Silicone hydrogel lens with a crosslinked hydrophilic coating

Abstract

To provide a method for producing silicone hydrogel contact lenses having coating with wettability and durability, at high cost-effectiveness and time efficiency.SOLUTION: The method involves heating a silicone hydrogel contact lens in an aqueous solution in the presence of a hydrophilic polymer material which has a positively charged azetidinium group, is water soluble and highly branched, and thermally crosslinkable, at a temperature of 40°C to 140°C for a period of time sufficient to covalently bond the thermally crosslinkable hydrophilic polymer material onto a surface of the silicone hydrogel contact lens, through covalent bonding formed respectively between one azetidinium group and one reactive functional group on the surface of the silicone hydrogel contact lens and / or in the vicinity of the surface, and thereby forming a crosslinked hydrophilic coating on the silicone hydrogel contact lens. Such a method can be advantageously implemented directly in a sealed lens package during autoclaving.SELECTED DRAWING: None

Description

Technical Field

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

[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-wetting), prone to adsorbing lipids or proteins from the eye environment, and have surfaces or at least some regions of their surfaces that may adhere to the eye. That is, silicone hydrogel contact lenses will generally require surface modification.

[0003] Known approaches for modifying the hydrophilicity of relatively hydrophobic contact lens materials involve the use of plasma treatment. For example, commercially available lenses such as Focus NIGHT & DAY (trademark) and O2OPTIX (trademark) (CIBA VISION), and PUREVISION (trademark) (Bausch & Lomb) utilize this approach in their production processes. For example, the advantages of plasma coatings such as those found in Focus NIGHT & DAY (trademark) are 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 it typically requires pre-forming the contact lens to be dried prior to plasma treatment and due to the relatively high capital investment associated with plasma treatment equipment.

[0004] Another approach for modifying the surface hydrophilicity of silicone hydrogel contact lenses is the incorporation of a wetting agent (hydrophilic polymer) into the lens formulation for manufacturing silicone hydrogel contact lenses, 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 a further post-process for modifying the surface hydrophilicity of the lens after casting of the silicone hydrogel contact lens. However, the wetting agent may not be compatible with the silicone component in the lens formulation, and this incompatibility may cloud the resulting lens. Further, such surface treatments are susceptible to lipid deposition and adsorption. In addition, such surface treatments cannot provide a durable surface for long-term wear.

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

[0006] Yet another approach for modifying the hydrophilicity of a relatively hydrophobic contact lens material is to attach hydrophilic polymers onto the contact lens by various mechanisms (see, 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. Patent Application Publication Nos. 2009 / 0145086A1, 2009 / 0145091A1, 2008 / 0142038A1, and 2007 / 0122540A1; all of which are hereby incorporated by reference in their entirety). These techniques can be used to make silicone hydrogel materials wettable, but typically they require a relatively long time and / or are difficult and involve multiple steps to obtain a hydrophilic coating and thus would not be cost effective and / or time efficient to implement in a high volume production environment.

[0007] Accordingly, there remains a need for a method of producing silicone hydrogel contact lenses having a wettable and durable coating (surface) in a cost effective and time efficient manner.

[0008] SUMMARY OF THE INVENTION In one aspect, the present invention is a method for producing silicone hydrogel contact lenses each having a crosslinked hydrophilic coating, comprising: (a) obtaining a silicone hydrogel contact lens and a water-soluble thermally crosslinkable hydrophilic polymer material, wherein the contact lens contains amino and / or carboxyl groups on and / or near the surface of the contact lens, and the hydrophilic polymer material comprises: (i) from about 20% to about 95% by weight of a first polymer chain derived from epichlorohydrin-functionalized polyamine or polyamidoamine; (ii) from about 5% to about 80% by weight of a hydrophilic moiety or a second polymer chain derived from at least one hydrophilic enhancer 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 moiety or the second polymer chain is covalently bonded 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 enhancer; and (iii) an azetidinium group that is part of the first polymer chain or a pendant or terminal group covalently bonded to the first polymer chain; and (b) heating the contact lens in an aqueous solution in the presence of the hydrophilic polymer material to a temperature of about 40°C to about 140°C and at this temperature for a time sufficient to covalently bond the hydrophilic polymer material to the surface of the contact lens via a second covalent bond formed between one azetidinium group of the hydrophilic polymer material and one amino and / or carboxyl group on and / or near the surface of the contact lens, thereby forming a crosslinked hydrophilic coating on the contact lens.

[0009] In another aspect, the present invention provides a silicone hydrogel contact lens obtained by the method of the present invention, which has an oxygen permeability of at least about 40 barrer, surface wettability characterized by a water contact angle of about 100 degrees or less, and good coating durability characterized by resistance to a finger rubbing test.

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

[0011] In yet another aspect, the present invention provides a water-soluble and thermally crosslinkable hydrophilic polymer material comprising: (a) from about 20% to about 95% by weight of a first polymer chain derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; (b) from about 5% to about 80% by weight of a second polymer chain derived from at least one hydrophilic enhancing polymer 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 second polymer chain is covalently bonded 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 polymer agent; and (c) a material comprising an azetidinium group that is part of the first polymer chain or a pendant or terminal group covalently bonded to the first polymer chain.

[0012] These and other aspects of the invention will become apparent from the following description of the presently preferred embodiments. This detailed description is merely illustrative of the 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 invention can be achieved without departing from the spirit and scope of the novel concepts of the disclosure.

[0013] Detailed Description of Embodiments of the Invention The 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 to the present invention without departing from the scope or essence of the invention. For example, features illustrated or described as part of one embodiment can be utilized in another embodiment to create still another embodiment. Thus, the present invention treats such modifications, variations, and combinations as falling within the scope of the appended claims and their equivalents. Other objects, features, and aspects of the present invention are disclosed in or will be apparent from the following detailed description. It will be understood by those skilled in the art that this discussion is merely illustrative of example embodiments and is not intended to limit the broader aspects of the present invention.

[0014] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature and laboratory procedures used herein are well known and commonly utilized in the art. These procedures use conventional methods as provided in the art and various general references. When a term is provided in the singular form, the inventors also contemplate the plural form of that term. The nomenclature and laboratory procedures described hereinafter are well known and commonly utilized in the art.

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

[0016] A "vinyl monomer," as used herein, refers to a compound having a single ethylenically unsaturated group and capable of polymerizing by actinic radiation or heat.

