Silicone hydrogel lenses with cross-linked hydrophilic coatings - Patent Application 20070122999

Abstract

A cost-effective and time-efficient method for producing silicone hydrogel contact lenses with a wettable and durable coating is provided. The method involves heating a silicone hydrogel contact lens in an aqueous solution in the presence of a water-soluble, highly branched, thermally crosslinkable hydrophilic polymeric material having positively charged azetidinium groups at a temperature of 40°C to 140°C for a time sufficient to covalently bond the thermally crosslinkable hydrophilic polymeric material to the surface of the silicone hydrogel contact lens via a covalent bond formed between each azetidinium group and one of the reactive functional groups on and / or near the surface of the silicone hydrogel contact lens, thereby forming a crosslinked hydrophilic coating on the silicone hydrogel contact lens. Such a method can advantageously be carried out directly within the sealed lens package during autoclaving.

Description

[Technical Field]

[0001] The present invention generally relates to a cost-effective and time-efficient method for applying a crosslinked hydrophilic coating to silicone hydrogel contact lenses to improve their hydrophilicity and lubricity. Additionally, the present invention provides ophthalmic lens products.

[0002] background Soft silicone hydrogel contact lenses are becoming increasingly popular due to their high oxygen permeability and comfort. However, silicone hydrogel materials are typically hydrophobic (non-wettable) and have surfaces, or at least some areas of their surfaces, that tend to adsorb lipids or proteins from the ocular environment and may adhere to the eye. Thus, silicone hydrogel contact lenses will generally require surface modification.

[0003] A known approach to modifying the hydrophilicity of relatively hydrophobic contact lens materials is through the use of plasma treatment; for example, commercially available lenses such as Focus NIGHT & DAY™ and O2OPTIX™ (CIBA VISION) and PUREVISION™ (Bausch & Lomb) utilize this approach in their production process. Advantages of plasma coatings, such as those found on Focus NIGHT & DAY™, include their durability, relatively high hydrophilicity / wettability, and low susceptibility to lipid and protein deposition and adsorption. However, plasma treatment of silicone hydrogel contact lenses may not be cost-effective because preformed contact lenses typically must be dried prior to plasma treatment, and because of the relatively high capital investment associated with plasma treatment equipment.

[0004] Another approach to modifying the surface hydrophilicity of silicone hydrogel contact lenses is the incorporation of a wetting agent (hydrophilic polymer) into the lens formulation used to manufacture the silicone hydrogel contact lens, as proposed in U.S. Patent Nos. 6,367,929, 6,822,016, 7,052,131, and 7,249,848. This method does not require additional post-processing to modify the surface hydrophilicity of the lens after the silicone hydrogel contact lens is cast. However, wetting agents are not always compatible with the silicone component in the lens formulation, and this incompatibility may cause the resulting lens to become cloudy. Furthermore, such surface treatments are susceptible to lipid deposition and adsorption. In addition, such surface treatments fail to provide a durable surface for extended wear.

[0005] Yet another approach to modifying the hydrophilicity of relatively hydrophobic contact lens materials is layer-by-layer (LbL) polyionic material deposition (see, e.g., U.S. Patent Nos. US 6,451,871, US 6,717,929, US 6,793,973, US 6,884,457, US 6,896,926, US 6,926,965, US 6,940,580, and US 7,297,725, and U.S. Patent Application Publications US 2007 / 0229758A1, US 2008 / 0174035A1, and US 2008 / 0152800A1). While LbL deposition can provide a cost-effective process for making silicone hydrogel materials wettable, the LbL coatings are not as durable as plasma coatings and may have a relatively high surface charge density, which may interfere with contact lens cleaning and disinfecting solutions. To improve durability, commonly owned, co-pending U.S. Patent Application Publications 2008 / 0226922 A1 and 2009 / 0186229 A1 (incorporated by reference in their entireties) propose crosslinking LbL coatings on contact lenses. However, crosslinked LbL coatings may have poorer hydrophilicity and / or wettability than the original LbL coating (before crosslinking) and still have a relatively high surface charge density.

[0006] Yet another approach to modifying the hydrophilicity of relatively hydrophobic contact lens materials is to attach hydrophilic polymers onto the contact lens by various mechanisms (e.g., U.S. Pat. Nos. 6,099,122, 6,436,481, 6,440,571, 6,447,920, 6,465,056, 6,521,352, 6,586,038, 6,623,747, 6,730,366, 6,734,321, 6,835,410, 6,878,399, 6,923,978, 6,440,571, and 6,500,481; U.S. Pat. Appl. Pub ... and 6,500,481; U.S. Pat. Appl. Pub. Nos. 6,099,122, 6,436,481, 6,440,571, and 6,500 (See, e.g., Patent Applications Nos. 2009 / 0145086A1, 2009 / 0145091A1, 2008 / 0142038A1, and 2007 / 0122540A1; all of which are incorporated herein by reference in their entireties.) While these techniques can be used to render silicone hydrogel materials wettable, they typically require a relatively long time and / or involve difficult, multiple steps to achieve a hydrophilic coating, and therefore would not be cost-effective and / or time-efficient to implement in a mass production environment.

[0007] Therefore, a need remains for a cost-effective and time-efficient method for producing silicone hydrogel contact lenses with wettable and durable coatings (surfaces).

[0008] Summary of the Invention In one aspect, the present invention provides a method for producing a silicone hydrogel contact lens, each having a crosslinked hydrophilic coating, comprising the steps of: (a) providing a silicone hydrogel contact lens and a water-soluble, thermally crosslinkable hydrophilic polymeric material, wherein the contact lens contains amino and / or carboxyl groups on and / or near the surface of the contact lens, the hydrophilic polymeric material comprising: (i) about 20% to about 95% by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; and (ii) about 5% to about 80% by weight of hydrophilic moieties or second polymer chains, each derived from at least one hydrophilic enhancing agent having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof, wherein the hydrophilic moieties or second polymer chains are each derived from an epichlorohydrin-functionalized polyamine or polyamidoamine. and (iii) an azetidinium group that is part of the first polymer chain or is pendant or terminal to the first polymer chain; and (b) heating the contact lens in an aqueous solution in the presence of a hydrophilic polymeric material to and at about 40° C. to about 140° C. for a time sufficient to covalently bond the hydrophilic polymeric material to the surface of the contact lens via a second covalent bond formed between one azetidinium group of the hydrophilic polymeric material and one of the amino and / or carboxyl groups on and / or near the surface of the contact lens, respectively, thereby forming a crosslinked hydrophilic coating on the contact lens.

[0009] In another aspect, the present invention provides a silicone hydrogel contact lens obtainable by the method of the present invention, the silicone hydrogel contact lens having an oxygen permeability of at least about 40 barrers, surface wettability characterized by a water contact angle of about 100 degrees or less, and good coating durability characterized by withstanding a finger rub test.

[0010] In yet another aspect, the present invention provides an ophthalmic product comprising a sterilized and sealed lens package, wherein the lens package contains a post-autoclaving lens packaging solution and a ready-to-use silicone hydrogel contact lens immersed therein, and the ready-to-use silicone hydrogel contact lens comprises a crosslinked hydrophilic coating obtained by autoclaving a parent silicone hydrogel contact lens having amino and / or carboxyl groups on and / or near the surface of the parent silicone hydrogel contact lens in a pre-autoclaving packaging solution containing a water-soluble, thermally crosslinkable hydrophilic polymeric material, the hydrophilic polymeric material comprising: (i) from about 20% to about 95% by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; (ii) from about 5% to about 80% by weight of hydrophilic moieties or carboxyl groups derived from at least one hydrophilic enhancing agent having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof; (ii) a second polymer chain (wherein the hydrophilic portion or second polymer chain is covalently attached to the first polymer chain via one or more covalent bonds formed between one azetidinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine, respectively, and one amino, carboxyl, or thiol group of the hydrophilicity enhancer), and (iii) an azetidinium group that is part of the first polymer chain or is pendant or terminal to the first polymer chain, and the hydrophilic polymer material is a silicone hydrogel contact lens. and a second covalent bond formed between one amino or carboxyl group on and / or near the surface of the silicone hydrogel contact lens and one azetidinium group of the hydrophilic polymeric material, respectively, and the post-autoclaving packaging solution comprises at least one buffer and a hydrolysis product of the hydrophilic polymeric material in an amount sufficient to maintain a pH of from about 6.0 to about 8.5, and has a tonicity of from about 200 to about 450 milliosmoles (mOsm) and a viscosity of from about 1 centipoise to about 20 centipoise.

[0011] In yet another aspect, the present invention provides a water-soluble, thermally crosslinkable hydrophilic polymeric material comprising: (a) about 20% to about 95% by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; (b) about 5% to about 80% by weight of second polymer chains derived from at least one hydrophilicity-enhancing polymeric agent having at least one reactive functional group selected from the group consisting of an amino group, a carboxyl group, a thiol group, and combinations thereof, wherein the second polymer chains are covalently attached to the first polymer chains through one or more covalent bonds formed between one azetidinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl, or thiol group of the hydrophilicity-enhancing polymeric agent, respectively; and (c) azetidinium groups that are part of the first polymer chains or are pendant or terminal groups covalently attached to the first polymer chains.

[0012] These and other aspects of the present invention will become apparent from the following description of the presently preferred embodiment. This detailed description is merely illustrative of the present invention and is not intended to limit the scope of the invention, which is defined by the appended claims and their equivalents. As will be apparent to those skilled in the art, many variations and modifications of the present invention can be effected without departing from the spirit and scope of the novel concepts of the present disclosure.

[0013] Detailed Description of Embodiments of the Invention Embodiments of the present invention will now be described in detail. It will be apparent to those skilled in the art that various modifications, variations, and combinations can be made in the present invention without departing from the scope or spirit of the invention. For example, features illustrated or described as part of one embodiment can be used on another embodiment to yield a still further embodiment. Accordingly, the present invention intends to cover all such modifications, variations, and combinations as come within the scope of the appended claims and their equivalents. Other objects, features, and aspects of the present invention are disclosed in or are obvious from the following detailed description. It will be appreciated by those skilled in the art that this discussion is merely a description of exemplary embodiments and is not intended to limit the invention in its broader aspects.

[0014] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Generally, the nomenclature and laboratory procedures used herein are well known and commonly employed in the art. Conventional methods are used for these procedures, as provided in the art and various general references. Where a term is provided in the singular, the inventors also contemplate the plural of that term. The nomenclature used herein and the laboratory procedures described below are well known and commonly employed in the art.

[0015] "Silicone hydrogel contact lenses" refer to contact lenses comprising a silicone hydrogel material. "Silicone hydrogel" refers to a silicone-containing polymeric material that can absorb at least 10 weight percent water when fully hydrated and that is obtained by copolymerization of a polymerizable composition comprising at least one silicone-containing vinyl monomer, at least one silicone-containing vinyl macromer, or a silicone-containing prepolymer having at least one ethylenically unsaturated group.

[0016] "Vinyl monomer," as used herein, refers to a compound that has a single ethylenically unsaturated group and that can be polymerized actinically or thermally.

[0017] The terms "olefinically unsaturated group" or "ethylenically unsaturated group" are used broadly herein and are intended to encompass any group containing at least one >C=C< group. Exemplary ethylenically unsaturated groups include, but are not limited to, those of the formula:

[0018] [ka] (meth)acryloyl, allyl, and the like represented by the following formula:

[0019] [ka] The term "C═C" includes vinyl, styrenyl, or other C═C containing groups.

[0020] The term "(meth)acrylamide" refers to methacrylamide and / or acrylamide.

[0021] The term "(meth)acrylate" refers to methacrylate and / or acrylate.

[0022] "Hydrophilic vinyl monomer," as used herein, refers to a vinyl monomer that is water-soluble or that, when fully hydrated, gives rise to a polymer that can absorb at least 10 weight percent water, typically as a homopolymer.

[0023] "Hydrophobic vinyl monomer," as used herein, refers to a vinyl monomer that yields a polymer that is water insoluble and can absorb less than 10 weight percent water, typically as a homopolymer.

[0024] "Macromer" or "prepolymer" refers to medium and high molecular weight compounds or polymers containing two or more ethylenically unsaturated groups. Medium and high molecular weight typically means average molecular weights greater than 700 Daltons.

[0025] "Crosslinker" refers to a compound having at least two ethylenically unsaturated groups. "Crosslinking agent" refers to a crosslinking agent having a molecular weight of about 700 daltons or less.

[0026] "Polymer" means a material formed by polymerizing / crosslinking one or more monomers or macromers or prepolymers.

[0027] As used herein, the "molecular weight" of a polymeric material (including monomeric or macromeric materials) refers to the weight average molecular weight unless otherwise specified or unless specific testing conditions are indicated.

[0028] The term "amino group", unless otherwise specified, refers to an amino group of the formula: -NHR', where R' is hydrogen or C1-C 20 The term "amino group" refers to a primary or secondary amino group of the formula (wherein the formula is an unsubstituted or substituted, straight-chain or branched alkyl group).

[0029] "Epichlorohydrin-functionalized polyamine" or "epichlorohydrin-functionalized polyamidoamine" refers to a polymer obtained by reacting a polyamine or polyamidoamine with epichlorohydrin to convert all or a substantial percentage of the amine groups of the polyamine or polyamidoamine to azetidinium groups.

[0030] An "azetidinium group" is a group represented by the following formula:

[0031] [ka] It refers to a group having a positive charge represented by the formula:

[0032] The term "thermally crosslinkable" with respect to a polymeric material or functional group means that the polymeric material or functional group is capable of undergoing a crosslinking (or coupling) reaction with another material or functional group at relatively elevated temperatures (about 40°C to about 140°C), whereas the polymeric material or functional group is not capable of undergoing the same crosslinking (or coupling) reaction with another material or functional group at room temperature (i.e., about 22°C to about 28°C, preferably about 24°C to about 26°C, especially about 25°C) for an extended period of time that is detectable, such as about 1 hour.

[0033] The term "phosphorylcholine" has the formula:

[0034] [ka] [wherein n is an integer of 1 to 5, and R1, R2, and R3 are each independently C1-C8 alkyl or C1-C8 hydroxyalkyl].

[0035] The term "reactive vinyl monomer" refers to a vinyl monomer that contains a carboxyl group or an amino group (ie, a primary or secondary amino group).

[0036] The term "non-reactive hydrophilic vinyl monomer" refers to a hydrophilic vinyl monomer that lacks a carboxyl group or an amino group (i.e., a primary or secondary amino group). The non-reactive vinyl monomer may include a tertiary or quaternary amino group.

[0037] The term "water-soluble" with respect to a polymer means that the polymer is soluble in water to a sufficient extent to form an aqueous solution of the polymer having a concentration of up to about 30% by weight at room temperature (as defined above).

[0038] "Water contact angle" refers to the average water contact angle (i.e., the contact angle measured by the Sessile Drop method), which is obtained by averaging contact angle measurements with at least three individual contact lenses.

[0039] The term "intactness" with respect to a coating on a silicone hydrogel contact lens is intended to describe the degree to which the contact lens can be stained with Sudan Black in the Sudan Black Staining Test described in Example 1. Good intactness of a coating on a silicone hydrogel contact lens means that there is virtually no Sudan Black staining of the contact lens.

[0040] The term "durable" with respect to a coating on a silicone hydrogel contact lens is intended to describe that the coating on the silicone hydrogel contact lens can withstand a finger rub test.

[0041] As used herein, "withstands a finger rub test" or "withstands a durability test" with respect to a coating on a contact lens means that after rubbing the lens with a finger according to the procedure described in Example 1, the water contact angle of the finger-rubbed lens is still about 100 degrees or less, preferably about 90 degrees or less, more preferably about 80 degrees or less, and most preferably about 70 degrees or less.

[0042] The intrinsic "oxygen permeability," Dk, of a material is the rate at which oxygen permeates through the material. For purposes of the present invention, the term "oxygen permeability (Dk)" in reference to a hydrogel (silicone or non-silicone) or contact lens means the oxygen permeability (Dk) corrected for the surface resistance to oxygen flux due to boundary layer effects, according to the procedure set forth in the Examples hereinafter. Oxygen permeability is conventionally expressed in units of barrers, where "barrer" is defined as [(cm 3 oxygen)(mm) / (cm 2 )(sec)(mmHg)]×10 -10 is defined as:

[0043] The "oxygen transmissibility" of a lens or material, Dk / t, is the rate at which oxygen passes through a particular lens or material having an average thickness of t [units of mm] over a measured area. Oxygen transmissibility is conventionally expressed in units of barrer / mm, where "barrer / mm" is the number of bars per square meter (cm 3 oxygen) / (cm 2 )(sec)(mmHg)]×10 -9 is defined as:

[0044] The "ion permeability" through the lens is correlated with the ionoflux diffusion coefficient, D([mm 2 / min) is expressed by the following formula: D = -n' / (A × dc / dx) [where n' = rate of ion transport [mol / min]; A = exposed lens area [mm 2 ];dc = concentration difference [mol / L];dx = lens thickness [mm]], which can be calculated by applying Fick's law.

[0045] "Ophthalmically compatible," as used herein, refers to a material or surface of a material that can be placed in intimate contact with the ocular environment for extended periods of time without significant damage to the ocular environment and without significant discomfort to the user.

[0046] The term "ophthalmologically safe" with respect to a packaging solution for sterilizing and storing contact lenses means that contact lenses stored in the solution are safe for direct placement on the eye without post-autoclaving cleaning, and that the solution is safe and sufficiently comfortable for daily contact with the eye through the contact lens. An autoclaved ophthalmologically safe packaging solution has a tonicity and pH that is compatible with the eye, and is substantially free of materials that are ocular irritants or ocular cytotoxic according to international ISO standards and U.S. FDA regulations.

[0047] The present invention generally relates to a cost-effective and time-efficient method for producing silicone hydrogel contact lenses with durable hydrophilic coatings through the use of water-soluble, thermally crosslinkable hydrophilic polymeric materials having azetidinium groups.

[0048] The present invention is based in part on the surprising discovery that water-soluble, azetidinium-containing, thermally crosslinkable hydrophilic polymeric materials (which are the partial reaction product of polyamine-epichlorohydrin or polyamidoamine-epichlorohydrin with at least one hydrophilicity enhancing agent having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof) can be used to form crosslinked coatings with good surface hydrophilicity and / or wettability, good hydrophilicity, and good scratch integrity on silicone hydrogel contact lenses having carboxylic acid and / or amino groups on or near their surfaces. At relatively high temperatures (as defined above), the positively charged azetidinium groups react with the amino groups, thiol groups, and carboxylate ions -COO - (i.e., the deprotonated form of the carboxyl group), to give Scheme 1:

[0049] [ka] where R is the remainder of the compound and L is -NR'- (where R' is hydrogen, C1-C 20The azetidinium group forms a neutral hydroxyl-containing covalent bond as illustrated in the figure (wherein the azetidinium group is an unsubstituted or substituted, linear or branched alkyl group, or a polymer chain -S-, or -OC(=O)-). Due to the thermally controllable reactivity of the azetidinium group, polyamine-epichlorohydrin or polyamidoamine-epichlorohydrin (PAE) has been widely used as a wetting enhancer. However, PAE has not been successfully utilized to form crosslinked coatings on contact lenses, likely because crosslinked PAE coatings are unable to impart the desired hydrophilicity, wettability, and lubricity to contact lenses. Surprisingly, it has now been discovered that water-soluble azetidinium-containing polymeric materials can be obtained by chemically modifying PAE with a hydrophilic enhancer (especially a hydrophilic polymer) having one or more functional groups each capable of reacting with one azetidinium group in a "thermal pretreatment" or "pretreatment" process. Such polymeric materials, which are still thermally crosslinkable (reactive) due to the presence of azetidinium groups, can be used to form crosslinked coatings on silicone hydrogel contact lenses having reactive functional groups (e.g., amino groups, carboxyl groups, thiol groups, or combinations thereof) on and / or near their surfaces. Surprisingly, it has been discovered that the resulting crosslinked coatings on contact lenses derived from the water-soluble azetidinium-containing polymeric materials exhibit improved surface hydrophilicity, wettability, and / or lubricity compared to control coatings obtained using either unmodified (original or starting) PAE alone or a mixture of PAE and a hydrophilicity enhancing agent (without undergoing the thermal pretreatment to prepare the water-soluble azetidinium-containing polymeric material).

