RU2818105C2 - Silicone hydrogel contact lenses having heterogeneous structure - Google Patents

Abstract

FIELD: optics.

SUBSTANCE: invention relates to silicone hydrogel contact lenses with a non-uniform structure, comprising a non-reactive polymer internal wetting agent, wherein said non-reactive polymer internal wetting agent is more concentrated on the surface of the lens than in its body. Claimed silicone hydrogel contact lens, which is a reaction product of the reaction mixture, contains a silicone-containing component; hydrophilic component; non-reactive polymer internal wetting agent; as well as a polymerisation initiator. Said contact lens has oxygen permeability of at least about 60 barrers, and the molar ratio in the lens of the polymer non-reactive internal wetting agent to silicone, without surface treatment, is higher on the surface of the lens than in its body.

EFFECT: creation of a silicone-hydrogel contact lens with further improved surface properties.

22 cl, 2 dwg, 21 tbl

Description

Related applications

This application claims benefit from U.S. Provisional Patent Application Serial No. 16/875,164, filed May 15, 2020, and U.S. Provisional Patent Application Serial No. 62/865,586, filed June 24, 2019, each of which is incorporated herein. document by reference in its entirety.

Scope of the invention

The present invention relates to silicone hydrogel contact lenses with a heterogeneous structure. More specifically, the present invention relates to silicone hydrogel contact lenses containing a non-reactive polymeric internal wetting agent, wherein the non-reactive polymeric internal wetting agent is more concentrated on the surface of the lens than in its body.

Prerequisites for creating the invention

Soft contact lenses are based on hydrogels. Many users find soft contact lenses comfortable enough to wear all day. Depending on the class of materials, there are two main types of contact lenses: traditional soft contact lenses, which are made from silicone-free hydrogels, and silicone hydrogel contact lenses.

Silicone hydrogels are water-swelling polymer networks with high oxygen permeability. One of the problems associated with silicone hydrogel is the inherent hydrophobicity of the lens surface, which reduces its compatibility with the eye. Many strategies have been used to overcome these hydrophobic properties. Some technologies rely on modifying the lens surface after manufacturing to make it hydrophilic, for example by applying a hydrophilic coating to the surface of the lens. Other technologies rely on the inclusion of an internal wetting agent in the lens. The advantage of this latter approach is that no surface modification is required after the lens is manufactured. The disadvantage is that the hydrophilic wetting agent is often poorly compatible with the hydrophobic constituents of the monomer mixture (such as silicone components), which consequently requires the use of compatibilizer materials, which increases the complexity of the formulation and increases the cost of the formulation.

A common wetting agent used to impart hydrophilicity to silicone hydrogel contact lenses is polyvinylpyrrolidone (PVP). In a typical manufacturing process, PVP is incorporated into a monomer reaction mixture containing a photoinitiator and other reactive components, which is then polymerized under ultraviolet or visible light (photochemical polymerization). The resulting product contains PVP evenly distributed throughout the lens.

One of the main advantages of PVP is its effect on the surface properties of the lens, such as surface wettability. Thus, although PVP is evenly distributed throughout the lens, it is typically present in a concentration sufficient to improve lens surface performance.

Silicone hydrogel contact lenses have become widespread in the industry. These lenses provide high oxygen permeability as well as a high level of comfort for many lens wearers. However, some users suffer from discomfort and excess deposits in the eyes, leading to loss of visual acuity when wearing such lenses, especially during extended periods of wear for several days in a row, such as up to 30 days. Such discomfort and deposits are associated with the hydrophobic properties of surfaces described above and the interaction of these surfaces with protein, lipids and mucin, as well as the hydrophilic surface of the eye. Thus, it would be an advantage in the art to develop new silicone hydrogel contact lenses with further improved surface properties.

Summary of the invention

The present invention relates to a silicone hydrogel contact lens containing a non-reactive polymeric internal wetting agent, wherein said wetting agent is enriched on the surface of the lens compared to the body of the lens. Such lenses provide more efficient use of the wetting agent due to its suitable location. This results in a number of advantages including, for example, better surface wettability with substantially the same total wetting agent concentration as existing lenses. Or, surface-enriched lenses may allow the use of less wetting agent to achieve substantially the same wettability as existing lenses, which in turn may simplify the manufacturing process and/or reduce costs.

Accordingly, in one aspect of the present invention there is provided a silicone hydrogel contact lens that is a reaction product of a reaction mixture containing: a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator, wherein said contact lens has an oxygen permeability of at least about 60 bbl, and wherein the molar ratio in the lens of polymeric non-reactive internal wetting agent to silicone, without surface treatment, is higher on the surface of the lens than in its body .

In another aspect of the present invention, a method for making a contact lens is provided. The method includes: (a) obtaining a reaction mixture containing a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; as well as a polymerization initiator; and (b) polymerizing the reaction mixture to form a contact lens, said method being carried out under conditions such that the contact lens has a molar ratio of polymeric non-reactive internal wetting agent to silicone, without surface treatment, that is higher on the surface of the lens than in its body.

Brief description of graphic materials

In fig. 1 shows FTIR spectra demonstrating PVP concentrations on the surface and in the body of the lens using PVP/silicone ratios for contact lenses of the present invention and comparison contact lenses.

In fig. 2 shows FTIR spectra demonstrating PVP concentrations on the surface and in the body of the lens using PVP/methacrylate ratios for contact lenses of the present invention and comparison contact lenses.

Detailed Description of the Invention

With respect to terms used in this specification, the following definitions are provided.

Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one skilled in the art to which the invention relates. Definitions for polymers are consistent with those described in the Compendium of Polymer Terminology and Nomenclature, IUPAC Recommendations 2008, edited by Richard G. Jones, Jaroslav Kahovec, Robert Stepto, Edward S. Wilks, Michael Hess, Tatsuki Kitayama, and W. Val Metanomski. All publications, patent applications, patents and other references mentioned herein are incorporated herein by reference.

As used herein, the term “(meth)” refers to the possible presence of an optional methyl substituent. Thus, the term "(meth)acrylates" refers to both methacrylates and acrylates.

It should be noted that wherever chemical structures are given, the variants presented as substituents in the structure can occur in any combination. Thus, if a structure contains substituents R* and R**, each with three lists of potential groups, 9 combinations are possible. The same applies to combinations of properties.

When using a subscript such as "n" in the standard formula [***] _n to indicate the number of repeating units in a polymer chemical formula, such formula should be understood to represent the number-average molecular weight of the macromolecule.

As used herein, the term “subject” includes humans and vertebrate animals.

"Ocular surface" includes the superficial and glandular epithelium of the cornea, conjunctiva, lacrimal glands, accessory lacrimal glands, nasolacrimal duct and meibomian glands, and their apical and basal matrices, puncta and adjacent or associated structures, including the eyelids, related as a functional system by continuity epithelium, innervation and endocrine and immune systems.

The term "contact lens" refers to an ophthalmic device that can be placed on the cornea of a patient's eye. The contact lens may provide a corrective, cosmetic, or therapeutic effect, including wound healing, drug or nutraceutical delivery, diagnostic assessment or monitoring, ultraviolet light absorption, reduction of visible or glare light, or any combination thereof. The contact lens may be made from any suitable material known in the art and may be a soft lens, a hard lens, or a hybrid lens comprising at least two separate parts with different physical, mechanical, or optical properties, such as elastic modulus, water content, light transmittance or combinations thereof.

The term "target macromolecule" is a macromolecule synthesized from a reaction monomer mixture containing monomers, macromers, prepolymers, cross-linkers, initiators, additives, diluents, etc.

The term "polymerizable compound" or "polymerizable component" means a compound containing one or more polymerizable groups. The term covers, for example, monomers, macromers, oligomers, prepolymers, crosslinkers, and the like.

“Polymerizable groups” are groups that can undergo chain growth polymerization, such as free radical and/or cationic polymerization, such as a carbon double bond group that can polymerize when exposed to radical polymerization initiation conditions. Non-limiting examples of free radical polymerizable groups include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N -vinyl lactams, N -vinyl amides, O-vinyl carbamates, O-vinyl carbonates and other vinyl groups. Free radical polymerizable groups preferably contain (meth)acrylate, (meth)acrylamide, N-vinyllactam, N-vinylamide, styryl functional groups or mixtures of any of the above. Free radical polymerizable groups more preferably contain (meth)acrylates, (meth)acrylamides and mixtures thereof. The polymerizable group may be substituted or unsubstituted. For example, the nitrogen atom in (meth)acrylamide may be bonded to a hydrogen, or the hydrogen may be replaced by an alkyl or cycloalkyl (which themselves may be further substituted).

Any type of free radical polymerization may be used, including, but not limited to, bulk, solution, suspension, and emulsion, as well as any controlled radical polymerization methods, such as stable free radical initiated polymerization, nitroxide-mediated living polymerization, atom transfer radical polymerization, polymerization by reversible addition and fragmentation, organotellurium compound-mediated living radical polymerization, etc.

A “monomer” is a monofunctional molecule that can undergo chain growth polymerization and, in particular, free radical polymerization, thereby creating a repeating unit in the chemical structure of the target macromolecule. Some monomers have bifunctional impurities that can act as cross-linking agents. “Hydrophilic monomer” is also a monomer that gives a clear, single-phase solution when mixed with deionized water at 25 °C at a concentration of 5 wt%. A “hydrophilic component” is a monomer, macromer, prepolymer, initiator, crosslinker, additive or polymer that produces a clear, single-phase solution when mixed with deionized water at 25°C at a concentration of 5% by weight. A “hydrophobic moiety” is a monomer, macromer, prepolymer, initiator, cross-linker, additive or polymer that is marginally soluble or insoluble in deionized water at 25 °C.

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

A "macromonomer" or "macromer" is a macromolecule that has one group that can undergo chain growth polymerization and, in particular, free radical polymerization, thereby creating a repeating unit in the chemical structure of the target macromolecule. Typically, the chemical structure of the macromer is different from the chemical structure of the target macromolecule, that is, the repeat unit of the side group of the macromer is different from the repeat unit of the target macromolecule or its main chain. The difference between a monomer and a macromer is only the chemical structure, molecular weight and molecular weight distribution of the side group. As a result, and as used herein, monomers are sometimes defined in the patent literature as polymerizable compounds having a relatively low molecular weight of approximately 1500 daltons or less, which obviously includes some macromers. In particular, monomers and macromers may include mono-n-butyl and monomethacryloxypropyl-terminated polydimethylsiloxane (molecular weight = 500-1500 g/mol) (mPDMS) and mono-(2-hydroxy-3-methacryloxypropyl)-propylether-terminated polydimethylsiloxane group and mono-n-butyl (molecular weight=500-1500 g/mol) (OH-mPDMS). Additionally, in the patent literature, macromers are sometimes defined as having one or more polymerizable groups, essentially expanding the general definition of macromer to include prepolymers. As a result, and as used herein, dual-functional and multifunctional macromers, prepolymers, and cross-linkers can be used interchangeably.

A "silicon-containing component" is a monomer, macromer, prepolymer, cross-linker, initiator, additive or polymer in a reactive composition with at least one silicon-oxygen bond, typically in the form of siloxy groups, siloxane groups, carbosiloxane groups and mixtures thereof.

Examples of silicone-containing components that are used in the present invention can be found in US Patent Nos. , 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, ,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, 0.711, 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. The contents of all these patents are incorporated herein by reference in their entirety.

A “polymer” is a target macromolecule consisting of repeating units of monomers used during polymerization.

"Homopolymer" is a polymer made from a single monomer; "copolymer" is a polymer made from two or more monomers; A "terpolymer" is a polymer made from three monomers. A “block copolymer” consists of blocks or segments of different composition. Diblock copolymers have two blocks. Triblock copolymers have three blocks. "Comb copolymers" or "graft copolymers" consist of at least one macromer.

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

An "initiator" is a molecule that can decompose into radicals that can subsequently react with a monomer to initiate a free radical polymerization reaction. The thermal initiator decomposes at a certain rate depending on the temperature; typical examples are azo compounds such as 1,1'-azobisobutyronitrile and 4,4'-azobis(4-cyanovaleric acid), peroxides such as benzoyl peroxide, tert-butyl peroxide, tert-butyl hydroperoxide, tert-butyl peroxybenzoate, dicumyl peroxide and lauroyl peroxide, peroxyacids such as peracetic acid and potassium persulfate, as well as a variety of redox systems. The photoinitiator decomposes by a photochemical process; typical examples are derivatives of benzyl, benzoin, acetophenone, benzophenone, camphorquinone and mixtures thereof, as well as a variety of monoacyl and bisacylphosphine oxides and combinations thereof.

A "crosslinker" is a bifunctional or multifunctional monomer or macromer that can participate in free radical polymerization at two or more sites in the molecule, thereby creating branch points and forming a polymer network. Common examples include ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, methylene bisacrylamide, triallyl cyanurate, etc.

A "prepolymer" is a reaction product of monomers that contains remaining polymerizable groups capable of undergoing further reaction to form a polymer.

A "polymer network" is a cross-linked macromolecule that can swell but cannot dissolve in solvents. "Hydrogels" are polymer networks that swell in water or aqueous solutions, usually absorbing at least 10% of the mass. water. "Silicone hydrogels" are hydrogels that are prepared from at least one silicone-containing component with at least one hydrophilic component. Hydrophilic components may also include non-reactive polymers.

“Conventional hydrogels” refer to polymer networks derived from monomers without any siloxy, siloxane or carbosiloxane groups. Traditional hydrogels are prepared from reaction mixtures containing hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate (HEMA), N-vinylpyrrolidone (NVP), N,N-dimethylacrylamide (DMA), or vinyl acetate. In US Patent Nos. 4,436,887, 4,495,313, 4,889,664, 5,006,622, 5,039,459, 5,236,969, 5,270,418, 5,298,533, 5,824,719, 6,420,453, 761, 6,767,979, 7,934,830, 8,138,290, and 8,389,597 describe the preparation of traditional hydrogels. Commercially available conventional hydrogels include, but are not limited to, etafilcon, genfilcon, gilafilcon, lenefilcon, nesofilcon, omafilcon, polymacon and vifilcon, including all variants thereof.

The term "silicone hydrogels" refers to polymer networks made from at least one hydrophilic component and at least one silicone-containing component. Examples of commercially available silicone hydrogels include aquafilcone, asmofilcone, balafilcone, comfilcone, delefilcone, enfilcone, fanfilcone, formofilcone, galifilcone, lotrafilcone, narafilcone, rhyofilcone, samfilcone, senofilcone, somofilcone, and stenfilcone, including all variants thereof, as well as silicone hydrogels manufactured in accordance with US patents 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, 9,461, 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, 85 , 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, 8,937,111, 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, 97,928, 9,297,929 , as well as WO 03/22321, WO 2008/061992 and US 2010/0048847. The contents of all named patents are incorporated herein by reference in their entirety.

An "interpenetrating polymer network" comprises two or more polymer networks that are at least partially intertwined at the molecular level, but are not covalently bonded to each other and cannot be separated without breaking the chemical bonds. A "semi-interpenetrating polymer network" comprises one or more networks and one or more polymers characterized by some molecular level mixing between the at least one network and the at least one polymer. A mixture of different polymers is a "polymer blend". Semi-interpenetrating mesh is technically a polymer mixture, but in some cases the polymers are so tightly intertwined that they cannot be easily removed.

"Reactive components" are the polymerizable compounds (such as monomers, macromers, oligomers, prepolymers and crosslinkers) in the reaction mixture (defined below), as well as any other components of the reaction mixture that are intended to remain substantially in the polymer network after polymerization and completion of all processing steps (such as extraction steps) and packaging steps. Reactive components can be held in the polymer network through covalent bonds, hydrogen bonds, electrostatic interactions, the formation of interpenetrating polymer networks, or any other means. Components intended to be released from the polymer network after use are still considered "reactive components." For example, pharmaceutical or nutraceutical components in a contact lens that are intended to be released during wear are considered “reactive components.” Components that are intended to be removed from the polymer network during the manufacturing process (eg, by extraction), such as diluents, are not “reactive” components.