[0017] The term "olefinically unsaturated group" or "ethylenically unsaturated group" is used herein in a broad sense and encompasses any group containing at least one >C=C< group. Exemplary ethylenically unsaturated groups include, but are not limited to, the following formula:

[0018] [Chemical formula] (meth)acryloyl, allyl, represented by the following formula:

[0019] [Chemical formula] vinyl, styrenyl, or other C=C-containing groups represented thereby.

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

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

[0022] As used herein, the term "hydrophilic vinyl monomer" refers to a vinyl monomer that is water-soluble or that, when fully hydrated, can absorb at least 10 weight percent water, typically resulting in a polymer, typically a homopolymer.

[0023] As used herein, the term "hydrophobic vinyl monomer" refers to a vinyl monomer that is water-insoluble and can absorb less than 10 weight percent water, typically resulting in a polymer, typically a homopolymer.

[0024] "Macromer" or "prepolymer" refers to a medium- and high-molecular weight compound or polymer containing two or more ethylenically unsaturated groups. Medium- and high-molecular weight typically means an average molecular weight exceeding 700 Daltons.

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

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

[0027] The "molecular weight" of a polymer material (including monomer or macro-monomer material), as used herein, unless otherwise specified or unless otherwise indicated by test conditions, refers to the weight-average molecular weight.

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

[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 proportion of the amine groups of the polyamine or polyamidoamine to azetidinium groups.

[0030] "Azetidinium group" refers to the following formula:

[0031]

Chemical formula

[0032] With respect to a polymer material or a functional group, the term "thermally crosslinkable" means that the polymer material or functional group can undergo a crosslinking (or coupling) reaction with another material or functional group at a relatively high temperature (about 40°C to about 140°C), whereas this polymer material or functional group cannot undergo the same crosslinking reaction (or coupling reaction) with another material or functional group even when the detection time is extended for about 1 hour at room temperature (i.e., about 22°C to about 28°C, preferably about 24°C to about 26°C, particularly about 25°C).

[0033] The term "phosphorylcholine" refers to an amphoteric ion represented by the following formula:

[0034] [Chemical formula] [wherein n is an integer from 1 to 5, and R1, R2 and R3 are, independently of one another, C1-C8 alkyl or C1-C8 hydroxyalkyl].

[0035] The term "reactive vinyl monomer" refers to a vinyl monomer having a carboxyl group or an amino group (i.e., a primary or secondary amino group).

[0036] The term "non-reactive hydrophilic vinyl monomer" refers to a hydrophilic vinyl monomer having no carboxyl group or amino group (i.e., a primary or secondary amino group). The non-reactive vinyl monomer can include a tertiary or quaternary amino group.

[0037] With respect to a polymer, the term "water-soluble" means that this polymer can be dissolved in water to such an extent that it forms 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 the measured values of the contact angles with at least three individual contact lenses.

[0039] Regarding the coating on a silicone hydrogel contact lens, the term "intactness" is intended to describe the degree to which the contact lens can be stained by Sudan black in the Sudan black staining test described in Example 1. Good intactness of the coating on a silicone hydrogel contact lens means that there is virtually no Sudan black staining of the contact lens.

[0040] Regarding the coating on a silicone hydrogel contact lens, the term "durability" is intended to describe the ability of the coating on the silicone hydrogel contact lens to withstand a finger rub test.

[0041] As used herein, "withstand a finger rub test" or "withstand 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 lens rubbed with the finger 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 passes through the material. In the present invention, the term "oxygen permeability (Dk)" with respect to a hydrogel (silicone or non-silicone) or a contact lens means the oxygen permeability (Dk) corrected for the surface resistance to the oxygen flux due to the boundary layer effect, according to the procedure shown in the examples described later in this specification. Oxygen permeability has conventionally been expressed in units of barrer, where "barrer" is defined as [(cm 3 oxygen)(mm) / (cm 2 )(seconds)(mmHg)]×10 -10 as defined.

[0043] The "oxygen transmission rate", Dk / t, of a lens or material is the rate at which oxygen passes through a specific lens or material having an average thickness of t [in units of mm] over the area being measured. The oxygen transmission rate has conventionally been expressed in units of barrer / mm, where "barrer / mm" here is [(cm 3 oxygen) / (cm 2 )(second)(mmHg)] × 10 -9 as defined.

[0044] The "ionic permeability" through a lens correlates with the ion flux diffusion coefficient. This ion flux diffusion coefficient, D ([in units of mm 2 / min]), is determined by applying Fick's law as per the following formula: D = -n’ / (A × dc / dx) [where n’ = the rate of ion transport [mol / min]; A = the area of the exposed lens [mm 2 ; dc = the concentration difference [mol / L]; dx = the thickness of the lens [mm]].

[0045] "Ophthalmic compatibility", as used herein, refers to a material or the surface of a material that can be in close contact with the eye environment for a long time without causing significant damage to the eye environment and without causing significant discomfort to the user.

[0046] The term "ophthalmically safe" with respect to a packaging solution for sterilizing and storing contact lenses means that the contact lenses stored in the solution are safe to be placed directly on the eye without washing after autoclaving, and that the solution is safe and sufficiently comfortable for daily contact with the eye through the contact lenses. An ophthalmically safe packaging solution after autoclaving has a tonicity and pH that are compatible with the eye, and substantially does not contain materials that are eye irritating or cytotoxic according to international ISO standards and US FDA regulations.

[0047] The present invention generally relates to a cost-effective and time-efficient method for manufacturing silicone hydrogel contact lenses with a durable hydrophilic coating by the use of a water-soluble and thermally crosslinkable hydrophilic polymer material having an azetidinium group.

