polymeric internal wetting agent, the lens has an advancing contact angle of 75° or less.

[0204] 27. The silicone hydrogel contact lens according to clause 6, wherein the advancing contact angle is 50° or less.

[0205] 28. A method for manufacturing a contact lens, the method comprising:

[0206] (a) providing a reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator; and

[0207] (b) polymerizing the reactive mixture to form a contact lens;

[0208] wherein the method is carried out under conditions such that, without surface treatment, the contact lens has a molar ratio of the polymeric non-reactive internal wetting agent to the silicone that is greater in the lens surface than in its bulk.

[0209] 29. The method according to clause 28, wherein the molar ratio of the polymeric non-reactive internal wetting agent to the silicone is at least 1.5 times in the lens surface than in its bulk.

[0210] 30. The method according to any one of clauses 28 to 29, wherein the molar ratio of the polymeric non-reactive internal wetting agent to the silicone is at least 2.3 times in the lens surface than in its bulk.

[0211] 31. The method according to any one of clauses 28 to 30, wherein the non-reactive polymer internal wetting agent is a polyamide.

[0212] 32. The method according to any one of clauses 28 to 31, wherein the non-reactive polymer internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl (meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof.

[0213] 33. The method according to any one of clauses 28 to 32, wherein in a lens that is a reaction product of a reactive mixture containing 2.5 wt% of the non-reactive polymer internal wetting agent, the lens has an advancing contact angle of 75° or less.

[0214] 34. The method according to clause 33, wherein the advancing contact angle is 50° or less.

[0215] 35. The method according to any one of clauses 28 to 34, wherein step (b) includes thermally curing the reactive mixture.

[0216] 36. The method according to clause 35, wherein the thermal curing is carried out at a temperature of 60 °C to 120 °C.

[0217] 37. The method according to any one of clauses 35 to 36, wherein the thermal curing is carried out at a temperature of 85 °C to 120 °C.

[0218] 38. The method according to any one of clauses 28 to 37, wherein after step (b) and before the extraction step of removing unpolymerized components from the contact lens, the contact lens contains no more than 0.3 wt% of unpolymerized polymerizable components.

[0219] 39. A silicone hydrogel contact lens prepared by the method according to any one of clauses 28 to 38.

[0220] 40. A method for importing a silicone hydrogel contact lens according to any one of clauses 21 to 27 into a certain country.

[0221] 41. The method according to clause 40, wherein the country is the United States.

[0222] Some embodiments of the present invention will now be described in detail in the following examples.

[0223] Examples

[0224] The contact lens diameter (DM) is measured on a calibrated Van Keuren micro optical comparator equipped with a Mitutoyo digital micrometer head. The contact lens is placed concave side down in a crystal cell completely filled with a borate buffered wetting solution. The top cover is placed over the cell to ensure no air is trapped underneath. The cell is then placed on the comparator stage and the lens image is focused and aligned such that one edge of the lens touches the center line on the screen. The first edge is marked and the lens is moved along its diameter until the second edge touches the center line on the screen, and the second edge is then marked by pressing the data button again. Typically, two diameter measurements are made and the average is reported in the data sheet.

[0225] The water content (WC) is measured gravimetrically. The lenses are equilibrated in the wetting solution for 24 hours. Each of the three test lenses is removed from the wetting solution with a cotton swab and placed on a blotting paper moistened with the wetting solution. Both sides of the lens are in contact with the blotting paper. The test lenses are placed in the weighing pan of a balance with tweezers and weighed. Two additional sets of samples are prepared and weighed. All weight measurements are made in triplicate and the average of those values is used for the calculation. The wet weight is defined as the total weight of the pan and the wet lens minus the weight of the pan weighed separately.

[0226] The dry weight is measured by placing the sample pan in a vacuum oven preheated to 60 °C for 30 minutes. A vacuum is applied until a pressure of at least 1 inch of mercury is obtained. A lower pressure is allowed. The vacuum valve and pump are closed and the lens is dried for at least 12 hours, typically overnight. The bleed valve is opened to allow dry air or dry nitrogen to enter. The oven is brought to atmospheric pressure. The pan is removed and weighed. The dry weight is defined as the total weight of the pan and the dry lens minus the weight of the pan weighed separately. The water content of the test lens is calculated as follows: water content % = (wet weight - dry weight) / wet weight × 100. The average and standard deviation of the water content are calculated and the average is reported as the water content % of the test lens.

[0227] The refractive index (RI) of the contact lens is measured with a Leica ARIAS 500 Abbe refractometer in manual mode or with a Reichert ARIAS 500 Abbe refractometer in automatic mode with a prism gap distance of 100 microns. The instrument is calibrated with deionized water at 20 °C (+ / - 0.2 °C). The prism assembly is opened and the test lens is placed on the lower prism between the magnetic points closest to the light source. If the prism is dry, a few drops of saline are applied to the bottom prism. The front surface of the lens abuts the bottom prism. The prism assembly is then closed. The control is adjusted so that the boundary between light and dark appears behind the crosshair area and the refractive index is measured. RI measurements are made on five test lenses. The average RI calculated from the five measurements is recorded as the refractive index along with its standard deviation.

[0228] Haze can be measured by the following method: At ambient temperature, place the hydrated test lens in borate buffered saline in a transparent glass cell above a flat black background. Illuminate from below with an optical fiber lamp (Dolan-Jenner PL-900 optical fiber lamp with a 0.5" diameter light guide) at a 66° angle perpendicular to the lens cell, and capture an image of the lens from above perpendicular to the lens cell with a camera (DVC 1300C:19130 RGB camera or equivalent equipped with a suitable zoom camera lens) placed 14 mm above the lens holder. Subtract the image of the blank cell containing borate buffered saline (baseline) by using EPIX XCAP V 3.8 software, thereby subtracting background scatter from the test lens scatter. Obtain the value of high-end scatter (frosted glass) by adjusting the light intensity between 900 and 910 average gray levels. Measure the value of background scatter (BS) using a glass cell filled with saline. Perform a quantitative analysis on the subtracted scattered light image by integrating the central 10 mm of the lens, and then compare it with a frosted glass standard. The light intensity / power setting is adjusted to achieve an average gray level value in the range of 900 - 910 for the frosted glass standard; at this setting, the baseline average gray level value is in the range of 50 - 70. Record the average gray level values of the baseline and the frosted glass standard and use them separately to generate levels from 0 to 100. In gray scale analysis, record the average value and standard deviation of the baseline, the frosted glass, and each test lens. For each lens, calculate the conversion value according to the following formula: The conversion value is equal to the average gray level value (lens minus baseline) divided by the average gray level value (frosted glass minus baseline), multiplied by 100%. Analyze three to five test lenses, average the results, and report as haze %.

[0229] Determined by a polarographic method generally described in ISO 9913-1:1996 and ISO 18369-4:2006, but with the following modifications Oxygen Permeability (Dk). The measurement is carried out in an environment containing 2.1% oxygen, which is created by equipping the test chamber with nitrogen and air inputs set at appropriate ratios, such as 1800 mL / min of nitrogen and 200 mL / min of air. Use the adjusted oxygen concentration to calculate t / Dk. Use a boric acid buffered saline solution. Measure the dark current by using a humidified pure nitrogen environment without applying the MMA lens. Do not dry the lens before measurement. Stack four lenses instead of using lenses with different thicknesses (t) measured in centimeters. Use a curved sensor instead of a flat sensor; the radius is 7.8 mm. The calculation for the 7.8 mm radius sensor and 10% (v / v) air flow is as follows

[0230] Dk / t = (measured current - dark current) × (2.97x10-8 mL O2 / (μA-sec-cm2-mmHg)

[0231] Edge correction is related to the Dk of the material.