The terms "reaction mixture" and "monomer reaction mixture" refer to a mixture of components that are mixed together that, under polymerization conditions, results in the formation of a polymer network (such as conventional or silicone hydrogels), as well as biomedical devices, ophthalmic devices and contact lenses made of them. The monomer reaction mixture may contain reactive components such as monomers, macromers, prepolymers, crosslinkers and initiators, additives such as wetting agents, polymers, dyes, light absorbing compounds such as UV absorbers, pigments, photochromic compounds, pharmaceutical compounds and /or nutraceutical compounds, any of which may be polymerizable or non-polymerizable, but capable of being retained in the resulting biomedical device (eg, contact lenses). The reaction mixture may also contain other components, such as diluents, which are intended to be removed from the device before use. It should be understood that the reaction mixture may contain a wide range of additives depending on the type of contact lens being manufactured and its purpose. The concentrations of the components of the reaction mixture are expressed in mass fractions of all components of the reaction mixture, with the exception of the diluent. When diluents are used, their concentrations are expressed in mass fractions of the total amount of all components in the reaction mixture (including the diluent).

The term "silicone hydrogel contact lens" refers to a hydrogel contact lens made from at least one silicone-containing compound. Silicone hydrogel contact lenses essentially have increased oxygen permeability compared to conventional hydrogels. To transfer oxygen to the eye, silicone hydrogel contact lenses use both their aqueous and polymer components.

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

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

"Alkyl" refers to an optionally substituted straight or branched chain alkyl group containing the specified number of carbon atoms. If no number is specified, alkyl (optionally including any substituents on alkyl) may contain from 1 to 16 carbon atoms. The alkyl group preferably contains from 1 to 10 carbon atoms, in another embodiment from 1 to 8 carbon atoms, in another embodiment from 1 to 6 carbon atoms, or in another embodiment from 1 to 4 carbon atoms. Examples of alkyl include methyl, ethyl, propyl, isopropyl, butyl, iso-, sec- and tert-butyl, pentyl, hexyl, heptyl, 3-ethylbutyl, etc. Examples of substituents on the alkyl group include 1, 2 or 3 groups independently selected from hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, thioalkyl, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Alkylene" means a divalent alkyl group such as -CH ₂ -, -CH ₂ CH ₂ -, -CH ₂ CH ₂ CH ₂ -, -CH ₂ CH(CH ₃ )CH ₂ - and -CH ₂ CH ₂ CH ₂ CH ₂ -.

The term "haloalkyl" refers to an alkyl group as defined above that is substituted with one or more halogen atoms, each halogen independently being F, Cl, Br or I. A preferred halogen is F. Preferred haloalkyl groups contain 1-6 carbon atoms , more preferably 1-4 carbon atoms and even more preferably 1-2 carbon atoms. The term "haloalkyl" includes perhaloalkyl groups such as -CF ₃ - or -CF ₂ CF ₃ -. The term "haloalkylene" means a divalent haloalkyl group such as -CH ₂ CF ₂ -.

"Cycloalkyl" refers to an optionally substituted cyclic hydrocarbon containing a specified number of carbon atoms in the ring. If no number is specified, then cycloalkyl may contain from 3 to 12 carbon atoms in the ring. Preferred cycloalkyl groups are C ₃ -C ₈ , C ₃ -C ₇ cycloalkyl, more preferably C ₄ -C ₇ cycloalkyl, and even more preferably C ₅ -C ₆ cycloalkyl. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Examples of substituents on a cycloalkyl group include 1, 2, or 3 groups independently selected from alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, thioalkyl, amido, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. The term "cycloalkylene" means a divalent cycloalkyl group such as 1,2-cyclohexylene, 1,3-cyclohexylene or 1,4-cyclohexylene.

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

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

The term “heteroaryl” refers to an aryl ring or ring system, as defined above, in which at least one carbon atom in the ring is replaced by a heteroatom selected from nitrogen, oxygen and sulfur. A heteroaryl ring may be fused or otherwise attached to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings, or heterocycloalkyl rings. Examples of heteroaryl groups include pyridyl, furyl and thienyl. The term "heteroarylene" means a divalent heteroaryl group.

The term "alkoxy" means an alkyl group attached to the parent moiety via an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy and isopropoxy. "Thioalkyl" means an alkyl group attached to the parent molecule through a sulfur-containing bridge. Examples of thioalkyl groups include, for example, methylthio, ethylthio, n-propylthio and isopropylthio. The term "aryloxy" means an aryl group attached to the parent moiety via an oxygen bridge. Examples include phenoxy. The term "cyclic alkoxy group" means a cycloalkyl group attached to the parent moiety via an oxygen bridge.

The term "alkylamine" refers to an alkyl group attached to the parent moiety via an -NH bridge. The term "alkyleneamine" means a divalent alkylamine group such as -CH ₂ CH ₂ NH-.

The term "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 (ie, a siloxane group), and a siloxanyl compound means a compound having at least one Si-O-Si group. The term "siloxanil" covers monomeric (eg, Si-O-Si) as well as oligomeric/polymeric structures (eg, -[Si-O] _n- , where n is 2 or more). Each silicon atom in the siloxanyl group is substituted with independently selected R ^A groups (where R ^A is defined as defined in (b)-(i) of Formula A) to fill the valency.

The term "silyl" refers to a structure of the formula R ₃ Si-, and "siloxy" refers to a structure of the formula R ₃ Si-O-, wherein each R in silyl or siloxy is independently selected from trimethylsiloxy, C ₁ -C ₈ alkyl (preferably C ₁ -C ₃ alkyl, more preferably alkyl or methyl) and C ₃ -C ₈ cycloalkyl.

The term "alkyleneoxy" refers to groups of the general formula -(alkylene-O) _p- or -(O-alkylene) _p- , wherein alkylene is defined as above and p is from 1 to 200, or from 1 to 100, or from 1 to 50, or from 1 to 25, or from 1 to 20, or from 1 to 10, and wherein each alkylene is independently optionally substituted by one or more groups independently selected from hydroxyl, halogen (e.g., fluorine), amino, amido, ether, carbonyl, carboxyl and combinations thereof. If p is greater than 1, then all alkylenes may be the same or different, and alkyleneoxy may have a block or random configuration. If the alkyleneoxy forms a terminal group on the molecule, the alkyleneoxy end may, for example, be hydroxy or alkoxy (eg, HO-[CH ₂ CH ₂ O] _p - or CH ₃ O-[CH ₂ CH ₂ O] _p -). Examples of alkyleneoxy include polyethyleneoxy, polypropyleneoxy, polybutyleneoxy and poly(ethyleneoxy-co-propyleneoxy).

The term "oxaalkylene" refers to an alkylene group, as defined above, in which one or more non-contiguous CH ₂ groups are replaced by an oxygen atom, for example -CH ₂ CH ₂ OCH(CH ₃ )CH ₂ -. The term "thiaalkylene" refers to an alkylene group, as defined above, in which one or more non-contiguous CH ₂ groups are replaced by a sulfur atom, for example -CH ₂ CH ₂ SCH(CH ₃ )CH ₂ -.

The term "linking group" refers to a functional group that links the polymerizable group to the parent molecule. The linking group can be any functional group that is compatible with the compound of which it is a part, that does not adversely affect the polymerization of the compound, and is stable under the polymerization conditions and the processing and storage conditions of the finished product. For example, the linking group may be a bond or may be one or more of alkylene, haloalkylene, amide, amine, alkylene amine, carbamate, ester (-CO ₂ -), arylene, heteroarylene, cycloalkylene, heterocycloalkylene, alkyleneoxy, oxaalkylene, thiaalkylene , haloalkyleneoxy (alkyleneoxy substituted with one or more halogen groups, for example -OCF ₂ -, -OCF ₂ CF ₂ -, -OCF ₂ CH ₂ -), siloxanyl, alkylene siloxanyl or combinations thereof. The linking group may optionally be substituted with 1 or more groups. Acceptable substituents may include groups independently selected from alkyl, halogen (eg, fluorine), hydroxyl, HO-alkyleneoxy, MeO-alkyleneoxy, siloxanyl, siloxy, siloxy-alkyleneoxy-, siloxy-alkylene-alkyleneoxy- (which may contain more than one alkyleneoxy group, and in which each methylene in the alkylene or alkyleneoxy is independently optionally substituted with hydroxyl), ether, amine, carbonyl, carbamate, and combinations thereof. The linking group may also be replaced by a polymerizable group such as (meth)acrylate (in addition to the polymerizable group to which the linking group is bonded).

Preferred linking groups include C ₁ -C ₈ alkylene (preferably C ₂ -C ₆ alkylene) and C ₁ -C ₈ oxaalkylene (preferably C ₂ -C ₆ oxaalkylene), each of which is optionally substituted with 1 or 2 groups, independently selected from hydroxyl and siloxy. Preferred linking groups also include carboxylate, amide, C ₁ -C ₈ alkylene carboxylate-C ₁ -C ₈ alkylene, or C ₁ -C ₈ alkylene amide-C ₁ -C ₈ alkylene.

If the linking group consists of combinations of functional groups described above (eg, alkylene and cycloalkylene), then these functional groups may be present in any order. For example, if in Formula A below L is specified as -alkylene-cycloalkylene-, then Rg-L can be either Rg-alkylene-cycloalkylene- or Rg-cycloalkylene-alkylene-. However, the order of listing represents the preferred order in which the functional groups appear in the compound, starting with the terminal polymerizable group (Rg or Pg) to which the linking group is attached. For example, if in formula A L is designated alkylene-cycloalkylene, then Rg-L is preferably Rg-alkylene-cycloalkylene-.

The phrase “without surface treatment” or “without performing surface treatment” means that the enrichment of non-reactive polymeric internal wetting agent on the surface, as well as the improvement in wettability of the lens surface of the present invention, is achieved without the need for separate treatment of the external surfaces of the lens to improve wettability. Surface treatment may include plasma treatment and coating. Coatings that impart properties other than improved wettability to the lens, such as antimicrobial coatings or the application of color or other cosmetic enhancement, are not considered surface treatments.

The term "surface" when used with respect to the presence of a non-reactive polymeric wetting agent means the outer region of the lens, for example, the region that can be analyzed using ATR infrared spectroscopy. Said surface may include the outer 2 microns of the lens. The term "body", as used in reference to the presence of a non-reactive polymeric wetting agent in a contact lens, means the entire lens, including its surface.

Unless otherwise stated, ratios, percentages, fractions, etc. are by weight.

Unless otherwise noted, numeric ranges such as in "2 to 10" include numbers that define the range (for example, 2 and 10).

As noted above, in one aspect of the present invention there is provided a silicone hydrogel contact lens that is a reaction product of a reaction mixture containing: a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator, wherein the contact lens has an oxygen permeability of at least about 60 bbl, and wherein the molar ratio in the lens of the polymeric non-reactive internal wetting agent to silicone of the silicone-containing component, without surface treatment, is higher on the surface of the lens than in its body

The molar ratio of polymeric nonreactive internal wetting agent to silicone in the silicone hydrogel contact lenses of the present invention can be at least 1.5 times greater on the surface of the lens than in the body. The molar ratio of polymeric non-reactive internal wetting agent to silicone may be at least 2 times greater, alternatively at least 2.3 times greater, alternatively at least 3 times greater, alternatively at least 3 times greater. 3.5 times more, alternatively at least 4 times more, alternatively at least 4.9 times more, alternatively at least 6 times more, alternatively at least 7 times more more, alternatively at least 7 times more, alternatively at least 9 times more on the surface of the lens than in its body. This and other component ratios can be measured using various methods. A typical method is described in the examples. The method uses infrared spectroscopy in both attenuated total internal reflection (ATR) and transmission modes to measure the relative amounts of the constituent molecules of the lens on the surface and in the body. In this method, silicone is identified by the vibrational pattern of silicone in the infrared spectrum of the material, which will be clear to those skilled in the art.

If silicone hydrogel lenses are made from materials containing (meth)acrylate groups, such groups are clearly visible under IR spectroscopy. Thus, in the presence of (meth)acrylate groups, the increased concentration of polymeric non-reactive internal wetting agent on the surface compared to the body can also be expressed as the molar ratio of polymeric non-reactive internal wetting agent to (meth)acrylates. As a result, contact lenses of the present invention made by such a method can have a molar ratio of polymeric nonreactive internal wetting agent to (meth)acrylate groups in the lens, without surface treatment, that is higher on the surface of the lens than in the body. For example, the molar ratio of polymeric non-reactive internal wetting agent to (meth)acrylates may be at least 1.5 times greater, alternatively at least 2 times greater, alternatively at least 2.5 times greater, alternatively at least 3 times more, alternatively at least 3.5 times more, alternatively at least 4 times more, alternatively at least 4.5 times more, alternatively alternatively at least 6 times more, alternatively at least 7 times more, alternatively at least 8 times more, alternatively at least 9 times more on the surface of the lens than in its body.

At the same time, as the concentration of the polymeric nonreactive internal wetting agent increases on the surface of the lens, the other constituent molecules can remain substantially uniformly distributed over the entire surface of the lens. For example, the hydrophilic portions of the polymer network, other than the polymer nonreactive internal wetting agent, which are introduced by the hydrophilic component (eg, hydroxyethyl methacrylate) of the reactive monomer mixture may be substantially uniformly distributed within the lens. As an example, the molar ratio of hydrophilic constituent molecules other than the polymeric nonreactive internal wetting agent to silicone in the silicone hydrogel contact lenses of the present invention may be no more than 1.2 times, or alternatively no more than 1.1 times more on the surface of the lens than in its body. As a further example, the molar ratio of hydrophilic constituent molecules other than the polymeric nonreactive internal wetting agent to silicone in a silicone hydrogel contact lens of the present invention may be approximately the same on the surface of the lens as in the body thereof.

As described above, the silicone hydrogel contact lenses of the present invention, by enriching the non-reactive polymeric internal wetting agent on the surface of the lens, provide a number of desirable properties. One such property is improved surface wettability (measured by dynamic contact angle). For example, it has been discovered that silicone hydrogel contact lenses, which are the product of a reaction mixture containing only 2% wt. or just 2.5% wt. non-reactive polymeric internal wetting agent exhibit a dynamic contact angle (Wilhelmy plate method), without surface treatment, of 75º or less, 70º or less, 60º or less, 50º or less, 45º or less, 40º or less, 35º or less, 30º or less, 25º or less, or 22º or less. In contrast, as demonstrated in the examples, lenses made from reactive mixtures containing the same amount of non-reactive polymeric internal wetting agent, but the wetting agent is not enriched at the surface, exhibit a contact angle greater than 75º (without surface treatment).

The silicone hydrogel contact lenses of the present invention contain a reaction product of a reaction mixture that contains a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator.

Silicone-containing components suitable for use in the invention contain one or more polymerizable compounds, each compound independently containing at least one polymerizable group, at least one siloxane group and one or more linking groups connecting the polymerizable group(s). s) with siloxane group(s). Silicone-containing components may, for example, contain from 1 to 220 siloxane repeating units, such as those described below. The silicone-containing component may also contain at least one fluorine atom.

The silicone-containing component may contain: 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 contain: one or more polymerizable groups that are independently (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinylamide, O-vinyl carbamate, O-vinyl carbonate, vinyl group or mixtures of the 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 contain: one or more polymerizable groups, which are independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinylamide, styryl, or mixtures thereof; 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 contain: one or more polymerizable groups, which are independently (meth)acrylate, (meth)acrylamide, or mixtures thereof; 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 contain one or more polymerizable groups of formula A:

wherein:

at least one R ^A represents a group of the formula R _g -L-, where R _g represents a polymerizable group and L represents a linking group, and each of the remaining R ^A independently represents:

(a) R _g -L-,

(b) C ₁ -C ₁₆ alkyl, optionally substituted with one or more of hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halogen, phenyl, benzyl, or combinations thereof,

(c) C ₃ -C ₁₂ cycloalkyl, optionally substituted with one or more of alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, amido, carbamate, carbonate, halogen, phenyl, benzyl or combinations thereof,

(d) C ₆ -C ₁₄ aryl, optionally substituted with one or more of alkyl, hydroxy, amino, amido, oxa, carboxy, alkylcarboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halogen, phenyl, benzyl, or combinations thereof,

(e) halogen,

(f) alkoxy, cyclic alkoxy or aryloxy,

(g) siloxy,

(h) alkyleneoxyalkyl or alkoxyalkyleneoxyalkyl, such as polyethyleneoxyalkyl, polypropyleneoxyalkyl or poly(ethyleneoxysopropyleneoxyalkyl), or

(i) a monovalent siloxane chain containing from 1 to 100 siloxane repeating units, optionally substituted with alkyl, alkoxy, hydroxy, amino, oxa, carboxy, alkylcarboxy, alkoxy, amido, carbamate, halogen, or combinations thereof; And

n is from 0 to 500, or from 0 to 200, or from 0 to 100, or from 0 to 20, and it is assumed that if n is different from 0, then n represents a distribution having a mode equal to the stated value. If n is 2 or more, the SiO units may contain the same or different R ^A substituents, and if different R ^A substituents are present, the n groups may have a random or block configuration.