[0048] The present invention is based in part on the surprising discovery that a water-soluble, azetidinium-containing, and thermally crosslinkable hydrophilic polymer material (which is a partial reaction product of a polyamine-epichlorohydrin or polyamidoamine-epichlorohydrin with at least one hydrophilic enhancer 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 a crosslinked coating having good surface hydrophilicity and / or wettability, good hydrophilicity, and good integrity on a silicone hydrogel contact lens having carboxylic acid and / or amino groups on or near its surface. At a relatively high temperature (as defined above), the positively charged azetidinium group reacts with functional groups such as amino groups, thiol groups, and carboxylate ions -COO - (i.e., the deprotonated form of the carboxyl group) as shown in Scheme 1:

[0049] [Chemical formula] [wherein R is the remainder of the compound and L is -NR'-(wherein R' is hydrogen, C1-C 20is a non-substituted or substituted linear or branched alkyl group), or a polymer chain -S-, or -OC(=O)-] to form a neutral hydroxyl-containing covalent bond as illustrated. Due to the thermally controllable reactivity of the azetidinium group, polyamine-epichlorohydrin or polyamidoamine-epichlorohydrin (PAE) is widely used as a wet strength agent. However, PAE has not been successfully utilized to form a crosslinked coating on contact lenses, probably because the crosslinked PAE coating cannot provide the hydrophilicity, wettability, and lubricity desired for contact lenses. Surprisingly, PAE can be chemically modified with a hydrophilic enhancer (especially a hydrophilic polymer) having one azetidinium group and one or more functional groups capable of reacting in a "thermal pretreatment" or "pretreatment" process, and now it has been discovered that a water-soluble azetidinium-containing polymer material can be obtained. Due to the presence of the azetidinium group, such a polymer material that can still be thermally crosslinked (reactive) can be used to form a crosslinked coating on a silicone hydrogel contact lens having reactive functional groups (e.g., amino groups, carboxyl groups, thiol groups, or combinations thereof) on and / or near its surface. And surprisingly, the resulting crosslinked coating on the contact lens derived from the water-soluble azetidinium-containing polymer material has improved surface hydrophilicity, wettability, and / or lubricity compared to the control coating obtained either by using unmodified (original or starting material) PAE alone or a mixture of PAE and a hydrophilic enhancer (without undergoing the thermal pretreatment for preparing the water-soluble azetidinium-containing polymer material).

[0050] The hydrophilic enhancer is thought to play at least two roles in improving the performance of the resulting crosslinked coating: forming a highly branched hydrophilic polymer material with pendant polymer chains and / or chain segments by adding hydrophilic polymer chains to the polyamine or polyamidoamine polymer chains; and reducing the crosslink density of the crosslinked coating by significantly reducing the number of azetidinium groups in the polymer material (coating material) that can be crosslinked. A coating with a loose structure and pendant polymer chains and / or chain segments is thought to impart good surface hydrophilicity, wettability and / or lubricity.

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

[0052] Typically, contact lenses that are hydrated and packaged in a packaging solution must be sterilized. Sterilization of the hydrated lenses during manufacturing and packaging is typically achieved by autoclaving. The autoclaving process involves heating the contact lens package under pressure to a temperature of about 118 °C to about 125 °C for approximately 20 to 40 minutes. It has been discovered that during autoclaving, a water-soluble azetidinium-containing polymer material can effectively crosslink with functional groups (e.g., amino groups, thiol groups, and / or carboxylic acid groups) on and / or near the surface of a silicone hydrogel contact lens to form a wettable and ophthalmically compatible crosslinked coating. During autoclaving, azetidinium groups that are not involved in the crosslinking reaction are hydrolyzed to 2,3-dihydroxypropyl (HO-CH2-CH(OH)-CH2-) groups, and the azetidinium-containing polymer material present in the lens packaging solution can, if applicable, be converted to a non-reactive polymer wetting material that can improve the comfort of lens insertion.

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

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

[0055] Those skilled in the art are well aware of the method for manufacturing contact lenses. For example, contact lenses can be manufactured by the conventional "rotational molding mold" as described in U.S. Patent No. 3,408,429, or by the full casting method in a stationary mold as described in U.S. Patents Nos. 4,347,198; 5,508,317; 5,583,463; 5,789,464; and 5,849,810. In the casting method, the lens formulation is typically injected into a molding mold and cured (i.e., polymerized and / or crosslinked) in the molding mold for manufacturing contact lenses. In the manufacture of silicone hydrogel contact lenses, as is well known to those skilled in the art, the lens formulation for casting generally contains at least one component selected from the group consisting of silicone-containing vinyl monomers, silicone-containing vinyl macromers, silicone-containing prepolymers, hydrophilic vinyl monomers, hydrophilic vinyl macromers, hydrophobic vinyl monomers, and combinations thereof. The silicone hydrogel contact lens formulation can also contain other necessary components known to those skilled in the art, such as, for example, crosslinking agents, UV absorbers, visible colorants (e.g., dyes, pigments, or mixtures thereof), antibacterial agents (e.g., preferably silver nanoparticles), bioactive agents, leachable lubricants, leachable tear stabilizers, and mixtures thereof. The formed silicone hydrogel contact lens can then be subjected to extraction with an extraction solvent to remove non-polymerized components from the molded lens, as is known to those skilled in the art, and can be subjected to a hydration process. A number of silicone hydrogel lens formulations are described in a number of patents and patent applications published prior to the filing date of the present application.

[0056] According to the present invention, a silicone hydrogel contact lens can essentially contain or can be modified to contain amino groups and / or carboxyl groups on and / or near its surface.

[0057] When a silicone hydrogel contact lens essentially contains amino groups and / or carboxyl groups on and / or in the vicinity of its surface, it is obtained by polymerizing a silicone hydrogel lens formulation containing a reactive vinyl monomer.

[0058] Examples of preferred reactive vinyl monomers are not particularly limited, but include 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 alkylacrylic acids (such as methacrylic acid, ethylacrylic acid, propylacrylic acid, butylacrylic acid, 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, this silicone hydrogel contact lens is made from a lens formulation containing at least one reactive vinyl monomer selected from the group consisting of 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 alkylacrylic acid, N,N-2-acrylamidoglycolic acid, and combinations thereof. This lens formulation preferably contains from about 0.1% to about 10%, more preferably from about 0.25% to about 7%, still 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 surface-treated to form a reactive base coating having amino groups and / or carboxyl groups on the surface of the contact lens. Examples of surface treatment are not particularly limited, but include energy-based surface treatment (e.g., plasma, electrostatic, irradiation, or other energy sources), chemical treatment, chemical vapor deposition, grafting of hydrophilic vinyl monomers or macromers onto the surface of an article, U.S. Pat. Nos. 6,451,871, 6,719,929, 6,793,973, 6,811,805, and 6,896,926, and U.S. Patent Application Publication Nos. 2007 / 0229758A1, 2008 / 0152800A1, and 2008 / 0226922A1 (which are all incorporated herein by reference in their entirety), including layer-by-layer coatings (''LbL coatings'') obtained by the methods described therein. As used herein, ''LbL coating'' refers to a coating obtained by layer-by-layer (''LbL'') of charged or chargeable (by protonation or deprotonation) and / or uncharged materials on a lens that is not covalently bonded to the polymer matrix of the contact lens. The 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., the reactive LbL-based coating embodiment), the resulting silicone hydrogel contact lens comprises a reactive LbL-based coating that includes at least one reactive polymer (i.e., a polymer having pendant amino groups 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 coating solution of the reactive polymer can be accomplished by immersing the contact lens in the coating solution or spraying the contact lens with the coating solution. One contact process involves immersing the contact lens solely in a bath of the coating solution for a certain period of time or successively immersing the contact lens in a series of baths of the coating solution for a certain short time for each bath. Another contact process involves solely spraying the coating solution. However, several alternative methods involve various combinations of spraying and dipping steps that can be devised by one of ordinary skill in the art. The contact time between the contact lens and the coating solution of the reactive polymer may continue for up to 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-based coating embodiment, the reactive polymer may 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 a base coating on a silicone hydrogel contact lens. Examples of such reactive polymers include, but are not particularly limited to, homopolymers of reactive vinyl monomers; copolymers of two or more reactive vinyl monomers; copolymers of reactive vinyl monomers and 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 having pendant amino groups; carboxyl-containing cellulose (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 include those described above, but carboxylic acid-containing vinyl monomers are the most preferred reactive vinyl monomers for preparing the reactive polymer for forming a reactive LbL-based coating.