[0232] For all Dk values less than 90 Barr:

[0233] t / Dk (edge correction) = (1 + (5.88 × t)) × (t / Dk)

[0234] For Dk values between 90 Barr and 300 Barr:

[0235] t / Dk (edge correction) = (1 + (3.56 × t)) × (t / Dk)

[0236] For Dk values greater than 300 Barr:

[0237] t / Dk (edge correction) = (1 + (3.16 × t)) × (t / Dk)

[0238] The un-edge-corrected Dk is calculated based on the reciprocal of the slope obtained from the linear regression analysis of the data, where the x variable is the center thickness in centimeters and the y variable is the t / Dk value. On the other hand, the edge-corrected (EC Dk) is calculated based on the reciprocal of the slope obtained from the linear regression analysis of the data, where the x variable is the center thickness in centimeters and the y variable is the edge-corrected t / Dk value. The resulting Dk values are reported in Barr.

[0239] The wettability of the lens is determined using the following method. At room temperature, deionized water is used as the probe solution, and the dynamic contact angle (Cahn DCA) is measured by the Wilhelmy plate method using a Cahn DCA-315 instrument. This experiment is carried out by immersing a lens specimen with known parameters into a wetting solution with a known surface tension, while measuring the force exerted on the sample due to wetting by a sensitive balance. Based on the force data collected during the sample immersion, the advancing contact angle of the wetting solution on the lens is determined. The receding contact angle is also determined from the force data while removing the sample from the liquid. The Wilhelmy plate method is based on the formula: Fg = γρcosθδ - B, where F = the wetting force between the liquid and the lens (mg), g = the acceleration due to gravity (980.665 cm / sec 2 )), γ = the surface tension of the probe liquid (dynes / cm), ρ = the perimeter of the liquid / lens meniscus in contact with the lens (cm), θ = the dynamic contact angle (degrees), and B = the buoyancy force (mg). When the immersion depth is zero, B is zero. Four test strips are cut from the central region of the contact lens. The width of each strip is approximately 5 mm, and they are equilibrated in the wetting solution. Subsequently, each sample is cycled four times, and the results are averaged to obtain the advancing contact angle and receding contact angle of the lens. The advancing dynamic contact angle and receding dynamic contact angle are listed in the table in that order.

[0240] The wettability of the lens can also be measured at room temperature using a KRUSS DSA-100TM instrument and deionized water as the probe solution by the sessile drop technique (sessile drop method). The lens to be tested is rinsed in deionized water to remove the residual wetting solution. Each test lens is placed on a lint-free absorbent towel moistened with the wetting solution. The two surfaces of the lens are brought into contact with the absorbent towel to remove the surface moisture without drying the lens. To ensure proper flattening, the lens is placed "bowl down" on the convex surface of a contact lens plastic mold. The plastic mold and the lens are placed on the sessile drop instrument holder, ensuring proper centering alignment of the syringe. Using the DSA 100 - Drop Shape Analysis software, a 3 to 4 microliter deionized water droplet is formed at the tip of the syringe, ensuring that the droplet is suspended above the lens. The droplet is gently released onto the lens surface by lowering the needle. After dispensing the droplet, the needle is immediately withdrawn. The droplet is allowed to equilibrate on the lens for 5 to 10 seconds, and the contact angle is measured between the droplet image and the lens surface. Typically, three to five lenses are evaluated, and the average contact angle is reported.

[0241] The mechanical properties of the contact lens are measured using a tensile testing machine, such as an Instron model 1122 or 5542 equipped with a load cell and pneumatic gripping control. A lens with a diopter of -1.00 is a preferred lens geometry due to its uniform thickness distribution at the center. A dogbone-shaped sample slice taken from a -1.00 diopter lens with a length of 0.522 inches, an "ear" width of 0.276 inches, and a "neck" width of 0.213 inches is loaded into the fixture and stretched at a constant strain rate of 2 inches per minute until it breaks. Before testing, the center thickness of the dogbone sample is measured using an electronic thickness gauge. The initial gauge length (Lo) and the length at break (Lf) of the sample are measured. At least five specimens of each composition are measured, and the percent elongation at break is calculated using the average value: Percent elongation = ((Lf - Lo) / Lo) × 100. The tensile modulus (M) is calculated as the slope of the initial linear portion of the stress-strain curve; the modulus is in pounds per square inch or psi. The tensile strength (TS) is calculated from the peak load and the initial cross-sectional area: Tensile strength = Peak load divided by the initial cross-sectional area; the unit of tensile strength is psi. Toughness is calculated from the fracture energy and the volume of the initial sample: Toughness = Fracture energy divided by the initial sample volume; the unit of toughness is in-lbs / in3. The elongation at break (ETB) is also recorded as the percent strain at break.

[0242] PQ1 uptake (PQ1) was measured chromatographically. An HPLC was calibrated with a series of standard PQ1 solutions having the following concentrations: 2, 4, 6, 8, 12, and 15 μg / mL. Lenses were placed into polypropylene contact lens cases having 3 mL of Optifree Replenish or a similar lens solution (PQ1 concentration = 10 micrograms / mL, commercially available from Alcon). Control lens cases containing 3 mL of solution but no test lenses were also prepared. The lenses and control solutions were stored at room temperature for 72 hours. 1 mL of solution was taken from each sample and control and mixed with trifluoroacetic acid (10 μL). Analysis was performed using an HPLC / ELSD and a Phenomenex Luna C5 (4.6 mm × 5 mm; 5 μm particle size) column with the following equipment and conditions: Agilent 1200 HPLC or equivalent and ELSD, operating at T = 100 °C, Gain value = 12, pressure = 4.4 bar, filter = 3 s; ELSD parameters may vary with the instrument; mobile phase A of water (0.1% TFA) and mobile phase B of acetonitrile (0.1% TFA), using a column temperature of 40 °C and an injection volume of 100 μL, using the chromatographic effluent curve and listed in Table C. A calibration curve was created by plotting the peak area values as a function of the concentration of the PQ1 standard solution. Subsequently, the concentration of PQ1 in the sample was calculated by solving the quadratic equation representing the calibration curve. Each analysis was performed on three lenses and the results averaged. PQ1 uptake was reported as the percentage loss of PQ1 in the lens-containing compared to the lens-free control after immersion.

[0243] Table C: HPLC Chromatogram Elution Curve

[0244] Time (minutes) ％A ％B Flow Rate (mL / minute) 0.00 100 0 1.2 1.00 100 0 1.2 5.00 0 100 1.2 8.50 0 100 1.2 8.60 100 0 1.2 11.00 100 0 1.2

[0245] The amount of cholesterol taken up by the contact lenses was determined by an LC-MS method (lipids). The lenses were soaked in a cholesterol solution and subsequently extracted with dichloromethane. The dichloromethane extract was evaporated and reconstituted with a heptane / isopropanol mixture for subsequent LC-MS analysis. Results were reported as micrograms of cholesterol per lens. A deuterated cholesterol internal standard was used to improve the accuracy and precision of the method.