In Formula A, each of the three ^RAs may contain a polymerizable group, alternatively, each of the two ^RAs may contain a polymerizable group, or alternatively, one ^RA may contain a polymerizable group.

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

Table A

1 monomethacryloxypropyl and mono-n-butyl terminated polydimethylsiloxanes (mPDMS) (preferably containing 3 to 15 SiO repeating units) 2 polydimethylsiloxane with monoacryloxypropyl and mono-n-butyl end groups 3 polydimethylsiloxane with mono(meth)acryloxypropyl and mono-n-methyl end groups 4 polydiethylsiloxane with mono(meth)acryloxypropyl and mono-n-butyl end groups 5 polydiethylsiloxane with mono(meth)acryloxypropyl and mono-n-methyl end groups 6 mono(meth)acrylamidoalkylpolydialkylsiloxanes 7 monoalkylpolydiarylsiloxanes with mono(meth)acryloxyalkyl end groups 8 3-methacryloxypropyltris(trimethylsiloxy)silane (TRIS) 9 3-methacryloxypropylbis(trimethylsiloxy)methylsilane 10 3-methacryloxypropylpentamethyldisiloxane eleven mono(meth)acrylamidoalkylpolydialkylsiloxanes 12 mono(meth)acrylamidoalkylpolydimethylsiloxanes 13 N-(2,3-dihydroxypropane)-N’-(propyltetra(dimethylsiloxy)dimethylbutylsilane)acrylamide 14 N-[3-tris(trimethylsiloxy)silyl]propylacrylamide (TRIS-Am) 15 2-Hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]propyl methacrylate (SiMAA) 16 2-hydroxy-3-methacryloxypropyloxypropyltris(trimethylsiloxy)silane 17
mono(2-hydroxy-3-methacryloxypropyl)propylether and mono-n-butyl terminated polydimethylsiloxanes (OH-mPDMS) (containing 4 to 30, or 4 to 20, or 4 to 15 SiO repeating units) 18 19 20 21 22 23 24

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

Table B

25 26
p is from 1 to 10 27
p is between 5 and 10 28 29 thirty 1,3-bis[4-(vinyloxycarbonyloxy)but-1-yl]tetramethyldisiloxane 31 3-(vinyloxycarbonylthio)propyl[tris(trimethylsiloxy)silane] 32 3-[tris(trimethylsiloxy)silyl]propylallylcarbamate 33 3-[tris(trimethylsiloxy)silyl]propylvinylcarbamate 34 tris(trimethylsiloxy)silylstyrene (Styryl-TRIS) 35 36 37 38 39 40 41

The silicone-containing component may be a hydroxyl-functionalized silicone-containing component. It is possible to use mixtures of silicone-containing components. For example, a suitable mixture may include a hydroxyl-functionalized silicone component and a non-hydroxyl-functionalized silicone component. By way of example, suitable mixtures may include, but are not limited to: a mixture of mono-(2-hydroxy-3-methacryloxypropyloxy)-propyl and mono-n-butyl terminated polydimethylsiloxane (OH mPDMS) of varying molecular weights, such as an OH mPDMS mixture, containing 4 and 15 repeating SiO units; a mixture of OH mPDMS with different molecular weights (for example, containing 4 and 15 SiO repeating units) together with a silicone cross-linker such as bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (ac-PDMS); a mixture of 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]propyl methacrylate (SiMAA) and polydimethylsiloxane (mPDMS) terminated with monomethacryloxypropyl and mono-n-butyl groups, such as mPDMS 1000.

Silicone-containing components for use in the present invention may have an average molecular weight of from about 400 to about 4000 daltons.

The silicone-containing component(s) may be included in the mixture in an amount of up to about 95 wt.%, from about 10 to about 80 wt.%, from about 20 to about 70 wt.%. from the total content of reactive components in the reaction mixture (except for diluents).

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

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)acrylamides), 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, glycerin methacrylate, polyethylene glycol monomethacrylate, (meth)acrylic acid, vinyl acetate, acrylonitrile and mixtures thereof.

Hydrophilic monomers can also be ionic, including anionic, cationic, zwitterionic, betaine, and mixtures thereof. Non-limiting examples of such charged monomers include (meth)acrylic acid, N-[(ethenyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropanoic acid (ACA1), 5-acrylamidopentanoic acid (ACA2), 3-acrylamido -3-methylbutanoic acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q-salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)-N, N -dimethyl-3-[(1-oxo-2-propen-1-yl) amino]-, internal salt (СBT), 1-propanaminium, N, N-dimethyl-N-[3-[(1-oxo- 2-propen-1-yl) amino]propyl]-3-sulfo-, internal salt (SBT), 3,5-dioxa-8-aza-4-phosphonaundec-10-en-1-amine, 4-hydroxy- N, N,N-trimethyl-9-oxo-, internal salt, 4-oxide (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 (MAPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio )propane-1-sulfonate (APDAPS) and methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

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

Non-limiting examples of hydrophilic monomers of O-vinylcarbamates and O-vinylcarbonates include N-2-hydroxyethylvinylcarbamate and N-carboxy-β-alanine N-vinyl ester. Additional examples of hydrophilic vinyl carbonate or vinyl carbamate monomers are described in US Pat. No. 5,070,215. Hydrophilic oxazolone monomers are described in US Pat. No. 4,910,277.

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

Hydrophilic monomers may also be macromers or prepolymers of linear or branched chain poly(ethylene glycol), poly(propylene glycol), or random or block copolymers of ethylene oxide and propylene oxide having polymerizable moieties such as (meth)acrylates, styrene, vinyl ethers, (meth)acrylamides, N-vinyl amides, etc. The macromer of such polyethers has one polymerizable group; prepolymers may have two or more polymerizable groups.

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 mixtures of DMA and HEMA. Other suitable hydrophilic monomers will be apparent to those skilled in the art.

In general, there are no particular restrictions on the amount of hydrophilic monomer present in the reaction mixture. The amount of hydrophilic monomer can be selected based on the desired characteristics of the resulting hydrogel, including water content, transparency, wettability, protein absorption, etc. Wettability can be measured using contact angle. Desirable contact angles are less than about 100˚, less than about 80˚ and less than about 60˚. The hydrophilic monomer may be present in an amount ranging from, for example, about 0.1 to about 100 wt%, alternatively ranging from about 1 to about 80 wt%, alternatively ranging from about 5 to about 65 wt%. wt., in another embodiment in the range from about 40 to about 60% wt. or in another embodiment in the range from about 55 to about 60% of the mass. of the total mass of reactive components in the reaction monomer mixture.

The reaction mixture of the present invention contains a non-reactive polymeric internal wetting agent. The non-reactive polymeric internal wetting agent may be a hydrophilic polymer. The non-reactive polymeric internal wetting agent may have a weight average molecular weight of at least about 50,000 daltons, alternatively at least about 100,000 daltons, alternatively at least about 150,000 daltons; or from about 150,000 to about 2,000,000 daltons; or from about 300,000 daltons to about 1,800,000 daltons. Higher molecular weight polymers may be used if they are compatible with the reaction monomer mixture.

Alternatively, the molecular weight of non-reactive polymeric internal wetting agents can be expressed using a K-value based on kinematic viscosity measurements as described in Encyclopedia of Polymer Science and Engineering, N-Vinyl Amide Polymers, Second edition, Vol. 17, pgs. 198-257, John Wiley & Sons Inc. In such a case, non-reactive polymeric internal wetting agents are preferred having K values greater than about 46, and in one embodiment of the present invention from about 46 to about 150. Also preferred are K values from about K60 to about K120, alternatively from about K80 to about K100 or alternatively about K90.

The amount of non-reactive polymeric internal wetting agent that can be added to the reactive monomer mixture of the present invention may vary depending on the other components used and the desired properties of the resulting product. For example, a non-reactive polymeric internal wetting agent may be included in amounts of about 0.5% by weight. up to about 35% of the mass; from about 1% wt. up to about 20% wt.; from about 1% wt. up to about 15% wt.; from about 2% wt. up to about 15 percent; or from about 2 to about 12 percent, all based on the total weight of all reactive components. The amount of non-reactive polymeric internal wetting agent can range from about 1% by weight. up to about 10% wt. based on the total mass of all reactive components.

Non-reactive polymeric internal wetting agents that can be used in the present invention include, but are not limited to, homopolymers, random copolymers, diblock copolymers, triblock copolymers, segmented block copolymers, graft copolymers, and mixtures thereof. Non-limiting examples of non-reactive polymeric internal wetting agents include polyamides, polyesters, polylactones, polyimides, polylactams, polyethers, polyacids in the form of homopolymers and copolymers obtained by free radical polymerization of the corresponding monomers, including 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 polymeric internal wetting agents can be made from any hydrophilic monomer, including those listed herein

Suitable non-reactive polymeric internal wetting agents include, but are not limited to, polyamides. As used herein, the term “polyamide” refers to polymers and copolymers containing repeating units containing amide groups. The polyamide may contain cyclic amide groups, acyclic amide groups, and combinations thereof, and may be any polyamide known to those skilled in the art. Acyclic polyamides contain side amide groups and are able to associate with hydroxyl groups. Cyclic polyamides contain cyclic amide groups and are capable of association with hydroxyl groups.

Examples of suitable acyclic polyamides include polymers and copolymers containing repeating units of formulas G1 and G2:

Formula G1

Formula G2

where X represents a direct bond, -(CO)- or -(CONHR ₄₄ )-, and R ₄₄ represents a C ₁ -C ₃ alkyl group; R ₄₀ is selected from H, substituted or unsubstituted C ₁ -C ₄ straight or branched chain alkyl groups; R ₄₁ is selected from H, substituted or unsubstituted C ₁ -C ₄ straight or branched chain alkyl groups, amino groups containing not more than two carbon atoms, amide groups containing not more than four carbon atoms, and alkoxy groups containing not more than two atoms carbon; R ₄₂ is selected from H, substituted or unsubstituted C ₁ -C ₄ straight or branched chain alkyl groups; or methyl, ethoxy, hydroxyethyl and hydroxymethyl; R ₄₃ is selected from H, substituted or unsubstituted C ₁ -C ₄ straight or branched chain alkyl groups; or methyl, ethoxy, hydroxyethyl and hydroxymethyl; wherein the number of carbon atoms in R ₄₀ and R ₄₁ taken together is 8 or less, including 7, 6, 5, 4, 3 or less; and where the number of carbon atoms in R ₄₂ and R ₄₃ taken together is 8 or less, including 7, 6, 5, 4, 3 or less. The number of carbon atoms in R ₄₀ and R ₄₁ taken together may be 6 or less, or 4 or less. The number of carbon atoms in R ₄₂ and R ₄₃ taken together may be 6 or less. As used herein, substituted alkyl groups include alkyl groups substituted with amino, amide, ether, hydroxyl, carbonyl, carboxyl groups, or combinations thereof.

R ₄₀ and R ₄₁ may be independently selected from H, substituted or unsubstituted C ₁ -C ₂ alkyl groups. X may be a direct bond, and R ₄₀ and R ₄₁ may be independently selected from H, substituted or unsubstituted C ₁ -C ₂ alkyl groups. R ₄₂ and R ₄₃ may be independently selected from H, substituted or unsubstituted C ₁ -C ₂ alkyl groups, methyl, ethoxy, hydroxyethyl and hydroxymethyl.

Acyclic polyamides may contain a majority of repeat units of Formula LV or Formula LVI, or acyclic polyamides may contain at least 50 mole percent of repeat units of Formula G or Formula G1, including at least 70 mole percent and at least 80 mole percent. Specific examples of the repeating units of Formula G and Formula G1 include repeating units derived from N-vinyl-N-methylacetamide, N-vinylacetamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N-vinyl -2-methylpropionamide, N-vinyl-N, N'-dimethylurea, N, N-dimethylacrylamide, methacrylamide and acyclic amides of formulas G2 and G3:

Formula G2

Formula G3

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

Formula G4

where R ₄₅ represents a hydrogen atom or a methyl group; where f is equal to an integer from 1 to 10; where X represents a direct bond, -(CO)- or -(CONHR ₄₆ )-, where R ₄₆ represents a C ₁ -C ₃ alkyl group. In the LIX formula, f can be 8 or less, including 7, 6, 5, 4, 3, 2, or 1. In the G4 formula, f can be 6 or less, including 5, 4, 3, 2, or 1. In the G4 formula, f can be 6 or less, including 5, 4, 3, 2, or 1. 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. If X is a direct relationship, f can be 2. In such In cases, the cyclic polyamide may be polyvinylpyrrolidone (PVP).

Cyclic polyamides may contain 50 mole percent or more of a repeating unit of formula G4, or cyclic polyamides may contain at least 50 mole percent of a repeating unit of formula G4, including at least 70 mole percent, and at least 80 mole percent.

Polyamides can also be copolymers containing repeating units of cyclic and acyclic amides. Additional repeating units can be formed from monomers selected from hydroxyalkyl(meth)acrylates, alkyl(meth)acrylates or other hydrophilic monomers, and siloxanes substituted with (meth)acrylates. Any of the monomers mentioned above as suitable hydrophilic monomers can be used as a comonomer to form additional repeating units. Specific examples of additional monomers that can be used to form polyamides include 2-hydroxyethyl(meth)acrylate, vinyl acetate, acrylonitrile, hydroxypropyl(meth)acrylate, methyl(meth)acrylate and hydroxybutyl(meth)acrylate, dihydroxypropyl(meth)acrylate, polyethylene glycol monomer (meth)acrylate, etc., and mixtures thereof. Ionic monomers can also be introduced. Examples of ionic monomers include (meth)acrylic acid, N-[(ethenyloxy)carbonyl]-β-alanine (VINAL, CAS number 148969-96-4), 3-acrylamidopropionic acid (ACA1), 5-acrylamidopentanoic acid (ACA2), 3-acrylamido-3-methylbutanoic acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)- N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, internal salt (CBT, carboxybetaine; CAS 79704-35-1), 1-propanaminium, N,N-dimethyl -N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-, internal salt (SBT, sulfobetaine, CAS 80293-60-3), 3,5-dioxa -8-aza-4-phosphondec-10-en-1-amine, 4-hydroxy-N, N,N-trimethyl-9-oxo-, internal salt, 4-oxide (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).

The monomer reaction mixture may contain both an acyclic polyamide and a cyclic polyamide or copolymers thereof. The acyclic polyamide may be any of the acyclic polyamides or copolymers thereof described herein, and the cyclic polyamide may be any of the cyclic polyamides or copolymers thereof described herein. The polyamide may be selected from the group consisting of polyvinylpyrrolidone (PVP), polyvinylmethacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof. The polyamide may be a mixture of PVP (eg, PVP K90) and PVMA (eg, having an M _w of approximately 570 kDa).

Preferred non-reactive polymeric internal wetting agents include polyamides, such as those selected from polyvinylpyrrolidone (PVP), polyvinylmethacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and the like. copolymers and mixtures. A particularly preferred non-reactive polymeric internal wetting agent is PVP, more preferably PVP K90. Another preferred wetting agent is PVMA.

Non-reactive polymeric internal wetting agents, such as polyamides, for use in the present invention are non-polymerizable and are therefore embedded in silicone hydrogels in the form of semi-interpenetrating networks. Polyamides are entrapped or physically held within silicone hydrogels. Silicone hydrogels may also contain polymerizable internal wetting agents such as polymerizable polyamides, for example polyamide macromers or prepolymers, in which case they are covalently incorporated into the silicone hydrogels. Mixtures of polymerizable and non-polymerizable polymer wetting agents can also be used.

The reaction mixture of the present invention contains a polymerization initiator. Preferably, the polymerization initiator is a thermal initiator. Thermal initiators decompose at elevated temperatures to form free radicals. Typical examples are azo compounds such as 1,1'-azobisisobutyronitrile and 4,4'-azobis(4-cyanovaleric acid). The amount of polymerization initiator is not particularly important and may range, for example, from about 0.1 to about 2.0% by weight. based on the total mass of all reactive components in the reaction mixture.

The reaction mixture may contain additional components such as, but not limited to, cross-linking agents, diluents, initiators, UV absorbers, visible light absorbers, photochromic compounds, drugs, nutraceuticals, antimicrobial agents, dyes, pigments, copolymerizable dyes and non-polymerizable dyes, and also their combinations.