[0063] Preferred examples of non-reactive hydrophilic vinyl monomers that do not contain a carboxyl or amino group are not particularly limited, but include 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-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, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, C1-C4-alkoxy polyethylene glycol (meth)acrylate 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 the copolymer), phosphorylcholine-containing vinyl monomers (including (meth)acryloyloxyethyl phosphorylcholine and those described in U.S. Patent No. 5,461,433, which is hereby incorporated by reference in its entirety), and combinations thereof.

[0064] Preferably, the reactive polymer for forming the reactive LbL-based coating is polyacrylic acid, polymethacrylic acid, poly(C2-C 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 12Alkyl acrylate-co-acrylamide], poly[C2-C 12 Alkyl acrylate-co-vinyl pyrrolidone], hydrolyzed poly[(meth)acrylic acid-co-vinyl acetate], hydrolyzed poly[C2-C 12 Alkyl acrylate-co-vinyl acetate], polyethyleneimine (PEI), polyallylamine hydrochloride (PAH) homo- or co-polymer, polyvinylamine homo- or co-polymer, or a combination thereof.

[0065] The weight average molecular weight M of the reactive polymer for forming a reactive LbL-based coating W is at least about 10,000 Daltons, preferably at least about 50,000 Daltons, more preferably about 100,000 Daltons to about 5,000,000 Daltons.

[0066] A solution of the reactive polymer for forming a reactive LbL-based 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 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. A solvent system containing at least one organic solvent can swell a silicone hydrogel contact lens, so it is thought that part of the reactive polymer penetrates into the silicone hydrogel contact lens to improve the durability of the reactive-based coating.

[0067] Any organic solvent can be used for the preparation of a solution of the reactive polymer. Examples of preferred organic solvents, although not particularly limited, are 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, 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 exo-norborneol, 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, 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 contains essentially amino groups and / or carboxyl groups on and / or near its surface, and further by subjecting it to surface treatment, a reactive LbL-based coating having amino groups and / or carboxyl groups therein is formed.,

[0069] In another preferred embodiment (reactive plasma-based coating), the silicone hydrogel contact lens is subjected to 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 described above) are polymerized under the influence of a plasma generated by an electric discharge (so-called plasma-induced polymerization). The term "plasma" means, for example, an ionized gas generated by a glow discharge, which can be composed of electrons in the ground state or any highly excited state of any type of excitation, ions of either polarity, gas atoms and molecules, and even photons. This is often referred to as "low-temperature plasma".For a general review of plasma polymerization and its use, reference is made to R. Hartmann, "Plasma polymerisation: Grundlagen, Technik und Anwendung, Jahrb. Oberflachentechnik (1993) 49, pp. 283-296, Battelle-Inst. e.V. Frankfurt / Main Germany; H. Yasuda, "Glow Discharge Polymerization", Journal of Polymer Science: Macromolecular Reviews, vol. 16 (1981), pp. 199-293; H. Yasuda, "Plasma Polymerization", 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 (19); O. Auciello et al. (ed.) "Plasma-Surface Interactions and Processing of Materials" publ. by Kluwer 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, this plasma-induced polymerization is the "afterglow" type plasma-induced polymerization described in WO 98028026, which is incorporated herein by reference in its entirety.In the "afterglow" type plasma polymerization, the surface of the contact lens is first treated with a non-polymerizable plasma gas (e.g., H2, He or Ar), and then in the subsequent step, the surface thus activated is exposed to a vinyl monomer having an amino group or a carboxyl group (any of the above reactive vinyl monomers), but the plasma output is turned off at this time. By activation, plasma-induced formation of radicals occurs on the surface, and this initiates the polymerization of the vinyl monomer present therein in the subsequent step.

[0070] In the present invention, the water-soluble and thermally crosslinkable hydrophilic polymer material containing an azetidinium group is derived from epichlorohydrin-functionalized polyamine or polyamidoamine, about 20% to about 95%, preferably about 35% to about 90%, more preferably about 50% to about 85% (by weight) of the first polymer chain, and at least one hydrophilic enhancer 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, about 5% to about 80%, preferably about 10% to about 65%, still more preferably about 15% to about 50% (by weight) of the hydrophilic moiety or the second polymer chain (i.e., having a composition including these). The composition of the hydrophilic polymer material is determined by the composition of the reaction mixture (based on the total weight of the reactants) used to prepare the hydrophilic polymer material that can be thermally crosslinked by the crosslinking reaction shown in Scheme I above. For example, if the reaction mixture contains about 75% by weight of epichlorohydrin-functionalized polyamine or polyamidoamine and about 25% by weight of at least one hydrophilic enhancer based on the total weight of the reactants, the resulting hydrophilic polymer material contains about 75% by weight of the first polymer chain derived from epichlorohydrin-functionalized polyamine or polyamidoamine and about 25% by weight of the hydrophilic moiety or the second polymer chain derived from the at least one hydrophilic enhancer. The azetidinium group of the hydrophilic polymer material that can be thermally crosslinked is the azetidinium group (of the epichlorohydrin-functionalized polyamine or polyamidoamine) that does not participate in the crosslinking reaction for preparing the hydrophilic polymer material that can be thermally crosslinked.