[0050] The hydrophilicity enhancer is believed to play at least two roles in improving the performance of the resulting crosslinked coating: by adding hydrophilic polymer chains to the polyamine or polyamidoamine polymer chains to form a highly branched hydrophilic polymeric material with pendant polymer chains and / or chain segments; and by significantly reducing the number of azetidinium groups in the crosslinkable polymeric material (coating material), thereby lowering the crosslink density of the crosslinked coating. Coatings with looser structures and pendant polymer chains and / or chain segments are believed to impart good surface hydrophilicity, wettability, and / or lubricity.

[0051] The present invention is also based in part on the discovery that the crosslinked coatings of the present invention can be advantageously formed directly on silicone hydrogel contact lenses in a lens package containing the contact lens immersed in a lens packaging solution in the presence of a water-soluble azetidinium-containing polymeric material. The presence of the azetidinium-containing polymeric material can be achieved either by adding the azetidinium-containing polymeric material to the lens packaging solution or by physical vapor deposition of a layer of the azetidinium-containing polymeric material onto the surface of the contact lens at room temperature prior to packaging.

[0052] Typically, contact lenses hydrated and packaged in a packaging solution must be sterilized. Sterilization of hydrated lenses during manufacture and packaging is typically achieved by autoclaving. The autoclaving process involves heating the contact lens package to a temperature of about 118°C to about 125°C under pressure for approximately 20 to 40 minutes. It has been discovered that during autoclaving, water-soluble azetidinium-containing polymeric materials can effectively crosslink with functional groups (e.g., amino, thiol, and / or carboxylic acid groups) on and / or near the surface of silicone hydrogel contact lenses to form wettable, ophthalmically compatible crosslinked coatings. During autoclaving, it is believed that azetidinium groups not participating in the crosslinking reaction are hydrolyzed to 2,3-dihydroxypropyl (HO-CH-CH(OH)-CH-) groups, converting the azetidinium-containing polymeric material present in the lens packaging solution, if applicable, into a non-reactive polymeric wetting material that can improve lens insertion comfort.

[0053] By utilizing the method of the present invention, the coating process can be combined with a sterilization step (autoclaving) in the manufacture of silicone hydrogel contact lenses. The resulting contact lenses not only have high surface hydrophilicity / wettability, minimal surface alteration, good abrasion resistance, and good durability, but also can be used directly from the lens package by patients without washing and / or rinsing because the packaging solution is ophthalmically compatible.

[0054] In one aspect, the present invention provides a method for producing a silicone hydrogel contact lens, each having a crosslinked hydrophilic coating, comprising the steps of: (a) providing a silicone hydrogel contact lens and a water-soluble, thermally crosslinkable hydrophilic polymeric material, wherein the contact lens contains amino and / or carboxyl groups on and / or near the surface of the contact lens, and the hydrophilic polymeric material comprises: (i) about 20% to about 95% by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; and (ii) about 5% to about 80% by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilic enhancing agent having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof, wherein the hydrophilic moieties or second polymer chains are each derived from an epichlorohydrin-functionalized polyamine or polyamidoamine. and (iii) an azetidinium group that is part of the first polymer chain or is pendant or terminal to the first polymer chain]; and (b) heating the contact lens in an aqueous solution in the presence of a hydrophilic polymeric material to and at about 40° C. to about 140° C. for a time sufficient to covalently bond the hydrophilic polymeric material to the surface of the contact lens via a second covalent bond formed between one azetidinium group of the hydrophilic polymeric material and one of the amino and / or carboxyl groups on and / or near the surface of the contact lens, respectively, thereby forming a crosslinked hydrophilic coating on the contact lens.

[0055] Those skilled in the art are familiar with methods for manufacturing contact lenses. For example, contact lenses can be manufactured in a conventional "rotomolding mold" as described in U.S. Patent No. 3,408,429, or by a static, fully cast-molded process as described in U.S. Patent Nos. 4,347,198; 5,508,317; 5,583,463; 5,789,464; and 5,849,810. In the cast-molding process, a lens formulation is typically poured into a mold and cured (i.e., polymerized and / or crosslinked) in the mold for producing the contact lens. In the manufacture of silicone hydrogel contact lenses, as is well known to those skilled in the art, the lens formulation for casting generally comprises at least one component selected from the group consisting of a silicone-containing vinyl monomer, a silicone-containing vinyl macromer, a silicone-containing prepolymer, a hydrophilic vinyl monomer, a hydrophilic vinyl macromer, a hydrophobic vinyl monomer, and combinations thereof. Silicone hydrogel contact lens formulations may also contain other necessary ingredients known to those skilled in the art, such as, for example, crosslinkers, UV absorbers, visible colorants (e.g., dyes, pigments, or mixtures thereof), antimicrobial agents (e.g., preferably silver nanoparticles), bioactive agents, leachable lubricants, leachable tear stabilizers, and mixtures thereof. The molded silicone hydrogel contact lenses may then be subjected to extraction with an extraction solvent, as known to those skilled in the art, to remove non-polymerized components from the molded lenses, and then subjected to a hydration process. Numerous silicone hydrogel lens formulations are described in numerous patents and patent applications published as of the filing date of this application.

[0056] In accordance with the present invention, silicone hydrogel contact lenses can inherently contain, or be modified to contain, amino and / or carboxyl groups on and / or near their surfaces.

[0057] Silicone hydrogel contact lenses inherently contain amino and / or carboxyl groups on and / or near their surfaces, which can be achieved by polymerizing a silicone hydrogel lens formulation containing reactive vinyl monomers.

[0058] Examples of preferred reactive vinyl monomers include, but are not limited to, amino-C2-C6 alkyl (meth)acrylate, C1-C6 alkylamino-C2-C6 alkyl (meth)acrylate, allylamine, vinylamine, amino-C2-C6 alkyl(meth)acrylamide, C1-C6 alkylamino-C2-C6 alkyl(meth)acrylamide, acrylic acid, C1-C 12 The silicone hydrogel contact lenses preferably contain alkyl acrylates (e.g., methacrylic acid, ethyl acrylate, propyl acrylate, butyl acrylate, etc.), N,N-2-acrylamidoglycolic acid, β-methyl-acrylic acid (crotonic acid), α-phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof. Preferably, the silicone hydrogel contact lenses contain amino-C2-C6 alkyl (meth)acrylates, C1-C6 alkylamino-C2-C6 alkyl (meth)acrylates, allylamine, vinylamine, amino-C2-C6 alkyl(meth)acrylamide, C1-C6 alkylamino-C2-C6 alkyl(meth)acrylamide, acrylic acid, C1-C6 alkylamino-C2-C6 alkyl(meth)acrylamide, C1-C6 alkylamino-C2-C6 alkyl(meth)acrylamide, C1-C6 alkylamino-C1 ... 12 The lens formulation is made from a lens containing at least one reactive vinyl monomer selected from the group consisting of alkylacrylic acid, N,N-2-acrylamidoglycolic acid, and combinations thereof, and preferably contains from about 0.1% to about 10%, more preferably from about 0.25% to about 7%, even more preferably from about 0.5% to about 5%, and most preferably from about 0.75% to about 3% (by weight) of the reactive vinyl monomer.

[0059] Silicone hydrogel contact lenses can also be subjected to surface treatments to form a reactive base coating having amino and / or carboxyl groups on the surface of the contact lens. Examples of surface treatments include, but are not limited to, energy-based surface treatments (e.g., plasma, electrostatic, irradiation, or other energy sources), chemical treatments, chemical vapor deposition, grafting of hydrophilic vinyl monomers or macromers onto the surface of the article, and layer-by-layer coatings ("LbL coatings") obtained by the methods described in U.S. Patent Nos. 6,451,871, 6,719,929, 6,793,973, 6,811,805, and 6,896,926, and U.S. Patent Application Publications 2007 / 0229758 A1, 2008 / 0152800 A1, and 2008 / 0226922 A1 (these are incorporated herein by reference in their entireties). "LbL coating," as used herein, refers to a coating that is not covalently bonded to the polymer matrix of a contact lens and that is obtained by layer-by-layer ("LbL") application of charged or chargeable (by protonation or deprotonation) and / or uncharged materials onto the lens. An LbL coating may be composed of one or more layers.

[0060] Preferably, the surface treatment is an LbL coating process. In this preferred embodiment (i.e., a reactive LbL-based coating embodiment), the resulting silicone hydrogel contact lens comprises a reactive LbL-based coating including at least one layer of a reactive polymer (i.e., a polymer having pendant amino and / or carboxyl groups), where the reactive LbL-based coating is obtained by contacting the contact lens with a solution of the reactive polymer. Contacting the contact lens with the reactive polymer coating solution can be done by immersing the contact lens in the coating solution or by spraying the contact lens with the coating solution. One contacting process involves exclusively immersing the contact lens in a bath of the coating solution for a fixed period of time, or by sequentially immersing the contact lens in a series of baths of the coating solution for a fixed short period of time for each bath. Another contacting process involves exclusively spraying the coating solution. However, several alternative methods involve various combinations of spraying and immersion steps that can be devised by one of ordinary skill in the art. The contact lens may be in contact with the reactive polymer coating solution for a maximum of about 10 minutes, preferably about 5 to about 360 seconds, more preferably about 5 to about 250 seconds, and even more preferably about 5 to about 200 seconds.

[0061] In this reactive LbL base coating embodiment, the reactive polymer can be a linear or branched polymer having pendant amino and / or carboxyl groups. Any polymer having pendant amino and / or carboxyl groups can be used as the reactive polymer for forming the base coating on a silicone hydrogel contact lens. Examples of such reactive polymers include, but are not limited to, homopolymers of reactive vinyl monomers; copolymers of two or more reactive vinyl monomers; copolymers of reactive vinyl monomers with one or more non-reactive hydrophilic vinyl monomers (i.e., hydrophilic vinyl monomers that do not contain either carboxyl or (primary or secondary) amino groups); polyethyleneimine (PEI); polyvinyl alcohol with pendant amino groups; carboxyl-containing celluloses (e.g., carboxymethyl cellulose, carboxyethyl cellulose, carboxypropyl cellulose); hyaluronate; chondroitin sulfate; poly(glutamic acid); poly(aspartic acid); and combinations thereof.

[0062] Examples of preferred reactive vinyl monomers are those mentioned above, however, carboxylic acid-containing vinyl monomers are the most preferred reactive vinyl monomers for preparing reactive polymers for forming reactive LbL base coatings.

[0063] Preferred examples of non-reactive hydrophilic vinyl monomers not containing a carboxyl or amino group include, but are not limited to, acrylamide (AAm), methacrylamide, N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA), N-vinylpyrrolidone (NVP), N,N-dimethylaminoethyl methacrylate (DMAEM), N,N-dimethylaminoethyl acrylate (DMAEA), N,N-dimethylaminopropyl methacrylamide (DMAPMAm), N,N-dimethylaminopropyl acrylamide (DMAPAAm), glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl- Included are 5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, C1-C4-alkoxypolyethylene glycol (meth)acrylates having a weight average molecular weight of 1500 daltons or less, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymers), phosphorylcholine-containing vinyl monomers (including (meth)acryloyloxyethyl phosphorylcholine and those described in U.S. Pat. No. 5,461,433, the entirety of which is incorporated herein by reference), and combinations thereof.

[0064] Preferably, the reactive polymer for forming the reactive LbL based coating is polyacrylic acid, polymethacrylic acid, poly(C2-C3) 12 alkylacrylic acid), poly[acrylic acid-co-methacrylic acid], poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone], poly[C2-C 12alkylacrylic acid-co-acrylamide], poly[C2-C 12 alkylacrylate-co-vinylpyrrolidone], hydrolyzed poly[(meth)acrylate-co-vinyl acetate], hydrolyzed poly[C2-C 12 alkylacrylic acid-co-vinyl acetate], polyethyleneimine (PEI), polyallylamine hydrochloride (PAH) homo- or copolymer, polyvinylamine homo- or copolymer, or combinations thereof.

[0065] The weight average molecular weight M of the reactive polymer to form the reactive LbL-based coating W is at least about 10,000 daltons, preferably at least about 50,000 daltons, and more preferably from about 100,000 daltons to about 5,000,000 daltons.

[0066] A solution of reactive polymers for forming a reactive LbL base coating on a contact lens can be prepared by dissolving one or more reactive polymers in water, a mixture of water and one or more water-miscible organic solvents, an organic solvent, or a mixture of one or more organic solvents. Preferably, the reactive polymers are dissolved in a mixture of water and one or more organic solvents, an organic solvent, or a mixture of one or more organic solvents. It is believed that a solvent system containing at least one organic solvent can swell a silicone hydrogel contact lens, allowing a portion of the reactive polymer to penetrate the silicone hydrogel contact lens and improve the durability of the reactive base coating.

[0067] Any organic solvent can be used to prepare the solution of the reactive polymer. Examples of preferred organic solvents include, but are not limited to, tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, ketones (e.g., acetone, methyl ethyl ketone, etc.), diethylene glycol n-butyl ether, diethylene glycol methyl ether, ethylene glycol phenyl ether, propylene glycol methyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether acetate, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, propylene glycol n-butyl ether, dipropylene glycol n-butyl ether, tripropylene glycol n-butyl ether, propylene glycol phenyl ether ethanol, dipropylene glycol dimethyl ether, polyethylene glycols, polypropylene glycols, ethyl acetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate, i-propyl lactate, methylene chloride, methanol, ethanol, 1- or 2-propanol, 1- or 2-butanol, tert-butanol, tert-amyl alcohol, menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-Dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol, 2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol Examples of suitable cyclopentanols include ethanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol, 3-hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol, 2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol, and 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl-2-pyrrolidone, N,N-dimethylpropionamide, dimethylformamide, dimethylacetamide, dimethylpropionamide, N-methylpyrrolidinone, and mixtures thereof.

[0068] In another preferred embodiment, the silicone hydrogel inherently contains amino and / or carboxyl groups on and / or near its surface and is further subjected to a surface treatment to form a reactive LbL base coating having amino and / or carboxyl groups therein.

[0069] In another preferred embodiment (reactive plasma-based coating), silicone hydrogel contact lenses are subjected to a plasma treatment to form a covalently bonded reactive plasma-based coating on the contact lens, i.e., one or more reactive vinyl monomers (any of those mentioned above) are polymerized under the influence of plasma generated by an electrical discharge (so-called plasma-induced polymerization). The term "plasma" refers to an ionized gas, such as that produced by a glow discharge, which may consist of electrons in the ground state or any higher state of excitation of any type, ions of either polarity, gas atoms and molecules, and even photons. This is often referred to as "low-temperature plasma."For reviews of plasma polymerization and its uses, see R. Hartmann, "Plasma polymerisation: Grundlagen, Technik und Anwendung, Jahrb. Oberflachentechnik (1993) 49, pp. 283-296, Battelle-Inst. eV Frankfurt / Main Germany; H. Yasuda, "Glow Discharge Polymerisation", Journal of Polymer Science: Macromolecular Reviews, vol. 16 (1981 ), pp. 199-293; H. Yasuda, "Plasma Polymerisation", Academic Press, Inc. (1985); Frank Jansen, "Plasma Deposition Processes", in "Plasma Deposited Thin Films", ed. by T. Mort and F. Jansen, CRC Press Boca Raton (1985); O. Auciello et al. (ed.) "Plasma-Surface Interactions and Processing of Materials", publ. by Kluwer Reference is made to Academic Publishers in NATO ASI Series; Series E: Applied Sciences, vol. 176 (1990), pp. 377-399; and N. Dilsiz and G. Akovali "Plasma Polymerization of Selected Organic Compounds", Polymer, vol. 37 (1996) pp. 333-341. Preferably, the plasma-induced polymerization is the "afterglow" type plasma-induced polymerization described in WO 98028026, the entire contents of which are incorporated herein by reference.In "afterglow" type plasma polymerization, the surface of the contact lens is first treated with a non-polymerizing plasma gas (e.g., H, He, or Ar), and then in a subsequent step the thus activated surface is exposed to a vinyl monomer having an amino or carboxyl group (any of the reactive vinyl monomers described above), while the plasma power is turned off. Activation results in the plasma-induced formation of radicals on the surface, which in a subsequent step initiates the polymerization of the vinyl monomer thereon.

[0070] In the present invention, the water-soluble, thermally crosslinkable hydrophilic polymeric material containing azetidinium groups comprises (i.e., has a composition including) about 20% to about 95%, preferably about 35% to about 90%, and more preferably about 50% to about 85% (by weight) of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, and about 5% to about 80%, preferably about 10% to about 65%, and even more preferably about 15% to about 50% (by weight) of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity enhancer having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof. The composition of the hydrophilic polymeric material is determined by the composition (based on the total weight of the reactants) of the reactant mixture used to prepare the thermally crosslinkable hydrophilic polymeric material by the crosslinking reaction shown in Scheme I above. For example, if the reactant mixture contains about 75 wt. % of epichlorohydrin-functionalized polyamine or polyamidoamine and about 25 wt. % of at least one hydrophilic enhancing agent, based on the total weight of the reactants, the resulting hydrophilic polymeric material will contain about 75 wt. % of the first polymer chains derived from the epichlorohydrin-functionalized polyamine or polyamidoamine and about 25 wt. % of the hydrophilic portion or second polymer chains derived from the at least one hydrophilic enhancing agent. The azetidinium groups of the thermally crosslinkable hydrophilic polymeric material are the azetidinium groups (of the epichlorohydrin-functionalized polyamine or polyamidoamine) that do not participate in the crosslinking reaction to prepare the thermally crosslinkable hydrophilic polymeric material.

[0071] Epichlorohydrin-functionalized polyamines or polyamidoamines can be obtained by reacting epichlorohydrin with polyamine polymers or polymers containing primary or secondary amino groups. For example, poly(alkyleneimines) or poly(amidoamines), which are polycondensates derived from polyamines and dicarboxylic acids (e.g., adipic acid-diethylenetriamine copolymers), can be reacted with epichlorohydrin to form epichlorohydrin-functionalized polymers. Similarly, aminoalkyl (meth)acrylates, mono-alkylaminoalkyl (meth)acrylates, aminoalkyl (meth)acrylamides, or mono-alkylaminoalkyl (meth)acrylamides can also be reacted with epichlorohydrin to form epichlorohydrin-functionalized polyamines. Reaction conditions for epichlorohydrin functionalization of polyamine or polyamidoamine polymers are taught in EP 1465931 (incorporated herein by reference in its entirety). Preferred epichlorohydrin-functionalized polymers are polyaminoamide-epichlorohydrin (PAE) (or polyamide-polyamine-epichlorohydrin or polyamide-epichlorohydrin), such as Kymene® or Polycup® resins (epichlorohydrin-functionalized adipic acid-diethylenetriamine copolymers) from Hercules or Polycup® or Servamine® resins from Servo / Delden.

[0072] Any suitable hydrophilicity enhancer can be used in the present invention so long as it contains at least one amino group, at least one carboxyl group, and / or at least one thiol group.

[0073] Preferred types of hydrophilicity enhancers include, but are not limited to, amino-, carboxyl-, or thiol-containing monosaccharides (e.g., 3-amino-1,2-propanediol, 1-thioglycerol, 5-keto-D-gluconic acid, galactosamine, glucosamine, galacturonic acid, gluconic acid, glucosamine acid, mannosamine, sugar acid 1,4-lactone, saccharic acid, ketodeoxynonulosonic acid, N-methyl-D-glucamine, 1-amino-1-deoxy-β-D-galactose, 1-amino-1-deoxysorbitol, amino-, carboxyl-, or thiol-containing disaccharides (e.g., chondroitin disaccharide sodium salt, di(β-D-xylopyranosyl)amine, digalacturonic acid, heparin disaccharide, hyaluronic acid disaccharide, lactobionic acid); and amino-, carboxyl-, or thiol-containing oligosaccharides (e.g., carboxymethyl-β-cyclodextrin sodium salt, trigalacturonic acid); and combinations thereof.

[0074] Another preferred type of hydrophilic enhancer is a hydrophilic polymer having one or more amino, carboxyl, and / or thiol groups. More preferably, the content of monomer units having amino (-NHR' (R' is as defined above), carboxyl (-COOH), and / or thiol (-SH) groups in the hydrophilic polymer as the hydrophilic enhancer is less than about 40%, preferably less than about 30%, more preferably less than about 20%, and even more preferably less than about 10% (wt %) based on the total weight of the hydrophilic polymer.