[0246] A stock cholesterol solution was prepared by placing 15.0 ± 0.5 milligrams of cholesterol into a 10 mL wide-mouth glass volumetric flask and then diluting with isopropanol.

[0247] The cholesterol immersion solution was prepared as follows: 0.430 ± 0.010 grams of lysozyme (purity = 93%), 0.200 ± 0.010 grams of albumin, and 0.100 ± 0.010 grams of β-lactoglobulin were placed into a 200 mL glass volumetric flask. Approximately 190 mL of PBS was added to the flask and vortexed to dissolve the contents. Subsequently, 2 mL of the cholesterol stock solution was added and diluted to volume with PBS. The volumetric flask was capped and shaken well. The concentration of the cholesterol immersion solution was approximately 15 μg / mL. Note: The masses of these components can be adjusted to account for purity fluctuations between batches such that the target concentration can be achieved.

[0248] Six contact lenses were removed from their packages and blotted dry with lint-free paper towels to remove excess wetting solution. The lenses were placed into six separate 8 mL glass vials (one lens per vial), and 3.0 mL of the cholesterol immersion solution was added to each vial. The vials were capped and placed into a New Brunswick Scientific incubator-shaker at 37 °C and 100 rpm for 72 hours. After incubation, each lens was rinsed three times with PBS in a 100 mL beaker and placed into a 20-mL scintillation vial.

[0249] To each scintillation vial containing a lens, 5 mL of dichloromethane and 100 μL of the internal standard solution were added. After a minimum extraction time of 16 hours, the supernatant liquid was transferred to a 5 mL disposable glass culture tube. The tube was placed into a Turbovap and the solvent was allowed to evaporate completely. 1 mL of diluent was placed into the culture tube and the contents were redissolved. The aforementioned diluent was a 70:30 (v / v) mixture of heptane and isopropanol. The diluent was also the mobile phase. The resulting solution was carefully transferred to an autosampler vial for LC-MS analysis.

[0250] The internal standard stock solution was prepared as follows: Approximately 12.5 + 2 mg of deuterated cholesterol (2,2,3,4,4,6-d6-cholesterol) was weighed into a 25 mL volumetric flask and then diluted with diluent. The concentration of the internal standard stock solution was approximately 500 μg / mL.

[0251] The internal standard solution was prepared as follows: By placing 1.0 mL of the internal standard stock solution into a 50 mL volumetric flask and then diluting to volume with diluent. The concentration of this intermediate internal standard solution was approximately 10 μg / mL.

[0252] The reference standard stock solution was prepared as follows: Approximately 50 + 5 mg of cholesterol was weighed into a 100 mL volumetric flask and then diluted with diluent. The concentration of cholesterol in this reference stock solution was approximately 500 μg / mL.

[0253] Subsequently, prepare working standard solutions according to Table D by placing appropriate amounts of the standard solutions into the listed 25 mL, 50 mL, or 100 mL volumetric flasks. After the standard solutions are added to the volumetric flasks, dilute the mixture to volume with diluent and vortex thoroughly.

[0254] Table D: Working Standard Solution Formulation

[0255]

[0256] Perform the following LC-MS analysis: Inject "Standard 4" six times to evaluate system suitability. The % RSD of the peak areas of the working standards and the internal standard must be < 5%, and the % RSD of their peak area ratios must be < 7% to pass system suitability. Inject working standards 1 - 6 to create a calibration curve. The square of the correlation coefficient (r 2 ) must be > 0.99. Inject the test sample, then inject the delimiter standard (Standard 4). The peak area ratio of the delimiter standard must be within ±10% of the average peak area ratio of the system suitability injections.

[0257] Construct the calibration curve by plotting the peak area ratio (reference standard / internal standard) values corresponding to the concentrations of the respective working standard solutions. The concentration of cholesterol in the sample is calculated by solving a quadratic equation and is expressed in micrograms per lens or μg / lens. Typical equipment and its settings for LC-MS analysis are listed below and shown in Tables E and F. The values of the instrument tuning parameters may change each time the mass spectrometer is tuned.

[0258] Turbovap conditions:

[0259] Temperature: 45 °C

[0260] Time: 30 minutes or longer until dry

[0261] Gas: Nitrogen at 5 psi

[0262] HPLC conditions:

[0263] HPLC: Thermo Accela HPLC instrument or equivalent

[0264] HPLC column: Agilent Zorbax NH2 (4.6 mm × 150 mm; 5 μm particle size)

[0265] Mobile phase: 70% heptane and 30% isopropanol

[0266] Column temperature: 30 °C

[0267] Injection volume: 25 μL

[0268] Flow rate: 1000 μL / minute

[0269] Table E: Mass Spectrometry Conditions

[0270]

[0271] Table F: Tuning Parameters

[0272] Instrument Tuning Parameters Value Discharge Current (arbitrary unit): 20 Capillary Temperature (°C): 240 Vaporizer Temperature (°C): 500 Tube Lens Offset (V): 68 Sheath Gas Pressure (arbitrary unit): 20 Auxiliary Gas Flow (arbitrary unit): 15

[0273] The Fourier transform infrared (FTIR) spectra were measured using a Thermo Scientific Nicolet iS50 instrument. Transmission FTIR spectra were measured by mounting the lens in the sample chamber such that the beam passed through the center of the lens, generating bulk or overall composition information. Attenuated total reflection (ATR) FTIR spectra were measured using a standard diamond ATR crystal (45° angle of incidence), generating surface composition information. Peak height analysis was performed using Thermo Scientific Omnic software.

[0274] Sample preparation: Prior to transmission or ATR FTIR analysis, the test lenses were soaked in deuterated saline for 1 hour. The water spectral bands in the FTIR spectra were shifted using deuterium oxide-exchanged water to provide a transmission spectral region suitable for observing the amide carbonyl region in the spectra. Deuterated saline was prepared using deuterium oxide in place of water according to ISO-10344. After removing the test lenses from the deuterated saline, the test lenses were analyzed by transmission or ATR analysis. For transmission analysis, 4 mm discs were cut from the center (thickness of approximately 100 μm) of the lens using a biopsy punch. The excised lens segments were placed in a (2.5 mm) diamond compression cell and tightened to thin the sample, allowing the FTIR beam to transmit through the material. The degree of compression was such that the spectral peaks of interest had intensities less than 2 absorbance units. A condenser was used to form a narrow beam waist, allowing a larger portion of the FTIR beam to penetrate the sample. For ATR analysis, the center of the uncut lens was placed on the diamond ATR crystal and held in place using a standard pressure clamp. Prior to clamping, a Teflon disc (0.81 mm thick) with a diameter of 7 mm was placed between the pressure clamp and the lens.

[0275] Data acquisition: Prior to analysis, background scans were performed using an empty compression cell or a clean ATR crystal without a lens sample. All contact lens spectra were corrected for these background absorbances using the usual correction procedures. Spectra were acquired by averaging 16 scans over a wavenumber range of 400 cm -1 to 4000 cm -1 using a resolution of 4 cm -1 .