As noted, one or more cross-linking agents, also referred to as cross-linking monomers, multifunctional macromers and prepolymers, may be included in the reaction mixture. Crosslinkers may be selected from bifunctional crosslinkers, trifunctional crosslinkers, tetrafunctional crosslinkers, and mixtures thereof, including silicone and non-silicon crosslinkers. Non-silicone-containing crosslinkers include ethylene glycol dimethacrylate (EGDMA), tetraethylene glycol dimethacrylate (TEGDMA), trimethylolpropane trimethacrylate (TMPTMA), triallyl cyanurate (TAC), glycerol methacrylate, methacryloxyethyl vinyl carbonate (HEMAVc), allyl methacrylate, methylene bisacrylamide (MBA) and polyethylene glycol dimethacrylate, wherein polyethylene glycol has a molecular weight of up to approximately 5000 daltons. Crosslinking agents can be used in varying amounts, for example, from about 0.000415 to about 0.0156 moles per 100 grams of reactive components in the reaction mixture. Examples of hydrophilic monomers and macromers that can act as crosslinkers and do not require additional crosslinkers into the reaction mixture include (meth)acrylate- and (meth)acrylamide-terminated polyesters. Other cross-linking agents are known to those skilled in the art that can be used to prepare the silicone hydrogels of the present invention.

It may be desirable to select crosslinking agents with the same reactivity as one or more other reactive components in the composition. In some cases, it may be desirable to select a mixture of crosslinkers with different reactivity to control some physical, mechanical or biological property of the resulting silicone hydrogel. The structure and morphology of silicone hydrogel can also be influenced by the diluent(s) and polymerization conditions used.

Multifunctional silicone-containing components, including macromers, crosslinkers, and prepolymers, can also be used to further increase elastic modulus while maintaining tensile strength. Silicone-containing crosslinking agents can be used alone or in combination with other crosslinking agents. An example of a silicone-containing component that acts as a cross-linking agent and does not require the addition of additional cross-linking agents to the reaction mixture is α,ω-bismethacryloxypropyl polydimethylsiloxane. Another example is bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (ac PDMS).

Cross-linking agents that have rigid chemical structures and polymerizable groups that participate in free radical polymerization can also be used. Non-limiting examples of suitable rigid structures include crosslinkers containing a phenyl and benzyl ring, 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. Rigid cross-linking agents may be included in amounts between about 0.5 and about 15%, or 2-10 or 3-7, based on the total weight of all reactive components. The physical and mechanical properties of the silicone hydrogels of the present invention can be optimized for a particular application by adjusting the components of the reaction mixture.

Non-limiting examples of silicone crosslinkers also include the multifunctional silicone components described in Table A above.

Classes of suitable diluents for silicone hydrogel reaction mixtures include alcohols having 2 to 20 carbon atoms, amides having 10 to 20 carbon atoms derived from primary amines, and carboxylic acids having 8 to 20 carbon atoms. Diluents may be primary, secondary or tertiary alcohols.

Essentially, the reactive components are mixed with a diluent to form a reaction mixture. Suitable diluents are known to those skilled in the art. Suitable diluents for silicone hydrogels are described in WO 03/022321 and US 6020445, the description of which is incorporated herein by reference.

Classes of suitable diluents for silicone hydrogel reaction mixtures include alcohols having 2 to 20 carbon atoms, amides having 10 to 20 carbon atoms derived from primary amines, and carboxylic acids having 8 to 20 carbon atoms. Primary and tertiary alcohols can be used. Preferred classes include alcohols having 5 to 20 carbon atoms and carboxylic acids having 10 to 20 carbon atoms.

Specific diluents that may be used include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropanol, 3,7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-octanol, 1-pentanol, 2 -pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, tert-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2- propanol, 1-propanol, ethanol, 2-ethyl-1-butanol, (3-acetoxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane, 1-tert-butoxy-2-propanol, 3,3-dimethyl-2-butanol , tert-butoxyethanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, 2-(diisopropylamino)ethanol, mixtures thereof, etc. Examples of amide diluents include N, N dimethyl propionamide and dimethyl acetamide.

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-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, mixtures thereof, etc.

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-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, 3,3 -dimethyl-2-butanol, 2-octyl-1-dodecanol, mixtures thereof, etc.

As such, there are no special restrictions on the amount of diluent present, if diluent is present. If a diluent is used, it may be present in an amount ranging from about 2 to about 70% by weight, including in the range from about 5 to about 50% by weight, and in the range from about 15 to about 40% by weight. of the total mass of reaction mixtures (including reactive and non-reactive formulas). Mixtures of diluents may be used.

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

The reaction mixture may contain: a hydrophilic component selected from DMA, HEMA and mixtures thereof; silicone-containing component selected from 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]propyl methacrylate (SiMAA), monomethacryloxypropyl- and mono-n-butyl-terminated polydimethylsiloxane (mPDMS), mono-terminated polydimethylsiloxane -(2-hydroxy-3-methacryloxypropyloxy)-propyl and mono-n-butyl groups (OH-mPDMS) and mixtures thereof; a non-reactive polymeric internal wetting agent (preferably polyamide, more preferably PVP or PVMA); and a polymerization initiator. For the hydrophilic component, mixtures of DMA and HEMA are preferred. For the silicone component, mixtures of SiMAA and mPDMS are preferred.

The reaction mixture may contain: a hydrophilic component containing a mixture of DMA and HEMA; a silicone-containing component containing an OH-mPDMS mixture having 2 to 20 repeat units (preferably a mixture having 4 to 15 repeat units). a non-reactive polymeric internal wetting agent (preferably polyamide, more preferably PVP or PVMA); and a polymerization initiator. The reaction mixture preferably further contains a silicone-containing cross-linking agent such as ac-PDMS.

The reaction mixture may contain: from about 1 to about 15 wt.%. a non-reactive polymeric internal wetting agent (preferably a polyamide, for example, an acyclic polyamide, a cyclic polyamide or mixtures thereof); polymerization initiator; at least one first monofunctional hydroxyl-substituted poly(disubstituted siloxane) having from 4 to 8 siloxane repeating units (for example, OH-mPDMS, where n is from 4 to 8, preferably n is 4); at least one second hydroxyl poly(siloxane) being a monofunctional hydroxyl poly(siloxane) having 10 to 200 or 10 to 100 or 10 to 50 or 10 to 20 siloxane repeat units (e.g., OH-mPDMS, where n is from 10 to 200 or 10-100, or 10-50, or 10-20, or preferably n is 15); from about 5 to about 35% of the mass. at least one hydrophilic monomer; and in some cases, a multifunctional hydroxyl poly(disubstituted siloxane) having from 10 to 200 or from 10 to 100 siloxane repeating units (eg, ac-PDMS). The first monofunctional hydroxyl poly(disubstituted siloxane) and the second hydroxyl substituted poly(disubstituted siloxane) are preferably present in concentrations providing a ratio of the mass fraction of the first monofunctional hydroxyl substituted poly(disubstituted siloxane) to the mass fraction of the second hydroxyl substituted poly(disubstituted siloxane) equal to 0.4-1 .3 or 0.4-1.0.

The reaction mixture can be polymerized in 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 on the surface of the lens. To achieve such enrichment, it is preferable to polymerize the reaction mixture to form a silicone hydrogel contact lens under thermal polymerization conditions. In particular, it has been found that by selecting a specific temperature range, it is possible to obtain silicone hydrogel contact lenses, which form the subject of the present invention. As discussed above, such lenses provide more efficient use of the wetting agent by placing the agent where it is needed, resulting, for example, in improved surface wettability at substantially the same total wetting agent concentration as existing lenses. Or, surface-enriched lenses may allow the use of less wetting agent to achieve substantially the same wettability as existing lenses, which in turn may simplify the manufacturing process and/or reduce costs.

The selected thermal polymerization conditions of the present invention also provide a more efficient polymerization process. In particular, it has further been found that under the thermal polymerization conditions described herein, the overall conversion of the polymerizable components of the reaction mixture into polymer is significantly optimized. For example, after polymerization of the reaction mixture, but before extraction, contact lenses made according to the methods of the present invention may contain less unpolymerized polymerizable components than lenses made by other methods, including other thermal polymerization methods. For example, the lens may contain no more than 0.3 wt.%. unpolymerized polymerizable components (after polymerization, but before extraction).

The present invention provides a method for manufacturing a contact lens. The method includes (a) obtaining a reaction mixture containing a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; as well as a polymerization initiator; and (b) polymerizing the reaction mixture to form a contact lens; In this case, this method is implemented under such conditions that the molar ratio of the polymer non-reactive internal wetting agent to silicone, without surface treatment, is higher on the surface of the lens than in its body. Preferably, the polymerization conditions may be thermal polymerization conditions. A preferred method includes: (a) preparing a reaction mixture containing a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; as well as a polymerization initiator; (b) polymerizing the reaction mixture under thermal polymerization conditions to form a contact lens; and (c) extracting the contact lens to remove unreacted components, wherein the thermal polymerization conditions in step (b) include polymerization at a temperature of from 60 to 120 degrees Celsius.

The reaction mixture (including additional components such as diluents) can be placed in a mold having the geometric contours of the finished contact lenses; after placement, the reaction mixture is polymerized under thermal polymerization conditions at a temperature of 60 to 120 degrees Celsius, as described above. The thermal polymerization temperature may be at least 65 degrees Celsius, alternatively at least 70 degrees Celsius, alternatively at least 75 degrees Celsius, alternatively at least 80 degrees Celsius, alternatively at least 85 degrees Celsius Celsius, alternatively at least 86 degrees Celsius, or alternatively at least 87 degrees Celsius. The thermal polymerization temperature may be up to 115 degrees Celsius, alternatively up to 110 degrees Celsius, alternatively up to 105 degrees Celsius, alternatively up to 100 degrees Celsius, alternatively up to 95 degrees Celsius, alternatively up to 94 degrees Celsius, or alternatively up to 93 degrees Celsius. The thermal polymerization temperature can be from 85 degrees Celsius to 95 degrees Celsius or from 87 degrees Celsius to 93 degrees Celsius. The thermal polymerization temperature can be 90 degrees Celsius.

The reaction mixture can be polymerized for a sufficient time to achieve the desired level of conversion. Preferably, the reaction mixture is polymerized for a sufficient time to achieve a conversion of at least 90 mole percent, or at least 95 mole percent conversion, or at least 98 mole percent conversion, or at least 99 mole percent conversion, or at least at least 99.8 mole percent conversion of the polymerizable components in the reaction mixture into a polymer. As an example, the polymerization time may be from 20 minutes to 90 minutes or from 30 minutes to 70 minutes. Preferably, the polymerization time is at least 30 minutes, or at least 45 minutes, or at least 60 minutes.

After polymerization, the lens may be subjected to extraction to remove unreacted components, after which the lens is removed from the mold. Extraction can be carried out using conventional extractants such as organic solvents such as alcohols, or can be carried out using aqueous solutions.

Aqueous solutions are solutions containing water. The aqueous solutions of the present invention may contain at least about 20 wt.%. water or at least approximately 50% of the mass. water, or at least approximately 70% of the mass. water, or at least about 95% of the mass. water. Aqueous solutions may also include additional water-soluble formulas such as inorganic salts or release agents, wetting agents, anti-friction additives, drug and nutraceutical formulas, combinations thereof, etc. Release agents are compounds or mixtures of compounds that, when combined with water, reduce the time required to remove a contact lens from a mold compared to the time required to remove such a lens using an aqueous solution that does not contain a release agent. Aqueous solutions may not require special handling such as cleaning, recycling or special disposal procedures.

Extraction may be accomplished, for example, by immersing the lens in an aqueous solution or by exposing the lens to a stream of an aqueous solution. The extraction may also include, for example, one or more of: heating the aqueous solution; stirring the aqueous solution; increasing the level of the auxiliary release agent in the aqueous solution to a level sufficient to remove the lens; mechanical or ultrasonic mixing of the lens; and introducing at least one leaching or extraction aid into the aqueous solution to a level sufficient to facilitate adequate removal of unreacted components from the lens. The above processes can be carried out sequentially or continuously with or without the additional effect of heating, stirring or both.

Physical agitation may be required to facilitate leaching and recovery. For example, the portion of the mold to which the finished lens is attached may be subject to vibration or back-and-forth movement within the aqueous solution. Other methods may involve passing ultrasonic waves through an aqueous solution.

The lenses can be sterilized by known methods such as, but not limited to, autoclaving.

The silicone hydrogel contact lenses according to the present invention preferably have the following properties. All values given are preceded by the modifier “approximately,” and devices can have any combination of these properties. Properties can be determined by methods known to those skilled in the art, for example, as described in US patent application US20180037690, the contents of which are incorporated herein by reference.

Water concentration, %: at least 20% or at least 25%, and up to 80% or up to 70%

Turbidity: 30% or less or 10% or less

Dynamic contact angle (Wilhelmy plate method): 80° or less, or 75° or less, or 50° or less

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

Oxygen permeability (Dk, barrera): at least 60, or at least 80, or at least 100, or at least 150, or at least 200

Tensile elongation at break: at least 100

The following properties (in addition to those listed above) may also be preferred for ionic silicone hydrogels:

Lysozyme Absorption (µg/lens): at least 100 or at least 150 or at least 500 or at least 700

Polyquaternium Absorbance 1 (PQ1) (%): 15 or less, or 10 or less, or 5 or less

Silicone hydrogel contact lenses made by thermal polymerization as described herein can exhibit a molar ratio of polymeric nonreactive internal wetting agent to silicone on the lens surface that is higher than on the surface of a contact lens having a similar composition but made by photochemical polymerization. For example, the molar ratio of polymeric non-reactive internal wetting agent to silicone on the surface of a lens made by thermal polymerization as described herein can be at least 2.5 times greater, alternatively at least 3 times greater, in alternatively at least 3.5 times larger, or alternatively at least 4 times larger, than on the surface of a contact lens having a similar composition but manufactured by photochemical polymerization. The term “similar composition” means that the components of the reaction mixtures are the same except for the free radical initiator, which may be a photochemical free radical initiator in the case of a photochemically polymerized lens, and a thermal free radical initiator in the case of a thermally polymerized lens.

Silicone hydrogel contact lenses made by thermal polymerization as described herein can exhibit a molar ratio of polymeric nonreactive internal wetting agent to silicone in the contact lens body that is substantially the same as in the body of a contact lens having a similar composition , but made by photochemical polymerization. The term “substantially the same” means that the molar ratio of polymeric nonreactive internal wetting agent to silicone in the thermally polymerized lens body is no more than 1.1 times greater than in the photochemically polymerized lens body. The molar ratio of polymeric nonreactive internal wetting agent to silicone in the thermally polymerized lens body may be the same as in the photochemically polymerized lens body.

The following paragraphs list non-limiting embodiments of the present invention:

1. Silicone hydrogel contact lens, which is a reaction product of a reaction mixture containing a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator, wherein the contact lens has an oxygen permeability of at least about 60 barrels, and in the lens, which is the reaction product of the reaction mixture containing only 2.0% of the mass. or just 2.5% wt. non-reactive polymeric internal wetting agent (based on the total weight of reactive components in the reaction mixture), the lens has a contact angle of 75º or less without surface treatment.

2. The contact lens according to claim 1, characterized in that said contact angle is 70º or less, or 60º or less, or 50º or less, or 45º or less, or 40º or less, or 35º or less, or 30º or less, or 25º or less, or 22º or less.

3. The contact lens according to claim 1 or 2, characterized in that the molar ratio of the polymeric non-reactive internal wetting agent to silicone, without surface treatment, is higher on the surface of the lens than in its body.

4. The silicone hydrogel contact lens according to claim 3, characterized in that the molar ratio of the polymeric non-reactive internal wetting agent to silicone is at least 1.5 times greater, or at least 2 times greater, or at least 2.3 times more, or at least 3 times more, or at least 3.5 times more, or at least 4 times more, or at least 4.9 times more, or at least 6 times more, or at least 7 times more, or at least 7 times more, or at least 9 times more on the surface of the lens than in its body.

5. Silicone hydrogel contact lens according to any one of paragraphs. 1-4, characterized in that said non-reactive polymeric internal wetting agent is a polyamide.

6. Silicone hydrogel contact lens according to any one of paragraphs. 1-5, characterized in that said polyamide is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide and copolymers and mixtures thereof.

7. A method for manufacturing a contact lens, including the following steps:

(a) obtaining a reaction mixture containing a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; as well as a polymerization initiator; And

(b) polymerizing the reaction mixture to form a contact lens;

Moreover, this method is carried out under such conditions that the lens is a reaction product of a reaction mixture containing only 2.0 wt.%. or just 2.5% wt. non-reactive polymeric internal wetting agent (based on the total weight of reactive components in the reaction mixture), and wherein the lens has a contact angle of 75º or less without surface treatment.