[0075] Another preferred class of hydrophilic polymers as hydrophilicity enhancers are amino- or carboxyl-containing polysaccharides, such as carboxymethylcellulose (repeating unit: -[CH 10-m O5(CH2CO2H) m ]- (where m is 1 to 3), carboxyethyl cellulose (repeating unit: -[CH 10-m O5(C2H4CO2H) m]- (where m is 1 to 3), carboxypropyl cellulose (repeating unit: -[CH 10-m O5(C3H6CO2H) m ]- (where m is 1 to 3), hyaluronic acid (having a carboxyl content of about 32% or less, estimated based on the composition: -(C 13 H 20 chondroitin sulfate (repeating unit: -(C 12 H 18 O 13 NSCO2H)—), or combinations thereof.

[0076] Another preferred class of hydrophilic polymers as hydrophilic enhancers includes, but is not limited to, poly(ethylene glycol) (PEG) with only one amino, carboxyl, or thiol group (e.g., PEG-NH2, PEG-SH, PEG-COOH); H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; multi-arm PEG with one or more amino, carboxyl, and / or thiol groups; PEG dendrimers with one or more amino, carboxyl, and / or thiol groups. diamino- or dicarboxyl-terminated homo- or copolymers of non-reactive hydrophilic vinyl monomers; monoamino- or monocarboxyl-terminated homo- or copolymers of non-reactive hydrophilic vinyl monomers; copolymers that are the polymerization product of a composition comprising (1) up to about 50% by weight, preferably about 0.1% to about 30%, more preferably about 0.5% to about 20%, and even more preferably about 1% to about 15% (by weight) of one or more reactive vinyl monomers and (2) at least one non-reactive hydrophilic vinyl monomer and / or at least one phosphorylcholine-containing vinyl monomer; and combinations thereof. The reactive vinyl monomers and non-reactive hydrophilic vinyl monomers are as described above.

[0077] More preferably, the hydrophilic polymer as the hydrophilicity enhancer is PEG-NH2; PEG-SH; PEG-COOH; H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; multi-arm PEG having one or more amino, carboxyl or thiol groups; PEG dendrimers having one or more amino, carboxyl or thiol groups; acrylamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, or a weight average molecular weight of 400 daltons or less. (1) a monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated homo- or copolymer of a non-reactive hydrophilic vinyl monomer selected from the group consisting of C1-C4-alkoxypolyethylene glycol (meth)acrylate, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, N,N-dimethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylamide, (meth)acryloyloxyethyl phosphorylcholine, and combinations thereof; (2) about 0.1% to about 30%, preferably about 0.5% to about 20%, and more preferably about 1% to about 15% (by weight) of (meth)acrylic acid, C2-C 12The copolymer is the polymerization product of a composition comprising alkyl acrylic acid, vinylamine, allylamine, and / or amino-C2-C4 alkyl (meth)acrylate, and (2) (meth)acryloyloxyethyl phosphorylcholine and / or at least one non-reactive hydrophilic vinyl monomer selected from the group consisting of acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of 400 Daltons or less, vinyl alcohol, and combinations thereof.

[0078] Most preferably, the hydrophilic polymer as the hydrophilicity enhancer is selected from the group consisting of PEG-NH2, PEG-SH, PEG-COOH, monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated polyvinylpyrrolidone, monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated polyacrylamide, monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly(DMA), monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly(DMA-co-NVP), monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly(NVP-co-N,N-dimethylaminoethyl(meth)acrylate), monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly(vinyl alcohol), monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly[(meth)acryloyloxyethylphosphorylcholine] homopolymer or copolyol. monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly(NVP-co-vinyl alcohol); monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly(DMA-co-vinyl alcohol); poly[(meth)acrylic acid-co-acrylamide] containing about 0.1% to about 30%, preferably about 0.5% to about 20%, and more preferably about 1% to about 15% (by weight) of (meth)acrylic acid; Poly[(meth)acrylic acid-co-NVP] containing about 0.5% to about 20%, more preferably about 1% to about 15% (by weight) of (meth)acrylic acid; copolymers that are the polymerization product of a composition containing (1) (meth)acryloyloxyethyl phosphorylcholine and (2) about 0.1% to about 30%, preferably about 0.5% to about 20%, more preferably about 1% to about 15% (by weight) of a carboxylic acid-containing vinyl monomer and / or an amino-containing vinyl monomer; and combinations thereof.

[0079] Functionalized PEGs and functionalized multi-armed PEGs are available from a variety of suppliers, such as Polyscience and Shearwater Polymers, Inc.

[0080] Monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated homo- or copolymers of one or more nonreactive hydrophilic vinyl monomers or phosphorylcholine-containing vinyl monomers can be prepared by the procedures described in U.S. Patent No. 6,218,508 (incorporated herein by reference in its entirety). For example, to prepare diamino- or dicarboxyl-terminated homo- or copolymers of nonreactive hydrophilic vinyl monomers, the nonreactive vinyl monomer, a chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid, or other hydroxymercaptans, aminomercaptans, or carboxyl-containing mercaptans), and optionally other vinyl monomers are copolymerized (thermally or by actinic radiation) with a reactive vinyl monomer (having an amino or carboxyl group) in the presence of a free radical initiator. Typically, the molar ratio of chain transfer agent to all vinyl monomers other than the reactive vinyl monomer is about 1:5 to about 1:100, while the molar ratio of chain transfer agent to the reactive vinyl monomer is 1:1. In such preparations, a chain transfer agent having an amino or carboxyl group is used to control the molecular weight of the resulting hydrophilic polymer by forming the terminal end of the resulting hydrophilic polymer, thereby providing one terminal amino or carboxyl group on the resulting hydrophilic polymer, while the reactive vinyl monomer provides the other terminal carboxyl or amino group on the resulting hydrophilic polymer. Similarly, to prepare monoamino- or monocarboxyl-terminated homo- or copolymers of a non-reactive hydrophilic vinyl monomer, the non-reactive vinyl monomer, a chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid, or other hydroxymercaptans, aminomercaptans, or carboxyl-containing mercaptans), and optionally other vinyl monomers are copolymerized (thermally or by actinic radiation) in the absence of any reactive vinyl monomer.

[0081] As used herein, a copolymer of a non-reactive hydrophilic vinyl monomer refers to the polymerization product of a non-reactive hydrophilic vinyl monomer and one or more additional vinyl monomers. Copolymers containing a non-reactive hydrophilic vinyl monomer and a reactive vinyl monomer (e.g., a carboxyl-containing vinyl monomer) can be prepared by any known radical polymerization method or obtained from a supplier. Copolymers containing methacryloyloxyethyl phosphorylcholine and a carboxyl-containing vinyl monomer are available from NOP Corporation (e.g., LIPIDURE®-A and -AF).

[0082] The weight average molecular weight M of a hydrophilic polymer (as a hydrophilic enhancer) having at least one amino, carboxyl or thiol group W is preferably about 500 to about 1,000,000, and more preferably about 1,000 to about 500,000.

[0083] In the present invention, the reaction between the hydrophilicity enhancer and the epichlorohydrin-functionalized polyamine or polyamidoamine is carried out at a temperature of about 40°C to about 100°C for a time sufficient to form a water-soluble, thermally crosslinkable hydrophilic polymeric material containing azetidinium groups (about 0.3 hours to about 24 hours, preferably about 1 hour to about 12 hours, and more preferably about 2 hours to about 8 hours).

[0084] In the present invention, the concentration of hydrophilicity enhancing agent relative to the epichlorohydrin-functionalized polyamine or polyamidoamine should be selected so that the resulting hydrophilic polymeric material is not water-insoluble (i.e., has a solubility of less than 0.005 g per 100 ml of water at room temperature) and so that more than about 99%, preferably about 98%, more preferably about 97%, and even more preferably about 96% of the azetidinium groups of the epichlorohydrin-functionalized polyamine or polyamidoamine are not used up.

[0085] In the present invention, the heating step is preferably carried out by autoclaving the silicone hydrogel contact lens immersed in the packaging solution in the sealed lens package for approximately 20 to 90 minutes at a temperature of about 118° C. to about 125° C. In this embodiment of the invention, the packaging solution is a buffered aqueous solution that is ophthalmically safe after autoclaving.

[0086] Lens packages (or containers) are well known to those skilled in the art for autoclaving and storing soft contact lenses. Any lens package can be used in the present invention. Preferably, the lens package is a blister package comprising a base and a cover, wherein the cover is removably sealed to the base, and the base contains a cavity for receiving a sterile packaging solution and a contact lens.

[0087] The lenses are packaged in individual packages, sealed, and sterilized (e.g., by autoclaving at about 120° C. or higher for at least 30 minutes) before being delivered to the user. Those skilled in the art will be familiar with methods for sealing and sterilizing lens packages.

[0088] In the present invention, the packaging solution contains at least one buffer and one or more other ingredients known to those skilled in the art, including, but not limited to, tonicity agents, surfactants, antimicrobial agents, preservatives, and lubricants (or water-soluble thickeners) (e.g., cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone).

[0089] The packaging solution contains a buffering agent in an amount sufficient to maintain the pH of the packaging solution within a desired range, preferably within a physiologically acceptable range of about 6 to about 8.5. Any known physiologically compatible buffering agent can be used. Buffering agents suitable as components of the contact lens care compositions of the present invention are known to those skilled in the art. Examples include boric acid, boric acid salts such as sodium borate, citric acid, citrate salts such as potassium citrate, bicarbonates such as sodium bicarbonate, TRIS (2-amino-2-hydroxymethyl-1,3-propanediol), Bis-Tris (bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane), bisaminopolyols, triethanolamine, ACES (N-(2-hydroxyethyl)-2-aminoethanesulfonic acid), BES (N,N-bis(2-hydroxyethyl) Examples of suitable bisaminopolyols include 1,3-bis(tris[hydroxymethyl]methylamino)propane (bis-TRIS-propane), ... The amount of each buffer in the packaging solution is preferably 0.001% to 2%, preferably 0.01% to 1%; most preferably about 0.05% to about 0.30% (wt %).

[0090] The packaging solution has a tonicity of about 200 to about 450 milliosmoles (mOsm), preferably about 250 to about 350 mOsm. The tonicity of the packaging solution can be adjusted by adding organic or inorganic substances that affect tonicity. Suitable ophthalmically acceptable tonicity agents include, but are not limited to, sodium chloride, potassium chloride, glycerol, propylene glycol, polyols, mannitols, sorbitol, xylitol, and mixtures thereof.

[0091] The packaging solution of the present invention has a viscosity at 25°C of about 1 to about 20 centipoise, preferably about 1.2 to about 10 centipoise, and more preferably about 1.5 to about 5 centipoise.

[0092] In a preferred embodiment, the packaging solution preferably contains from about 0.01% to about 2%, more preferably from about 0.05% to about 1.5%, even more preferably from about 0.1% to about 1%, and most preferably from about 0.2% to about 0.5% (by weight) of the water-soluble, thermally crosslinkable hydrophilic polymeric material of the present invention.

[0093] The packaging solution of the present invention can contain a thickening polymer, which is preferably nonionic. Increasing the viscosity of the solution can provide a film on the lens, which can facilitate comfortable contact lens wear. The thickening component also acts to cushion the ocular surface during insertion and reduce eye irritation.

[0094] Preferred thickening polymers include, but are not limited to, water-soluble cellulose ethers (e.g., methyl cellulose (MC), ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), or mixtures thereof), water-soluble polyvinyl alcohols (PVA), high molecular weight poly(ethylene oxide) having a molecular weight greater than about 2000 daltons (up to 10,000,000 daltons), polyvinylpyrrolidone having a molecular weight of about 30,000 daltons to about 1,000,000 daltons, copolymers of N-vinylpyrrolidone and at least one dialkylaminoalkyl (meth)acrylate having 7 to 20 carbon atoms, and combinations thereof. Water-soluble cellulose ethers and copolymers of vinylpyrrolidone and dimethylaminoethyl methacrylate are the most preferred thickening polymers. Copolymers of N-vinylpyrrolidone and dimethylaminoethyl methacrylate are commercially available (e.g., Copolymer 845 and Copolymer 937, manufactured by ISP).

[0095] The thickening polymer is present in the packaging solution in an amount of about 0.01% to about 5% by weight, preferably about 0.05% to about 3% by weight, and more preferably about 0.1% to about 1% by weight, based on the total weight of the packaging solution.

[0096] The packaging solution can further include polyethylene glycol having a molecular weight of about 1200 or less, more preferably 600 or less, and most preferably from about 100 to about 500 daltons.

[0097] When at least one of the crosslinking coating and packaging solution contains a polymeric material having polyethylene glycol segments, the packaging solution preferably contains an α-oxo-polybasic acid or a salt thereof in an amount sufficient to reduce the susceptibility of the polyethylene glycol segments to oxidative degradation. A commonly owned, co-pending patent application (U.S. Patent Application Publication No. 2004 / 0116564 A1, incorporated herein in its entirety) discloses that an oxo-polybasic acid or a salt thereof can reduce the susceptibility of PEG-containing polymeric materials to oxidative degradation.

[0098] Exemplary α-oxo-polybasic acids or biocompatible salts thereof include, but are not limited to, citric acid, 2-ketoglutaric acid, or malic acid or a biocompatible (preferably ophthalmically compatible) salt thereof. More preferably, the α-oxo-polybasic acid is citric acid or malic acid or a biocompatible (preferably ophthalmically compatible) salt thereof (e.g., sodium, potassium, etc.).

[0099] In the present invention, the packaging solution may further comprise a mucin-like substance, an ophthalmic benefit substance, and / or a surfactant.

[0100] Exemplary mucin-like substances include, but are not limited to, polyglycolic acid, polylactide, etc. Mucin-like substances can be used as guest substances that can be continuously and slowly released over an extended period of time onto the ocular surface for the treatment of dry eye syndrome. The mucin-like substance is preferably present in an effective amount.

[0101] Exemplary ophthalmic beneficial agents include, but are not limited to, 2-pyrrolidone-5-carboxylic acid (PCA), amino acids (e.g., taurine, glycine, etc.), alpha-hydroxy acids (e.g., glycolic acid, lactic acid, malic acid, tartaric acid, mandelic acid, and citric acid and their salts), linoleic acid and gamma-linoleic acid, and vitamins (e.g., B5, A, B6, etc.).

[0102] The surfactant may be virtually any ophthalmically acceptable surfactant, including nonionic, anionic, and amphoteric surfactants. Examples of preferred surfactants include, but are not limited to, poloxamers (e.g., Pluronic® F108, F88, F68, F68LF, F127, F87, F77, P85, P75, P104, and P84), polamines (e.g., Tetronic® 707, 1107, and 1307), polyethylene glycol esters of fatty acids (e.g., Tween® 20, Tween® 80), C 12 -C 18 These include polyoxyethylene or polyoxypropylene ethers of alkanes (e.g., Brij® 35), polyoxyethylene stearate (Myrj® 52), polyoxyethylene propylene glycol stearate (Atlas® G2612), and amphoteric surfactants under the trade names Mirataine® and Miranol®.

[0103] Silicone hydrogel contact lenses obtained by the methods of the present invention preferably have a surface hydrophilicity / wetability characterized by an average water contact angle of about 90 degrees or less, more preferably about 80 degrees or less, even more preferably about 70 degrees or less, and most preferably about 60 degrees or less.

[0104] In another preferred embodiment, the method of the present invention can further comprise the steps of contacting the silicone hydrogel contact lens with an aqueous solution of a thermally crosslinkable hydrophilic polymeric material at room temperature to form a top layer of thermally crosslinkable hydrophilic polymeric material (i.e., an LbL coating) on ​​the surface of the silicone hydrogel contact lens, prior to the heating step; immersing the silicone hydrogel contact lens with the top layer of thermally crosslinkable hydrophilic polymeric material in a packaging solution in a lens package; sealing the lens package; and autoclaving the lens package containing the silicone hydrogel contact lens to form a crosslinked hydrophilic coating on the silicone hydrogel contact lens. Because of its positive charge, the thermally crosslinkable hydrophilic polymeric material is believed to be capable of forming an LbL coating on the silicone hydrogel contact lens (i.e., through physical interaction) that is not covalently bonded to the surface of the silicone hydrogel contact lens, particularly for contact lenses having negatively charged carboxyl groups on their surface.

[0105] Although the various embodiments, including preferred embodiments, of the present invention are described separately above, it will be understood that each of these can be combined and / or used together in any desired manner in the method of the present invention for producing a silicone hydrogel contact lens with a crosslinked hydrophilic coating.

[0106] In another aspect, the present invention provides a silicone hydrogel contact lens obtainable by the method of the above invention.

[0107] In yet another aspect, the present invention provides an ophthalmic product comprising a sterilized and sealed lens package, wherein the lens package comprises a post-autoclaving lens packaging solution and a ready-to-use silicone hydrogel contact lens immersed therein, and the ready-to-use silicone hydrogel contact lens comprises a crosslinked hydrophilic coating obtained by autoclaving a parent silicone hydrogel contact lens having amino and / or carboxyl groups on and / or near the surface of the parent silicone hydrogel contact lens in a pre-autoclaving packaging solution containing a water-soluble, thermally crosslinkable hydrophilic polymeric material, the hydrophilic polymeric material comprising: (i) about 20% to about 95%, preferably about 35 to about 90%, more preferably about 50% to about 85% (by weight) of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; (ii) at least one reactive group selected from the group consisting of an amino group, a carboxyl group, a thiol group, and combinations thereof; about 5% to about 80%, preferably about 10% to about 65%, and even more preferably about 15% to about 50% (by weight) of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity enhancing agent having a reactive functional group, wherein the hydrophilic moieties or second polymer chains are covalently attached to the first polymer chains via one or more covalent bonds formed between one azetidinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl, or thiol group of the hydrophilicity enhancing agent, respectively; and (ii) i) an azetidinium group that is part of a first polymer chain or that is pendant or terminally bonded to the first polymer chain, and the hydrophilic polymeric material is covalently bonded to the silicone hydrogel contact lens via a first covalent bond formed between one amino or carboxyl group on and / or near the surface of the silicone hydrogel contact lens and one azetidinium group of the thermally crosslinkable hydrophilic polymeric material, respectively; and the post-autoclaving packaging solution has a pH of about 6.0 to about 8.and a tonicity of about 200 to about 450 milliosmoles (mOsm), preferably about 250 to about 350 mOsm, and a viscosity of about 1 centipoise to about 20 centipoise, preferably about 1.2 centipoise to about 10 centipoise, and more preferably about 1.5 centipoise to about 5 centipoise at 25°C; the post-autoclave packaging solution comprises a polymeric wetting material that is the hydrolysis product of a thermally crosslinkable hydrophilic polymeric material after autoclaving; and the ready-to-use silicone hydrogel contact lens has a surface hydrophilicity / wetability characterized by an average water contact angle of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, even more preferably about 60 degrees or less, and most preferably about 50 degrees or less.

[0108] "Ready-to-use silicone hydrogel contact lenses" refer to silicone hydrogel contact lenses that are ophthalmically compatible and have been sterilized by autoclaving. "Original silicone hydrogel contact lenses" refer to silicone hydrogel contact lenses that lack a cross-linked hydrophilic coating and have not been sterilized by autoclaving.

[0109] Various embodiments have been described above, including preferred embodiments of silicone hydrogel contact lenses essentially having amino and / or carboxyl groups, silicone hydrogel contact lenses having a reactive base coating, reactive vinyl monomers, non-reactive vinyl monomers, reactive polymers for forming reactive LbL base coatings, plasma coatings, epichlorohydrin-functionalized polyamines or polyamidoamines, hydrophilicity enhancing agents, water-soluble hydrophilic polymeric materials having azetidinium groups, heating processes, lens packages, packaging solutions, and surface wettability of silicone hydrogel contact lenses having crosslinked hydrophilic coatings of the present invention, which can be combined and / or used together in these two aspects of the present invention.

[0110] The ready-to-use silicone hydrogel contact lenses of the present invention have an oxygen permeability of at least about 40 barrers, preferably at least about 50 barrers, more preferably at least about 60 barrers, and even more preferably about 70 barrers; a center thickness of about 30 to about 200 microns, more preferably about 40 to about 150 microns, even more preferably about 50 to about 120 microns, and most preferably about 60 to about 110 microns; a modulus of elasticity of about 1.5 MPa or less, preferably about 1.2 MPa or less, more preferably about 1.0 MPa or less, and even more preferably about 0.3 MPa to about 1.0 MPa; and a viscosity of preferably at least about 1.5 x 10 -6 mm 2 / min, more preferably at least about 2.6 x 10 -6 mm 2 / min, and even more preferably at least about 6.4 x 10 -6 mm 2 / min, ionoflux diffusion coefficient, D; a water content of preferably about 18% to about 70%, more preferably about 20% to about 60% (by weight) when fully hydrated; or a combination thereof. It has.