[0276] Identify the infrared absorption bands of the following functional groups: 1715 cm-1 The ester carbonyl group (corresponding to methacrylate or acrylate) at, 1657 cm -1 The cyclic amide carbonyl group (corresponding to PVP) at, 1618 cm -1 The acyclic amide carbonyl group (corresponding to DMA) at, 840 cm -1 The branched organosilicon (corresponding to SiMAA) at, and 796 cm -1 The linear organosilicon (corresponding to mPDMS) at. Generally speaking, an absorption band is selected as the internal standard. For example, the linear organosilicon band at 796 cm -1 can be selected, or the (meth)acrylate absorption band at 1715 cm -1 can be selected. Then, the concentration change of the functional group, which is a substitute for the concentration change of the polymerizable monomer mixture component or the polymer component, can be measured by comparing the ratio of the band height of the functional group (or component) band between samples to the band height of the internal standard band. For example, the FTIR absorption band ratio of PVP to linear organosilicon (expressed as the PVP / silicon ratio in the figure and representing the molar ratio) can be used to compare the relative concentrations of PVP between samples. Similarly, the FTIR absorption band ratio of PVP to (meth)acrylate (expressed as the PVP / methacrylate ratio in the figure) can also be used to compare the relative concentrations of PVP between samples. The ATR FTIR band is used to compare the surface concentration; the transmission FTIR band is used to compare the bulk concentration. In a series of samples or contact lenses, one sample or lens can be selected as the reference standard, and an arbitrary number, say 100, can be assigned to its ratio, and then the other samples in the series can be normalized to the reference standard for the sake of comparison. Since the components of the reference lens (photochemically cured lens) used for normalization in the following examples are basically uniformly distributed in the lens, the relative concentrations of the components in the surface and bulk of the test lens (such as a thermally cured lens) can be compared, as well as the comparison between the thermally cured lens and the photochemically cured lens.

[0277] During thermal polymerization, the contents of residual monomers and macromonomers were determined at different times by using high performance liquid chromatography with ultraviolet detection (HPLC / UV). The cured lenses were taken out of the oven, demolded, weighed, and extracted with 5 mL of a 90:10 (v / v) methanol / isopropanol solution by sonication in a temperature-controlled water bath for 1 hour. Usually, 3 lenses were immersed in 5 mL of the mixed solvent. The extracts were analyzed as described below. If the concentration of the residue was not within the calibration range, the extract was diluted with methanol so that the concentration had a calibration range suitable for accurate quantification.

[0278] For DMA, HEMA, and TEGDMA, stock solutions were prepared by dissolving 0.1000 grams of each component in a 100 mL volumetric flask with sufficient 90:10 (v / v) methanol / isopropanol solution to fill the flask to the calibration line. The stock solution was then diluted (partially serially) to prepare calibration samples with the following concentrations: 500, 200, 100, 50, 20, 10, 5, 1, and 0.5 micrograms per milliliter (μg / mL). These calibration samples were used to generate a calibration curve suitable for HPLC-UV analysis. The chromatographic conditions for the analysis of DMA, HEMA, and TEGDMA are listed below.

[0279] Chromatography Conditions

[0280] Column: Agilent Zorbax Eclipse Plus 18, 4.6 mm × 75 mm × 1.8 μm

[0281] Phenomenex security guard cartridge

[0282] Column temperature: 30 °C

[0283] UV detector: 217 nm

[0284] Injection volume: 5 μl

[0285] Mobile phase (gradient mobile phase is listed in Table G (v / v))

[0286] Eluent A: Deionized water with 0.05% H3PO4

[0287] Eluent B: Acetonitrile with 0.05% H3PO4

[0288] Eluent C: Methanol

[0289] Flow rate: 1 mL / minute;

[0290] Table G: Gradient Mobile Phase

[0291] Time (minutes) ％A ％B ％C 0 95 5 0 3 95 5 0 10 50 50 0 13 50 50 0 15 0 10 90 16 95 5 0 21 95 5 0 35 95 5 0

[0292] At each time point, the concentrations (μg / mL) of DMA, HEMA, and TEGDMA in the lens extract were determined. The amounts of these components in the sample were then calculated as a percentage of the sample weight using these extract concentrations as follows:

[0293] Component % = [(μg / mL * extraction volume * dilution factor * 10 -6 g / μg) / (g sample weight)] * 100. Finally, the percentage of unreacted components was calculated as a percentage relative to T0 using the following formula: T x % at T = (Tx (% measured at x) / (% measured at T0) * 100, where T0 represents 100% of the unreacted component or % at the zero point of the reaction time, and T x represents the amount of the unreacted component at time point x).

[0294] For Norbloc and SiMAA, stock solutions were prepared by dissolving 0.0500 g of Norbloc and 0.1000 g of SiMAA in a 100 mL volumetric flask with sufficient 90:10 (v / v) methanol / isopropanol solution to fill the flask to the calibration line. Then the stock solution was diluted (partially continuously) to prepare calibration samples with the following concentrations: 250, 100, 50, 25, 10, 5, 2.5, 0.5, and 0.25 micrograms per milliliter (μg / mL) for Norbloc, and 1000, 400, 200, 100, 40, 20, 10, 2, and 1 micrograms per milliliter (μg / mL) for SiMAA. These calibration samples were used to generate a calibration curve suitable for HPLC-UV analysis. The chromatographic conditions for Norbloc and SiMAA analysis are listed below.

[0295] Chromatography Conditions

[0296] Column: Agilent Zorbax Eclipse Plus 18, 4.6 mm × 75 mm × 1.8 μm

[0297] Phenomenex security guard cartridge

[0298] Column temperature: 30 °C

[0299] UV detector: 217 nm

[0300] Injection volume: 5 μl

[0301] Mobile phase (gradient mobile phase is listed in Table H (v / v))

[0302] Eluent A: Deionized water with 0.05% H3PO4

[0303] Eluent B: Acetonitrile with 0.05% H3PO4

[0304] Eluent C: 50:50 (v / v) methanol / isopropanol

[0305] Flow rate: 1 mL / min;

[0306] Table H: Gradient Mobile Phase

[0307] Time (minutes) ％A ％B ％C 0 30 70 0 8 30 70 0 11 0 100 0 12 0 80 20 15 0 80 20 16 30 70 0 21 30 70 0

[0308] At each time point, the concentrations (μg / mL) of Norbloc and SiMAA in the lens extracts were determined. Then, using these extract concentrations, the amounts of these components in the samples were calculated as a percentage of the sample weight as follows:

[0309] Component % = [(μg / mL * extraction volume * dilution factor * 10 -6 g / μg) / (g sample weight)] * 100. Finally, the percentage of unreacted component was calculated using the following formula, expressed as a percentage relative to T0: T x % at T = ( % measured at T x / % measured at T0) * 100 (where T0 represents 100% unreacted component or % at the zero time point of reaction, and T x represents the amount of unreacted component at time point x).

[0310] For mPDMS, a stock solution was prepared by dissolving 0.2000 g of mPDMS in a 100 mL volumetric flask with sufficient 90:10 (v / v) methanol / isopropanol solution to fill the flask to the calibration line. Then, this stock solution was diluted (partially serially) to prepare calibration samples with the following concentrations: 1000, 400, 200, 100, 40, 20, 10, 2, and 1 μg / mL. These calibration samples were used to generate a calibration curve suitable for HPLC-UV analysis. The chromatographic conditions for mPDMS analysis are listed below.