8. The method according to claim 7, characterized in that said contact angle is 70º or less, 60º or less, 50º or less, 45º or less, 40º or less, 35º or less, 30º or less, 25º or less, 22º or less.

9. The method according to claim 7 or 8, characterized in that the molar ratio of the polymeric non-reactive internal wetting agent to silicone, without treating the surface of the lens, is higher on the surface of the lens than in its body.

10. The method according to claim 9, characterized in that said molar ratio of polymeric non-reactive internal wetting agent to silicone is at least 1.5 times greater, or at least 2 times greater, or at least 2.3 times more, or at least 3 times more, or at least 3.5 times more, or at least 4 times more, or at least 4.9 times more, or at least 6 times more more, or at least 7 times more, or at least 7 times more, or at least 9 times more on the surface of the lens than in its body.

11. Method according to any one of paragraphs. 7-10, characterized in that the non-reactive polymeric internal wetting agent is a polyamide.

12. Method according to any one of paragraphs. 7-11, characterized in that the non-reactive polymeric internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDM), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, as well as their copolymers and mixtures.

13. Silicone hydrogel contact lens, which is a thermally polymerized reaction product of a reaction mixture containing: a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator, wherein said contact lens has an oxygen permeability of at least about 60 barrels, and wherein said lens has a molar ratio of polymeric non-reactive internal wetting agent to silicone on its surface that is greater than on the surface of a contact lens having a similar composition, but made using photochemical polymerization.

14. The silicone hydrogel contact lens according to claim 13, characterized in that the specified molar ratio of the polymeric non-reactive internal wetting agent to silicone on the surface of the thermally polymerized lens is at least 2.5 times greater, alternatively at least 3 times more, alternatively at least 3.5 times more, or alternatively at least 4 times more, than on the surface of a contact lens having a similar composition but manufactured by photochemical polymerization.

15. Silicone hydrogel contact lens according to any one of paragraphs. 13-14, characterized in that the specified molar ratio of polymeric non-reactive internal wetting agent to silicone in the body of a thermally polymerized lens is essentially the same as in the body of a contact lens having a similar composition, but manufactured using photochemical polymerization.

16. Silicone hydrogel contact lens according to any one of paragraphs. 13-15, characterized in that said non-reactive polymeric internal wetting agent is a polyamide.

17. Silicone hydrogel contact lens according to any one of paragraphs. 13-16, characterized in that said non-reactive polymeric internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide and copolymers thereof, and mixtures.

18. A method for manufacturing a contact lens, which includes the following steps:

(a) obtaining a reaction mixture containing a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; as well as a polymerization initiator;

(b) thermally polymerizing the reaction mixture to form a contact lens; And

(c) extraction of the contact lens to remove non-polymerized components,

wherein said method is carried out under conditions such that the molar ratio of polymeric non-reactive internal wetting agent to silicone on the surface of a contact lens according to the invention is greater than on the surface of a contact lens having a similar composition, but manufactured by photochemical polymerization.

19. The method of claim 18, wherein said molar ratio of polymeric non-reactive internal wetting agent to silicone on the surface of the thermally polymerized lens is at least 2.5 times greater, alternatively at least 3 times greater, alternatively alternatively at least 3.5 times greater, or alternatively at least 4 times greater than the surface of a contact lens having a similar composition but produced by photochemical polymerization.

20. Method according to any one of paragraphs. 18-19, characterized in that the specified molar ratio of polymeric non-reactive internal wetting agent to silicone in the body of a thermally polymerized lens is essentially the same as in the body of a contact lens having a similar composition, but manufactured using photochemical polymerization.

21. Silicone hydrogel contact lens, which is a reaction product of a reaction mixture containing a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator, wherein said contact lens has an oxygen permeability of at least about 60 bbl, and wherein the molar ratio in the lens of polymeric non-reactive internal wetting agent to silicone, without surface treatment, is higher on the surface of the lens than in its body .

22. The silicone hydrogel contact lens according to claim 21, characterized in that the specified molar ratio of the polymeric non-reactive internal wetting agent to silicone is at least 1.5 times greater on the surface of the lens than in its body.

23. Silicone hydrogel contact lens according to any one of paragraphs. 21-22, characterized in that the specified molar ratio of the polymeric non-reactive internal wetting agent to silicone is at least 2.3 times greater on the surface of the lens than in its body.

24. Silicone hydrogel contact lens according to any one of paragraphs. 21-23, characterized in that said non-reactive polymeric internal wetting agent is a polyamide.

25. Silicone hydrogel contact lens according to any one of paragraphs. 21-24, characterized in that said non-reactive polymeric internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide and copolymers thereof, and mixtures.

26. Silicone hydrogel contact lens according to any one of paragraphs. 21-25, characterized in that the lens, which is a reaction product of a reaction mixture containing 2.5 wt.% non-reactive polymeric internal wetting agent, has a contact angle of 75º or less.

27. The silicone hydrogel contact lens according to claim 6, characterized in that said contact angle is 50º or less.

28. A method for manufacturing a contact lens, which includes the following steps:

(a) obtaining a reaction mixture containing a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; as well as a polymerization initiator; And

(b) polymerizing the reaction mixture to form a contact lens;

In this case, this method is implemented under such conditions that the molar ratio of the polymer non-reactive internal wetting agent to silicone, without surface treatment, is higher on the surface of the lens than in its body.

29. The method according to claim 28, characterized in that the specified molar ratio of the polymeric non-reactive internal wetting agent to silicone on the surface of the lens is at least 1.5 times greater than in its body.

30. Method according to any one of paragraphs. 28-29, characterized in that the specified molar ratio of the polymeric non-reactive internal wetting agent to silicone on the surface of the lens is at least 2.3 times greater than in its body.

31. Method according to any one of paragraphs. 28-30, characterized in that said non-reactive polymeric internal wetting agent is a polyamide.

32. Method according to any one of paragraphs. 28-31, characterized in that said non-reactive polymeric internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, as well as their copolymers and mixtures.

33. Method according to any one of paragraphs. 28-32, characterized in that the lens, which is a reaction product of a reaction mixture containing 2.5 wt.% non-reactive polymeric internal wetting agent, has a contact angle of 75º or less.

34. The method according to claim 33, characterized in that said impingement contact angle is 50º or less.

35. Method according to any one of paragraphs. 28-34, characterized in that step (b) includes thermal polymerization of the reaction mixture.

36. The method according to claim 35, characterized in that said thermal polymerization is carried out at a temperature from 60 to 120 degrees Celsius.

37. Method according to any one of paragraphs. 35-36, characterized in that said thermal polymerization is carried out at a temperature from 85 to 120 degrees Celsius.

38. Method according to any one of paragraphs. 28-37, characterized in that after step (b) and before the extraction step to remove unpolymerized components from the contact lens, the contact lens contains no more than 0.3 wt%. non-polymerized polymerizable components.

39. A silicone hydrogel contact lens manufactured using the method according to any one of claims. 28-38.

40. Method of importing silicone hydrogel contact lenses into the country according to any one of paragraphs. 21-27.

41. The method according to claim 40, characterized in that said country is the United States of America.

Some embodiments of the invention will be described in detail in the examples below.

EXAMPLES

Contact lens diameter (DM) was measured using a calibrated Van Keuren micro-optical comparator equipped with Mitutoyo electronic digital micrometer heads. The contact lens was placed concave side down into a crystal cell completely filled with borate-buffered storage solution. The lid was placed on the cell, removing all the air from under it. Subsequently, the cell was placed on the comparator stage and the lens image was focused and aligned so that one edge of the lens touched the center line on the screen. The first edge was marked, the lens was moved along the diameter until the second edge touched the center line on the screen, and the second edge was subsequently marked by pressing the data button again. Typically, two diameter measurements are made and the average is reported in the data tables.

Water content (WC) was measured gravimetrically. The lenses were kept in the storage solution for 24 hours. Each of the three test lenses was removed from the storage solution using a sponge-tipped applicator and placed on blotting pads soaked in the storage solution. Both sides of the lens are blotted with a napkin. Using tweezers, the lenses to be tested were placed on a tared scale and weighed. Two more sets of samples are prepared and weighed. All mass measurements were repeated three times and the average value of the obtained values was used in further calculations. Wet mass is defined as the total mass of the scale pan and wet lenses minus the mass of the scale pan alone.

Dry mass was measured by placing the sample dishes in a vacuum oven, which was preheated to 60 °C, for 30 minutes. Vacuum was applied until the pressure reached at least 1 inch Hg. Art.; Lower pressures are also acceptable. The vacuum valve and pump are turned off and the lenses are dried for at least 12 hours, usually overnight; Open the purge valve to allow dry air or dry nitrogen to enter. The oven is allowed to reach atmospheric pressure. The bowls are removed and weighed. Dry mass is defined as the total mass of the scale pan and dry lenses minus the mass of the scale pan only. The water content of the test lens was calculated as follows: % water content = (wet weight - dry weight) / wet weight × 100. The mean and standard deviation for the water content were calculated and the mean was reported as the percentage of water in the test lens.

The refractive index (RI) of the contact lens was measured using a Leica ARIAS 500 Abbe refractometer in manual mode or a Reichert ARIAS 500 Abbe refractometer in automatic mode with a prism gap of 100 microns. The device was calibrated using deionized water at 20 °C (+/-0.2 °C). The prism assembly was opened and the lens to be tested was placed on the lower prism between the magnetic points closest to the light source. If the lens was dry, a few drops of saline solution were applied to the lower prism. The front curved surface of the lens was placed opposite the lower prism. Then the prism assembly was closed. After adjusting the controls until a shadow line appeared in the sighting field, the refractive index was measured. RI measurements were performed on the five lenses tested. The average RI value calculated from the five measurements was recorded as the refractive index along with its standard deviation.

Haze can be measured by placing a hydrated test lens in a borate-buffered saline solution in a clear glass cell at room temperature on a black flat background, illuminated from below with a fiber optic lamp (Dolan-Jenner PL-900 fiber optic light source with a 0.5 diameter waveguide light). inch) at an angle of 66° perpendicular to the lens cell and shooting from above, perpendicular to the lens cell, a video camera (DVC 1300C:19130 RGB camera or equivalent with a zoom lens) mounted 14 mm above the lens holder. Background scattering was subtracted from the scattering of the test lens by subtracting the image of an empty borate-buffered saline cell (baseline) using EPIX XCAP V 3.8 software. By adjusting the light intensity until it was in the range from 900 to 910 of the average value on the gray scale, we achieved the value of the upper limit of scattering (ground glass). The amount of background scattering was measured using a saline-filled glass cell. The subtracted scattered light image is quantitatively analyzed by integrating over the central 10 mm of the lens and then compared to a ground glass standard. By adjusting the intensity/power settings of the light, we achieved an average gray scale value in the range from 900 to 910 for the frosted glass standard; With these parameters, the average gray scale value for the baseline was in the range of 50-70. The average gray scale value for the baseline and ground glass standard was recorded and used to construct a scale from zero to 100, respectively. In the gray scale analysis, the means and their standard deviations were recorded for baseline, ground glass, and each lens tested. For each lens, a scale value was calculated according to the following equation: the scale value is equal to the average gray scale value (lens minus baseline) divided by the average gray scale value (ground glass minus baseline) and multiplied by 100%. Three to five test lenses were analyzed and the results were averaged and recorded as % haze.

Oxygen permeability (Dk) was measured by a polarographic method essentially described in ISO 9913-1:1996 and ISO 18369-4:2006, but with the following modifications. The measurement was carried out in an environment containing 2.1% oxygen, created by installing nitrogen and air inlets on the test chamber, adjusted to the appropriate gas flow, for example 1800 ml/min nitrogen and 200 ml/min air. The t/Dk value is calculated using the corrected oxygen concentration. A borate buffered saline solution was used. Dark current was measured using a clean humidified nitrogen environment instead of using MMA lenses. Lenses were not used before measurement. Instead of using lenses of different thicknesses (t), measured in centimeters, four lenses were stacked on top of each other. Instead of a flat sensor, a curved sensor with a radius of 7.8 mm was used. Calculations for a sensor with a radius of 7.8 mm and a relative air flow of 10% (v/v) were carried out as follows:

Dk/t = (measured current - dark current) × (2.97 × 10 ^-8 ml O2/(μA-sec-cm ² mmHg)

Edge correction depended on the Dk value of the material.

For all Dk values less than 90 bbl:

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

For Dk values from 90 to 300 bbl:

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

For Dk values greater than 300 bbl:

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

Uncorrected Dk values were calculated from the reciprocal of the slope obtained by linear regression analysis of the data in which the x variable was the central thickness in centimeters and the y variable was the t/Dk value. On the other hand, edge-corrected Dk (EC Dk) values were calculated from the reciprocal of the slope obtained by linear regression analysis of data in which the x variable was the central thickness in centimeters and the y variable was the edge-corrected t/Dk value. edge. The measured Dk values were given in barrels.

Lens wettability was determined using the methods described below. The dynamic contact angle was determined by the Wilhelmy plate method using a Cahn DCA-315 instrument at room temperature and using deionized water as a probe solution (Cahn DCA). The experiment was carried out by immersing a lens sample with known parameters in a storage solution with a known surface tension and measuring with an accurate scale the force caused by wetting on the sample. The contact angle when the storage solution flows onto the lens was determined from the force data obtained when the sample was immersed. The contact angle during drainage was determined in a similar way from the force data obtained when removing the sample from the liquid. The Wilhelmy plate method is based on the following formula: Fg=γρcosθ - B, where F is the wetting force between the liquid and the lens (mg), g is the gravitational acceleration (980.665 cm/sec2), γ is the surface tension of the probe fluid (dynes/cm) , ρ is the fluid/lens meniscus perimeter of the contact lens (cm), θ is the dynamic contact angle (degrees), and B is the hydrostatic lift force (mg). The value of B is zero at zero diving depth. Four test strips were cut from the central area of the contact lens. Each strip was approximately 5 mm wide and was soaked in storage solution. Then, four measurement cycles were carried out with each sample and the results were averaged to obtain the contact angles of the lenses during inflow and runoff. The dynamic contact angles of inflow and outflow are listed in the tables in this order.

Lens wettability can also be determined by the sessile drop method using the KRUSS DSA-100 TM instrument at room temperature using deionized water as a probe solution (seasy drop). Test lenses were rinsed in deionized water to remove any remaining storage solution. Each lens tested was placed on lint-free blotters soaked in storage solution. Both sides of the lens were blotted with a tissue to remove water from the surface without drying the lens. To ensure proper alignment, the lenses were placed "cup" side down on the convex surface of plastic contact lens molds. The plastic casting mold and lens were placed in the holder of the stationary drop device, ensuring proper centering of the syringe. Using DSA 100 drop shape analysis software, a drop of 3–4 μL of deionized water was formed at the end of the syringe, ensuring that the drop of liquid hung without touching the lens. The drop was smoothly lowered onto the surface of the lens by moving the needle down. The needle was retracted immediately after the drop was dispensed. The liquid droplet was allowed to equilibrate on the lens for 5 to 10 seconds, and the contact angle between the droplet image and the lens surface was measured. Typically, three to five lenses were evaluated and the average contact angle was recorded.

The mechanical properties of contact lenses were measured using a tensile testing machine, such as an Instron model 1122 or 5542, equipped with strain gauge controls and pneumatic grippers. The minus one diopter lens is the preferred lens geometry due to the uniform thickness of the central profile. A dumbbell-shaped sample cut from a -1.00 lens, measuring 0.522 inches long, 0.276 inches wide, and 0.213 inches wide at the neck, was mounted in clamps and stretched at a constant tension rate of 2 inches/min until breaking. Before testing, the thickness of the center of the dumbbell-shaped specimen was measured using an electronic thickness gauge. The initial length of the sample (Lo) and the length of the sample at break (Lf) were measured. At least five samples of each composition were measured and the average values were used to calculate the percent tensile elongation at break: percent elongation = ((Lf - Lo) / Lo) × 100. The tensile modulus (M) was calculated as angular coefficient of the initial linear section of the stress-tension curve; The units of elastic modulus are pounds per square inch (psi). Tensile strength (TS) was calculated from the peak load and the initial cross-sectional area: tensile strength=peak load divided by the initial cross-sectional area; The units of tensile strength are psi. Tensile stiffness was calculated from the energy at break and the original volume of the sample: tensile stiffness=energy at break divided by the original volume of the sample; The units of tensile stiffness are inch-lb/ ⁱⁿ³ . Elongation at break (ETB) was also recorded as percentage elongation at break.