[0111] The water content of silicone hydrogel contact lenses can be measured by the bulk method disclosed in US Pat. No. 5,849,811.

[0112] In a further aspect, the present invention provides a water-soluble, thermally crosslinkable hydrophilic polymeric material comprising: (a) from about 20% to about 95%, preferably from about 35% to about 90%, and more preferably from about 50% to about 85% (by weight) of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; (b) from about 5% to about 80%, preferably from about 10% to about 15% of first polymer chains derived from at least one hydrophilic enhancing polymeric agent having at least one reactive functional group selected from the group consisting of an amino group, a carboxyl group, a thiol group, and combinations thereof; Provided is a material comprising: (a) 0% to about 65%, and even more preferably about 15% to about 50% (by weight) of a second polymer chain, wherein the second polymer chain is covalently attached to the first polymer chain via one or more covalent bonds formed between one azetidinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl, or thiol group of the hydrophilicity-enhancing polymeric agent, respectively; and (c) an azetidinium group that is part of the first polymer chain or a pendant group covalently attached to the first polymer chain.

[0113] Various embodiments, including preferred embodiments of reactive vinyl monomers, non-reactive vinyl monomers, epichlorohydrin-functionalized polyamines or polyamidoamines, and hydrophilic polymers as hydrophilicity enhancers, are described above and can be combined and / or used together in any manner in this aspect of the invention.

[0114] The above disclosure will enable one of ordinary skill in the art to practice the present invention. Various modifications, variations, and combinations can be made to the various embodiments described herein. Reference to the following examples is proposed to enable the reader to better understand the specific embodiments and advantages thereof. It is intended that the specification and examples be considered as illustrative.

[0115] Although various embodiments of the invention have been described using specific terms, devices, and methods, such description is for purposes of illustration only. The words used are words of description rather than of limitation. It will be understood that modifications and variations can be made by those skilled in the art without departing from the spirit or scope of the invention as set forth in the following claims. It will further be understood that aspects of the various embodiments can be interchanged in whole or in part or can be combined and / or used together in any manner. Accordingly, the spirit and scope of the appended claims should not be limited to the description of the preferred versions contained therein.

[0116] Example 1 Oxygen permeability measurement The apparent oxygen permeability of a lens and the oxygen transmissibility of a lens material are measured by techniques similar to those described in U.S. Patent No. 5,760,100 and in Winterton et al., The Cornea: Transactions of the World Congress on the Cornea 111, H.D. Cavanagh Ed., Raven Press: New York 1988, pp. 273-280, both of which are incorporated herein by reference in their entireties. Oxygen flux (J) is measured at 34°C in a wet cell (i.e., gas flow maintained at approximately 100% relative humidity) using a Dk1000 instrument (available from Applied Design and Development Co., Norcross, GA) or similar analytical device. An air flow with a known percentage of oxygen (e.g., 21%) is measured at a flow rate of approximately 10-20 cm. 3 / min, while the nitrogen flow was approximately 10-20 cm 3The sample is passed over the other side of the lens at a rate of 1 / min. The sample is equilibrated in the test medium (i.e., saline or distilled water) at the designated test temperature for at least 30 minutes (but not more than 45 minutes) before measurement. Any test medium used as a coating layer is equilibrated at the designated test temperature for at least 30 minutes (but not more than 45 minutes) before measurement. The stir motor speed is set to 1200±50 rpm, which corresponds to a display setting of 400±15 on the stepper motor controller. The atmospheric pressure surrounding the system, P 測定値 The thickness (t) of the lens in the area exposed for the test is determined by measuring approximately 10 points with a Mitotoya micrometer VL-50, or similar device, and averaging the measurements. The oxygen concentration in the nitrogen stream (i.e., oxygen diffusing through the lens) is measured using a DK1000 device. The apparent oxygen permeability, Dk, of the lens material is app is calculated from the following formula: R: Dk app =Jt / (P 酸素 ) (In the formula, J = oxygen flux [microliters O2 / cm 2 -min] P 酸素 =(P 測定値 -P 水蒸気 ) = (O2% in airflow [mmHg] = partial pressure of oxygen in the airflow P 測定値 = atmospheric pressure (mmHg) P 水蒸気 = 0 mmHg (in dry cell) at 34°C (mmHg) P 水蒸気 = 40 mmHg (in wet cell) at 34°C (mmHg) t = average lens thickness in the exposed test area (mm) Dk app is expressed in units of barrers).

[0117] The apparent oxygen transmissibility (Dk / t) of a material is the apparent oxygen permeability (Dk app ) divided by the average lens thickness (t).

[0118] The above measurements are not corrected for so-called boundary layer effects, which result from the use of a water or saline bath at the apex of the contact lens during oxygen flux measurements. Boundary layer effects cause the reported apparent Dk of a silicone hydrogel material to be lower than its actual intrinsic Dk value. Furthermore, the relative impact of boundary layer effects is greater in thin lenses than in thick lenses. The net effect is that the reported Dk value appears to change as a function of lens thickness when it should remain constant.

[0119] The intrinsic Dk value of a lens can be estimated based on the Dk value corrected for surface resistance to oxygen flux due to boundary layer effects as follows:

[0120] The apparent oxygen permeability values ​​(single point) of control lotrafilcon A (Focus® N&D®, CIBA VISION CORPORATION) or lotrafilcon B (AirOptix™, CIBA VISION CORPORATION) lenses are measured using the same instrument. The control lenses are of similar refractive power to the test lenses and are measured at the same time as the test lenses.

[0121] By measuring oxygen flux through a range of thicknesses of Lotrafilcon A or Lotrafilcon B (control) lenses using the same equipment as in the procedure for measuring apparent Dk described above, the intrinsic Dk values ​​of the control lenses (Dk i The thickness series should cover a thickness range of approximately 100 μm or more. Preferably, the thickness range of the control lenses includes the thickness of the test lenses. The Dk of these control lenses app should be measured with the same equipment as the test lenses, and ideally at the same time as the test lenses. The equipment settings and measurement parameters should remain constant throughout the experiment. Individual samples may be measured multiple times if necessary.

[0122] From the results of the control lens, the residual oxygen resistance value, Rr Ask for.

[0123]

number

[0124] Using the residual oxygen resistance value obtained above, the correct oxygen permeability Dk of the test lens can be calculated based on formula (2). c Calculate (estimated characteristic Dk). Dk c = t / [(t / Dk a )-R r ] (2)

[0125] The estimated intrinsic Dk of the test lens is calculated by subtracting the apparent Dk (Dk a_std ) can be used to calculate what the standard thickness of a lens would be in the same test environment based on equation (3). std ) = 85 μm. Typical thickness of Lotrafilcon B = 60 μm. Dk a_std = t std / [(t std / Dk c )+R r_std ] (3)

[0126] Ion permeability measurement The ion permeability of the lenses is measured by the procedure described in U.S. Patent No. 5,760,100, which is incorporated herein by reference in its entirety. The ion permeability values ​​reported in the following examples are relative ionoflux diffusion coefficients (D / D) for the lens material, Alsacon, as a control material.ref ) Alsacon is 0.314 x 10 -3 mm 2 / min.

[0127] Lubricity evaluation The lubricity rating system is a qualitative ranking scheme using a 0-5 scale, with 0 or a lower number indicating good lubricity, with 1 assigned to Oasys™ / TruEye™ commercial lenses and 5 assigned to commercial Air Optix™ lenses. Samples are rinsed at least three times with excess DI water and then transferred to PBS before evaluation. Prior to evaluation, hands are rinsed with soapy water, rinsed extensively with DI water, and then dried with a KimWipe® towel. Samples are handled between the fingers, and a numerical value is assigned to each sample compared to the standard lens described above. For example, if the lenses are judged to be only slightly better than the Air Optix™ lenses, they are assigned a number of 4. Regarding consistency, all ratings were collected independently by the same two operators to avoid bias, and the data so far reveals very good qualitative agreement and consistency in the evaluations.

[0128] Surface Hydrophilicity / Wettability Test The water contact angle of a contact lens is a general measure of the surface hydrophilicity (or wettability) of the contact lens. Specifically, a lower water contact angle corresponds to a more hydrophilic surface. The average contact angle (sessile drop method) of a contact lens is measured using a VCA 2500 XE contact angle measuring instrument manufactured by AST, Inc., located in Boston, Massachusetts. This instrument can measure advancing or receding contact angles or settled (static) contact angles. Measurements are performed on fully hydrated contact lenses immediately after wiping them dry, as follows: The contact lenses are removed from their vials and washed three times in approximately 200 ml of fresh DI water to remove loosely bound packaging additives from the lens surface. The lenses are then placed on a clean, lint-free cloth (Alpha Wipe TX1009), pressed firmly to remove surface water, placed on a contact angle measuring platform, and air-dried with a blast of dry air. Finally, the sessile drop contact angle is automatically measured using software provided by the manufacturer. The DI water used to measure the contact angle has a resistivity of >18 MΩcm, and the drop volume used is 2 μl. Typically, uncoated silicone hydrogel lenses (after autoclaving) have a sessile contact angle of approximately 120 degrees. The tweezers and measuring stage are thoroughly cleaned with isopropanol and rinsed with DI water before contact with the contact lens.

[0129] Water Break-up Time (WBUT) Test The wettability of lenses (post-autoclaving) is also determined by measuring the time it takes for the water film to begin to break down on the lens surface. Briefly, lenses are removed from the vial and washed three times in ≈200 ml of fresh DI water to remove loosely bound packaging additives from the lens surface. The lenses are removed from the solution and held up to a bright light source. The time required for the water film to break (de-wet) and expose the underlying lens material is visually recorded. Uncoated lenses typically break the water film immediately upon removal from DI water and are assigned a WBUT of 0 seconds. Lenses that exhibit a WBUT ≥ 5 seconds are considered wettable and are expected to exhibit adequate wettability (ability to support a tear film) on the eye.

[0130] Coating Integrity Test The integrity of the coating on the surface of a contact lens can be tested by the Sudan Black staining test as follows: A contact lens with a coating (LbL coating, plasma coating, or any other coating) is immersed in a Sudan Black staining solution (Sudan Black in Vitamin E oil). Sudan Black dye is hydrophobic and has a strong tendency to be adsorbed to hydrophobic materials or to be adsorbed onto hydrophobic lens surfaces or onto hydrophobic spots on the partially coated surface of a hydrophobic lens (e.g., SiHy contact lenses). If the coating on the hydrophobic lens is intact, no staining spots should be observed on or within the lens. All lenses under test are fully hydrated.

[0131] Coating durability testing The lenses are finger-rubbed 30 times with Solo-care® Multipurpose Lens Care Solution, followed by a saline rinse. The above procedure is repeated a predetermined number of times, e.g., 1 to 30 times (i.e., the number of consecutive finger-rubbing tests, simulating a washing and soaking cycle). The lenses are then subjected to the Sudan Black test (i.e., the coating integrity test described above) to determine whether the coating is still intact. To survive the finger-rubbing test, there should be no significant increase in stain spots (e.g., stain spots should not cover more than about 5% of the total lens surface). Water contact angles are measured to determine coating durability.

[0132] Debris adhesion test Contact lenses with highly charged surfaces are susceptible to increased debris accumulation during patient manipulation. A paper towel is rubbed onto gloved hands, and then the lenses are rubbed with fingers on both sides to transfer debris to the lens surface. The lenses are lightly rinsed and then examined under a microscope. Each lens is scored using a qualitative rating scale ranging from 0 (no debris accumulation) to 4 (debris accumulation equivalent to that of the PAA-coated control lens). Lenses with a score of "0" or "1" are considered acceptable.

[0133] Surface crack test Excessive cross-linking of the coating layer can result in surface cracks visible under a dark field microscope after the lens is rubbed. The lens is rubbed inverted and any crack lines are noted. The lens is rated using a qualitative rating system from 0 (no cracks) to 2 (severe cracks). Any severe crack lines are considered unacceptable.

[0134] Determination of azetidinium content The azetidinium content in the PAE can be determined by one of the following assays.

[0135] PPVS assay PAE charge density (i.e., azetidinium content) can be determined by the PPVS assay, a colorimetric titration assay in which the titrant is potassium vinyl sulfate (PPVS) and toluidine blue is the indicator. See SK Kam and J. Gregory, "Charge determination of synthetic cationic polyelectrolytes by colloid titration," in Colloid & Surface A: Physicochem. Eng. Aspect, 159: 165-179 (1999). PPVS binds to positively charged species, such as toluidine blue and the azetidinium group of PAE. A decrease in toluidine blue absorbance intensity indicates a proportional PAE charge density (azetidinium content).

[0136] PES-Na assay The PES-Na assay is another colorimetric titration assay for measuring PAE charge density (azetidinium content). In this assay, the titrant is sodium polyethylene sulfonate (PES-Na) instead of PPVS. This assay is identical to the PPVS assay described above.

[0137] PCD assay The PCD assay is a potentiometric titration assay for measuring PAE charge density (azetidinium content). The titrant is sodium polyethylene sulfonate (PES-Na), PPVS, or other titrants. The PAE charge is detected by an electrode, for example, using the Muetek PCD-04 Particle Charge Detector manufactured by BTG. The measurement principle of this detector is described on the BTG website (http: / / www.btg.com / products.asp?langage=1&appli=5&numProd=357&cat=prod). It can be seen at.

[0138] NMR method The active positively charged moiety in a PAE is the azetidinium group (AZR). The NMR ratio method is the ratio of the number of AZR-specific protons to the number of non-AZR-associated protons. This ratio is an indicator of the charge or AZR density for the PAE.

[0139] Example 2 Preparation of CE-PDMS macromer In the first step, α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn=2000, Shin-Etsu, KF-6001a) was capped with isophorone diisocyanate (IPDI) by reacting 49.85 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane with 11.1 g of IPDI in the presence of 0.063 g of dibutyltin dilaurate (DBTDL) in 150 g of anhydrous methyl ethyl ketone (MEK). The reaction was held at 40°C for 4.5 hours to form IPDI-PDMS-IPDI. In the second step, a mixture of 164.8 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn = 3000, Shin-Etsu, KF-6002) and 50 g of anhydrous MEK was added dropwise to the IPDI-PDMS-IPDI solution, which also contained 0.063 g of DBTDL. The reactor was maintained at approximately 40 °C for 4.5 hours to form HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. MEK was then removed under reduced pressure. In the third step, an additional 7.77 g of isocyanatoethyl methacrylate (IEM) and 0.063 g of DBTDL were added to cap the terminal hydroxyl groups with methacryloyloxyethyl groups, forming IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM (CE-PDMS macromer).

[0140] Alternative preparation of CE-PDMS macromers 240.43 g of KF-6001 was added to a 1 L reactor equipped with a stirrer, thermometer, cryostat, dropping funnel, and nitrogen / vacuum inlet adapter, and then high vacuum (2 × 10 -2The reactor is dried by applying 1000 mBar of pressure. Next, under 1 atmosphere of dry nitrogen, 320 g of distilled MEK is added to the reactor and the mixture is thoroughly stirred. 0.235 g of DBTDL is added to the reactor. After warming the reactor to 45°C, 45.86 g of IPDI is added to the reactor via a dropping funnel over 10 minutes with gentle stirring. The reaction is held at 60°C for 2 hours. Next, 630 g of KF-6002 dissolved in 452 g of distilled MEK is added and stirred until a homogeneous solution is formed. 0.235 g of DBTDL is added and the reactor is maintained at approximately 55°C overnight under a blanket of dry nitrogen. The next day, the MEK is removed by flash distillation. The reactor is cooled, and then 22.7 g of IEM is charged to the reactor, followed by approximately 0.235 g of DBTDL. After approximately 3 hours, an additional 3.3 g of IEM is added and the reaction is allowed to proceed overnight. The next day, the reaction mixture is cooled to about 18° C. to yield a CE-PDMS macromer with terminal methacrylate groups.

[0141] Example 3 Preparation of Lens Formulations A lens formulation is prepared by dissolving the ingredients in 1-propanol to have the following composition: 33 wt. % CE-PDMS macromer prepared in Example 2, 17 wt. % N-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24 wt. % N,N-dimethylacrylamide (DMA), 0.5 wt. % N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt) (L-PEG), 1.0 wt. % Darocur 1173 (DC1173), 0.1 wt. % Visitint (tris(trimethylsiloxy)silylpropyl methacrylate, a blue pigment dispersion of 5% copper phthalocyanine in TRIS), and 24.5 wt. % 1-propanol.

[0142] Lens preparation Lenses are prepared from the lens formulation prepared above by a casting process in a reusable mold similar to the molds shown in Figures 1-6 of U.S. Patent No. 7,384,590 and U.S. Patent No. 7,387,759 (Figures 1-6). The mold includes a female half made of quartz (or CaF2) and a male half made of glass (or PMMA). The UV irradiation source is approximately 4 mW / cm 2 The UV light source is a Hamamatsu lamp equipped with a WG335 and a TM297 cutoff filter at an intensity of 1000 nm. The lens formulation in the mold is irradiated with UV light for approximately 25 seconds. The cast lenses are extracted with isopropanol (or methyl ethyl ketone, MEK), rinsed in water, and coated with polyacrylic acid (PAA) by immersing the lenses in a propanol solution of PAA (0.1% by weight, acidified with formic acid to a pH of approximately 2.5) and hydrated in water. The resulting lenses with the reactive PAA-LbL base coating are determined to have the following properties: ionic permeability of approximately 8.0 to 9.0 times that of Alsacon lens material; apparent Dk (single point) of approximately 90 to 100; water content of approximately 30% to 33%; and elastic modulus of approximately 0.60 MPa to approximately 0.65 MPa.

[0143] Example 4 In-package coating (IPC) saline is prepared by adding 0.2% polyamidoamine-epichlorohydrin (PAE, Kymene) to phosphate-buffered saline (PBS), and then adjusting the pH to 7.2-7.4.

[0144] The lenses from Example 3 are placed in polypropylene lens packaging shells with 0.6 mL of IPC saline (half of the IPC saline is added before inserting the lenses), and the blisters are then sealed with aluminum foil and autoclaved at 121°C for approximately 30 minutes to form a crosslinked coating (PAA-x-PAE coating) on ​​the lenses.

[0145] The lenses are then evaluated for debris adhesion, surface cracking, lubricity, contact angle, and water break-up time (WBUT). The test lenses (packaged / autoclaved in IPC saline, i.e., lenses with PAA-x-PAE coating) show no debris adhesion, while the control lenses (packaged / autoclaved in PBS, i.e., lenses with PAA-LbL base coating) show severe debris adhesion. The test lenses have a low water contact angle (WCA) (≈20°) but a WBUT of less than 2 seconds. When observed under a dark-field microscope, severe crack lines are visible after lens manipulation (lens inversion and finger rubbing). The test lenses are significantly less lubricious than the control lenses as determined by a qualitative finger rub test (lubricity rating of 4).

[0146] Example 5 Poly(acrylamide-co-acrylic acid) partial sodium salt (≈80% solids, poly(AAm-co-AA) (80 / 20), Mw 520,000, Mn 150,000) was purchased from Aldrich and used as received.

[0147] IPC saline is prepared by dissolving 0.02% poly(AAm-co-AA) (80 / 20) and 0.2% PAE (Kymene) in PBS. The pH is adjusted to 7.2-7.4. PBS contains 0.76% NaCl, 0.044% NaH2PO4·H2O. It is prepared by dissolving 0.2O and 0.388% NaH2PO4·2H2O in water.

[0148] Lenses with the PAA-LbL base coating prepared in Example 3 are placed in polypropylene lens packaging shells with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). The blisters are then sealed with aluminum foil and autoclaved at about 121°C for about 30 minutes. A three-layer crosslinked coating of PAA-x-PAE-x-poly(AAm-co-AA) is believed to form on the lenses during autoclaving.