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

[0072] Any suitable hydrophilic enhancer can be used in the present invention as 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 are not particularly limited, but include 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, glucosaminic 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, 1-methylamino-1-deoxysorbitol, N-aminoethylgluconamide); 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 hydrophilicity 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 hydrophilicity 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 hydrophilic polymer as a preferred type of hydrophilicity enhancer is an amino- or carboxyl-containing polysaccharide, e.g., carboxymethyl cellulose (approximate carboxyl content of about 40% or less based on the composition of the repeating unit: -[C6H 10-m O5(CH2CO2H) m -(where m is from 1 to 3)), carboxyethyl cellulose (repeating unit: -[C6H 10-m O5(C2H4CO2H) m-(Here, m is 1 to 3), estimated based on the composition, having a carboxyl content of about 36% or less), carboxypropyl cellulose (repeating unit: -[C6H 10-m O5(C3H6CO2H) m -(Here, m is 1 to 3), estimated based on the composition, having a carboxyl content of about 32% or less), hyaluronic acid (repeating unit: -(C 13 H 20 O9NCO2H)-, estimated based on the composition, having a carboxyl content of about 11%), chondroitin sulfate (repeating unit: -(C 12 H 18 O 13 NSCO2H)-, estimated based on the composition, having a carboxyl content of about 9.8%), or a combination thereof, etc.

[0076] The hydrophilic polymer as another preferred type of hydrophilic enhancer is not particularly limited, but includes the following: poly(ethylene glycol) (PEG) having 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 having one or more amino, carboxyl and / or thiol groups; PEG dendrimer having one or more amino, carboxyl and / or thiol groups; homo- or co-polymers of diamino- or dicarboxyl-terminated non-reactive hydrophilic vinyl monomers; homo- or co-polymers of monoamino- or monocarboxyl-terminated non-reactive hydrophilic vinyl monomers; a copolymer which is a polymerization product of a composition containing (1) one or more reactive vinyl monomers of about 50% by weight or less, preferably about 0.1% to about 30%, more preferably about 0.5% to about 20%, still more preferably about 1% to about 15% (by weight) 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 monomer and the non-reactive hydrophilic vinyl monomer 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 dendrimer 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, C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of 400 daltons or less, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, (meth)acrylic acid N,N-dimethylaminoethyl, N,N-dimethylaminopropyl (meth)acrylamide, (meth)acryloyloxyethyl phosphorylcholine, and monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymers of non-reactive hydrophilic vinyl monomers selected from the group consisting of these combinations; (1) about 0.1% to about 30%, preferably about 0.5% to about 20%, more preferably about 1% to about 15% (by weight) of (meth)acrylic acid, C2-C 12A copolymer which is a polymerization product of a composition containing alkyl acrylate, 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 PEG-NH2; PEG-SH; PEG-COOH; polyvinylpyrrolidone with monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminals; polyacrylamide with monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminals; poly(DMA) with monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminals; poly(DMA-co-NVP) with monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminals; poly(NVP-co-(meth)acrylic acid N,N-dimethylaminoethyl) with monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminals; poly(vinyl alcohol) with monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminals; poly[(meth)acryloyloxyethyl phosphorylcholine] homopolymer or copolymer with monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminals; poly(NVP-co-vinyl alcohol) with monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminals; poly(DMA-co-vinyl alcohol) with monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminals; poly[(meth)acrylic acid-co-acrylamide] containing about 0.1% to about 30%, preferably about 0.5% to about 20%, more preferably about 1% to about 15% (by weight) of (meth)acrylic acid; poly[(meth)acrylic acid-co-NVP] containing about 0.1% to about 30%, preferably about 0.5% to about 20%, more preferably about 1% to about 15% (by weight) of (meth)acrylic acid; a copolymer which is a 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] PEG having functional groups and multi-arm PEG having functional groups can be obtained from various suppliers, such as Polyscience, and Shearwater Polymers, Inc.

[0080] Homopolymers or copolymers of one or more non-reactive hydrophilic vinyl monomers or of phosphorylcholine-containing vinyl monomers having monoamino-, monocarboxy-, diamino- or dicarboxy termini can be prepared by the procedure described in U.S. Patent No. 6,218,508, which is hereby incorporated by reference in its entirety. For example, to prepare a diamino- or dicarboxy-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer, this 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 (by heat or actinic radiation) in the presence of a free radical initiator with a reactive vinyl monomer (having an amino or carboxyl group). Generally, the molar ratio of the chain transfer agent to all vinyl monomers other than the reactive vinyl monomer is from about 1:5 to about 1:100, while the molar ratio of the chain transfer agent to the reactive vinyl monomer is 1:1. In such a preparation, the chain transfer agent having an amino or carboxyl group is used to control the molecular weight of the resulting hydrophilic polymer and to form the terminal of the resulting hydrophilic polymer, thereby providing one terminal amino or carboxyl group to the resulting hydrophilic polymer, while the reactive vinyl monomer provides the other terminal carboxyl or amino group to the resulting hydrophilic polymer. Similarly, to prepare a monoamino- or monocarboxy-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer, this 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 (by heat or 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 a polymerization product of a non-reactive hydrophilic vinyl monomer and one or more additional vinyl monomers. Copolymers containing non-reactive hydrophilic vinyl monomers and reactive vinyl monomers (e.g., carboxyl-containing vinyl monomers) can be prepared by any well-known radical polymerization method or obtained from suppliers. Copolymers containing methacryloyloxyethyl phosphorylcholine and carboxyl-containing vinyl monomers can be obtained from NOP Corporation (e.g., LIPIDURE®-A and -AF).

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

[0083] In the present invention, the reaction between the hydrophilic 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 and thermally crosslinkable hydrophilic polymer material containing azetidinium groups (about 0.3 hours to about 24 hours, preferably about 1 hour to about 12 hours, more preferably about 2 hours to about 8 hours).

[0084] In the present invention, the concentration of the hydrophilic enhancer relative to the epichlorohydrin-functionalized polyamine or polyamidoamine is such that the resulting hydrophilic polymer material is not water-insoluble (i.e., solubility less than 0.005 g per 100 ml of water at room temperature) and that less than about 99%, preferably less than about 98%, more preferably less than about 97%, still more preferably less than about 96% of the azetidinium groups of the epichlorohydrin-functionalized polyamine or polyamidoamine are consumed.