PQ1 absorbance level (PQ1) was measured by chromatography. The HPLC analyzer was calibrated using a series of PQ1 standard solutions with concentrations of 2, 4, 6, 8, 12 and 15 μg/ml. The lenses were placed in polypropylene contact lens cases with 3 ml of Optifree Replenish solution or a similar lens solution (PQ1 concentration = 10 micrograms/ml) commercially available from Alcon. We also prepared a control lens case containing 3 ml of solution without the contact lens. Lenses and control solutions were kept at room temperature for 72 hours. From each of the samples and control samples, 1 ml of solution was removed and mixed with trifluoroacetic acid (TFA) (10 μl). Analysis was performed using HPLC/Evaporative Light Scattering Detector (ELSD) and Phenomenex Luna C5 columns (particle size 4.6 mm × 5 mm; 5µ µm) using the following equipment and conditions: Agilent 1200 HPLC analyzer or equivalent with evaporative light scattering detector (ELSD), operating at temperature T=100°C, gain=12, pressure=4.4 bar, filter time constant=3s; ELSD parameters may vary from device to device; using mobile phase A water (0.1% trifluoroacetic acid) and mobile phase B acetonitrile (0.1% trifluoroacetic acid), at a column temperature of 40° C and with an injected sample volume of 100 µl. The elution profile used is shown in Table C. The calibration curve was obtained by plotting peak area versus concentration of PQ1 standard solutions. The concentration of PQ1 in the sample was then calculated by solving the quadratic equation representing the calibration curve. Three lenses were used for each analysis and the results were averaged. PQ1 absorption is given as the percentage loss of PQ1 after soaking with a lens compared to the amount of PQ1 present in the control sample without a lens.

Table C. HPLC Elution Profile

Time (minutes) %A %B Flow rate(ml/min) 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

The amount of cholesterol absorbed by the contact lens was determined by LC-MS (lipids). The lenses were soaked in a cholesterol solution and subsequently extracted with dichloromethane. The dichloromethane extract was evaporated and reconstituted in a heptane/isopropanol mixture, followed by LC-MS analysis. The results are given in micrograms of cholesterol per lens. To increase the accuracy and reliability of the method, an internal standard of deuterated cholesterol was used.

A cholesterol stock solution was prepared by placing 15.0 ± 0.5 milligrams of cholesterol in a 10-mL wide-neck glass volumetric flask, followed by dilution with isopropanol.

A cholesterol lens soak solution was prepared by placing 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 in a 200-mL glass volumetric flask, adding approximately 190 milliliters of phosphate-saline solution to the flask. buffer solution (PBS) and stirring to dissolve the contents. 2 milliliters of cholesterol stock solution was then added and diluted to final volume by adding PBS. The volumetric flask was capped and shaken well. The concentration of the cholesterol solution for soaking lenses was approximately 15 μg/ml. Note. The masses of these components can be adjusted to account for batch-to-batch variations in purity to achieve target concentrations.

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

5 ml of dichloromethane and 100 μl of internal standard solution were added to each scintillation vial with lens. After a minimum of 16 hours of extraction, the settled buoyant liquid was transferred to a 5 mL disposable glass culture tube. The tube was placed in a Turbovap evaporator and the solvent was completely evaporated. Then 1 ml of diluent was added to the culture tubes to redissolve the contents. The above diluent was a mixture of heptane and isopropanol in a ratio of 70: 30 (v/v). The diluent was also the mobile phase. The resulting solution was carefully transferred into an autosampler vial and prepared for LC-MS analysis.

An internal standard stock solution was prepared by dispensing approximately 12.5+2 mg of deuterated cholesterol (2,2,3,4,4,6-d ₆ -cholesterol) into a 25 ml volumetric flask followed by dilution with diluent. The concentration of the internal standard stock solution was approximately 500 μg/ml.

The internal standard solution was prepared by placing 1.0 mL of the internal standard stock solution in a 50 mL volumetric flask and then diluting with diluent to the final volume. The concentration of this intermediate internal standard solution was approximately 10µ µg/ml.

A stock solution of the reference standard was prepared by dispensing approximately 50+5 mg cholesterol into a 100 mL volumetric flask followed by dilution with diluent. The cholesterol concentration of this reference standard stock solution was approximately 500 μg/ml.

Working standard solutions were then prepared according to Table D by placing appropriate quantities of standard solutions into the listed 25 mL, 50 mL, or 100 mL volumetric vials. After adding standard solutions to volumetric flasks, the mixtures were diluted with diluent to the final volume and mixed well.

Table D. Compositions of working standard solutions

Name
worker
Name Volume of internal standard solution (ml) Volume of reference standard stock solution (µL) Finite
volume
(ml) Approximate
cholesterol concentration
(µµg/ml) Standard 1 10 20 100 0.10 Standard 2 5 25 50 0.25 Standard 3 5 50 50 0.50 Standard 4 5 100 50 1.00 Standard 5 2.5 125 25 2.50 Standard 6 2.5 250 25 5.00

The following LC-MS analysis was performed: 6 injections of standard 4 were made to evaluate the suitability of the system. To pass the system suitability test, the relative standard deviation (RSD%) of peak areas for working standards and internal standards must be < 5%, and the RSD% of their peak area ratios must be < 7%. Entered working standards 1-6 to create a calibration curve. The square of the correlation coefficient (r ² ) must be > 0.99. Test samples were injected followed by a control standard (standard 4). The peak area ratio of the control standard should differ by no more than ±10% from the average peak area ratio of the samples injected to verify the suitability of the system.

A calibration curve was constructed by plotting the peak area ratio (reference standard/internal standard) that corresponds to the concentration of each working standard solution. The cholesterol concentration in the sample is calculated by solving a quadratic equation and expressed in micrograms per lens or μg/lens. Typical LC/MS analysis equipment and parameters are listed below and shown in Tables E and F. Instrument settings can be changed with each mass spectrometer setup.

Evaporation conditions in the Turbovap system:

Temperature: 45°C

Time: 30 minutes or more until dry

Gas: nitrogen at 5 psi

HPLC conditions:

HPLC: Thermo Accela HPLC instrument or equivalent

HPLC Column: Agilent Zorbax NH2 (4.6 mm × 150 mm; 5µ µm particle size)

Mobile phase: 70% heptane and 30% isopropanol

Column temperature: 30 °C

Injected sample volume: 25 µl

Flow rate: 1000µ µL/min

Table E. Mass Spectrometry Conditions

Thermo Finnigan TSQ Quantum Ultra MS settings Meaning Ionization APCI Polarity Positive Scan type SIM APCI probe position D Mass (m/z) of reference standards 369.2 Mass (m/z) of internal standards 375.3 Width by mass (m/z) 1.0 Scan time (s) 0.10 Data type center of mass Q3 Peak Width (FWHM) 0.40 Skimmer offset (V) 10

Table F. Settings

Instrument Settings Meaning Discharge current (arbitrary units) 20 Capillary temperature (°C) 240 Evaporator temperature (°C) 500 Displacement of tube with lens (V) 68 Shielding gas pressure (conventional units) 20 Auxiliary gas consumption (conventional units) 15

Fourier transform infrared (FTIR) spectra were measured using a Thermo Scientific Nicolet iS50 instrument. FTIR transmittance spectra were measured by placing a lens in the sample chamber such that the beam passed through the center of the lens, thereby obtaining general information about the volume or composition. Attenuated total internal reflection (ATR) FTIR spectra were measured using a standard ATR diamond crystal (45° incidence angle), thereby providing information on surface composition. Peak height analysis was performed using Thermo Scientific Omnic software.

Sample Preparation Before conducting transmission analysis or ATR FTIR analysis, test lenses were soaked in deuterated saline solution for 1 hour. Exchange of water for deuterium oxide shifts the water bands in the FTIR spectrum to provide a clear spectral region for observing the amide carbonyl region of the spectrum. Deuterated saline solution was prepared according to ISO-10344 using deuterium oxide instead of water. After removal from the deuterated saline solution, the test lens was analyzed using transmittance analysis or ATR analysis. For transmittance analysis, a 4 mm disc was cut from the center of the lens (∼100 μm thick) using biopsy forceps. The cut section of the lens was placed in a diamond compression cell (2.5 mm) and compressed to thin the sample and thus allow the FTIR beam to pass through the material. The degree of compression is such that the spectral peaks of interest have an intensity of less than 2 optical units. A beam capacitor is used to create a narrow beam belt, thereby allowing most of the FTIR beam to penetrate the sample. For ATR analysis, the center of an uncut lens was placed on an ATR diamond crystal and held in place using a standard clamp. Before clamping, a Teflon disk with a diameter of 7 millimeters (0.81 millimeters thick) was placed between the clamping clamp and the lens.

Data Collection: Prior to analysis, a background scan was performed using an empty compression cell or a blank ATR crystal without a lens sample. All contact lens spectra were corrected for these background absorptions using a routine correction procedure. Spectra were obtained by averaging 16 scans in the wavelength range from 400 to 4000 cm ^-1 with a resolution of 4 cm ^-1 .

Infrared absorption bands were identified for the following functional groups: carbonyl ester at 1715 cm ^-1 (corresponding to methacrylate or acrylate), cyclic carbonyl amide at 1657 cm ^-1 (corresponding to PVP), acyclic carbonyl amide at 1618 cm ^-1 (corresponding to DMA) , branched silicone at 840 cm ^-1 (corresponding to SiMAA) and linear silicone at 796 cm ^-1 (corresponding to mPDMS). Typically, an absorption band is chosen as the internal standard. For example, a linear silicone band at 796 cm ^-1 or a (meth)acrylate absorption band at 1715 cm ^-1 may be selected. Changes in the concentration of the functional group, as a surrogate for changes in the concentration of the polymerized component of the reactive monomer mixture or polymer ingredient, can then be measured by comparing the ratio of the functional group (or component) band height divided by the internal standard band height from sample to sample. For example, the FTIR absorption band ratio of PVP and linear silicone (denoted in the figures as the PVP/silicone ratio and representing molar ratios) can be used to compare the relative concentrations of PVP between samples. Likewise, the FTIR absorption band ratio (denoted as PVP/methacrylate ratio in the figures) can also be used to compare the relative concentrations of PVP and (meth)acrylate. ATR FTIR bands are used to compare surface concentrations; FTIR passbands are used to compare concentrations within the lens body. In a series of samples or contact lenses, one sample or lens can be selected as the reference standard and its ratio assigned an arbitrary number, say 100, and the other samples in the series can then be normalized to the reference standard for easy comparison. Because the components of the reference lens used for normalization in the following examples (a photochemically polymerized lens) are substantially uniformly distributed throughout the lens, it is possible to compare the relative concentrations of components on the surface and in the body of test lenses, such as thermally polymerized lenses, as well as comparisons between thermally polymerized and thermally polymerized lenses. photochemically polymerized lenses.

Residual monomer and macromer levels were determined at different times during thermal polymerization using high performance liquid chromatography using ultraviolet detection (HPLC/UV). The polymerized lenses were removed from the oven and molds, weighed and extracted using 5 ml of 90:10 (v/v) methanol/isopropanol solution by sonication for 1 h in a temperature-controlled water bath, while Typically, 3 lenses were immersed in 5 ml of mixed solvent. Extracts were analyzed as described below. If residue concentrations were outside the calibration range, extracts were diluted with methanol to bring the concentration within the calibration range for accurate quantification.

For DMA, HEMA, and TEGDMA, a stock solution was prepared by dissolving 0.1000 g of each component in a 100 mL volumetric flask with enough 90:10 (v/v) methanol/isopropanol solution to fill the flask to the line. This stock solution was then diluted to prepare calibration samples (partially in batch) at 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 construct a calibration curve for HPLC-UV analysis. The chromatographic conditions used for the analysis of DMA, HEMA and TEGDMA are listed below.

Chromatographic conditions

Column: Agilent Zorbax Eclipse Plus 18, 4.6 x 75 mm x 1.8 µm

Phenomenex protective cartridge

Column temperature: 30 °C

UV detector: 217 nm

Injected sample volume: 5 µl

Mobile phase (gradient mobile phase given in Table G (v/v))

Eluent A: Deionized water with _0.05 % _H3PO4

Eluent B: Acetonitrile with 0.05% H ₃ PO ₄

Eluent C: Methanol

Flow rate: 1ml/min

Table G. Gradient mobile phase

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

At each time point, the concentration of DMA, HEMA, and TEGDMA in the lens extract was determined (μg/ml). The extract concentrations were then used to calculate the amount of these components in the sample, expressed as a percentage of the sample weight, as follows:

% component = [(µg/ml * extract volume * dilution factor * 10 ^-6 g/µg) / (g sample mass)] * 100. Finally, the percentage of unreacted component, expressed as a percentage relative to T ₀ , was calculated using the following formula : % at time T _x = (% measured at time T _x / % measured at time T ₀ ) * 100 (where T ₀ represents 100% of the unreacted component or at reaction time zero, and T _x represents amount of unreacted component at time x).

For Norbloc and SiMAA, a stock solution was prepared by dissolving 0.0500 grams of Norbloc and 0.1000 grams of SiMAA in a 100-mL volumetric flask with enough 90:10 (v/v) methanol/isopropanol solution to fill the flask to the line. This stock solution was then diluted to prepare calibration samples (partially in batch) at 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 construct calibration curves for HPLC-UV analysis. The chromatographic conditions used for the analysis of Norbloc and SiMAA are listed below.

Chromatographic conditions

Column: Agilent Zorbax Eclipse Plus 18, 4.6 x 75 mm x 1.8 µm

Phenomenex protective cartridge

Column temperature: 30 °C

UV detector: 217 nm

Injected sample volume: 5 µl

Mobile phase (gradient mobile phase given in Table H (v/v))

Eluent A: Deionized water with _0.05 % _H3PO4

Eluent B: Acetonitrile with 0.05% H ₃ PO ₄

Eluent C: 50:50 (v/v) methanol/isopropanol

Flow rate: 1ml/min

Table H. Gradient mobile phase

Time (minutes) %A %B %C 0 thirty 70 0 8 thirty 70 0 eleven 0 100 0 12 0 80 20 15 0 80 20 16 thirty 70 0 21 thirty 70 0

At each time point, the concentration of Norbloc and SiMAA (μg/ml) in the lens extract was determined. The extract concentrations were then used to calculate the amount of these components in the sample, expressed as a percentage of the sample weight, as follows:

% component = [(µg/ml * extract volume * dilution factor * 10 ^-6 g/µg) / (g sample mass)] * 100. Finally, the percentage of unreacted component, expressed as a percentage relative to T ₀ , was calculated using the following formula : % at time T _x = (% measured at time T _x / % measured at time T ₀ ) * 100 (where T ₀ represents 100% of the unreacted component or at reaction time zero, and T _x represents amount of unreacted component at time x).

For mPDMS, a stock solution was prepared by dissolving 0.2000 grams of mPDMS in a 100 mL volumetric flask with enough 90:10 (v/v) methanol/isopropanol solution to fill the flask to the line. This stock solution was then diluted to prepare calibration samples (partially in batch) at the following concentrations: 1000, 400, 200, 100, 40, 20, 10, 2, and 1 micrograms per milliliter (μg/ml). These calibration samples were used to construct a calibration curve for HPLC-UV analysis. The chromatographic conditions used for mPDMS analysis are listed below.

Chromatographic conditions

Column: Agilent Zorbax Eclipse XDB18, 4.6 x 50 mm x 1.8 µm

Phenomenex protective cartridge

Column temperature: 30 °C

UV detector: 217 nm

Injected sample volume: 20 µl

Mobile phase (gradient mobile phase given in Table I (v/v))

Eluent A: Deionized water

Eluent B: Acetonitrile

Eluent C: Isopropanol

Flow rate: 1ml/min

Table I. Gradient mobile phase

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 thirty 8 0 70 thirty 8.1 50 48 2 10 50 48 2

At each time point, the concentration of mPDMS (μg/ml) in the lens extract was determined. Extract concentrations were then used to calculate the amount of mPDMS in the sample, expressed as a percentage of 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, expressed as a percentage relative to T ₀ , was calculated using the following formula: % at time T _x = (% measured at time T _x / % measured at time T ₀ ) * 100 (where T ₀ represents 100% unreacted mPDMS or at reaction time zero, and T _x represents the amount of unreacted mPDMS at time x).