[0311] Chromatography Conditions

[0312] Column: Agilent Zorbax Eclipse XDB18, 4.6 mm × 50 mm × 1.8 μm

[0313] Phenomenex security guard cartridge

[0314] Column temperature: 30 °C

[0315] UV detector: 217 nm

[0316] Injection volume: 20 μL

[0317] Mobile phase (gradient mobile phase is listed in Table I (v / v))

[0318] Eluent A: Deionized water

[0319] Eluent B: Acetonitrile

[0320] Eluent C: Isopropanol

[0321] Flow rate: 1 mL / min;

[0322] Table I: Gradient Mobile Phase

[0323] Time (minutes) ％A ％B ％C 0 50 48 2 0.5 50 48 2 2 0 60 40 5 0 60 40 5.1 0 70 30 8 0 70 30 8.1 50 48 2 10 50 48 2

[0324] At each time point, the concentration of mPDMS (μg / mL) in the lens extract was measured. Then, the amount of mPDMS in the sample was calculated using these extract concentrations, expressed as a percentage of the sample weight, as follows: % mPDMS = [(μg / mL * extract volume * dilution factor * 10 -6 g / μg) / (g sample weight)] * 100. Finally, the percentage of unreacted mPDMS was calculated using the following formula, expressed as a percentage relative to T0: T x % at = ( x % measured at / % measured at T0) * 100 (where T0 represents 100% unreacted mPDMS or the % at the zero time point of the reaction, and T x represents the amount of unreacted mPDMS at time point x).

[0325] The present invention will now be described in connection with the following examples. Before describing the multiple exemplary embodiments of the present invention, it should be understood that the present invention is not limited to the construction details and processes mentioned in the following description. The present invention can have other embodiments and can be practiced or implemented in various ways.

[0326] The following abbreviations will be used in the examples and have the following meanings :

[0327] RMM: Reactive monomer mixture

[0328] L: Liter

[0329] mL: Milliliter

[0330] nm: Nanometer

[0331] g: Gram

[0332] μg: Microgram

[0333] Da: Dalton or gram / mole

[0334] kDa: Kilodalton

[0335] FTIR: Fourier transform infrared spectroscopy

[0336] ATR: Attenuated total reflection

[0337] HPLC: High performance liquid chromatography

[0338] UV: Ultraviolet spectroscopy

[0339] WC: Water content (wt%)

[0340] EC Dk: Edge-corrected oxygen permeability (barrer)

[0341] M: Modulus (psi)

[0342] TS: Tensile Strength (psi)

[0343] ETB: Elongation at Break (%)

[0344] RI: Refractive Index

[0345] Sessile Drop Method: Advancing Contact Angle (degrees)

[0346] Cahn DCA: Advancing and Receding Contact Angles (degrees)

[0347] BC: Bottom or Rear Curved Plastic Mold Made of PP, TT, Z, or Their Blends

[0348] FC: Front Curved Plastic Mold Made of PP, TT, Z, or Their Blends

[0349] PP: Polypropylene, i.e., Homopolymer of Propylene

[0350] TT: Tuftec, i.e., Hydrogenated Styrene-Butadiene Block Copolymer (Asahi Kasei Chemicals)

[0351] Z: Zeonor, i.e., Polycycloolefin Thermoplastic Polymer (Nippon Zeon Co Ltd)

[0352] TL03 Lighting: Phillips TLK 40W / 03 Bulb

[0353] LED: Light Emitting Diode

[0354] DMA: N,N-Dimethylacrylamide (Jarchem)

[0355] HEMA: 2-Hydroxyethyl Methacrylate (Bimax)

[0356] PVP K90: Poly(N-vinylpyrrolidone) (ISP Ashland)

[0357] PVMA: Polyvinylmethylacetamide

[0358] TEGDMA: Tetraethylene Glycol Dimethacrylate (Esstech)

[0359] mPDMS: Mono-n-butyl End-Capped and Mono-methacryloxypropyl End-Capped Polydimethylsiloxane (M n = 800 to 1500 Daltons) (Gelest)

[0360] SiMAA: 2-Acrylate, 2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl ester (Toray) or 3-(3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy)-2-hydroxypropyl methacrylate or 2-hydroxy-3-[3-methyl-3,3-bis(trimethylsilyloxy)silylpropoxy]propyl methacrylate

[0361] Irgacure or Omnirad 184: 1-Hydroxy-cyclohexyl-phenyl-ketone (IGM Resins, BASF or Ciba Specialty Chemicals)

[0362] Irgacure or Omnirad 1870: Blend of bis(2,6-dimethoxybenzoyl)-2,4,4-trimethyl-pentylphosphine oxide and 1-hydroxy-cyclohexyl-phenyl-ketone (BASF or Ciba Specialty Chemicals)

[0363] AIBN: Azobisisobutyronitrile or 2,2'-azobis(2-methylpropionitrile), 2-(azo(1-cyano-1-methylethyl))-2-methylpropionitrile

[0364] Norbloc: 2-(2′-Hydroxy-5-methacryloyloxyethylphenyl)-2H-benzotriazole (Janssen)

[0365] Blue HEMA: 1-Amino-4-[3-(4-(2-methacryloyloxy-ethoxy)-6-chlorotriazin-2-ylamino)-4-sulfophenylamino]anthraquinone-2-sulfonic acid, as described in U.S. Patent No. 5,944,853

[0366] D3O: 3,7-Dimethyl-3-octanol (Vigon)

[0367] DIW: Deionized water

[0368] IPA: Isopropyl alcohol

[0369] PS: Borate buffer wetting solution: Dissolve 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 in sufficient deionized water to fill a 2-liter volumetric flask.

[0370] WC: Water content (wt%)

[0371] Haze: %

[0372] EC Dk: Edge corrected oxygen permeability (Barrer)

[0373] M: Modulus (psi)

[0374] TS: Tensile strength (psi)

[0375] ETB: Elongation at break (%

[0376] Lipid: micrograms of cholesterol per lens or μg / lens

[0377] RI: Refractive index

[0378] Sessile drop method: Advancing contact angle (degrees)

[0379] Cahn DCA: Advancing and receding contact angles in that order in the table (degrees)

[0380] Parentheses: Parentheses () in the table are used to indicate the standard deviation of the measurement

[0381] Preparation 1 - Polyvinyl Methylacetamide (PVMA)