[0149] The test lenses (packaged / autoclaved in IPC saline, i.e., lenses with PAA-x-PAE-x-poly(AAm-co-AA) coatings) are free of debris and have a WBUT of greater than 10 seconds. When observed under a dark field microscope, crack lines are visible after the test lenses are rubbed. The test lenses are much more lubricious than the test lenses from Example 4, but still not as lubricious as the control lenses packaged in PBS (lubricity rating of 1-2).

[0150] Example 6 IPC saline is prepared by dissolving 0.02% poly(AAm-co-AA) (80 / 20) and 0.2% PAE (Kymene) in PBS and adjusting the pH to 7.2-7.4. The saline is then heated to approximately 70°C for 4 hours (thermal pretreatment) to form a water-soluble, thermally crosslinkable hydrophilic polymeric material containing azetidinium groups in the IPC saline. After thermal pretreatment, the IPC saline is filtered using a 0.22 micron polyethersulfone (PES) membrane filter and allowed to cool back to room temperature.

[0151] The lenses with the PAA-LbL base coating prepared in Example 3 are placed in polypropylene lens packaging shells with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). The blisters are then sealed with aluminum foil and autoclaved at about 121°C for about 30 minutes to form a crosslinked coating (PAA-x-hydrophilic polymer material) on the lenses.

[0152] The test lenses (packaged in heat-pretreated IPC saline, i.e., lenses with a PAA-x-hydrophilic polymer material coating) show no debris buildup after rubbing against a paper towel, while the control lenses (packaged in PBS, i.e., lenses with a non-covalently bound layer of PAA thereon) show severe debris buildup. The test lenses have a WBUT of greater than 10 seconds. When viewed under a dark field microscope, no crack lines are visible after the test lenses are rubbed. The test lenses are very lubricious in the finger rub test, comparable to the control lenses (lubricity rating of 0).

[0153] A series of experiments was conducted to examine the effect of IPC saline heat pretreatment conditions (duration and / or temperature) on the surface properties of the resulting IPC saline-coated lenses. Depending on the azetidinium functional group of the PAE and the concentration of PAE used, heat treatment times of about 6 hours or more at about 70°C yield lenses with similar susceptibility to debris deposition as control lenses. Heat treatment at 50°C for only 4 hours yields lenses that exhibit surface crack lines under dark-field microscopy after rubbing between fingers, similar to the test lenses of Example 5 that were not heat pretreated with IPC saline.

[0154] Example 7 Poly(acrylamide-co-acrylic acid) partial sodium salt (≒90% solids, poly( AAm-co-AA) 90 / 10, Mw 200,000) from Polysciences, Inc. Buy it and use it as is.

[0155] IPC saline is prepared by dissolving 0.07% PAAm-PAA (90 / 10) and 0.2% PAE (Kymene) in PBS and adjusting the pH to 7.2-7.4. The saline is then thermally pretreated at approximately 70°C for approximately 4 hours to form a water-soluble, thermally crosslinkable hydrophilic polymeric material containing azetidinium groups. After thermal pretreatment, the IPC saline is filtered using a 0.22 micron polyethersulfone (PES) membrane filter and allowed to cool back to room temperature.

[0156] Lenses with the PAA-LbL base coating prepared in Example 3 and uncoated Lotrafilcon B lenses (manufactured by CIBA VISION CORPORATION) immersed in an acidic propanol solution of PAA (approximately 0.1%, pH ≈ 2.5) are placed in polypropylene lens packaging shells along with 0.6 mL of heat-pretreated IPC saline (half of the IPC saline is added before inserting the lenses). The blisters are then sealed with aluminum foil and autoclaved at 121°C for approximately 30 minutes to form a crosslinked coating (PAA-x-hydrophilic polymer material) on the lenses.

[0157] The test lenses (both Lotrafilcon B and lenses of Example 3 with PAA-x-hydrophilic polymeric material coatings) are free of debris. The test lenses have a WBUT of greater than 10 seconds. When viewed under a dark field microscope, no crack lines are visible after the lens is rubbed between fingers. The lenses are very lubricious in the qualitative finger rub test (lubricity rating of 0).

[0158] Example 8 In a design of experiments (DOE), IPC saline was prepared containing about 0.05% to about 0.09% PAAm-PAA and about 0.075% to about 0.19% PAE (Kymene) in PBS. The IPC saline was heat treated at 60°C for 8 hours, and lenses from Example 3 were packaged in the heat-pretreated IPC saline. No differences in the final lens surface properties were observed; all lenses exhibited excellent lubricity, resistance to debris adhesion, excellent wettability, and no evidence of surface cracking.

[0159] Example 9 In a design of experiments (DOE), IPC saline is prepared containing approximately 0.07% PAAm-PAA and sufficient PAE (≈0.15% PAE) to provide an initial azetidinium content of approximately 9 millimolar equivalents per liter. Thermal pretreatment conditions are varied from 50°C to 70°C in a central composite design, and pretreatment times are varied from approximately 4 to approximately 12 hours. A 24-hour pretreatment time at 60°C is also tested. 10 ppm hydrogen peroxide is then added to the saline to prevent bioburden growth, and the IPC saline is filtered using a 0.22 micron polyethersulfone [PES] membrane filter.

[0160] The lenses from Example 3 are packaged in heat-pretreated IPC saline, and the blisters are then autoclaved at 121°C for 45 minutes. All lenses have excellent lubricity, wettability, and resistance to surface cracking. Some of the lenses show debris adhesion from the paper towel, as shown in Table 1.

[0161] [Table 1]

[0162] Example 10 Copolymers of methacryloyloxyethyl phosphorylcholine (MPC) and one carboxyl-containing vinyl monomer (CH2=CH(CH3)C(O)OC2H4OC(O)C2H4COOH (MS), methacrylic acid (MA)) are evaluated in an in-package coating system in combination with PAE in the absence and presence of butyl methacrylate (BMA).

[0163] Prepare PBS containing NaCl (0.75 wt%), NaH2PO4·H2O (0.0536 wt%), Na2HPO4·2H2O (0.3576 wt%), and DI water (97.59 wt%) with 0.2% PAE (Polycup 3160). Adjust the pH to approximately 7.3.

[0164] 0.25% of one of several MPC copolymers is then added to form an IPC saline solution, which is then heat-pretreated at 70°C for 4 hours to form a water-soluble, heat-crosslinkable, hydrophilic polymeric material containing azetidinium groups. After 4 hours, the heat-pretreated IPC saline solution is filtered through a 0.2 micron polyethersulfone [PES] membrane filter (Fisher Scientific catalog #09-741-04, Thermo Scientific nalgene #568-0020 (250 ml)).

[0165] Lenses with the PAA-LbL base coating prepared in Example 3 are packaged in a thermally pretreated IPC saline solution and autoclaved at 121° C. for approximately 30 minutes. Table 2 shows that all lenses have excellent surface properties.

[0166] [Table 2]

[0167] Example 11 PAA coated lens Lenses cast from the lens formulation prepared in Example 3 by the molding process described in Example 3 are removed and coated by immersion in a series of baths: three MEK baths (22, 78, and 224 seconds); a DI water bath (56 seconds); two PAA coating solution baths (prepared by dissolving 3.6 g of PAA (MW: 450 kDa, Lubrizol) in 975 ml of 1-propanol and 25 ml of formic acid) for 44 and 56 seconds respectively; and three DI water baths for 56 seconds each.

[0168] PAE / PAA coated lenses The prepared lenses with the PAA base coating are successively immersed in the following baths: two PAE coating solution baths (prepared by dissolving 0.25 wt. % PAE (Polycup 172, Hercules) in DI water, adjusting the pH to about 5.0 with sodium hydroxide, and finally filtering the resulting solution through a 5 μm filter) for 44 and 56 seconds each; and three DI water baths for 56 seconds each. After this treatment, the lenses have one layer of PAA and one layer of PAE.

[0169] Lenses with PAA-x-PAE-x-CMC coating A batch of lenses with one layer of PAA and one layer of PAE on them is packaged in 0.2% sodium carboxymethylcellulose (CMC, Product# 7H 3SF PH, Ashland Aqualon) in phosphate-buffered saline (PBS), the pH of which is then adjusted to 7.2-7.4. The blisters are then sealed and autoclaved at 121°C for approximately 30 minutes to form a crosslinked coating (PAA-x-PAE-x-CMC) on the lenses.

[0170] Lenses with PAA-x-PAE-x-HA coating Another batch of lenses with one layer of PAA and one layer of PAE on them is packaged in 0.2% hyaluronic acid (HA, Product# 6915004, Novozymes) in phosphate-buffered saline (PBS), then the pH is adjusted to 7.2-7.4. The blisters are then sealed and autoclaved at 121°C for approximately 30 minutes to form a crosslinked coating (PAA-x-PAE-x-HA) on the lenses.

[0171] The resulting lenses with either the PAA-x-PAE-x-CMC or PAA-x-PAE-x-HA coatings exhibit no Sudan Black staining, no debris buildup, and no cracking under microscopic examination. The lenses with the PAA-x-PAE-x-CMC coatings have an average contact angle of 30±3 degrees, while the lenses with the PAA-x-PAE-x-HA coatings have an average contact angle of 20±3 degrees.

[0172] Example 12 Preparation of IPC solution A reaction mixture was prepared by dissolving 2.86 wt% methoxy-poly(ethylene glycol)-thiol, average Mw 2000 (Product# MPEG-SH-2000, Laysan Bio Inc.) in PBS along with 2 wt% PAE (Kymene), and the final pH was adjusted to 7.5. The solution was heat-treated at 45°C for approximately 4 hours to form a thermally crosslinkable hydrophilic polymeric material containing MPEG-SH-2000 groups chemically grafted onto the polymer by reaction with the azetidinium groups in the PAE. After heat treatment, the solution was diluted 10-fold with PBS containing 0.25% sodium citrate, the pH was adjusted to 7.2-7.4, and then filtered using a 0.22 micron polyethersulfone (PES) membrane filter. This final IPC saline solution contains 0.286% by weight of hydrophilic polymeric material (consisting of approximately 59% by weight of MPEG-SH-2000 chains and approximately 41% by weight of PAE chains) and 0.25% sodium citrate. PBS is prepared by dissolving 0.74% NaCl, 0.053% NaH2PO4·H2O, and 0.353% Na2HPO4·2H2O in water.

[0173] Lenses with cross-linked coatings The PAA-coated lenses from Example 11 are packaged in the above IPC saline solution in polypropylene lens packaging shells and then autoclaved at about 121° C. for about 30 minutes to form a crosslinked coating on the lenses.

[0174] The final lenses show no debris buildup or crack lines after rubbing the lenses. The lenses are very lubricious in a finger rub test, comparable to the control PAA coated lenses.

[0175] A series of experiments was conducted to test the effect of conditions (reaction time and mPEG-SH-2000 solution concentration (at a constant PAE concentration of 2%)) on the surface properties of the resulting lenses coated with IPC saline. The results are shown in Table 3.

[0176] [Table 3]

[0177] As the solution concentration of mPEG-SH-2000 increases, the lens lubricity increases accordingly. The increase in surface contact angle is likely due to the increased density of terminal methyl groups on the surface with increasing grafting density. At high grafting densities, corresponding to a solution concentration of 0.6%, the contact angle approaches that measured on a flat substrate grafted with a monolayer of polyethylene glycol (PEG) (Reference: Langmuir 2008, 24, 10646-10653).

[0178] Example 13 A series of experiments was conducted to test the effect of the molecular weight of mPEG-SH. IPC saline solutions were prepared similarly to the procedure described in Example 12, but using one of the following mPEG-SH: mPEG-SH 1000, mPEG-SH 2000, mPEG-SH 5000, and mPEG-SH 20000. All saline solutions were subjected to heat treatment at 45°C for 4 hours and 10-fold dilution. The results and reaction conditions are shown in Table 4.

[0179] [Table 4]

[0180] Example 14 The reaction mixture was prepared by dissolving 2.5% methoxy-poly(ethylene glycol)-thiol, average MW 2000 (Product# MPEG-SH-2000, Laysan Bio Inc.), and 10% PAE (Kymene) in PBS and 0.25% sodium citrate dihydrate. The pH of this final solution was then adjusted to 7.5, and the vessel was degassed by bubbling nitrogen gas through it for 2 hours to minimize thiol oxidation. This solution was then heat-treated at 45°C for approximately 6 hours to form a thermally crosslinkable hydrophilic polymeric material containing MPEG-SH-2000 groups chemically grafted to the polymer via reaction with the azetidinium groups in the PAE. After heat treatment, the solution was diluted 50-fold with PBS containing 0.25% sodium citrate, the pH was adjusted to 7.2-7.4, and then filtered using a 0.22 micron polyethersulfone (PES) membrane filter. The final IPC saline solution contains about 0.30% by weight of polymeric material (consisting of about 17% by weight MPEG-SH-2000 and about 83% by weight PAE) and 0.25% sodium citrate dihydrate.

[0181] The PAA coated lenses from Example 11 are packaged in the above IPC saline solution in polypropylene lens packaging shells and then autoclaved at about 121° C. for about 30 minutes to form a crosslinked coating on the lenses.

[0182] The final lenses show no debris buildup or crack lines after rubbing the lenses. The test lenses are very lubricious in finger rub tests, comparable to the control PAA coated lenses.

[0183] Example 15 The reaction mixture was prepared by dissolving 3.62% methoxy-poly(ethylene glycol)-amine, average MW 550 (Product# MPEG-NH2-550, Laysan Bio Inc.) in PBS with 2% PAE (Kymene) and adjusting the final pH to 10. This solution was heat-treated at 45°C for approximately 4 hours to form a thermally crosslinkable hydrophilic polymeric material containing MPEG-NH2-550 groups chemically grafted to the polymer by reaction with the azetidinium groups in the PAE. After heat treatment, the solution was diluted 10-fold with PBS containing 0.25% sodium citrate, the pH was adjusted to 7.2-7.4, and then filtered using a 0.22 micron polyethersulfone (PES) membrane filter. The final IPC saline solution contains approximately 0.562% by weight of polymeric material (consisting of approximately 64% by weight of MPEG-SH-2000 and approximately 36% by weight of PAE) and 0.25% sodium citrate dihydrate. This PBS is prepared by dissolving 0.74% sodium chloride, 0.053% NaH2PO4·H2O, and 0.353% NaH2PO4·2H2O in water.

[0184] The PAA coated lenses from Example 11 are packaged in the above IPC saline solution in polypropylene lens packaging shells and then autoclaved at about 121° C. for about 30 minutes to form a crosslinked coating on the lenses.

[0185] The final lens shows neither debris buildup nor crack lines after rubbing the lens.

[0186] Example 16 Poloxamer 108 (sample) and Nelfilcon A (CIBA VISION) were used as they were. Nelfilcon A is a polymerizable polyvinyl alcohol obtained by modifying polyvinyl alcohol (e.g., Gohsenol KL-03 manufactured by Nippon Gohsei) with N-(2,2-dimethoxyethyl)acrylamide under cyclic acetal-forming reaction conditions (Buehler et al., CHIMIA, 53 (1999), 269-274, the entire contents of which are incorporated herein by reference). Approximately 2.5% of the vinyl alcohol units in Nelfilcon A are modified with N-(2,2-dimethoxyethyl)acrylamide.

[0187] IPC saline is prepared by dissolving 0.004% Poloxamer 108, 0.8% Nelfilcon A, 0.2% PAE (Kymene, Polycup 3160), 0.45% NaCl, and 1.1% NaHPO 2H O in DI water. This saline is heat-pretreated by stirring at approximately 65–70°C for 2 hours. After heat pretreatment, the saline is allowed to cool to room temperature and then filtered using a 0.2 μm PES filter.

[0188] The lenses prepared in Example 3 are placed in polypropylene lens packaging shells with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). The blisters are then sealed with aluminum foil and autoclaved at 121°C for approximately 30 minutes.

[0189] The test lens shows no debris buildup after rubbing against a paper towel. The lens has a WBUT of greater than 10 seconds. When viewed under a dark field microscope, no crack lines are visible after rubbing the lens between the fingers. The lens is much more lubricious than the lens from Example 4, but still not as lubricious as the control lens packaged in PBS.

[0190] Example 17 A. Synthesis of 80% Ethylenically Functionalized Chain-Extended Polysiloxane KF-6001A (α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane, Mn=2000, manufactured by Shin-Etsu) and KF-6002A (α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane, Mn=3400, manufactured by Shin-Etsu) are dried separately in a single-neck flask under high vacuum at approximately 60°C for 12 hours (or overnight). The OH molar equivalents of KF-6001A and KF-6002A are determined by titration of the hydroxyl group and used to calculate the millimole equivalents to be used in the synthesis.

[0191] A 1-liter reaction vessel is vacuumed overnight to remove water and the vacuum is broken with dry nitrogen. 75.00 g (75 meq) of dry KF6001A is charged to the reactor, followed by 16.68 g (150 meq) of freshly distilled IPDI. The reactor is purged with nitrogen and heated to 45°C with stirring, followed by 0.30 g of DBTDL. The reactor is sealed and a positive flow of nitrogen is maintained. An exotherm occurs, after which the reaction mixture is allowed to cool and stir (55°C for 2 hours). Once the exotherm has occurred, 248.00 g (150 meq) of dry KF6002A is added to the reactor at 55°C, followed by 100 μL of DBTDL. The reactor is stirred for 4 hours. Heating is discontinued and the reactor is allowed to cool overnight. The nitrogen bubbling is discontinued and the reactor is opened to the atmosphere with gentle stirring for 30 minutes. A hydroxyl-terminated chain-extended polysiloxane with three polysiloxane segments, HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH (or HO-CE-PDMS-OH), is formed.

[0192] For 80% ethylene-functionalized polysiloxane, add 18.64 g (120 meq) of IEM along with 100 μL of DBTDL to a reactor. Stir the reactor for 24 hours, then decant the product (80% IEM-capped CE-PDMS) and store frozen.

[0193] B. Synthesis of Non-UV-Absorbing Amphoteric Branched Polysiloxane Prepolymer A 1 L jacketed reactor is equipped with a 500 mL addition funnel, overhead stirring, a reflux condenser with nitrogen / vacuum inlet adapter, a thermometer, and a sampling adapter. The reactor is charged with 45.6 g of the 80% IEM cap CE-PDMS prepared above and sealed. A solution of 0.65 g of hydroxyethyl methacrylate (HEMA), 25.80 g of DMA, and 27.80 g of tris(trimethylsilyl)siloxypropyl) methacrylate (TRIS) in 279 g of ethyl acetate is charged to the addition funnel. The reactor is degassed at <1 mbar for 30 minutes at room temperature using a high vacuum pump. The monomer solution is degassed for three 10-minute cycles at 100 mbar and room temperature, with the vacuum broken with nitrogen between degassing cycles. The monomer solution is then charged to the reactor, and the reaction mixture is stirred and heated to 67°C. While heating, a solution of 1.50 g of mercaptoethanol (chain transfer agent, CTA) and 0.26 g of azoisobutyronitrile dissolved in 39 g of ethyl acetate is charged to the dropping funnel and deoxygenated at 100 mbar and RT for three 10-minute periods. Once the reactor temperature reaches 67 °C, the initiator / CTA solution is added to the PDMS / monomer solution in the reactor. The reaction is allowed to proceed for 8 hours, then heating is discontinued and the reactor temperature is allowed to reach room temperature within 15 minutes.

[0194] The resulting reaction mixture is then siphoned into a dry, single-neck flask with an airtight lid, and 4.452 g of IEM is added along with 0.21 g of DBTDL. The mixture is stirred at room temperature for 24 hours to form a non-UV absorbing amphoteric branched polysiloxane prepolymer. 100 mL of a hydroxy-tetramethylenepiperonyloxy solution in ethyl acetate (2 g / 20 mL) is added to the mixture. This solution was then evaporated in a rotary evaporator at 30°C for 200 g ( The concentrate is concentrated to 50% of the original volume and filtered through a 1 μm pore size filter paper. After solvent exchange, the solution is further concentrated to the desired concentration.