The invention will be described below with reference to the following examples. Before describing several examples of the invention, it should be understood that the invention is not limited to the design features or method steps presented in the following description. The invention also has other embodiments and can be practiced or carried out in various ways.

The following abbreviations will be used in the examples, the meanings of which are given below.

RMM: reactive mixture of monomers

l: liter(s)

ml: milliliter(s)

nm: nanometer(s)

g: gram(s);

mcg: microgram(s)

Yes: dalton or g/mol

kDa: kilodalton

FTIR: Fourier transform infrared spectroscopy

ATR: Attenuated total internal reflection

HPLC: high performance liquid chromatography;

UV: ultraviolet spectroscopy

WC: water content (wt.%)

EC Dk: edge corrected oxygen permeability (barrera)

M: modulus of elasticity (psi)

TS: tensile strength (psi)

ETB: Elongation at Break (%)

RI: refractive index

Sedentary drop: contact angle (degrees)

Cahn DCA: inflow and outflow contact angles (degrees)

BC: plastic casting mold for base or back curvature, made of PP, TT, Z or mixtures thereof

FC: plastic casting mold for anterior curvature, made of PP, TT, Z or mixtures thereof

PP: polypropylene, which is a homopolymer of propylene

TT: Tuftec, which is a hydrogenated styrene-butadiene block copolymer (Asahi Kasei Chemicals)

Z: Zeonor which is a polycycloolefin thermoplastic polymer (Nippon Zeon Co Ltd)

TL03 light sources: Phillips TLK 40W/03 lamps

LED: LED

DMA: N,N-dimethylacrylamide (Jarchem)

HEMA: 2-hydroxyethyl methacrylate (Bimax)

PVP K90: poly(N-vinylpyrrolidone) (ISP Ashland)

PVMA: polyvinyl methyl acetamide

TEGDMA: tetraethylene glycol dimethacrylate (Esstech)

mPDMS: polydimethylsiloxane with mono-n-butyl and monomethacryloxypropyl end groups (M _n =800-1500 daltons) (Gelest)

SiMAA: 2-propenoic acid, 2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl ether (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-di(trimethylsiloxy )silylpropoxy]propyl methacrylate

Irgacure or Omnirad 184: 1-hydroxy-cyclohexylphenylketone (IGM Resins, BASF or Ciba Specialty Chemicals)

Irgacure or Omnirad 1870: mixture of bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide and 1-hydroxycyclohexylphenylketone (BASF or Ciba Specialty Chemicals)

AIBN: Azobiisobutyronitrile or 2,2′-azobis(2-methylpropionitrile), 2-(azo(1-cyano-1-methylethyl))-2-methylpropanenitrile

Norbloc: 2-(2'-hydroxy-5-methacryloxyethylphenyl)-2H-benzotriazole (Janssen)

Blue HEMA: 1-amino-4-[3-(4-(2-methacryloyloxyethoxy)-6-chlorotriazin-2-ylamino)-4-sulfophenylamino]anthraquinone-2-sulfonic acid, as described in US Patent No. 5,944,853

D3O: 3,7-dimethyl-3-octanol (Vigon)

DIW: deionized water

IPA: isopropyl alcohol

PS: Borate Buffered Storage Solution: 18.52 grams (300 mmol) boric acid, 3.7 grams (9.7 mmol) sodium borate decahydrate and 28 grams (197 mmol) sodium sulfate were dissolved in enough deionized water to fill 2 liter volumetric flask.

WC: water content (wt.%)

Turbidity: %

EC Dk: edge corrected oxygen permeability (barrera)

M: modulus of elasticity (psi)

TS: tensile strength (psi)

ETB: Elongation at Break (%)

Lipids: microgram cholesterol per lens or mcg/lens.

RI: refractive index

Sedentary drop: contact angle (degrees)

Cahn DCA: inflow and outflow contact angles (degrees) in the order shown in the tables

Parentheses: Parentheses ( ) in tables are used to indicate the standard deviation of measurements.

Drug 1 - polyvinylmethylacetamide (PVMA)

PVMA was prepared as follows. 380 ml (3.48 mol) of distilled N-vinyl-N-methylacetamide and 187 mg (1.14 mmol) of azobisisobutyronitrile were placed in a three-neck round-bottom flask with a reflux condenser, a magnetic armature and a thermocouple, and nitrogen gas was bubbled through the reaction mixture for 2 hours. to remove oxygen. The reaction mixture was then heated at 75 °C for 24 hours, during which time the reaction mixture solidified. The reaction product was quenched in air and isolated using Isolation Procedure 1 or Isolation Procedure 2. Isolation Procedure: The reaction product was dissolved in water, extensively dialyzed in a dialysis membrane tube (Spectra Pore MWCO 3500) and freeze-dried (60% yield) (freeze-drying system). dryers LABCONCO, Freezone® TriadTM, model No. 7400030). Molecular weight was determined by gel permeation chromatography with multi-angle scattering (SEC-MALS) analysis. In the SEC-MALS setup, an aqueous acetonitrile solution consisting of 80% (v/v) 50 mM Na ₂ SO4 and 20% (v/v) acetonitrile was used as the mobile phase at a flow rate of 0.5 ml/min at 40 °C. Two TSK-gel Tosoh Biosciences columns [SuperAW4000 and SuperAW5000] with an integrated 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) were used sequentially. Absolute molecular weight and polydispersity data were calculated using the Wyatt ASTRA VI SEC/LS software package. About 40 milligrams of PVMA was dissolved in the storage solution in a 10-mL volumetric flask. Storage solution: 18.52 grams (300 mmol) boric acid, 3.7 grams (9.7 mmol) sodium borate decahydrate, and 28 grams (197 mmol) sodium sulfate were dissolved in enough deionized water to fill a 2-liter measuring cup. flasks. 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 mass of the three samples was 570.3 kDa; the resulting polydispersity coefficient is 1.96.

Examples 1-9

Reaction mixtures of monomers were obtained from 77% wt. compositions listed in table 1, and 23% of the mass. D3O diluent. The monomer reaction mixtures were individually filtered through a 3-μm pore size filter using a stainless steel syringe. Subsequently, during use, about 0.074 grams of AIBN (thermal initiator) was dissolved in 20.0000 grams of RMM. The mass fraction of AIBN was about 0.37 wt%. in the final RMM.

The RMM with AIBN was degassed at ambient temperature using vacuum (40 torr) for at least 20 minutes. Then, in a glove box under a nitrogen atmosphere with less than 0.2 percent oxygen at room temperature, 75-80 μl of the reaction mixture was applied to the Zeonor FC using an Eppendorf pipette. Then, BC made from 55:45 (v/v) Z:TT mixture was placed in FC. The molds were kept in a glove box for at least twelve hours before application. About 20 pallets, each containing eight mold assemblies, were placed in an adjacent oven maintained at a temperature of about 65-70°C, set in a glove box, and the lenses were cured under these conditions for about 24 hours.

The lenses were manually removed from the molds and released by suspending the lenses in approximately one liter of 70% IPA for at least 12 hours, followed by soaking two more times in approximately 450 ml of fresh 70% IPA for approximately 45 minutes; then once in fresh DIW for about 45 minutes; then once in the storage solution for about 45 minutes. Lenses were equilibrated and stored in borate buffered storage solution before autoclaving at 121°C for 30 minutes in vials. Various physical and mechanical properties of sterile lenses were determined, which are listed in Table 2.

One of ordinary skill in the art will determine that this lens removal process may be modified depending on lens composition and mold materials, the concentration of the aqueous isopropanol solutions, the number of washes with each solvent, and the duration of each step. The goal of the lens retrieval process is to remove all lenses without causing damage and to move from swollen diluent grids to swollen storage solution grids.

Table 1. Composition components

Component
(wt.%) Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 mPDMS: 31.15 31.14 31.14 31.13 31.14 31.15 31.16 31.05 SiMAA 28.13 28.11 28.13 28.12 28.14 28.14 28.18 28.08 DMA 31.13 30.63 30.15 29.64 29.15 28.64 27.12 25.74 HEMA 6.03 6.05 6.04 6.04 6.03 6.03 6.04 6.01 Blue HEMA 0.03 0.03 0.03 0.03 0.03 0.02 0.03 0.03 TEGDMA 1.53 1.51 1.51 1.52 1.50 1.51 1.46 1.52 PVP K90 0 0.50 1.00 1.52 2.02 2.50 4.01 5.56 Norbloc 2.01 2.03 2.02 2.02 1.98 2.01 2.01 2.02 General 100 100 100 100 100 100 100 100

Table 2. Lens properties

% wt. PVP K90 Cahn D.C.A. Fixed drop Water content Turbidity Mechanical characteristics EC Dk Lipids R.I. Elastic modulus ETB Example 1 0.0 119 (15), 31 (19) 106 (4) 31 (0) 10 (2) 107 (17) 163 (50) 129 -- 1.4475 (0.0033) Example 2 0.5 104 (16), 15 (19) 106 (2) 32 (0) 2 (1) 115 (13) 173 (50) 102 9.20 (1.28) 1.4359 (0.0032) Example 3 1.0 89 (15), 19 (13) 92 (8) 33 (0) 5 (1) 102 (15) 193 (29) 107 8.09 (1.21) 1.4315 (0.0019) Example 4 1.5 61 (16), 16 (17) 95 (6) 32 (1) 4 (0) 109 (9) 197 (51) 110 9.96 (2.03) 1.4265 (0.0020) Example 5 2.0 19 (18), 16 (13) 58 (14) 34 (0) 20) 106 (9) 175 (40) 120 8.87 (2.10) 1.4237 (0.0015) Example 6 2.5 32 (9)
31 (19) 65 (5) 34 (0) 3 (1) 102 (15) 170 (32) 94 8.30 (2.19) 1.4167 (0.0027) Example 7 4.0 31 (7)
30 (14) 51 (3) 35 (0) 5 (1) 107 (12) 177 (33) 105 6.06 (1.17) 1.4149 (0.0017) Example 8 5.6 42 (11), 26 (9) 51 (9) 36 (0) 6 (1) 113 (9) 205 (28) 116 6.24 (1.01) 1.4193 (0.0015)

As shown in Table 2, lenses produced by thermal polymerization demonstrated good wettability, as measured by Cahn DCA and sessile drop methods at low levels of internal wetting agent PVP K90, while maintaining a good balance between physical and mechanical properties suitable for soft contact lenses.

Comparative example 1

The reaction mixture of monomers was obtained from 77% wt. composition given in table 3, and 23% wt. D3O diluent. 0.0524 grams of Irgacure 1870 and 0.0215 grams of Irgacure 184 were then dissolved in 20 grams of the monomer reaction mixture by stirring overnight and then filtered through a 3 μm pore size filter using a stainless steel syringe.

The RMM was degassed at ambient temperature by applying a vacuum (40 torr) for at least 20 minutes. Then, in a glove box under a nitrogen atmosphere with less than 0.2 percent oxygen at room temperature, 75 μl of the reaction mixture was applied to the Zeonor FC using an Eppendorf pipette. Then, BC made from 55:45 (v/v) Z:TT mixture was placed in FC. The molds were kept in a glove box for at least twelve hours before application. The pallets, each containing eight mold assemblies, were transferred to an adjacent glove box, which was maintained at 64°C, and the lenses were cured on top for 12 minutes using TLO3 lamps at an intensity of approximately 4.5 mW/cm ² at the location of the tray.

Lenses were manually removed from the molds, with most lenses stuck to the FC, and released by suspending the lenses in approximately one liter of 70% IPA for at least 12 hours, followed by soaking two more times in approximately 450 ml of fresh 70% IPA. percent IPA for about 45 minutes; then once in fresh DIW for about 45 minutes; then once in the storage solution for about 45 minutes. Lenses were equilibrated and stored in borate buffered storage solution before autoclaving at 121°C for 30 minutes in vials. Various physical and mechanical properties of sterile lenses were determined, which are listed in Table 4.

One of ordinary skill in the art will determine that this lens removal process may be modified depending on lens composition and mold materials, the concentration of the aqueous isopropanol solutions, the number of washes with each solvent, and the duration of each step. The goal of the lens removal process is to remove all lenses without causing damage and to move from swollen diluent grids to swollen storage solution grids.

Comparative example 2

The reaction mixture of monomers was obtained from 77% wt. composition given in table 3, and 23% wt. D3O diluent. 0.0391 grams of Irgacure 1870 and 0.0157 grams of Irgacure 184 were then dissolved in 15 grams of the monomer reaction mixture by stirring overnight and then filtered through a 3 μm pore size filter using a stainless steel syringe.

The RMM was degassed at ambient temperature by applying a vacuum (40 torr) for at least 20 minutes. Then, in a glove box under a nitrogen atmosphere with less than 1 percent oxygen at room temperature, 75 μl of the reaction mixture was applied to the Zeonor FC using an Eppendorf pipette. Then, BC made from 55:45 (v/v) Z:TT mixture was placed in FC. The molds were kept in a glove box for at least twelve hours before application. The pallets, each containing eight mold assemblies, were transferred to an adjacent glove box, which was maintained at 64°C, and the lenses were cured on top for 15 minutes using 435 nm, 4 mW LED lamps. cm ² at the location of the tray.

Lenses were manually removed from the molds, with most lenses stuck to the FC, and released by suspending the lenses in approximately one liter of 70% IPA for at least 12 hours, followed by soaking two more times in approximately 450 ml of fresh 70% IPA. percent IPA for about 45 minutes; then once in fresh DIW for about 45 minutes; then once in the storage solution for about 45 minutes. Lenses were equilibrated and stored in borate buffered storage solution before autoclaving at 121°C for 30 minutes in vials. Various physical and mechanical properties of sterile lenses were determined, which are listed in Table 4.

One of ordinary skill in the art will determine that this lens removal process may be modified depending on lens composition and mold materials, the concentration of the aqueous isopropanol solutions, the number of washes with each solvent, and the duration of each step. The goal of the lens retrieval process is to remove all lenses without causing damage and to move from swollen diluent grids to swollen storage solution grids.

Table 3. Composition components and polymerization system

Example 6 Comparative note 1 Comparative note 2 Polymerization Thermal TL03 LED 435 nm Component
(wt.%) mPDMS: 31.15 31.15 31.15 SiMAA 28.14 28.14 28.14 DMA 28.64 28.64 28.64 HEMA 6.03 6.03 6.03 Blue HEMA 0.02 0.02 0.02 TEGDMA 1.51 1.51 1.51 PVP K90 2.50 2.50 2.50 Norbloc 2.01 2.01 2.01 General 100 100 100

Table 4. Lens properties

% wt. PVP K90 Cahn D.C.A. Fixed drop Water content Turbidity Mechanical characteristics EC Dk R.I. Elastic modulus ETB Example 6
Thermal 2.5 32 (9)
31 (19) 65 (5) 34 (0) 3 (1) 102 (15) 170 (32) 94 1.4167 (0.0027) Comp. approx. 1
TLO3 2.5 105 (6), 27 (6) 101 (3) 35 (0) 5 (1) 98 (13) 259 (28) 91 1.4269 (0.0001) Comp. approx. 2
435 nm LED 2.5 85 (18), 26 (1) 99 (4) 35 (1) 4 (1) 114 (12) 208 (54) 100 1.4265 (0.0014)

As shown in Table 4, lenses produced by thermal polymerization demonstrated good wettability, as measured by Cahn DCA and sessile drop methods at low levels of internal wetting agent PVP K90, while maintaining a good balance between physical and mechanical properties suitable for soft contact lenses, in while photochemically polymerized lenses were significantly less wettable as measured using the Cahn DCA and sessile drop method.

Examples 8-11

Reaction mixtures of monomers were obtained from 77% wt. compositions listed in table 5, and 23% of the mass. D3O diluent. PVMA from Preparation 1 was used. The monomer reaction mixtures were individually filtered through a 3 μm filter using a stainless steel syringe. Subsequently, during use, about 0.037 grams of AIBN (thermal initiator) was dissolved in 10.0000 grams of RMM. The mass fraction of AIBN was about 0.37 wt%. in the final RMM.

The RMM with AIBN was degassed at ambient temperature using vacuum (40 torr) for at least 20 minutes. Then, in a glove box under a nitrogen atmosphere with less than 0.2 percent oxygen at room temperature, 70-75 μl of the reaction mixture was applied to the Zeonor FC using an Eppendorf pipette. Then, BC made from 55:45 (v/v) Z:TT mixture was placed in FC. The molds were kept in a glove box for at least twelve hours before application. About 20 pallets, each containing eight mold assemblies, were placed in an adjacent oven maintained at a temperature of about 65-70°C, set in a glove box, and the lenses were cured under these conditions for about 24 hours.