[0382] Prepare PVMA as follows: Add 380 mL (3.48 mol) of distilled N-vinyl-N-methylacetamide and 187 mg (1.14 mmol) of azobisisobutyronitrile to a 3-neck round bottom flask equipped with a reflux condenser, magnetic stir bar, and thermocouple, and bubble nitrogen through the reaction mixture to purge oxygen for 2 hours. Then, heat the reaction mixture at 75 °C for 24 hours, during which time the reaction mixture is solidified. Quench the reaction product in air and separate it by Post-treatment Process 1 or Post-treatment Process 2. Post-treatment process: Dissolve the reaction product in water and dialyze it thoroughly in a dialysis membrane tubing (SpectraPore MWCO 3500), then lyophilize (60% yield) (LABCONCO, Triad TMFreeze-drying system, model 7400030). Molecular weights were determined by size-exclusion chromatography and multi-angle light scattering (SEC-MALS). The SEC-MALS setup used an aqueous acetonitrile solution as the mobile phase, which consisted of 80% (v / v) 50 mM Na2SO4 and 20% (v / v) acetonitrile, with a flow rate of 0.5 mL / minute and a temperature of 40 °C. Two Tosoh Biosciences TSK gel columns in series [SuperAW4000 and SuperAW5000] were used, with an on-line Agilent 1200 UV / VIS diode array detector, a Wyatt Optilab rEX interferometric refractometer, and a Wyatt mini-DAWN Treos multi-angle laser scattering (MALS) detector (λ = 658 nm). Absolute molecular weight and polydispersity data were calculated using the Wyatt ASTRA VI SEC / LS software package. Approximately 40 mg of PVMA was dissolved in the wetting solution in a 10 mL volumetric flask. Wetting solution: 18.52 g (300 mmol) of boric acid, 3.7 g (9.7 mmol) of sodium borate decahydrate, and 28 g (197 mmol) of sodium sulfate were dissolved in sufficient deionized water to fill a 2 L volumetric flask. Three different solutions were prepared and tested. Before injection into the SEC-MALS system, all solutions were filtered through a 0.45 micron nylon membrane filter. The number-average molecular weight of the three samples was 290.5 kDa; the weight-average molecular weight of the three samples was 570.3 kDa; resulting in a polydispersity index of 1.96.

[0383] Examples 1 to 9

[0384] A reactive monomer mixture was prepared, which consisted of 77 wt% of the formulation listed in Table 1 and 23 wt% of diluent D3O. The reactive monomer mixture was filtered separately using a stainless-steel syringe through a 3 μm filter. Then, at the time of use, approximately 0.074 g of AIBN (thermal initiator) was dissolved in 20.0000 g of RMM. The weight percentage of AIBN in the final RMM was approximately 0.37 wt%.

[0385] The RMM with AIBN was degassed at ambient temperature by applying a vacuum (40 Torr) for at least 20 minutes. Then, in a glove box with a nitrogen atmosphere and less than about 0.2% oxygen, approximately 75 μL to 80 μL of the reactive mixture was dispensed into the FC made of Zeonor at room temperature using an Eppendorf pipette. Then, the BC made of a 55:45 (w / w) Z:PP blend was placed on the FC. Before dispensing, the mold was equilibrated in the glove box for at least twelve hours. Approximately 20 trays, each containing eight mold components, were transferred to an adjacent oven maintained at about 65 °C to 70 °C and located in the glove box, and the lenses were cured under these conditions for about 24 hours.

[0386] The lenses were manually demolded and detached by suspending the lenses in approximately one liter of 70% IPA for at least 12 hours, then soaking twice more with approximately 450 mL of fresh 70% IPA for about 45 minutes each; then soaking once with fresh DIW for about 45 minutes; and then soaking once with the wetting solution for about 45 minutes. The lenses were equilibrated and stored in a borate buffer wetting solution, and then autoclaved at 121 °C for 30 minutes in a vial. Various physical and mechanical properties of the sterile lenses were measured and listed in Table 2.

[0387] Those of ordinary skill in the art recognize that the exact lens detachment process can vary depending on the lens formulation and molding material in terms of the concentration of the aqueous isopropanol solution, the number of washes with each solvent, and the duration of each step. The purpose of the lens detachment process is to detach all lenses without defects and transform from a diluent-swollen network to a wetting solution-swollen hydrogel.

[0388] Table 1: Formulation Components

[0389]

[0390]

[0391] Table 2: Lens Characteristics

[0392]

[0393] As shown in Table 2, the lenses made by thermal curing exhibited good wettability, as measured by Cahn DCA and the sessile drop method at a low content of the internal wetting agent PVP K90, while maintaining a good balance of physical and mechanical properties suitable for soft contact lenses.

[0394] Comparative Example 1

[0395] Prepare a reactive monomer mixture consisting of 77 wt% of the formulation listed in Table 3 and 23 wt% of diluent D3O. Then, dissolve 0.0524 g of Irgacure 1870 and 0.0215 g of Irgacure 184 in 20 g of this reactive monomer mixture by stirring overnight, and then filter through a 3 μm filter using a stainless steel syringe.

[0396] Degas the RMM at ambient temperature by applying a vacuum (40 Torr) for at least 20 minutes. Then, in a glove box with a nitrogen atmosphere and less than about 0.2% oxygen, pipette approximately 75 μL of the reactive mixture into an FC made of Zeonor at room temperature. Then place a BC made of a 55:45 (w / w) Z:PP blend on the FC. Before dispensing, allow the mold to equilibrate in the glove box for at least twelve hours. Transfer a tray containing eight mold assemblies each to an adjacent glove box maintained at 64 °C, and cure the lenses from the top for 12 minutes using a TLO3 lamp with an intensity of about 4.5 mW / cm 2 at the tray position.

[0397] Manually demold the lenses, where most of the lenses adhere to the FC, and detach the lenses by suspending them in approximately one liter of 70% IPA for at least 12 hours, then soaking twice more in approximately 450 mL of fresh 70% IPA for approximately 45 minutes each; then soaking once in fresh DIW for approximately 45 minutes; then soaking once in a wetting solution for approximately 45 minutes. Equilibrate and store the lenses in a borate buffered wetting solution, and then autoclave them in vials at 121 °C for 30 minutes. Determine various physical and mechanical properties of the sterile lenses and list them in Table 4.

[0398] Those of ordinary skill in the art recognize that the exact lens detachment process can vary depending on the lens formulation and molding material in terms of the concentration of the aqueous isopropanol solution, the number of washes with each solvent, and the duration of each step. The purpose of the lens detachment process is to detach all lenses without defects and transform from a diluent-swollen network to a wetting solution-swollen hydrogel.

[0399] Comparative Example 2

[0400] Prepare a reactive monomer mixture consisting of 77 wt% of the formulation listed in Table 3 and 23 wt% of diluent D3O. Then, dissolve 0.0391 g of Irgacure 1870 and 0.0157 g of Irgacure 184 in 15 g of this reactive monomer mixture by stirring overnight, and then filter through a 3 μm filter using a stainless steel syringe.

[0401] The RMM was degassed at ambient temperature by applying a vacuum (40 Torr) for at least 20 minutes. Then, in a glove box with a nitrogen atmosphere and less than about 1% oxygen, approximately 75 μL of the reactive mixture was dispensed into the FC made of Zeonor at room temperature using an Eppendorf pipette. Then the BC made of a 55:45 (w / w) Z:PP blend was placed on the FC. Before dispensing, the mold was equilibrated in the glove box for at least twelve hours. Each tray containing eight mold components was transferred to an adjacent glove box maintained at 64 °C, and the lenses were cured from the top and bottom for 15 minutes using a 435 nm LED lamp with an intensity of about 4 mW / cm 2 at the tray position.

[0402] The lenses were manually demolded, with most of the lenses adhering to the FC, and the lenses were detached by suspending them in approximately one liter of 70% IPA for at least 12 hours, then soaking them twice more in approximately 450 mL of fresh 70% IPA for approximately 45 minutes each; then soaking them once in fresh DIW for approximately 45 minutes; and then soaking them once in a wetting solution for approximately 45 minutes. The lenses were equilibrated and stored in a borate buffer wetting solution, and then autoclaved at 121 °C for 30 minutes in a vial. Various physical and mechanical properties of the sterile lenses were determined and listed in Table 4.