[0195] C. Synthesis of UV-absorbing amphoteric branched polysiloxane prepolymer A 1 L jacketed reactor was equipped with a 500 mL dropping funnel, an overhead stirrer, and nitrogen / Attach a reflux condenser with a vacuum introduction adapter, a thermometer, and a sampling adapter. Next, the reactor was filled with the 80% IEM cap CE-PDMS prepared above. Charge 98g of HEMA in 263g of ethyl acetate and seal the reactor. g, DMA 25.354 g, Norbloc methacrylate 1.38 g, TRIS 26.0 34 g of the solution is placed in the dropping funnel. The reactor is vacuum pumped at <1 mbar for 30 minutes. Degas the monomer solution at 1°C, breaking the vacuum with nitrogen between degassing cycles. The monomer solution is then added to the reactor and degassed for three cycles of 10 min at 00 mbar and RT. The reaction mixture is then stirred and heated to 67°C. While heating, 38% ethyl acetate is added. 1.480 g of mercaptoethanol (chain transfer agent, CTA) and azoisobutane were dissolved in 1.480 g of A solution of 0.260 g of tyronitrile was placed in a dropping funnel and heated at 100 mbar and room temperature for 10 minutes. Once the reactor temperature reaches 67°C, the initiator / CTA solution is added to the P Add the DMS / monomer solution. Allow the reaction to proceed for 8 hours, then turn off the heat and allow to stand for 15 minutes. The reactor temperature is then brought to room temperature.

[0196] The resulting reaction mixture was then siphoned into a dry, single-neck flask with an airtight lid and acrylic acid was added. 3.841 g of isocyanatoethyl is added along with 0.15 g of DBTDL. Stir at room temperature for approximately 24 hours to form a UV-absorbing amphoteric branched polysiloxane prepolymer. To this mixture, a solution of hydroxy-tetramethylenepiperonyloxy in ethyl acetate ( Add 100 μL of 2 g / 20 mL of HCl. Then, evaporate the solution on a rotary evaporator. The mixture is concentrated at 30°C to 200 g (≒50%) and filtered through a 1 μm pore size filter paper.

[0197] D-1: Lens formulation containing non-UV absorbing polysiloxane prepolymer In a 100 mL brown flask, 4.31 g of the synthetic macromer solution (82.39% in 1-propanol) prepared in Example C-2 is added. In a 20 mL vial, 0.081 g of TPO and 0.045 g of DMPC are dissolved in 10 g of 1-propanol and then transferred to the macromer solution. The mixture is concentrated to 5.64 g using a rotary evaporator at 30° C., after which 0.36 g of DMA is added, and the formulation is homogenized at room temperature. 6 g of clear lens formulation D-1 is obtained.

[0198] D-2: Lens Formulation with UV-Absorbing Polysiloxane Prepolymer (4% DMA) 24.250 g of the macromer solution (43.92% in ethyl acetate) prepared in Example D-2 is added to a 100 mL brown flask. 0.15 g of TPO and 0.75 g of DMPC are dissolved in 20 g of 1-propanol in a 50 mL vial and then transferred to the macromer solution. 20 g of solvent is removed using a rotary evaporator at 30° C., followed by the addition of 20 g of 1-propanol. After two cycles, the mixture is concentrated to 14.40 g. 0.6 g of DMA is added to the mixture, and the mixture is homogenized at room temperature. 15 g of clear lens formulation D-2 is obtained.

[0199] D-3: Lens formulation containing UV-absorbing polysiloxane prepolymer (2% DMA / 2% HEA) In a 100 mL brown flask, 24.250 g of the macromer solution (43.92% in ethyl acetate) prepared in Example D-2 is added. In a 50 mL vial, 0.15 g of TPO and 0.75 g of DMPC are dissolved in 20 g of 1-propanol and then transferred to the macromer solution. 20 g of solvent is removed using a rotary evaporator at 30° C., followed by the addition of 20 g of 1-propanol. After two cycles, the mixture is concentrated to 14.40 g. 0.3 g of DMA and 0.3 g of HEA are added to the mixture, and the mixture is homogenized at room temperature. 15 g of clear lens formulation D-3 is obtained.

[0200] Example 18 E: Covalent bonding of modified PAE coating polymer The amine-containing monomers N-(3-aminopropyl) methacrylamide hydrochloride (APMAA-HCl) or N-(2-aminoethyl) methacrylamide hydrochloride (AEMAA-HCl) were purchased from Polysciences and used as received. Poly(amidoamine epichlorohydrin) (PAE) was received as an aqueous solution from Ashland and used as received. Poly(acrylamide-co-acrylic acid) (poly(AAm-co-AA) (90 / 10)) from Polysciences, mPEG-SH from Laysan Bio, and poly(MPC-co-AeMA) (i.e., a copolymer of methacryloyloxyethyl phosphorylcholine (MPC) and aminoethyl methacrylate (AeMA)) from NOF were used as received.

[0201] The APMAA-HCl monomer is dissolved in methanol and added to lens formulations D-1, D-2 and D-3 (prepared in Example 17) to achieve a concentration of 1% by weight.

[0202] Reactive packaging saline is prepared by dissolving the ingredients listed in Table 5 in DI water along with the appropriate buffer salts. After heat pretreatment, the saline is allowed to cool to room temperature and then filtered using a 0.2 μm PES filter.

[0203] [Table 5]

[0204] Lens formulations D-1, D-2, and D3 prepared in Example 17 are modified by the addition of APMMA-HCl monomer (stock solution of APMMA-HCl in methanol). DSM lenses are illuminated at 16 mW / cm using a 330 nm filter. 2 while the LS lens is cured at 4.6 mW / cm using a 380 nm filter. 2 and harden it.

[0205] DSM Lens The female mold of a polypropylene lens mold is filled with approximately 75 microliters of the lens formulation prepared as described above, and the mold is closed with the male (base curve) mold of the polypropylene lens mold. The contact lenses are then exposed to approximately 16 mW / cm UV irradiation (Hamamatsu lamp with a 330 nm cutoff filter) for approximately 5 minutes. 2 The resulting composition is cured at a strength of 0.15.

[0206] LS lens LS lenses are prepared from the lens formulations prepared as described above by a casting process in a reusable mold similar to the molds shown in Figures 1-6 of U.S. Patent No. 7,384,590 and U.S. Patent No. 7,387,759 (Figures 1-6). The mold includes a female half made of quartz (or CaF2) and a male half made of glass (or PMMA). The UV irradiation source is approximately 4.6 mW / cm2. 2 The UV light is a Hamamatsu lamp equipped with a 380 nm cutoff filter at an intensity of 1000 nm. The lens formulation in the mold is irradiated with UV light for approximately 30 seconds.

[0207] Lens formulation D-1 modified with APMAA-HCl is cured by the DSM and LS methods described above, while lens formulations D-2 or D-3 are cured by the LS method described above.

[0208] The molded lenses are extracted in methyl ethyl ketone, hydrated, and packaged in one of the saline solutions listed in Table 5. The lenses are placed in polypropylene lens packaging shells with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). The blisters are then sealed with aluminum foil and autoclaved at 121°C for 30 minutes.

[0209] Upon evaluation of the lens surface, all test lenses were found to be free of debris. When viewed under a dark field microscope, no crack lines were visible after the lens was rubbed between the fingers.

[0210] Lens surface wettability (WBUT), lubricity, and contact angle were measured, and the results are summarized in Table 6. Lenses are manufactured by DSM processes unless otherwise noted. Lubricity is rated on a qualitative scale of 0 to 4, with lower numbers indicating higher lubricity. In general, lens surface properties are slightly improved after application of the in-package coating.

[0211] [Table 6]

[0212] Example 19 Lenses are manufactured using lens formulation D-2 (Example 17) with the addition of APMAA monomer to a concentration of 1%. LS lenses are prepared from the lens formulation prepared above by a casting process in a reusable mold similar to the molds shown in Figures 1-6 of U.S. Patent No. 7,384,590 and U.S. Patent No. 7,387,759 (Figures 1-6). The mold includes a female half made of glass and a male half made of quartz. The UV radiation source is approximately 4.6 mW / cm. 2 The UV light is a Hamamatsu lamp equipped with a 380 nm cutoff filter at an intensity of 1000 nm. The lens formulation in the mold is irradiated with UV light for approximately 30 seconds.

[0213] The cast lenses are extracted with methyl ethyl ketone (MEK), rinsed in water, and coated with polyacrylic acid (PAA) by immersing the lenses in a propanol solution of PAA (0.0044% by weight, acidified to approximately pH 2.5 with formic acid) and hydrated in water.

[0214] IPC saline is prepared according to the composition described in Example 9 with pre-reaction conditions at approximately 60°C for 8 hours. The lenses are placed in polypropylene lens packaging shells with 0.6 mL of IPC saline (half of the saline is added before inserting the lenses). The blisters are then sealed with aluminum foil and autoclaved at 121°C for 30 minutes.

[0215] Evaluation of the lens surface revealed that all test lenses were free of debris. When viewed under a dark field microscope, no crack lines were visible after the lens was rubbed between fingers. The wettability (WBUT) of the lens surface was greater than 10 seconds, the lubricity was rated "1," and the contact angle was approximately 20°.

[0216] Example 20 Preparation of Lens Formulations A lens formulation is prepared by dissolving the ingredients in 1-propanol to have the following composition: about 32% by weight of the CE-PDMS macromer prepared in Example 2, about 21% by weight of TRIS-Am, about 23% by weight of DMA, about 0.6% by weight of L-PEG, about 1% by weight of DC 1173, about 0.1% by weight of Visitint (a 5% copper phthalocyanine blue pigment dispersion in TRIS), about 0.8% by weight of DMPC, about 200 ppm of H-TEMPO, and about 22% by weight of 1-propanol.

[0217] Lens preparation Lenses are prepared from the lens formulation prepared above by a casting process in a reusable mold (quartz female half and glass male half) similar to the molds shown in Figures 1-6 of U.S. Patent No. 7,384,590 and U.S. Patent No. 7,387,759 (Figures 1-6). The lens formulation in the mold is exposed to UV light (13.0 mW / cm) for approximately 24 seconds. 2) is irradiated.

[0218] PAA coating solution The PAA coating solution was prepared by dissolving a certain amount of PAA (MW: 450 kDa, manufactured by Lubrizol) in a predetermined volume of 1-propanol to have a concentration of about 0.36–0.44 wt %, and adjusting the pH to about 1.7–2.3 with formic acid.

[0219] PAA coated lens The cast contact lenses are extracted and coated by immersion in the following series of baths: a DI water bath (approximately 56 seconds); six MEK baths (approximately 44, 56, 56, 56, 56, and 56 seconds, respectively); a DI water bath (approximately 56 seconds); one bath of a PAA coating solution (approximately 0.36-0.44 wt%, acidified with formic acid to approximately pH 1.7-2.3) in 100% 1-propanol (approximately 44 seconds); one bath of a 50% / 50% mixture of water / 1-propanol (approximately 56 seconds); four DI water baths, each approximately 56 seconds; one PBS bath, approximately 56 seconds; and one DI water bath, approximately 56 seconds.

[0220] IPC Saline Poly(AAm-co-AA) (90 / 10) partial sodium salt (≈90% solids, poly(AAm-co-AA) 90 / 10, Mw 200,000) was purchased from Polysciences, Inc. and used as received. PAE (Kymene, 0.46 azetidinium content as determined by NMR) was purchased from Ashland as an aqueous solution and used as received. IPC saline was prepared by dissolving approximately 0.07 wt% poly(AAm-co-AA) (90 / 10) and approximately 0.15% PAE (millimolar equivalent of approximately 8.8 mmol of initial azetidinium) in PBS (approximately 0.044 wt% NaH2PO4·H2O, approximately 0.388 wt% NaH2PO4·2H2O, approximately 0.79 wt% NaCl) and adjusting the pH to 7.2–7.4. The IPC saline solution is then thermally pretreated at approximately 70°C for approximately 4 hours (thermal pretreatment). During this thermal pretreatment, the poly(AAm-co-AA) and PAE partially crosslink with each other (i.e., not all of the azetidinium groups in the PAE are used up), thereby forming a water-soluble, thermally crosslinkable hydrophilic polymeric material in the IPC saline solution containing azetidinium groups within a branched polymer network. After thermal pretreatment, the IPC saline solution is filtered using a 0.22 micron polyethersulfone (PES) membrane filter and allowed to cool back to room temperature. Next, 10 ppm hydrogen peroxide is added to the final IPC saline solution to prevent bioburden growth, and the IPC saline solution is filtered using a 0.22 micron PES membrane filter.

[0221] Application of cross-linked coatings The lenses with the PAA-LbL base coating prepared above are placed in polypropylene lens packaging shells (one lens per shell) with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). The blisters are then sealed with aluminum foil and autoclaved at approximately 121°C for approximately 30 minutes to form SiHy contact lenses with a crosslinked coating (PAA-x-hydrophilic polymer material).

[0222] SiHy lens characterization The resulting SiHy contact lenses with crosslinked coatings (PAA-x-hydrophilic polymeric materials) show no debris buildup after rubbing against a paper towel, whereas control lenses (packaged in PBS, i.e., lenses with a non-covalently bound layer of PAA thereon) show severe debris buildup. The lenses have an oxygen permeability (Dk) of approximately 146 barrers. c or estimated intrinsic Dk), a bulk modulus of elasticity of about 0.76 MPa, a water content of about 32% by weight, a relative ion permeability of about 6 (compared to Alsacon lenses), a contact angle of about 34-47 degrees, and a WBUT of greater than 10 seconds. When observed under a dark field microscope, no crack lines are visible after rubbing the test lenses. The lenses are highly lubricious in a finger rub test, comparable to the control lenses.

[0223] Example 21 The SiHy lenses and IPC saline in the autoclaved lens packages prepared in Examples 6, 14, and 20 are subjected to the following biocompatibility testing.

[0224] In vitro cytotoxicity assessment SiHy lenses are evaluated by the USP Direct Contact Material Assay. Lens extractables are evaluated by the USP MEM Elution and ISO CEN Cell Growth Inhibition Assays, and IPC saline in the package after autoclaving is evaluated by the Modified Elution test method. All lenses and lens extracts evaluated were fully within the acceptance criteria for each test, with no unacceptable cytotoxicity observed.

[0225] In vivo testing The ISO Systemic Toxicity in the Mouse demonstrates that there is no evidence of systemic toxicity in mice from lens extracts. The ISO Ocular Irritation Study in the Rabbit demonstrates that lens extracts are not considered irritants to rabbit ocular tissue. The ISO Ocular Irritation Study in the Rabbit demonstrates that IPC saline in packaging after autoclaving is not considered irritating to rabbit ocular tissue. Lenses worn for 22 consecutive days in a daily disposable wear format are not irritating in the rabbit model, and eyes treated with test lenses are similar to eyes treated with control lenses. The ISO Sensitization Study (Guinea Pig Maximization Testing of Packaging Solutions) demonstrates that IPC saline after autoclaving does not cause any delay in skin contact sensitization in guinea pigs. The ISO Sensitization Study (Guinea Pig Maximization Testing of Lens Extracts) demonstrates that sodium chloride and sesame oil extracts of lenses do not cause any delay in skin contact sensitization in guinea pigs.

[0226] Genotoxicity testing When IPC saline and SiHy lens extract from the lens package were tested in the Bacterial Reverse Mutation Assay (Ames Test), it was found that the lens extract and IPC saline were not considered mutagenic against Salmonella typhimurium tester strains TA98, TA100, TA1535, and TA1537, as well as Escherichia coli WPuvrA. When SiHy lens extract was tested in the Mammalian Erythrocyte Micronucleus Assay, it was found to be non-clastogenic and negative in the mouse bone marrow micronucleus test. When IPC saline from the lens package was tested in the Chromosome Aberration Test in Chinese Hamster Ovary, the IPC saline was negative for the induction of structural and numerical chromosomal aberrations using CHO cells in both the non-activated and S9 activated test systems. When the SiHy lens extract was tested by Cell Gene Mutation Test (Mouse Lymphoma Mutagenesis Assay), the lens extract was shown to be negative in the Mouse Lymphoma Mutagenesis Assay.

[0227] Example 22 The surface compositions of preformed SiHy contact lenses (i.e., SiHy contact lenses without any coating and before application of the PAA-based coating), PAA-coated SiHy contact lenses (i.e., these lenses before sealing and autoclaving in lens packages containing IPC saline), and SiHy contact lenses with crosslinked coatings (all prepared by the procedure described in Example 20) are determined by characterizing the vacuum-dried contact lenses with X-ray photoelectron spectroscopy (XPS). XPS is a method for measuring the surface composition of lenses with a sampling depth of approximately 10 nm. The surface compositions of the three types of lenses are reported in Table 7.

[0228] [Table 7]

[0229] Table 7 shows that when a PAA coating is applied to a SiHy lens (preformed without a coating), the carbon and oxygen atomic composition approaches that of PAA (60% C and 40% O), and the silicon atomic composition is substantially reduced (from 12.1% to 4.5%). When a crosslinked coating is further applied over the PAA coating, the surface composition becomes dominated by carbon, nitrogen, and oxygen, which are triatomic compositions (excluding hydrogen, since XPS does not count hydrogen in surface compositions). These results indicate that the outermost layer of the crosslinked coated SiHy contact lens likely consists essentially of a hydrophilic polymeric material that is the reaction product of poly(AAm-co-AA) (90 / 10) (60% C, 22% O, and 18% N) and PAE.

[0230] The following vacuum-dried commercially available SiHy lenses were also subjected to XPS analysis. The surface compositions of these commercially available SiHy contact lenses are reported in Table 8.

[0231] [Table 8]

[0232] The SiHy contact lenses of the present invention have a nominal silicon content of about 1.4% in the surface layer, which is much lower than that of commercially available SiHy lenses without plasma coating (Acuvue® Advance®, Acuvue® Oasys®, TruEye™, Biofinity®, Avaira™), as well as PureVision® (plasma oxidation) and Premio™ (unknown plasma treatment), and is also lower than that of SiHy lenses (N&D® Aqua™ and Air Optix® Aqua™) with a plasma-deposited coating having a thickness of about 25 nm. This very low Si% value is comparable to that of the control sample, Goodfellow polyethylene (LDPE, d=0.015 mm; LS356526 This is comparable to the percentage of silicon atoms in the SiHy contact lenses of the present invention (SDS; ET31111512; 3004622910). These results indicate that the very low values ​​in the XPS analysis of the vacuum-dried SiHy contact lenses of the present invention, like the fluorine content in fluorine-free lenses, likely result from contaminants introduced during the preparation process, including the vacuum drying process and XPS analysis. In the SiHy contact lenses of the present invention, silicon is successfully shielded from exposure.

[0233] SiHy contact lenses of the present invention (prepared by the procedure described in Example 20), commercially available SiHy contact lenses (CLARITI™ 1 Day, ACUVUE® TruEye™ (narafilcon A and narafilcon B)), polyethylene sheet from Goodfellow (LDPE, d=0.015 mm; LS356526 XPS analysis of DAILIES® (SDS; ET31111512; 3004622910), DAILIES® (polyvinyl alcohol hydrogel lenses, i.e., non-silicone hydrogel lenses), and ACUVUE® Moist (polyhydroxyethyl methacrylate hydrogel lenses, i.e., non-silicone hydrogel lenses) is also performed. All lenses are vacuum dried. Polyethylene sheet, DAILIES®, and ACUVUE® Moist are used as controls because they do not contain silicone. The silicon atomic composition in the surface layer of the test samples is as follows: 1.3±0.2 (polyethylene sheet); 1.7±0.9 (DAILIES®); 2.8±0.9 (ACUVUE® Moist); 3.7±1.2 (three SiHy lenses prepared by the procedure described in Example 20); 5.8±1.5 (CLARITI® 1 Day); 7.8±0.1 (ACUVUE® TruEye™ (Narafilcon A)); and 6.5±0.1 (ACUVUE® TruEye™ (Narafilcon B)). The results of the SiHy contact lenses of the present invention are closer to those of conventional hydrogels and closer to silicone hydrogels.

[0234] Example 23 Synthesis of UV-absorbing amphoteric branched copolymers A 1 L jacketed reactor was equipped with a 500 mL dropping funnel, overhead stirring, a reflux condenser with nitrogen / vacuum inlet adapter, a thermometer, and a sampling adapter. 89.95 g of the 80% partially ethylenically functionalized polysiloxane prepared in Example 17, Section A, was charged to the reactor and then degassed at room temperature for approximately 30 minutes under a vacuum of less than 1 mbar. A monomer solution prepared by combining 1.03 g of HEMA, 50.73 g of DMA, 2.76 g of Norbloc methacrylate, 52.07 g of TRIS, and 526.05 g of ethyl acetate was charged to the 500 mL dropping funnel and then degassed at room temperature for 10 minutes under a vacuum of 100 mbar and then backfilled with nitrogen gas. The monomer solution was degassed for two additional cycles under the same conditions. The monomer solution was then charged to the reactor. The reaction mixture was heated to 67°C with moderate stirring. While heating, a solution consisting of 2.96 g of mercaptoethanol (chain transfer agent, CTA), 0.72 g of 2,2'-azobis(2-methylpropionate)dimethyl (V-601, initiator), and 76.90 g of ethyl acetate is charged to the dropping funnel and subsequently subjected to the same degassing process as the monomer solution. Once the reactor temperature reaches 67°C, the initiator / CTA solution is also added to the reactor. The reaction is carried out at 67°C for 8 hours. After the copolymerization is complete, the reactor temperature is cooled to room temperature.