[0085] In the present invention, the heating step is preferably carried out by autoclaving a silicone hydrogel contact lens immersed in a packaging solution in a sealed lens package at a temperature of about 118°C to about 125°C for approximately 20 to 90 minutes. In this embodiment of the present invention, this packaging solution is a buffer aqueous solution that is safe for ophthalmic use 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 including a base and a cover (where this cover is sealed to be removable from the base, and this base includes a cavity for receiving a sterile packaging solution and a contact lens).

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

[0088] In the present invention, the packaging solution contains at least one buffering agent and one or more other components known to those skilled in the art. Examples of other components are not particularly limited, but include tonicity agents, surfactants, antibacterial agents, preservatives, and lubricants (or water-soluble thickeners) (e.g., cellulose derivatives, polyvinyl alcohol, polyvinyl pyrrolidone).

[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 from 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, borates such as sodium borate, citric acid, citrates such as potassium citrate, carbonates 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)-2-aminoethanesulfonic acid), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), MOPS (3-[N-morpholino]-propanesulfonic acid), PIPES (piperazine-N,N’-bis(2-ethanesulfonic acid)), TES (N-[tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid), salts thereof, phosphate buffers such as Na2HPO4, NaH2PO4, and KH2PO4 or mixtures thereof. A preferred bisaminopolyol is 1,3-bis(tris[hydroxymethyl]-methylamino)propane (bis-TRIS-propane). The amount of each buffering agent in the packaging solution is preferably from 0.001% to 2%, preferably from 0.01% to 1%; most preferably from about 0.05% to about 0.30% (by weight).

[0090] The packaging solution has an osmolarity of about 200 to about 450 milliosmoles (mOsm), preferably about 250 to about 350 mOsm. The osmolarity of the packaging solution can be adjusted by adding organic or inorganic substances that affect osmolarity. Suitable ophthalmically acceptable tonicity agents are not particularly limited and include 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 of about 1 centipoise to about 20 centipoises, preferably about 1.2 centipoises to about 10 centipoises, more preferably about 1.5 centipoises to about 5 centipoises at 25°C.

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

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

[0094] Preferred thickening polymers are not particularly limited, but include water-soluble cellulose ethers (e.g., methylcellulose (MC), ethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), or mixtures thereof), water-soluble polyvinyl alcohols (PVA), high molecular weight poly(ethylene oxide) having a molecular weight of more 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, more preferably about 0.1% to about 1% by weight, based on the total amount of the packaging solution.

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

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

[0098] Exemplary α-oxo-polybasic acids or their biocompatible salts are not particularly limited and include citric acid, 2-ketoglutaric acid, or malic acid or their biocompatible (preferably ophthalmic-compatible) salts. More preferably, the α-oxo-polybasic acid is citric acid or malic acid or their biocompatible (preferably ophthalmic-compatible) salts (e.g., sodium, potassium, etc.).

[0099] In the present invention, the packaging solution can further contain a mucin-like substance, a substance beneficial for ophthalmic use, and / or a surfactant.

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

[0101] Exemplary substances beneficial for ophthalmic use are not particularly limited and include 2-pyrrolidone-5-carboxylic acid (PCA), amino acids (e.g., taurine, glycine, etc.), α-hydroxy acids (e.g., glycolic acid, lactic acid, malic acid, tartaric acid, mandelic acid, and citric acid and their salts, etc.), linoleic acid and γ-linolenic 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 particularly 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 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] The silicone hydrogel contact lens obtained by the method of the present invention is characterized by having surface hydrophilicity / wettability, preferably having 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, before the heating step, the method of the present invention involves contacting a silicone hydrogel contact lens at room temperature with an aqueous solution of a hydrophilic polymer material capable of thermally crosslinking to form a top layer of the hydrophilic polymer material capable of thermally crosslinking (i.e., an LbL coating) on the surface of the silicone hydrogel contact lens; immersing the silicone hydrogel contact lens having this top layer of the hydrophilic polymer material capable of thermally crosslinking in a packaging solution in a lens package; sealing the lens package; and further including the step of autoclaving the lens package containing this silicone hydrogel contact lens to form a crosslinked hydrophilic coating on the silicone hydrogel contact lens. Since it has a positive charge, it is considered that the hydrophilic polymer material capable of thermally crosslinking can form an LbL coating that is not covalently bonded to the surface of the silicone hydrogel contact lens on the silicone hydrogel contact lens (i.e., through physical interactions), especially in the case of a contact lens having a carboxyl group with a negative charge on its surface).

[0105] Although various embodiments including preferred embodiments of the present invention are described separately above, it goes without saying that 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 provided with a crosslinked hydrophilic coating.

[0106] In another aspect, the present invention provides a silicone hydrogel contact lens obtained 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, where the lens package contains a lens packaging solution and a ready-to-use silicone hydrogel contact lens after autoclaving, and the ready-to-use silicone hydrogel contact lens has an amino group and / or a carboxyl group on and / or near the surface of the original silicone hydrogel contact lens, and the original silicone hydrogel contact lens is obtained by autoclaving in a pre-autoclaving packaging solution containing a water-soluble thermally crosslinkable hydrophilic polymer material, and the hydrophilic polymer material comprises: (i) a first polymer chain derived from epichlorohydrin-functionalized polyamine or polyamidoamine, about 20% to about 95%, preferably about 35% to about 90%, more preferably about 50% to about 85% (by weight); (ii) a hydrophilic moiety or a second polymer chain derived from at least one hydrophilic enhancer having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, thiol group, and combinations thereof, about 5% to about 80%, preferably about 10% to about 65%, still more preferably about 15% to about 50% (by weight) (where the hydrophilic moiety or the second polymer chain is covalently bonded 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 enhancer), and (iii) an azetidinium group which is part of the first polymer chain or a pendant or terminal group covalently bonded to the first polymer chain, and the hydrophilic polymer 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 water-soluble thermally crosslinkable hydrophilic polymer material, and the post-autoclaving packaging solution has a pH of about 6.0 to about 8.Contains at least one buffer in an amount sufficient to maintain a pH of 5, and has an osmolality of about 200 to about 450 milliosmoles (mOsm), preferably about 250 to about 350 mOsm, and a viscosity at 25 °C of about 1 centipoise to about 20 centipoises, preferably about 1.2 centipoises to about 10 centipoises, more preferably about 1.5 centipoises to about 5 centipoises, and the autoclaved packaging solution contains a polymeric wetting material that is a hydrolysis product of a heat-crosslinkable hydrophilic polymer material after autoclaving, and the immediately usable silicone hydrogel contact lens is characterized by having 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, and has surface hydrophilicity / wettability.