The lenses were manually removed from the molds and released by suspending the lenses in approximately one liter of 70% IPA for at least 12 hours, followed by soaking two more times in approximately 450 ml of fresh 70% IPA for approximately 45 minutes; then once in fresh DIW for about 45 minutes; then once in the storage solution for about 45 minutes. Lenses were equilibrated and stored in borate buffered storage solution before autoclaving at 121°C for 30 minutes in vials. Various physical and mechanical properties of sterile lenses were determined, which are listed in Table 6.

One of ordinary skill in the art will determine that this lens removal process may be modified depending on lens composition and mold materials, the concentration of the aqueous isopropanol solutions, the number of washes with each solvent, and the duration of each step. The goal of the lens retrieval process is to remove all lenses without causing damage and to move from swollen diluent grids to swollen storage solution grids.

Table 5. Composition components

Component
(wt.%) Example 8 Example 9 Example 10 Example 11 mPDMS: 31.14 31.14 31.13 31.16 SiMAA 28.12 28.13 28.12 28.13 DMA 29.62 29.14 28.64 27.14 HEMA 6.03 6.03 6.02 6.03 Blue HEMA 0.03 0.03 0.03 0.03 TEGDMA 1.51 1.51 1.51 1.50 PVMA 1.53 2.02 2.54 4.00 Norbloc 2.02 2.01 2.03 2.02 General 100 100 100 100

Table 6. Lens properties

% wt. PVMA Cahn D.C.A. Fixed drop Water content Turbidity Mechanical characteristics EC Dk Lipids R.I. Elastic modulus ETB Example 8 1.5 56 (15), 16 (11) 86 (7) 34 (0) 5 (1) 132 (9) 220 (28) 110 5.45 (1.03) 1.4262 (0.0002) Example 9 2 21 (10), 25 (10) 72 (6) 33 (0) 4 (0) 126 (7) 218 (30) 103 4.81 (0.29) 1.4223 (0.0002) Example 10 2.5 22 (13), 14 (14) 46 (16) 36 (0) 5 (1) 114 (8) 204 (31) 93 4.75 (0.29) 1.4195 (0.0004) Example 11 4 11 (9, 0) 33 (3) 35 (0) 6 (1) 115 (13) 199 (55) 116 4.55 (0.71) 1.4179 (0.0006)

As shown in Table 6, lenses produced by thermal polymerization demonstrated good wettability, as measured by Cahn DCA and sessile drop methods at low levels of internal PVMA wetting agent, while maintaining a good balance between physical and mechanical properties suitable for soft contact lenses.

Comparative examples 3-6

Reaction mixtures of monomers were obtained from 77 wt.%. compositions listed in table 7, and 23% of the mass. D3O diluent. About 0.0655 grams of Irgacure 1870 and about 0.0270 grams of Irgacure 184 were then dissolved in 25 grams of these monomer reaction mixtures by stirring overnight and then filtered through a 3 μm pore size filter using a stainless steel syringe.

The RMM was degassed at ambient temperature by applying a vacuum (40 torr) for at least 20 minutes. Then, in a glove box under a nitrogen atmosphere with less than 0.2 percent oxygen at room temperature, 70-75 μl of the reaction mixture was applied to the Zeonor FC using an Eppendorf pipette. Then, BC made from 55:45 (v/v) Z:TT mixture was placed in FC. The molds were kept in a glove box for at least twelve hours before application. All pallets, each containing eight mold assemblies, were transferred to an adjacent glove box, which was maintained at 65°C, and the lenses were cured on top for 12 minutes using TLO3 lamps at an intensity of about 4.0-4. 5 mW/cm ² at the location of the tray.

Lenses were manually removed from the molds, with most lenses stuck to the FC, and released by suspending the lenses in approximately one liter of 70% IPA for at least 12 hours, followed by soaking two more times in approximately 450 ml of fresh 70% IPA. percent IPA for about 45 minutes; then once in fresh DIW for about 45 minutes; then once in the storage solution for about 45 minutes. Lenses were equilibrated and stored in borate buffered storage solution before autoclaving at 121°C for 30 minutes in vials. Various physical and mechanical properties of sterile lenses were determined, which are listed in Table 8.

One of ordinary skill in the art will determine that this lens removal process may be modified depending on lens composition and mold materials, the concentration of the aqueous isopropanol solutions, the number of washes with each solvent, and the duration of each step. The goal of the lens retrieval process is to remove all lenses without causing damage and to move from swollen diluent grids to swollen storage solution grids.

Table 7. Composition components

Component
(wt.%) Comp. approx. 3 Comp. approx. 4 Comp. approx. 5 Comp. approx. 6 mPDMS: 31.14 31.14 31.13 31.16 SiMAA 28.12 28.13 28.12 28.13 DMA 29.62 29.14 28.64 27.14 HEMA 6.03 6.03 6.02 6.03 Blue HEMA 0.03 0.03 0.03 0.03 TEGDMA 1.51 1.51 1.51 1.50 PVMA 1.53 2.02 2.54 4.00 Norbloc 2.02 2.01 2.03 2.02 General 100 100 100 100

Table 8. Lens properties

% wt. PVMA Cahn D.C.A. Fixed drop Water content Turbidity Mechanical characteristics EC Dk Lipids R.I. Elastic modulus ETB Comp. approx. 3 1.5 102 (14), 34 (10) 95 (8) 34 (0) 5 (1) 100 (5) 256 (29) 100 8.57 (2.48) 1.4278 (0.0001) Comp. approx. 4 2 104 (8), 34 (7) 90 (11) 37 (0) 4 (0) 109 (7) 245 (20) 90 8.39 (1.11) 1.4256 (0.0009) Comp. approx. 5 2.5 77 (44), 17 (17) 102 (8) 37 (0) 7 (1) 99 (8) 239 (29) 98 6.34 (0.92) 1.4269 (0.0013) Comp. approx. 6 4 37 (14)
7 (10) 63 (13) 39 (0) 8 (1) 99 (7) 239 (55) 96 5.15 (0.34) 1.4234 (0.0026)

As shown in Table 8, lenses produced by photochemical polymerization exhibited substantially lower wettability, as measured by Cahn DCA and sessile drop methods, at low levels of internal PVMA wetting agent, compared to similar lenses produced by thermal polymerization (see Table 8). table 6).

Examples 12-14

Reaction mixtures of monomers were obtained from 77 wt.%. compositions listed in table 9, and 23% of the mass. D3O diluent. The monomer reaction mixtures were individually filtered through a 3-μm pore size filter using a stainless steel syringe. Subsequently, during use, about 0.0285 grams of AIBN (thermal initiator) was dissolved in 10.0000 grams of RMM. The mass fraction of AIBN was about 0.28 wt%. in the final RMM.

The RMM with AIBN was degassed at ambient temperature using vacuum (40 torr) for at least 20 minutes. Then, in a glove box under a nitrogen atmosphere with less than 0.1-0.2 percent oxygen at room temperature, 75 μl of the reaction mixture was applied to the Zeonor FC using an Eppendorf pipette. The BC, also made of Zeonor material, was subsequently placed on the FC. The molds were kept in a glove box for at least twelve hours before application.

Example 12: Several pallets, each containing eight mold assemblies, were placed in an adjacent oven maintained at approximately 60°C, set in a glove box, and the lenses were cured under these conditions for approximately 6 hours.

Example 13: A similar procedure was carried out, except that several pallets, each containing eight mold assemblies, were placed in an adjacent oven maintained at approximately 90°C, set in a glove box, and the lenses were cured under these conditions. for about 6 hours.

Example 14: A similar procedure was followed except that (1) FC was made from a 90:10 (w/w) Z:TT mixture, (2) BC was made from a 90:10 (w/w) mixture. ) Z:PP mixtures and (3) several pallets, each containing eight mold assemblies, were placed in an adjacent oven maintained at about 120°C, set in a glove box, and the lenses were cured under these conditions for about 0.5 hours.

The lenses were manually removed from the molds and released by suspending the lenses in approximately one liter of 70% IPA for at least 12 hours, followed by soaking two more times in approximately 450 ml of fresh 70% IPA for approximately 45 minutes; then once in fresh DIW for about 45 minutes; then once in the storage solution for about 45 minutes. Lenses were equilibrated and stored in borate buffered storage solution before autoclaving at 121°C for 30 minutes in vials.

One of ordinary skill in the art will determine that this lens removal process may be modified depending on lens composition and mold materials, the concentration of the aqueous isopropanol solutions, the number of washes with each solvent, and the duration of each step. The goal of the lens retrieval process is to remove all lenses without causing damage and to move from swollen diluent grids to swollen storage solution grids.

The thermally polymerized sterilized lenses of Examples 12-14, as well as sterilized lenses of similar composition but which were photochemically polymerized (indicated in the figures as Comparative Example 7 or Comparative Note 7) were analyzed using transmittance analysis and ATR FTIR analysis and normalized to photochemically polymerized lenses. As shown in FIG. 1 and 2, the surface concentration of PVP in thermally polymerized lenses was higher than the surface concentration of PVP in photochemically polymerized lenses. In addition, the PVP/silicone molar ratio of thermally polymerized lenses was higher at the surface than at the core.

Table 9. Composition components

Component
(wt.%) Note 12 -14 mPDMS: 31.05 SiMAA 28.05 DMA 24.06 HEMA 5.97 Blue HEMA 0.20 TEGDMA 1.65 PVP K90 7.00 Norbloc 2.00 General 100

Examples 15-17

Example 15: Example 13 was repeated except that (1) FC was made from 90:10 (w/w) Z:TT, (2) BC was made from 90:10 (w/w) Z:PP and (3) lenses were removed at various time points for HPLC-UV analysis of residual monomers and macromers. Data on residual components are given in Table 10.

Example 16: Example 14 was repeated except that the lenses were removed at various time points for HPLC-UV analysis of residual monomers and macromers. Data on residual components are given in Table 11.

Example 17: Example 14 was repeated again, except that the lenses were removed at various time points for HPLC-UV analysis of residual monomers and macromers. Data on residual components are given in Table 12.

Table 10. Example 15: Residual monomers - thermal polymerization at 90 °C

Polymerization time (hour) [DMA]
% [HEMA]
% [TEGDMA]
% [Norbloc]
% [SiMAA]:
% [mPDMS]
% General
% 0.5 9,379 1,597 0.415 0.620 7,553 9,824 29,388 1 0.199 0.009 <0.001 0.004 0.072 0.140 0.425 2 0.047 0.007 <0.001 0.001 0.021 0.060 0.136 3 0.034 0.005 <0.001 0.002 0.040 0.055 0.136 6 0.153 0.043 <0.001 0.023 0.103 0.056 0.379 12 0.124 0.050 <0.001 0.025 0.258 0.099 0.556

Table 11. Example 16. Residual monomers - thermal polymerization at 120°C

Polymerization time
(hour) [DMA]
% [HEMA]
% [TEGDMA]
% [Norbloc]
% [SiMAA]:
% [mPDMS]
% General
% 0.17 12,955 2,889 0.646 1.038 13,150 17,977 48,656 0.33 0.402 0.017 0.002 0.004 0.048 0.182 0.655 0.5 0.055 0.005 <0.001 0.002 0.023 0.085 0.170 0.5 0.065 0.003 <0.001 0.009 0.026 0.095 0.198 1 0.064 0.013 <0.001 0.007 0.014 0.100 0.198 2 0.048 0.014 0.001 0.008 0.059 0.161 0.292 6 0.029 0.013 0.008 0.011 0.340 0.313 0.713 12 0.024 0.014 0.012 0.013 0.476 0.492 1.031

Table 12. Example 17. Residual monomers - thermal polymerization at 120°C

Polymerization time (hour) [DMA]
% [HEMA]
% [TEGDMA]
% [Norbloc]
% [SiMAA]:
% [mPDMS]
% General
% 0.5 0.106 0.007 <0.001 0.004 0.029 0.110 0.255 1.0 0.115 0.030 <9.991 0.003 0.037 0.079 0.265 2.0 0.051 0.028 0.004 0.004 0.203 0.108 0.398 6.0 0.021 0.018 0.014 0.009 1.012 0.396 1,470 12.0 0.012 0.011 0.022 0.011 1.032 0.577 1.665 26.0 0.002 0.004 0.011 0.016 0.275 0.782 1,090

As demonstrated in Tables 10-12, the reaction mixtures of monomers thermally polymerized to a high degree of conversion both at 90°C after approximately 2-3 hours with a total unreacted content of less than about 0.2% by weight, and at 120°C after approximately 0.5-1 hour with a total content of unreacted components of less than about 0.3 wt%.

Claims (25)

1. Silicone hydrogel contact lens, which is a reaction product of a reaction mixture containing a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; and a polymerization initiator, wherein said contact lens has an oxygen permeability of at least about 60 bbl, and wherein the molar ratio in the lens of polymeric non-reactive internal wetting agent to silicone, without surface treatment, is higher on the surface of the lens than in its body . 2. Silicone hydrogel contact lens according to claim 1, characterized in that the specified molar ratio of the polymeric non-reactive internal wetting agent to silicone is at least 1.5 times greater on the surface of the lens than in its body. 3. Silicone hydrogel contact lens according to any one of paragraphs. 1,2, characterized in that the specified molar ratio of the polymeric non-reactive internal wetting agent to silicone is at least 2.3 times greater on the surface of the lens than in its body. 4. Silicone hydrogel contact lens according to any one of paragraphs. 1-3, characterized in that said non-reactive polymeric internal wetting agent is a polyamide. 5. Silicone hydrogel contact lens according to any one of paragraphs. 1-4, characterized in that said non-reactive polymeric internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, as well as their copolymers and mixtures. 6. Silicone hydrogel contact lens according to any one of paragraphs. 1-5, characterized in that the lens, which is a reaction product of a reaction mixture containing only 2.0 wt.% non-reactive polymeric internal wetting agent, has a contact angle of 75° or less. 7. The silicone hydrogel contact lens according to claim 6, characterized in that said contact angle is 50° or less. 8. Silicone hydrogel contact lens according to any one of paragraphs. 1-7, containing up to about 95% of the mass. silicone-containing component. 9. Silicone hydrogel contact lens according to any one of paragraphs. 1-8, containing from about 1 to about 80% of the mass. hydrophilic component. 10. Silicone hydrogel contact lens according to any one of paragraphs. 1-9, containing from about 0.5 to about 35% of the mass. a non-reactive polymeric internal wetting agent. 11. A method for producing a contact lens, which includes the following steps: (a) obtaining a reaction mixture containing a silicone-containing component; hydrophilic component; a non-reactive polymeric internal wetting agent; as well as a polymerization initiator; And (b) polymerizing the reaction mixture to form a contact lens; wherein said method is carried out under such conditions that the molar ratio of the polymeric non-reactive internal wetting agent to silicone, without surface treatment, is higher on the surface of the lens than in its body. 12. The method according to claim 11, characterized in that the specified molar ratio of the polymeric non-reactive internal wetting agent to silicone on the surface of the lens is at least 1.5 times greater than in its body. 13. Method according to any one of paragraphs. 11,12, characterized in that the specified molar ratio of the polymeric non-reactive internal wetting agent to silicone on the surface of the lens is at least 2.3 times greater than in its body. 14. Method according to any one of paragraphs. 11-13, characterized in that said non-reactive polymeric internal wetting agent is a polyamide. 15. Method according to any one of paragraphs. 11-14, characterized in that said non-reactive polymeric internal wetting agent is selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, as well as their copolymers and mixtures. 16. Method according to any one of paragraphs. 11-15, characterized in that the lens, which is a reaction product of a reaction mixture containing only 2.0 wt.% non-reactive polymeric internal wetting agent, has a contact angle of 75° or less. 17. The method according to claim 16, characterized in that said impingement contact angle is 50º or less. 18. Method according to any one of paragraphs. 11-17, characterized in that step (b) includes thermal polymerization of the reaction mixture. 19. The method according to claim 18, characterized in that said thermal polymerization is carried out at a temperature from 60 to 120 degrees Celsius. 20. Method according to any one of paragraphs. 18,19, characterized in that the specified thermal polymerization is carried out at a temperature from 85 to 120 degrees Celsius. 21. Method according to any one of paragraphs. 11-20, characterized in that after step (b) and before the extraction step to remove unpolymerized components from the contact lens, the contact lens contains no more than 0.3 wt%. non-polymerized polymerizable components. 22. A silicone hydrogel contact lens manufactured using the method according to any one of claims. 11-21.