[0235] Synthesis of UV-absorbing amphoteric branched prepolymers The copolymer solution prepared above is ethylenically functionalized to form an amphoteric branched prepolymer by adding 8.44 g of IEM (i.e., the desired molar equivalent of 2-isocyanatoethyl methacrylate) in the presence of 0.50 g of DBTDL. The mixture is stirred at room temperature under sealed conditions for 24 hours. The prepared prepolymer is then stabilized with 100 ppm of hydroxy-tetramethylenepiperonyloxy, and the solution is then concentrated to 200 g (≈50%) and filtered through a 1 μm pore size filter paper. After exchanging the reaction solvent with 1-propanol by repeated cycles of evaporation and dilution, the solution is ready for formulation. The solids content is measured by removing the solvent in a vacuum oven at 80°C.

[0236] Preparation of Lens Formulations A lens formulation is prepared having the following composition: 71% by weight of the above prepared prepolymer; 4% by weight of DMA; 1% by weight of TPO; 1% by weight of DMPC; 1% by weight of Brij 52 (from); and 22% by weight of 1-PrOH.

[0237] Lens preparation Lenses are manufactured by casting the lens formulation prepared above under the spatial constraints of UV irradiation using a reusable mold similar to those shown in Figures 1-6 of U.S. Patent No. 7,384,590 and U.S. Patent No. 7,387,759 (Figures 1-6). The mold includes a female half made of glass and a male half made of quartz. The UV irradiation source is approximately 4.6 mW / cm. 2 The UV light is a Hamamatsu lamp equipped with a 380 nm cutoff filter at an intensity of 1000 nm. The lens formulation in the mold is irradiated with UV light for approximately 30 seconds.

[0238] Cast lenses are extracted with methyl ethyl ketone (MEK), rinsed in water, and coated with polyacrylic acid (PAA) by immersing the lenses in a propanol solution of PAA (0.004% by weight, acidified to approximately pH 2.0 with formic acid) and hydrated in water.

[0239] IPC saline is prepared under pre-reaction conditions at approximately 60°C for 6 hours from a composition containing approximately 0.07% PAAm-PAA and sufficient PAE (≈0.15% PAE) to provide an initial azetidinium content of approximately 8.8 millimolar equivalents / liter. Five ppm hydrogen peroxide is then added to the IPC saline to prevent bioburden growth, and the IPC saline is filtered using a 0.22 micron polyethersulfone [PES] membrane filter. Lenses are placed in polypropylene lens packaging shells with 0.6 mL of IPC saline (half of the saline is added before lens insertion). The blisters are then sealed with aluminum foil and autoclaved at 121°C for 30 minutes.

[0240] Lens characterization The resulting lens has the following properties: E' ≈ 0.82 MPa; Dk c ≈159.4 (Lotrafilcon B is used as the control lens, with an average center thickness of 80 μm and an intrinsic Dk of 110); IP≈2.3; Water%≈26.9; and UVA / UVB %T≈4.6 / 0.1. When viewed under a dark field microscope, no crack lines are visible after rubbing the test lenses. The lenses are very lubricious in the finger rub test, comparable to the control lenses.

[0241] Example 24 Preparation of Lens Formulations Formulation I is prepared by dissolving the components in 1-propanol to have the following composition: 33 wt % of the CE-PDMS macromer prepared in Example 2, 17 wt % of N-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24 wt % of N,N-dimethylacrylamide (DMA), 0.5 wt % of N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt) (L-PEG), 1.0 wt % of Darocur 1173 (DC1173), 0.1 wt % of Visitint (tris(trimethylsiloxy)silylpropyl methacrylate, a blue pigment dispersion of 5% copper phthalocyanine in TRIS), and 24.5 wt % of 1-propanol.

[0242] Formulation II is prepared by dissolving the components in 1-propanol to have the following composition: about 32 wt % of the CE-PDMS macromer prepared in Example 2, about 21 wt % of TRIS-Am, about 23 wt % of DMA, about 0.6 wt % of L-PEG, about 1 wt % of DC1173, about 0.1 wt % of Visitint (a blue pigment dispersion of 5% copper phthalocyanine in TRIS), about 0.8 wt % of DMPC, about 200 ppm of H-TEMPO, and about 22 wt % of 1-propanol.

[0243] Lens preparation Lenses are prepared from the lens formulations prepared above by casting in reusable molds (quartz half female and glass half male) similar to those shown in Figures 1-6 of U.S. Patent No. 7,384,590 and U.S. Patent No. 7,387,759 (Figures 1-6). The UV radiation source is approximately 4 mW / cm. 2 The lamp is a Hamamatsu lamp equipped with a WG335+TM297 cutoff filter at an intensity of 1000 uV. The lens formulation in the mold is irradiated with UV light for approximately 25 seconds. The cast lenses are extracted with methyl ethyl ketone (MEK) (or propanol or isopropanol).

[0244] Application of PAA Prime Coatings to SiHy Contact Lenses A polyacrylic acid coating solution (PAA-1) was prepared by dissolving an amount of PAA (MW: 450 kDa, manufactured by Lubrizol) in a volume of 1-propanol to have a concentration of approximately 0.39 wt %, and adjusting the pH to approximately 2.0 with formic acid.

[0245] Another PAA coating solution (PAA-2) was prepared by dissolving an amount of PAA (MW: 450 kDa, manufactured by Lubrizol) in a volume of organic solvent (50 / 50, 1-propanol / HO) to have a concentration of about 0.39 wt %, and adjusting the pH to about 2.0 with formic acid.

[0246] The SiHy contact lenses obtained above are subjected to one of the immersion processes shown in Tables 9 and 10.

[0247] [Table 9]

[0248] [Table 10]

[0249] Application of cross-linked hydrophilic coating Poly(acrylamide-co-acrylic acid) partial sodium salt, poly(AAm-co-AA)(90 / 10) (≈90% solids, poly(AAm-co-AA)(90 / 10), Mw 200,000) was purchased from Polysciences, Inc. and used as received. PAE (Kymene, azetidinium content of 0.46 as determined by NMR) was purchased from Ashland as an aqueous solution and used as received. In-package crosslinking (IPC) saline was prepared by dissolving approximately 0.07 wt% poly(AAm-co-AA) (90 / 10) and approximately 0.15% PAE (millimolar equivalent of approximately 8.8 mmol of initial azetidinium) in phosphate-buffered saline (PBS) (approximately 0.044 wt% NaH2PO4·H2O, approximately 0.388 wt% NaH2PO4·2H2O, approximately 0.79 wt% NaCl) and adjusting the pH to 7.2-7.4. The IPC saline was then thermally pretreated at approximately 70 °C for approximately 4 hours (thermal pretreatment). During this thermal pretreatment, the poly(AAm-co-AA) and PAE partially crosslinked with each other (i.e., not all of the azetidinium groups in the PAE were consumed), forming a water-soluble, thermally crosslinkable hydrophilic polymeric material in the IPC saline containing azetidinium groups within a branched polymer network. After heat pretreatment, the IPC saline is filtered through a 0.22 micron polyethersulfone (PES) membrane filter and cooled back to room temperature. 10 ppm hydrogen peroxide is then added to the final IPC saline to prevent bioburden growth, and the IPC saline is filtered through a 0.22 micron polyethersulfone (PES) membrane filter.

[0250] The lenses with the PAA prime coating prepared above are placed in polypropylene lens packaging shells (one lens per shell) with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). The blisters are then sealed with aluminum foil and autoclaved at about 121°C for about 30 minutes to form SiHy lenses with crosslinked hydrophilic coatings.

[0251] SiHy lens characterization The resulting SiHy contact lenses, with a crosslinked hydrophilic coating and a center thickness of about 0.95 microns, have an oxygen permeability (Dk) of about 142 to about 150 barrers. c or estimated intrinsic Dk), a bulk elastic modulus of about 0.72 to about 0.79 MPa, a water content of about 30% to about 33% by weight, a relative ion permeability of about 6 (compared to Alsacon lenses), and a contact angle of about 34 to about 47 degrees.

[0252] Characterization of nanotextured surfaces on contact lenses Transmission-Differential-Interference-Contrast (TDIC) method The contact lens is placed on a glass slide and flattened by compressing the lens between the slide and a glass coverslip. The contact lens surface is positioned and examined using a Nikon ME600 microscope with transmitted differential interference contrast optics, focusing through the lens, using a 40x objective. The resulting TDIC image is then evaluated to determine the presence of wrinkled surface patterns (e.g., random and / or ordered worm-like patterns).

[0253] Reflection-Differential-Interference-Contrast (RDIC) Method: The lens is placed on a glass slide and flattened by making four radial cuts at approximately 90-degree intervals. Excess saline is blown off the surface using compressed air. The lens surface is then examined using a Nikon Optiphot-2 with reflective differential interference optics using 10x, 20x, and 50x objectives for the presence of wrinkled surface patterns on the contact lens surface. A representative image of each side is acquired using the 50x objective. The contact lens is then turned over, excess saline is removed, and the other side of the contact lens is examined in the same manner. The resulting RDIC images are then evaluated to determine the presence of wrinkled surface patterns (e.g., random and / or ordered worm-like patterns).

[0254] Dark-field optical microscopy (DFLM) DFLM is generally based on dark-field illumination, a method for enhancing the contrast of observed samples. This technique consists of a light source outside or blocked from the observer's field of view to illuminate the sample at an angle relative to normal transmitted light. Unscattered light from the light source is not focused by the objective lens, so it is not part of the image and the image background appears dark. Because the light source illuminates the sample at an angle, the light observed in the sample image is light scattered by the sample toward the observer, creating a contrast between this scattered light from the sample and the dark background of the image. This contrast mechanism makes dark-field illumination particularly useful for observing scattering phenomena such as haze.

[0255] DFLM is used to assess contact lens haziness as follows. Because the dark-field setting involves scattered light, it is believed that dark-field data may provide a worst-case estimate of haziness. In an 8-bit grayscale digital image, each image pixel is assigned a grayscale intensity (GSI) value ranging from 0 to 255. Zero represents a pixel that is completely black, and 255 represents a pixel that is completely white. Increased scattered light captured in the image produces pixels with high GSI values. This GSI value can then be used as a mechanism to quantify the amount of scattered light observed in the dark-field image. Haziness is represented by averaging the GSI values ​​of all pixels in an area of ​​interest (AOI) (e.g., the entire lens, or the lenticular or optic portion of the lens). The experimental setup consists of a microscope or equivalent optical device, an attached digital camera, and a dark-field stand with an annular light and a variable-intensity light source. The optical device is designed and positioned so that the entire contact lens to be observed fills the field of view (typically a field of view of approximately 15 mm x 20 mm). The illumination is set to a level appropriate for observing the desired changes in the sample. The light intensity is adjusted and calibrated to the same level for each set of samples using density / light scattering standards known to those skilled in the art. For example, one standard consists of two overlapping plastic cover slips (identical and slightly or moderately matte). Such a standard consists of three areas with different average GSIs, including two areas: a mid-grayscale level and a saturated white (edge). The black area represents the empty dark field. The black and saturated white areas can be used to verify the camera's gain and offset (contrast and brightness) settings. The mid-gray level can provide three points for verifying the camera's linear response. The light intensity is adjusted so that the average GSI of the empty dark field approaches 0 and that of the specified AOI in the standard digital image is the same each time within ±5 GSI units. After light intensity calibration, the contact lens is immersed in 0.2 μm filtered phosphate buffered saline in a quartz Petri dish or dish of similar transparency placed in a DFLM stand.An 8-bit grayscale digital image of the lens when viewed with the calibrated illumination is then acquired, and the average GSI of the specified AOI in the subset of images containing the lens is determined. This is repeated for the contact lenses in the sample set. The light intensity calibration is reevaluated periodically throughout the study to ensure consistency. The level of opacity under the DFLM test is defined as DFLM opacity = (GSI / 255) x 100%.

[0256] SiHy contact lenses (whose PAA prime coatings are obtained by either the 20-0 or 80-0 immersion process) are determined to have an average DFLM haze of about 73% and exhibit a wrinkled surface pattern (random, worm-like pattern) that is visually observable when the hydrated contact lenses are examined by either the RDIC or TDIC methods described above, but this wrinkled surface pattern has virtually no adverse effect on the light transmission of the contact lenses.

[0257] SiHy contact lenses (whose PAA prime coatings are obtained by any of the immersion processes 20-1 to 20-4) are determined to have a low average DFLM haze of approximately 26% (probably due to the presence of Visitint pigment particles) and do not exhibit a noticeable wrinkled surface pattern (random worm-like pattern) when examined under either the RDIC or TDIC described above.

[0258] A high percentage of SiHy contact lenses (whose PAA prime coating is obtained by immersion process 20-5) have been determined to have a moderate average DFLM opacity of about 45% and exhibit a slightly noticeable wrinkled surface pattern when examined under either the RDIC or TDIC described above, but this wrinkled surface pattern has virtually no adverse effect on the light transmittance of the contact lenses.

[0259] SiHy contact lenses (whose PAA prime coatings are obtained by any of the immersion processes 80-1, 80-2, 80-3, 80-5, and 80-6) do not exhibit a noticeable wrinkled surface pattern when examined under either the RDIC or TDIC described above. However, SiHy contact lenses (whose PAA prime coatings are obtained by any of the immersion processes 80-0 and 80-4) exhibit a noticeable wrinkled surface pattern when examined under either the RDIC or TDIC described above. However, this wrinkled surface pattern has virtually no adverse effect on the light transmittance of the contact lenses.

Claims

1. 1. A method of making a silicone hydrogel contact lens having a crosslinked hydrophilic coating thereon, comprising: (a) providing a silicone hydrogel contact lens having amino and / or carboxyl groups on and / or near the surface of the contact lens, and a water-soluble, thermally crosslinkable hydrophilic polymeric material, wherein the silicone hydrogel contact lens contains amino or carboxyl groups, or both, on and / or near the surface of the contact lens, and the hydrophilic polymeric material comprises: (i) 20% to 95%, preferably 35% to 90%, and more preferably 50% to 85% (by weight) of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; (ii) a first polymer chain selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof; and (iii) positively charged azetidinium groups that are part of the first polymer chain or are pendant or terminal groups covalently attached to the first polymer chain, wherein the hydrophilic moiety or second polymer chain is covalently attached to the first polymer chain via one or more covalent bonds formed between one azetidinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl, or thiol group of the hydrophilic enhancing agent, respectively; and (b) heating the silicone hydrogel contact lens in the presence of a hydrophilic polymeric material in an aqueous solution to and at 40°C to 140°C for a time sufficient to covalently bond the hydrophilic polymeric material to the surface of the silicone hydrogel contact lens via a second covalent bond formed between each one azetidinium group of the hydrophilic polymeric material and one of the reactive functional groups on and / or near the surface of the contact lens, thereby forming a crosslinked hydrophilic coating on the silicone hydrogel contact lens, wherein the silicone hydrogel contact lens comprising the crosslinked hydrophilic coating has a surface wettability characterized by an average water contact angle of preferably 90 degrees or less, more preferably 80 degrees or less, even more preferably 70 degrees or less, and most preferably 60 degrees or less.

2. 2. The method according to claim 1, wherein the hydrophilic enhancer is a hydrophilic polymer having one or more amino, carboxyl and / or thiol groups, and the content of monomer units having amino, carboxyl or thiol groups in the hydrophilic polymer as the hydrophilic enhancer is less than 40%, preferably less than 30%, more preferably less than 20%, and even more preferably less than 10% (wt %) based on the total weight of the hydrophilic polymer.

3. 3. The method according to claim 1 or 2, wherein the hydrophilic polymer as the hydrophilic enhancer is polyethylene glycol having only one amino, carboxyl or thiol group; polyethylene glycol having two terminal amino, carboxyl and / or thiol groups; multi-arm polyethylene glycol having one or more amino, carboxyl and / or thiol groups; polyethylene glycol dendrimer having one or more amino, carboxyl and / or thiol groups.

4. 3. The method according to claim 1 or 2, wherein the hydrophilic polymer as the hydrophilicity enhancing agent is a copolymer which is a polymerization product of a composition comprising: (1) 60% by weight or less, preferably 0.1% to 30%, more preferably 0.5% to 20%, and even more preferably 1% to 15% (by weight) of at least one reactive vinyl monomer; and (2) at least one non-reactive hydrophilic vinyl monomer and / or at least one phosphorylcholine-containing vinyl monomer; or a combination thereof, wherein: The reactive vinyl monomer is amino-(meth)acrylate. １ -C ６ Alkyl (meth)acrylic acid C １ -C ６ Alkylamino-C １ -C ６ Alkyl, arylamine, vinylamine, amino-C １ -C ６ Alkyl (meth)acrylamide, C １ -C ６ Alkylamino-C １ -C ６ Alkyl (meth)acrylamide, acrylic acid, C １ -C １２ alkylacrylic acid, N,N-2-acrylamidoglycolic acid, β-methyl-acrylic acid, α-phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof, preferably (meth)acrylic acid, C ２ -C １２ Alkyl acrylic acid, vinylamine, allylamine, (meth)acrylic acid amino-C ２ -C ４ Alkyl, amino-C ２ -C ４ alkyl(meth)acrylamides, and combinations thereof; Non-reactive hydrophilic vinyl monomers include acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminopropyl methacrylamide, N,N-dimethylaminopropyl acrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, C having a weight average molecular weight of 1500 daltons or less １ -C ４ -alkoxy polyethylene glycol (meth)acrylate, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymer), and combinations thereof, preferably acrylamide, N,N-dimethyl acrylamide, N-vinyl pyrrolidone, N-vinyl-N-methyl acetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C 100 having a weight average molecular weight of 400 Daltons or less １ -C ４ -alkoxy polyethylene glycol (meth)acrylate, vinyl alcohol, and combinations thereof.

5. The hydrophilic polymer as the hydrophilicity enhancer is selected from a group consisting of acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, (meth)acrylate glycerol, (meth)acrylate hydroxyethyl, N-hydroxyethyl (meth)acrylamide, (meth)acryloyloxyethyl phosphorylcholine, and C having a weight average molecular weight of 400 daltons or less. １ -C ４ 3. The method of claim 1, wherein the vinyl monomer is a monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated homo- or copolymer of a non-reactive hydrophilic vinyl monomer selected from the group consisting of alkoxypolyethylene glycol (meth)acrylate, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, N,N-dimethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylamide, and combinations thereof.

6. 3. The method according to claim 1, wherein the hydrophilic polymer as the hydrophilicity enhancer is an amino- or carboxyl-containing polysaccharide, hyaluronic acid, chondroitin sulfate, or a combination thereof.

7. The weight average molecular weight M of the hydrophilic polymer used as the hydrophilicity enhancer Ｗ The method according to any one of claims 2 to 6, wherein is 500 to 1,000,000, preferably 1,000 to 500,000.

8. 3. The method of claim 1, wherein the hydrophilicity enhancer is an amino-, carboxyl-, or thiol-containing monosaccharide; an amino-, carboxyl-, or thiol-containing disaccharide; or an amino-, carboxyl-, or thiol-containing oligosaccharide.

9. 9. The method of any one of claims 1 to 8, wherein the heating step is carried out in a lens package containing a silicone hydrogel contact lens immersed in packaging solution, more preferably by autoclaving the silicone hydrogel contact lens immersed in the packaging solution in a sealed lens package at a temperature of 118°C to 125°C for approximately 20 to 90 minutes to form a crosslinked hydrophilic coating on the silicone hydrogel contact lens, wherein the packaging solution contains at least one buffer in an amount sufficient to maintain a pH of 6.0 to 8.5, and has a tonicity of 200 to 450 milliosmoles (mOsm), preferably 250 to 350 mOsm, and a viscosity at 25°C of 1 to 20 centipoise, preferably 1.2 to 10 centipoise, more preferably 1.5 to 5 centipoise.