[0108] "Immediately usable silicone hydrogel contact lens" refers to a silicone hydrogel contact lens that is suitable for ophthalmic use and is sterilized by autoclaving. "Original silicone hydrogel contact lens" refers to a silicone hydrogel contact lens that lacks a crosslinked hydrophilic coating and has not been sterilized by autoclaving.

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

[0110] The immediately usable silicone hydrogel contact lens of the present invention has an oxygen permeability of at least about 40 barrer, preferably at least about 50 barrer, more preferably at least about 60 barrer, and even more preferably about 70 barrer; 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; preferably at least about 1.5×10 -6 mm 2 / min, more preferably at least about 2.6×10 -6 mm 2 / min, and even more preferably at least about 6.4×10 -6 mm 2 / min of the ion flux 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 and has.

[0111] The water content of the silicone hydrogel contact lens can be measured by the Bulk method disclosed in US 5,849,811.

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

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

[0114] Based on the above disclosure, those of ordinary skill in the art should be able to practice the present invention. Various modifications, variations, and combinations can be made to the various embodiments described herein. References to the following examples are proposed to enable the reader to better understand the specific embodiments and advantages. This specification and the examples are intended to be considered as illustrative.

[0115] The various embodiments of the present invention are described using specific terms, devices, and methods, but such descriptions are for illustrative purposes only. The terms used are more of an explanatory nature than limiting. Of course, those skilled in the art can make changes and variations without departing from the essence or scope of the present invention as set forth in the following claims. Further, of course, aspects of the various embodiments can be exchanged in whole or in part, or combined and / or used together in any way. Accordingly, the essence and scope of the appended claims are not limited to the description of the preferred views contained therein.

[0116] Example 1 Oxygen permeability measurement The apparent oxygen permeability of the lens and the oxygen transmission rate of the lens material are measured by a method similar to that described in U.S. Patent No. 5,760,100 and the paper by Winterton et al. (The Cornea: Transactions of the World Congress on the Cornea 111, H.D. Cavanagh Ed., Raven Press: New York 1988, pp273 - 280) (both of which are hereby incorporated by reference in their entirety). The oxygen flux (J) is measured at 34°C in a wet cell (i.e., where the gas flow is maintained at approximately 100% relative humidity) using a Dk1000 device (available from Applied Design and Development Co., Norcross, GA) or a similar analytical device. An air stream having a known proportion of oxygen (e.g., 21%) is passed over one side of the lens at a rate of about 10 - 20 cm 3 / min, while a nitrogen stream is at about 10 - 20 cm 3Pass it to the opposite side of the lens at a speed of / minute. The sample is equilibrated in a test medium (i.e., physiological saline or distilled water) at a predetermined test temperature for at least 30 minutes (but not exceeding 45 minutes) before measurement. Any test medium used as the coating layer is equilibrated in a test medium (i.e., physiological saline or distilled water) at a predetermined test temperature for at least 30 minutes (but not exceeding 45 minutes) before measurement. The speed of the stirring motor is set to 1200 ± 50 rpm, corresponding to a display setting of 400 ± 15 on the stepping motor controller. The atmospheric pressure, P 測定値 is measured. The thickness (t) of the lens in the area exposed for testing is determined by measuring about 10 locations with a Mitotoya micrometer VL-50 or a similar device and averaging the measured values. The oxygen concentration in the nitrogen stream (i.e., the oxygen diffusing through the lens) is measured using a DK1000 device. The apparent oxygen permeability of the lens material, Dk app is obtained from the following formula : Dk app = Jt / (P 酸素 ) (where J = oxygen flux [microliters O2 / cm 2 - minute] P 酸素 = (P 測定値 - P 水蒸気 ) = (O2% in air stream) [mmHg] = partial pressure of oxygen in air stream P 測定値 = atmospheric pressure (mmHg) P 水蒸気 = 0 mmHg at 34 °C (in dry cell) (mmHg) P 水蒸気 = 40 mmHg at 34 °C (in wet cell) (mmHg) t = average thickness of the lens in the exposed test area (mm) Dk app is expressed in units of barrer).

[0117] The apparent oxygen transmission rate (Dk / t) of the material can be calculated by dividing the apparent oxygen permeability (Dk app ) by the average thickness (t) of the lens.

[0118] The above measured values have not been corrected for the so-called boundary layer effect, which results from the use of a water or saline bath at the apex of the contact lens during oxygen flux measurement. Due to the boundary layer effect, the reported value of the apparent Dk of the silicone hydrogel material is lower than the actual intrinsic Dk value. Furthermore, the relative impact of the boundary layer effect is greater for thinner lenses than for thicker lenses. The net effect is that the reported Dk value appears to vary as a function of lens thickness when it should remain constant.

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

[0120] Measure the apparent oxygen permeability value (at one point) of a control lotrafilcon A (lotrafilcon A) (Focus® N&D®, manufactured by CIBA VISION CORPORATION) or lotrafilcon B (lotrafilcon B) (AirOptix™, manufactured by CIBA VISION CORPORATION) lens using the same apparatus. The control lens has the same refractive power as the test lens and is measured simultaneously with the test lens.

[0121] Using the same apparatus as in the procedure for the above apparent Dk measurement, measure the oxygen flux through a series of thicknesses of lotrafilcon A or lotrafilcon B (control) lenses to obtain the intrinsic Dk value (Dk i ) of the control lens. The series of thicknesses should cover a thickness range of approximately 100 μm or more. Preferably, the thickness range of the control lens includes the thickness of the test lens. The Dk app of these control lenses must be measured with the same apparatus as the test lens and, ideally, simultaneously with the test lens. The apparatus settings and measurement parameters should be kept constant throughout the experiment. Individual samples may be measured multiple times if necessary.

[0122] Calculate the residual oxygen resistance value, R, from the results of the control lenses using Equation (1).r Find it.