[0403] Those of ordinary skill in the art recognize that the exact lens detachment process can vary depending on the lens formulation and molding material in terms of the concentration of the aqueous isopropanol solution, the number of washes with each solvent, and the duration of each step. The purpose of the lens detachment process is to detach all lenses without defects and transform from a diluent-swollen network to a wetting solution-swollen hydrogel.

[0404] Table 3: Formulation Components and Curing System

[0405]

[0406] Table 4: Lens Characteristics

[0407]

[0408] As shown in Table 4, the lenses made by thermal curing exhibited good wettability, as measured by Cahn DCA and the sessile drop method at a low content of the internal wetting agent PVP K90, while maintaining a good balance of physical and mechanical properties suitable for soft contact lenses, whereas the photochemically cured lenses were significantly less wettable, as measured by advancing Cahn DCA and the sessile drop method.

[0409] Examples 8 to 11

[0410] Prepare a reactive monomer mixture consisting of 77 wt% of the formulation listed in Table 5 and 23 wt% of diluent D3O. Use the PVMA from Preparation Example 1. Filter the reactive monomer mixture separately through a 3 μm filter using a stainless steel syringe. Then, at the time of use, dissolve approximately 0.037 g of AIBN (thermal initiator) in 10.0000 g of RMM. The weight percentage of AIBN in the final RMM is approximately 0.37 wt%.

[0411] Degas the RMM with AIBN at ambient temperature by applying a vacuum (40 Torr) for at least 20 minutes. Then, in a glove box with a nitrogen atmosphere and less than approximately 0.2% oxygen, dispense approximately 70 μL to 75 μL of the reactive mixture into an FC made of Zeonor at room temperature using an Eppendorf pipette. Then place a BC made of a 55:45 (w / w) Z:PP blend on the FC. Before dispensing, allow the mold to equilibrate in the glove box for at least twelve hours. Transfer approximately 20 trays, each containing eight mold components, to an adjacent oven maintained at approximately 65 °C to 70 °C and located in the glove box, and cure the lenses under these conditions for approximately 24 hours.

[0412] Manually demold the lenses and detach the lenses by suspending them in approximately one liter of 70% IPA for at least 12 hours, then soaking them twice more with approximately 450 mL of fresh 70% IPA for approximately 45 minutes each; then soaking them once with fresh DIW for approximately 45 minutes; then soaking them once with a wetting solution for approximately 45 minutes. Equilibrate and store the lenses in a borate buffer wetting solution, then autoclave them in a vial at 121 °C for 30 minutes. Determine various physical and mechanical properties of the sterile lenses and list them in Table 6.

[0413] Those of ordinary skill in the art recognize that the exact lens detachment process can vary depending on the lens formulation and the molding material in terms of the concentration of the aqueous isopropanol solution, the number of washes with each solvent, and the duration of each step. The purpose of the lens detachment process is to detach all lenses without defects and transform from a diluent-swollen network to a wetting solution-swollen hydrogel.

[0414] Table 5: Formulation Components

[0415]

[0416]

[0417] Table 6: Lens Characteristics

[0418]

[0419] As shown in Table 6, the lenses made by thermal curing exhibit good wettability, as measured by Cahn DCA and the sessile drop method with a low content of the internal wetting agent PVMA, while maintaining a good balance of physical and mechanical properties suitable for soft contact lenses.

[0420] Comparative Examples 3 to 6

[0421] Prepare a reactive monomer mixture consisting of 77 wt% of the formulation listed in Table 7 and 23 wt% of the diluent D3O. Then, dissolve approximately 0.0655 g of Irgacure 1870 and approximately 0.0270 g of Irgacure 184 in 25 g of this reactive monomer mixture by stirring overnight, and then filter through a 3 μm filter using a stainless steel syringe.

[0422] Degas the RMM at ambient temperature by applying a vacuum (40 Torr) for at least 20 minutes. Then, in a glove box with a nitrogen atmosphere and less than approximately 0.2% oxygen, dispense approximately 70 μL to 75 μL of the reactive mixture into an FC made of Zeonor at room temperature using an Eppendorf pipette. Then place a BC made of a 55:45 (w / w) Z:PP blend on the FC. Before dispensing, allow the mold to equilibrate in the glove box for at least twelve hours. Transfer each tray containing eight mold assemblies to an adjacent glove box maintained at 65 °C, and cure the lenses from the top for 12 minutes using a TLO3 lamp with an intensity of approximately 4.0 mW / cm 2 to 4.5 mW / cm 2 of the TLO3 lamp.

[0423] Manually demold the lenses, where most of the lenses adhere to the FC, and detach the lenses by suspending them in approximately one liter of 70% IPA for at least 12 hours, then soaking twice more with approximately 450 mL of fresh 70% IPA for approximately 45 minutes each; then soak once with fresh DIW for approximately 45 minutes; then soak once with a wetting solution for approximately 45 minutes. Equilibrate and store the lenses in a borate buffer wetting solution, and then autoclave them in a vial at 121 °C for 30 minutes. Measure various physical and mechanical properties of the sterile lenses and list them in Table 8.

[0424] Those of ordinary skill in the art recognize that the exact lens release process can vary depending on the lens formulation and molding material, in terms of the concentration of the isopropyl alcohol aqueous solution, the number of washes with each solvent, and the duration of each step. The purpose of the lens release process is to release all lenses without defects and transform from a network swollen by a diluent to a hydrogel swollen by a wetting solution.

[0425] Table 7: Formulation Components

[0426]

[0427] Table 8: Lens Characteristics

[0428]

[0429] As shown in Table 8, compared to similar lenses made by thermal curing (see Table 6), lenses made by photochemical curing exhibit generally reduced wettability, as measured by Cahn DCA and the sessile drop method at low levels of the internal wetting agent PVMA.

[0430] Examples 12 to 14

[0431] Prepare a reactive monomer mixture consisting of 77 wt% of the formulation listed in Table 9 and 23 wt% of the diluent D3O. Filter the reactive monomer mixture separately through a 3 μm filter using a stainless steel syringe. Then, at the time of use, dissolve approximately 0.0285 grams of AIBN (thermal initiator) in 10.0000 grams of RMM. The weight percentage of AIBN in the final RMM is approximately 0.28 wt%.

[0432] Degas the RMM with AIBN at ambient temperature by applying a vacuum (40 Torr) for at least 20 minutes. Then, in a glove box with a nitrogen atmosphere and less than approximately 0.1% to 0.2% oxygen, pipette approximately 75 μL of the reactive mixture into an FC made of Zeonor at room temperature. Then, place a BC also made of Zeonor on top of the FC. Before dispensing, allow the mold to equilibrate in the glove box for at least twelve hours.

[0433] Example 12: Transfer several trays each containing eight mold assemblies to an adjacent oven maintained at approximately 60 °C and located in a glove box, and cure the lenses under these conditions for approximately 6 hours.

[0434] Example 13: The same procedure, except that several trays each containing eight mold assemblies are transferred to an adjacent oven maintained at approximately 90 °C and located in a glove box, and cure the lenses under these conditions for approximately 6 hours.