10. 10. The method of claim 9, wherein the packaging solution comprises 0.01% to 2%, preferably 0.05% to 1.5%, more preferably 0.1% to 1%, even more preferably 0.2% to 0.5% (by weight) of the thermally crosslinkable hydrophilic polymeric material.

11. 10. The method of claim 9, further comprising, prior to the heating step, contacting the silicone hydrogel contact lens with an aqueous solution of a thermally crosslinkable hydrophilic polymeric material at room temperature to form a top layer of a thermally crosslinkable hydrophilic polymeric material on the surface of the silicone hydrogel contact lens; immersing the silicone hydrogel contact lens with the top layer of the thermally crosslinkable hydrophilic polymeric material in a lens package in a packaging solution; and sealing the lens package.

12. The silicone hydrogel contact lens comprises 0.1% to 10%, more preferably 0.25% to 7%, even more preferably 0.5% to 5%, and most preferably 0.75% to 3% (by weight) of a reactive vinyl monomer [(meth)acrylate amino-C ２ -C ６ Alkyl (meth)acrylic acid C １ -C ６ Alkylamino-C ２ -C ６ Alkyl, arylamine, vinylamine, amino-C ２ -C ６ Alkyl (meth)acrylamide, C １ -C ６ Alkylamino-C ２ -C ６ Alkyl (meth)acrylamide, acrylic acid, C １ -C １２ and a reactive vinyl monomer selected from the group consisting of alkylacrylic acid, N,N-2-acrylamidoglycolic acid, β-methyl-acrylic acid, α-phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof; preferably, the reactive vinyl monomer is selected from the group consisting of amino-C(meth)acrylate. ２ -C ６ Alkyl (meth)acrylic acid C １ -C ６ Alkylamino-C ２ -C ６ Alkyl, vinylamine, allylamine, amino-C ２ -C ６ Alkyl (meth)acrylamide, C １ -C ６ Alkylamino-C ２ -C ６ Alkyl (meth)acrylamide, acrylic acid, C １ -C １２ 12. The method of any one of claims 1 to 11, wherein the lens is prepared by polymerizing a silicone hydrogel lens formulation comprising a compound selected from the group consisting of alkyl acrylates, ...

13. The method of any one of claims 1 to 12, wherein the silicone hydrogel contact lens comprises a reactive base coating that includes amino and / or carboxyl groups.

14. 14. The method of claim 13, wherein the reactive base coating comprises at least one layer of a reactive polymer having pendant amino and / or carboxyl groups and is obtained by contacting a silicone hydrogel contact lens with a solution of the reactive polymer, wherein the reactive polymer is an amino-C １ ~C ４ Alkyl (meth)acrylamide, Amino (meth)acrylate-C １ ~C ４ Alkyl, C １ ~C ４ Alkylamino-C １ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid C １ ~C ４ Alkylamino-C １ ~C ４ Homopolymers of alkyl, aryl, or vinylamines; polyethyleneimine; polyvinyl alcohol with pendant amino groups; linear or branched polyacrylic acid; C １ ~C １２ Homopolymer of alkylacrylic acid; Amino-C ２ ~C ４ Alkyl (meth)acrylamide, Amino (meth)acrylate-C ２ ~C ４ Alkyl, C １ ~C ４ Alkylamino-C ２ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid C １ ~C ４ Alkylamino-C ２ ~C ４ Alkyl, acrylic acid, C １ ~C １２ alkylacrylic acid, maleic acid, and / or fumaric acid and at least one non-reactive hydrophilic vinyl monomer (preferably acrylamide, N,N-dimethyl(meth)acrylamide, N-vinylpyrrolidone, glycerol methacrylate, N,N-2-acrylamidoglycolic acid, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 2-methyl-3-methylene-2-pyrrolidone, 5-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, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, (meth)acryloyloxyethyl phosphorylcholine, C having a weight average molecular weight of 1500 daltons or less １ -C ４ -alkoxypolyethylene glycol (meth)acrylate, copolymers with N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in the copolymer), and combinations thereof; carboxyl-containing cellulose; hyaluronate; chondroitin sulfate; poly(glutamic acid); poly(aspartic acid); or combinations thereof.

15. The reactive polymers for forming the base coating include polyacrylic acid, polymethacrylic acid, poly(C ２ -C １２ alkylacrylic acid), poly[acrylic acid-co-methacrylic acid], poly[C ２ -C １２ alkylacrylic acid-co-(meth)acrylic acid], poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone], poly[C ２ -C １２ alkylacrylic acid-co-acrylamide], poly[C ２ -C １２ alkylacrylic acid-co-vinylpyrrolidone], hydrolyzed poly[(meth)acrylic acid-co-vinyl acetate], hydrolyzed poly[C ２ -C １２ 14. The method of claim 13, wherein the polymer is selected from the group consisting of alkyl acrylic acid-co-vinyl acetate, polyethyleneimine (PEI), polyallylamine hydrochloride (PAH) homo- or copolymer, polyvinylamine homo- or copolymer, or a combination thereof.

16. 16. The method of claim 14 or 15, wherein the reactive polymer is dissolved in a mixture of water and one or more organic solvents, an organic solvent, or a mixture of one or more organic solvents.

17. 14. The method of claim 13, wherein the reactive base coating on the contact lens is obtained by polymerizing at least one amino- or carboxyl-containing vinyl monomer under the influence of a plasma.

18. 18. A silicone hydrogel contact lens product obtainable by the method of any one of claims 1 to 17, wherein the silicone hydrogel contact lens has at least one property selected from the group consisting of: an oxygen permeability of at least 40 barrers, preferably at least 50 barrers, more preferably at least 60 barrers, and even more preferably at least 70 barrers; an elastic modulus of 1.5 MPa or less, preferably 1.2 MPa or less, more preferably 1.0 MPa or less, and even more preferably between 0.3 MPa and 1.0 MPa; a water content of preferably between 18% and 70%, and more preferably between 20% and 60% (by weight) when fully hydrated; and combinations thereof.

19. 1. An ophthalmic lens product comprising a sterile and sealed lens package, wherein: the lens package contains a post-autoclaved lens packaging solution and a ready-to-use silicone hydrogel contact lens immersed therein; The ready-to-use silicone hydrogel contact lens comprises a crosslinked hydrophilic coating obtained by autoclaving a parent silicone hydrogel contact lens having amino and / or carboxyl groups on and / or near the surface of the parent silicone hydrogel contact lens in a pre-autoclave packaging solution containing a water-soluble, thermally crosslinkable hydrophilic polymeric material; The thermally crosslinkable hydrophilic polymeric material comprises: (i) 20% to 95%, preferably 35% to 90%, and more preferably 50% to 85% (by weight) of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; (ii) 5% to 80%, preferably 10% to 65%, and even more preferably 15% to 50% (by weight) of hydrophilic portions or second polymer chains derived from at least one hydrophilicity enhancing agent having at least one reactive functional group selected from the group consisting of an amino group, a carboxyl group, a thiol group, and combinations thereof; and (iii) azetidinium groups that are part of the first polymer chains or that are pendant or terminal groups covalently attached to the first polymer chains; the thermally crosslinkable hydrophilic polymeric material is covalently bonded to the silicone hydrogel contact lens via a first covalent bond formed between one amino or carboxyl group on and / or near the surface of the original silicone hydrogel contact lens and one azetidinium group of the thermally crosslinkable hydrophilic polymeric material, respectively; and the post-autoclaving packaging solution comprises at least one buffer in an amount sufficient to maintain a pH of 6.0 to 8.5, has a tonicity of 200 to 450 milliosmoles (mOsm), preferably 250 to 350 mOsm, at 25° C., and a viscosity of 1 to 20 centipoise, preferably 1.2 to 10 centipoise, and more preferably 1.5 to 5 centipoise; the post-autoclaving packaging solution comprises a polymeric wetting material that is a hydrolysis product of a thermally crosslinkable hydrophilic polymeric material after autoclaving; A ready-to-use silicone hydrogel contact lens product having a surface hydrophilicity / wetability characterized by an average water contact angle of 90 degrees or less, preferably 80 degrees or less, more preferably 70 degrees or less, and even more preferably 60 degrees or less.

20. 20. The ophthalmic lens product of claim 19, wherein the hydrophilic enhancer is a hydrophilic polymer having one or more amino, carboxyl and / or thiol groups, and wherein the content of monomer units having amino, carboxyl or thiol groups in the hydrophilic polymer as the hydrophilic enhancer is less than 40%, preferably less than 30%, more preferably less than 20%, and even more preferably less than 10% (wt %) based on the total weight of the hydrophilic polymer.

21. 21. An ophthalmic lens product according to claim 19 or 20, wherein the hydrophilic polymer as a hydrophilic enhancer is polyethylene glycol having only one amino, carboxyl or thiol group; polyethylene glycol having two terminal amino, carboxyl and / or thiol groups; multi-arm polyethylene glycol having one or more amino, carboxyl and / or thiol groups; or polyethylene glycol dendrimer having one or more amino, carboxyl and / or thiol groups.

22. 21. The ophthalmic lens product according to claim 19 or 20, wherein the hydrophilic polymer as the hydrophilicity enhancer is a copolymer that is the polymerization product of a composition comprising: (1) 60% by weight or less, preferably 0.1% to 30%, more preferably 0.5% to 20%, and even more preferably 1% to 15% (by weight) of at least one reactive vinyl monomer; and (2) at least one non-reactive hydrophilic vinyl monomer and / or at least one phosphorylcholine-containing vinyl monomer; or a combination thereof, wherein: The reactive vinyl monomer is amino-(meth)acrylate. １ -C ６ Alkyl (meth)acrylic acid C １ -C ６ Alkylamino-C １ -C ６ Alkyl, arylamine, vinylamine, amino-C １ -C ６ Alkyl (meth)acrylamide, C １ -C ６ Alkylamino-C １ -C ６ Alkyl (meth)acrylamide, acrylic acid, C １ -C １２ alkylacrylic acid, N,N-2-acrylamidoglycolic acid, β-methyl-acrylic acid, α-phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof, preferably (meth)acrylic acid, C ２ -C １２ Alkyl acrylic acid, vinylamine, allylamine, (meth)acrylic acid amino-C ２ -C ４ Alkyl, amino-C ２ -C ４ alkyl(meth)acrylamides, and combinations thereof; Non-reactive hydrophilic vinyl monomers include acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminopropyl methacrylamide, N,N-dimethylaminopropyl acrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, C having a weight average molecular weight of 1500 daltons or less １ -C ４ -alkoxy polyethylene glycol (meth)acrylate, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymer), and combinations thereof, preferably acrylamide, N,N-dimethyl acrylamide, N-vinyl pyrrolidone, N-vinyl-N-methyl acetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C 100 having a weight average molecular weight of 400 Daltons or less １ -C ４ -alkoxypolyethylene glycol (meth)acrylate, vinyl alcohol, and combinations thereof.

23. The hydrophilic polymer as the hydrophilicity enhancer is selected from a group consisting of acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, (meth)acrylate glycerol, (meth)acrylate hydroxyethyl, N-hydroxyethyl (meth)acrylamide, (meth)acryloyloxyethyl phosphorylcholine, and C having a weight average molecular weight of 400 daltons or less. １ -C ４ 21. The ophthalmic lens product of claim 19 or 20, which is a monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated homo- or copolymer of non-reactive hydrophilic vinyl monomers selected from the group consisting of alkoxypolyethylene glycol (meth)acrylate, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, N,N-dimethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylamide, and combinations thereof.

24. 21. The ophthalmic lens product according to claim 19 or 20, wherein the hydrophilic polymer as the hydrophilicity enhancer is an amino- or carboxyl-containing polysaccharide, hyaluronic acid, chondroitin sulfate, or a combination thereof.

25. 21. The ophthalmic lens product of claim 19 or 20, wherein the hydrophilicity enhancer is an amino-, carboxyl-, or thiol-containing monosaccharide; an amino-, carboxyl-, or thiol-containing disaccharide; an amino-, carboxyl-, or thiol-containing oligosaccharide; and combinations thereof.

26. The weight average molecular weight M of the hydrophilic polymer used as the hydrophilicity enhancer Ｗ The ophthalmic lens product according to any one of claims 20 to 24, wherein the .DELTA..times ...

27. 27. The ophthalmic lens product of any one of claims 19 to 26, wherein the pre-autoclaving packaging solution comprises 0.01% to 2%, preferably 0.05% to 1.5%, more preferably 0.1% to 1%, and even more preferably 0.2% to 0.5% (by weight) of thermally crosslinkable hydrophilic polymeric material.

28. The parent silicone hydrogel contact lens contains 0.1% to 10%, more preferably 0.25% to 7%, even more preferably 0.5% to 5%, and most preferably 0.75% to 3% (by weight) of a reactive vinyl monomer [(meth)acrylate amino-C １ -C ６ Alkyl (meth)acrylic acid C １ -C ６ Alkylamino-C １ -C ６ Alkyl, arylamine, vinylamine, amino-C １ -C ６ Alkyl (meth)acrylamide, C １ -C ６ Alkylamino-C １ -C ６ Alkyl (meth)acrylamide, acrylic acid, C １ -C １２ 28. The ophthalmic lens product of any one of claims 19 to 27, produced by polymerizing a silicone hydrogel lens formulation comprising an alkyl acrylate, N,N-2-acrylamidoglycolic acid, β-methyl-acrylic acid, α-phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof.

29. The ophthalmic lens product of any one of claims 19 to 28, wherein the original silicone hydrogel contact lens comprises a reactive base coating that includes amino or carboxyl groups.

30. 30. The ophthalmic lens product of claim 29, wherein the reactive base coating comprises at least one layer of a reactive polymer having pendant amino and / or carboxyl groups, and the reactive base coating is obtained by contacting a silicone hydrogel contact lens with a solution of the reactive polymer, wherein the reactive polymer is an amino-C １ ~C ４ Alkyl (meth)acrylamide, Amino (meth)acrylate-C １ ~C ４ Alkyl, C １ ~C ４ Alkylamino-C １ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid C １ ~C ４ Alkylamino-C １ ~C ４ Homopolymers of alkyl, aryl, or vinylamines; polyethyleneimine; polyvinyl alcohol with pendant amino groups; linear or branched polyacrylic acid; C １ ~C １２ Homopolymer of alkylacrylic acid; Amino-C １ ~C ４ Alkyl (meth)acrylamide, Amino (meth)acrylate-C １ ~C ４ Alkyl, C １ ~C ４ Alkylamino-C １ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid C １ ~C ４ Alkylamino-C １ ~C ４ Alkyl, acrylic acid, C １ ~C １２ alkylacrylic acid, maleic acid, and / or fumaric acid and at least one hydrophilic vinyl monomer (preferably acrylamide, N,N-dimethyl(meth)acrylamide, N-vinylpyrrolidone, glycerol methacrylate, N,N-2-acrylamidoglycolic acid, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl ... rolidone, 5-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, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, phosphorylcholine-containing vinyl monomer, C having a weight average molecular weight of 1500 daltons or less １ -C ４ -alkoxypolyethylene glycol (meth)acrylate, copolymers with N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in the copolymer), and combinations thereof; carboxyl-containing cellulose; hyaluronate; chondroitin sulfate; poly(glutamic acid); poly(aspartic acid); or combinations thereof.

31. 31. The ophthalmic lens product of claim 30, wherein the reactive polymer is dissolved in a mixture of water and one or more organic solvents, an organic solvent, or a mixture of one or more organic solvents.

32. 32. The ophthalmic lens product of claim 31, wherein the reactive base coating on the contact lens is obtained by polymerizing at least one amino- or carboxyl-containing vinyl monomer under the influence of a plasma.

33. 33. The ophthalmic lens product of any one of claims 19 to 32, wherein the ready-to-use silicone hydrogel contact lens has at least one property selected from the group consisting of: an oxygen permeability of at least 40 barrers, preferably at least 50 barrers, more preferably at least 60 barrers, and even more preferably at least 70 barrers; an elastic modulus of 1.5 MPa or less, preferably 1.2 MPa or less, more preferably 1.0 MPa or less, and even more preferably between 0.3 MPa and 1.0 MPa; a water content of preferably between 18% and 70%, and more preferably between 20% and 60% (by weight) when fully hydrated; and combinations thereof.

34. 1. A water-soluble, thermally crosslinkable hydrophilic polymeric material comprising: (a) 20% to 95%, preferably 35% to 90%, and more preferably 50% to 85% (by weight) of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; (b) 5% to 80%, preferably 10% to 65%, and more preferably 15% to 50% (by weight) of second polymer chains derived from at least one hydrophilicity enhancing agent having at least one reactive functional group selected from the group consisting of an amino group, a carboxyl group, a thiol group, and combinations thereof, wherein the second polymer chains are covalently attached to the first polymer chains via one or more covalent bonds formed between one azetidinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl, or thiol group of the hydrophilicity enhancing polymeric agent, respectively; and (c) a material comprising an azetidinium group that is part of a first polymer chain or that is a pendant group covalently attached to a first polymer chain.

35. 35. The hydrophilic polymer material of claim 34, wherein the hydrophilic enhancing polymeric agent is a hydrophilic polymer having one or more amino, carboxyl and / or thiol groups, and the content of amino, carboxyl or thiol groups in the hydrophilic polymer as the hydrophilic enhancing agent is less than 40%, preferably less than 30%, more preferably less than 20%, and even more preferably less than 10% (wt %) based on the total weight of the hydrophilic polymer.

36. 36. The hydrophilic polymer material of claim 34 or 35, wherein the hydrophilic polymer as a hydrophilic enhancer is polyethylene glycol having only one amino, carboxyl or thiol group; polyethylene glycol having two terminal amino, carboxyl and / or thiol groups; multi-arm polyethylene glycol having one or more amino, carboxyl and / or thiol groups; polyethylene glycol dendrimer having one or more amino, carboxyl and / or thiol groups.

37. 36. The hydrophilic polymer material according to claim 34 or 35, wherein the hydrophilic polymer as the hydrophilicity enhancer is a copolymer which is a polymerization product of a composition comprising: (1) 60% by weight or less, preferably 0.1% to 30%, more preferably 0.5% to 20%, and even more preferably 1% to 15% (by weight) of at least one reactive vinyl monomer; and (2) at least one non-reactive hydrophilic vinyl monomer and / or at least one phosphorylcholine-containing vinyl monomer; or a combination thereof, wherein: The reactive vinyl monomer is amino-(meth)acrylate-C １ -C ６ Alkyl (meth)acrylic acid C １ -C ６ Alkylamino-C １ -C ６ Alkyl, arylamine, vinylamine, amino-C １ -C ６ Alkyl (meth)acrylamide, C １ -C ６ Alkylamino-C １ -C ６ Alkyl (meth)acrylamide, acrylic acid, C １ -C １２ alkylacrylic acid, N,N-2-acrylamidoglycolic acid, β-methyl-acrylic acid, α-phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof, preferably (meth)acrylic acid, C ２ -C １２ Alkyl acrylic acid, vinylamine, allylamine, (meth)acrylic acid amino-C ２ -C ４ Alkyl, amino-C ２ -C ４ alkyl(meth)acrylamides, and combinations thereof; The non-reactive hydrophilic vinyl monomers include acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminopropyl methacrylamide, N,N-dimethylaminopropyl acrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, and N-hydroxyethyl acrylamide. , N-[tris(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, C having a weight average molecular weight of 1500 daltons or less １ -C ４ -alkoxy polyethylene glycol (meth)acrylate, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymer), and combinations thereof, preferably acrylamide, N,N-dimethyl acrylamide, N-vinyl pyrrolidone, N-vinyl-N-methyl acetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C 100 having a weight average molecular weight of 400 Daltons or less １ -C ４ -alkoxy polyethylene glycol (meth)acrylate, vinyl alcohol, and combinations thereof.

38. The hydrophilic polymer as the hydrophilicity enhancer is selected from a group consisting of acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, (meth)acrylate glycerol, (meth)acrylate hydroxyethyl, N-hydroxyethyl (meth)acrylamide, (meth)acryloyloxyethyl phosphorylcholine, and C having a weight average molecular weight of 400 daltons or less. １ -C ４ 36. The hydrophilic polymeric material of claim 34 or 35, which is a monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated homo- or copolymer of a non-reactive hydrophilic vinyl monomer selected from the group consisting of alkoxypolyethylene glycol (meth)acrylate, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, N,N-dimethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylamide, and combinations thereof.

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