[0435] Example 14: The same procedure was followed, except that: (1) the FC was made from a 90:10 (w / w) blend of Z:TT, (2) the BC was made from a 90:10 (w / w) blend of Z:PP, and (3) several trays each containing eight mold components were transferred to an adjacent oven maintained at about 120 °C and located in a glove box, and the lenses were cured under these conditions for about 0.5 hours.

[0436] The lenses were manually demolded and removed by suspending the lenses in about one liter of 70% IPA for at least 12 hours, then soaking twice more with about 450 mL of fresh 70% IPA for about 45 minutes each; then soaking once with fresh DIW for about 45 minutes; then soaking once with a wetting solution for about 45 minutes. The lenses were equilibrated and stored in a borate buffered wetting solution and then autoclaved at 121 °C for 30 minutes in a vial.

[0437] Those of ordinary skill in the art will recognize that the exact lens removal process can vary depending on the lens formulation and molding material in terms of the concentration of the aqueous isopropanol solution, the number of washes with each solvent, and the duration of each step. The purpose of the lens removal process is to remove all lenses without defects and to transform from a diluent-swollen network to a wetting solution-swollen hydrogel.

[0438] For the thermally cured disinfected lenses of Examples 12 to 14 and the photochemically cured disinfected lenses of similar composition (shown as Comparative Example 7 or Comparative Example 7 in the figures), both transmission and ATR FTIR methods were used for analysis and normalized to the photochemically cured lenses. As Figure 1 and Figure 2 shown, the surface concentration of PVP in the thermally cured lenses is higher than that in the photochemically cured lenses. In addition, the molar ratio of PVP / silicone in the thermally cured lenses is higher at the surface than in the core.

[0439] Table 9: Formulation Components

[0440]

[0441] Examples 15 to 17

[0442] Example 15: Example 13 was repeated, except that: (1) the FC was made from 90:10 (w / w) Z:TT, (2) the BC was made from 90:10 (w / w) Z:PP, and (3) the lenses were removed at different time points for HPLC-UV analysis of residual monomers and macromonomers. The residual component data are listed in Table 10.

[0443] Example 16: Example 14 was repeated, except that the lens was removed at different time points for HPLC-UV analysis of the residual monomers and macromonomers. The residual component data are listed in Table 11.

[0444] Example 17: Example 14 was repeated again, except that the lens was removed at different time points for HPLC-UV analysis of the residual monomers and macromonomers. The residual component data are listed in Table 12.

[0445] Table 10: Residual Monomers in Example 15 - Thermal Curing at 90°C

[0446]

[0447]

[0448] Table 11: Residual Monomers in Example 16 - Thermal Curing at 120°C

[0449]

[0450] Table 12: Residual Monomers in Example 17 - Thermal Curing at 120°C

[0451]

[0452] As shown in Tables 10 to 12, the reactive monomer mixture was thermally cured to a high conversion rate in both cases: with less than about 0.2 wt% total unreacted components after about 2 to 3 hours at 90 °C; with less than about 0.3 wt% total unreacted components after about 0.5 to 1 hour at 120 °C.

Claims

1. An organosilicon hydrogel contact lens, the organosilicon hydrogel contact lens being a reaction product of a reactive mixture, the reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymer internal wetting agent; and a thermal initiator, the contact lens having an oxygen permeability of at least 60 Barrers, and wherein without surface treatment, the molar ratio of the non-reactive polymer internal wetting agent to silicone in the lens is greater at the lens surface than in its bulk; and wherein the reactive mixture is thermally cured at a temperature of 60 degrees Celsius to 120 degrees Celsius for at least 30 minutes.

2. The organosilicon hydrogel contact lens according to claim 1, wherein the molar ratio of the non-reactive polymer internal wetting agent to silicone is at least 1.5 times greater at the lens surface than in its bulk.

3. The organosilicon hydrogel contact lens according to any one of claims 1 to 2, wherein the molar ratio of the non-reactive polymer internal wetting agent to silicone is at least 2.3 times greater at the lens surface than in its bulk.

4. The organosilicon hydrogel contact lens according to any one of claims 1 to 2, wherein the non-reactive polymer internal wetting agent is a polyamide.

5. The organosilicon hydrogel contact lens according to any one of claims 1 to 2, wherein the non-reactive polymer internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl (meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof.

6. The organosilicon hydrogel contact lens according to any one of claims 1 to 2, wherein in a lens that is a reaction product of a reactive mixture containing as low as 2.0 wt% of the non-reactive polymer internal wetting agent, the lens has an advancing contact angle of 75° or less.

7. The organosilicon hydrogel contact lens according to claim 6, wherein the advancing contact angle is 50° or less.

8. The organosilicon hydrogel contact lens according to any one of claims 1 to 2 and 7, based on all reactive components of the reactive mixture, the organosilicon hydrogel contact lens comprises at most 95 wt% of the silicone-containing component.

9. The organosilicon hydrogel contact lens according to any one of claims 1 to 2 and 7, based on all reactive components of the reactive mixture, the organosilicon hydrogel contact lens comprises 1 wt% to 80 wt% of the hydrophilic component.

10. The silicone hydrogel contact lens according to any one of claims 1 to 2 and 7, based on all reactive components of the reactive mixture, the silicone hydrogel contact lens comprises 0.5% to 35% by weight of a non-reactive polymeric internal wetting agent.

11. A method for manufacturing a contact lens, the method comprising: (a) Provide a reactive mixture, the reactive mixture comprising: a silicone-containing component; a hydrophilic component; a non-reactive polymer internal wetting agent; and a thermal initiator; and (b) Polymerize the reactive mixture to form the contact lens; wherein the method is carried out under conditions such that, without surface treatment, the contact lens has a molar ratio of the non-reactive polymer internal wetting agent to silicone that is greater at the lens surface than in its bulk, and wherein step (b) comprises thermally curing the reactive mixture at a temperature of 60 degrees Celsius to 120 degrees Celsius for at least 30 minutes.

12. The method according to claim 11, wherein the molar ratio of the non-reactive polymeric internal wetting agent to the silicone is at least 1.5 times in the lens surface than in its bulk.

13. The method according to any one of claims 11 to 12, wherein the molar ratio of the non-reactive polymeric internal wetting agent to the silicone is at least 2.3 times in the lens surface than in its bulk.

14. The method according to any one of claims 11 to 12, wherein the non-reactive polymeric internal wetting agent is a polyamide.

15. The method according to any one of claims 11 to 12, wherein the non-reactive polymeric internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl (meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof.

16. The method according to any one of claims 11 to 12, wherein in a lens that is a polymerization product of a reactive mixture containing as low as 2.0% by weight of the non-reactive polymeric internal wetting agent, the lens comprises an advancing contact angle of 75° or less.

17. The method according to claim 16, wherein the advancing contact angle is 50° or less.

18. The method according to any one of claims 11 to 12 and 17, wherein the thermal curing is carried out at a temperature of 85 degrees Celsius to 120 degrees Celsius.

19. The method according to any one of claims 11 to 12 and 17, wherein after step (b) and before an extraction step of removing unpolymerized components from the contact lens, the contact lens comprises no more than 0.3% by weight of unpolymerized polymerizable components.

20. A silicone hydrogel contact lens prepared by the method according to any one of claims 11 to 19.

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