[0123]

Number

[0124] By using the residual oxygen resistance value obtained above, based on Equation (2), calculate the correct oxygen permeability Dk of the test lens c (estimated intrinsic Dk). Dk c = t / [(t / Dk a ) - R r (2)

[0125] The estimated intrinsic Dk of the test lens can be used to calculate, based on Equation (3), what the apparent Dk (Dk a_std ) would be for a lens of standard thickness in the same test environment. The standard thickness (t std ) of Rotraficon A = 85 μm. The standard thickness of Rotraficon 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 lens is measured by the procedure described in U.S. Patent No. 5,760,100 (which is hereby incorporated by reference in its entirety). The ion permeability values reported in the following examples are relative ion flux diffusion coefficients (D / D with respect to the lens material, Alsacon, as a control materialref ) and Alsacon has an ion flux diffusion coefficient of 0.314×10 -3 mm 2 per minute.

[0127] Lubricity evaluation The scoring method for lubricity is a qualitative ranking scheme that uses a scale of 0 to 5, where 0 or small numbers indicate good lubricity. 1 is assigned to the Oasys (trademark) / TruEye (trademark) commercially available lens, and 5 is assigned to the commercially available Air Optix (trademark) lens. Samples are rinsed at least three times with excess DI water and then transferred to PBS before evaluation. Before evaluation, hands are rinsed with soapy water, rinsed extensively with DI water, and then dried with a KimWipe (registered trademark) towel. Samples are handled by pinching them with the fingers, and a numerical value is assigned to each sample compared to the above standard lenses. For example, if the lens is determined to be only slightly better than the Air Optix (trademark) lens, a number of 4 is assigned to them. Regarding consistency, all scores are independently collected by the same two operators to avoid bias, and this data has so far revealed very good qualitative agreement and consistency in this evaluation.

[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 low water contact angle corresponds to a highly hydrophilic surface. The average contact angle (sessile drop method) of the contact lens is measured using a VCA 2500 XE contact angle measuring device manufactured by AST, Inc., located in Boston, Massachusetts. This device can measure the advancing or receding contact angle or the fixed (static) contact angle. The measurement is performed on a fully hydrated contact lens immediately after blotting and drying as follows. The contact lens is removed from the vial and washed three times in approximately 200 ml of fresh DI water to remove loosely bound packaging additives from the lens surface. Next, the lens is placed on a lint-free clean cloth (Alpha Wipe TX1009), pressed firmly to remove surface water, placed on the contact angle measurement stage, air-dried with a blast of dry air, and finally the sessile drop contact angle is automatically measured using the software provided by the manufacturer. The DI water used to measure the contact angle has a resistivity of >18 MΩcm, and the droplet volume used is 2 μl. Typically, an uncoated silicone hydrogel lens (after autoclaving) has a sessile drop contact angle of approximately 120 degrees. The tweezers and the measurement stage are thoroughly washed with isopropanol and rinsed with DI water before contacting the contact lens.

[0129] Water Break-up Time (WBUT) test The wettability of the lens (after autoclave treatment) is also determined by measuring the time it takes for the water film to start breaking on the lens surface. Briefly, the lens is 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 lens is removed from this solution and held in front of a bright light source. The time required for the water film to break (de-wet) and expose the underlying lens material is recorded visually. Uncoated lenses typically have an immediate water film break when removed from DI water and are assigned a WBUT of 0 seconds. Lenses showing a WBUT ≥ 5 seconds are considered wettable and are expected to exhibit appropriate wettability (ability to support the tear film) on the eye.

[0130] Coating Integrity Test The integrity of the coating on the surface of the contact lens can be tested by a 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 adsorb to hydrophobic materials or onto hydrophobic spots on the hydrophobic lens surface or on a surface partially coated on a hydrophobic lens (e.g., SiHy contact lens). 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 Test The lens is rubbed 30 times with the Solo-care (registered trademark) multi-purpose lens care solution using the finger, and then rinsed with physiological saline. The above procedure is repeated a predetermined number of times, for example, 1 to 30 times (i.e., the number of times of the continuous finger rubbing test simulating the cleaning and immersion cycles). Next, the lens is subjected to the Sudang black test (i.e., the above-mentioned coating integrity test) to inspect whether the coating is still intact. To withstand the finger rubbing test, there is no significant increase in the stained spots (for example, the stained spots do not cover more than about 5% of the total lens surface). The water contact angle is measured to determine the coating durability.

[0132] Debris adhesion test Contact lenses with a highly charged surface are prone to an increase in debris adhesion during patient handling. Rub a paper towel against a gloved hand, and then rub both sides of the lens with the finger to transfer debris onto the lens surface. Rinse the lens gently and then observe it under a microscope. Each lens is scored using a qualitative scoring scale of 0 (no debris adhesion) to 4 (equivalent debris adhesion to the PAA-coated control lens). Lenses with a score of "0" or "1" are considered acceptable.

[0133] Surface cracking test Due to excessive cross-linking of the coating layer, surface cracks that are visible under a dark-field microscope may occur after rubbing the lens. Invert the lens and rub it, and record any crack lines. The lens is scored using a qualitative scoring method of 0 (no cracks) to 2 (severe cracks). Any severe crack lines are considered unacceptable.

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

[0135] PPVS assay The PAE charge density (i.e., azetidinium content) can be determined by a colorimetric titration assay using polyvinylsulfate potassium (PPVS) as the titrant and Toluidine Blue as the indicator. See S-K 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 groups of PAE. A proportional decrease in the absorbance intensity of Toluidine Blue indicates the PAE charge density (azetidinium content).

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

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

[0138] NMR method The active positively charged moiety in 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-related protons. This ratio is an indicator of the charge or AZR density for 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) is capped with isophorone diisocyanate (IPDI) by reacting 49.85 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane with 11.1 g of IPDI in 150 g of methyl ethyl ketone anhydride (MEK) in the presence of 0.063 g of dibutyltin dilaurate (DBTDL). This reaction is carried out by holding 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 is added dropwise to the IPDI-PDMS-IPDI solution to which an additional 0.063 g of DBTDL has been added. By maintaining the reactor at about 40 °C for 4.5 hours, HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH is formed. Next, MEK is removed under reduced pressure. In the third step, the terminal hydroxyl groups are capped with methacryloyloxyethyl groups by the additional addition of 7.77 g of isocyanatoethyl methacrylate (IEM) and 0.063 g of DBTDL in the third step to form IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM (CE-PDMS macromer).

[0140] Alternative Preparation of CE-PDMS Macromer 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 -2It is dried by applying a vacuum of 0.1 mBar). Next, 320 g of distilled MEK is added to the reactor under dry nitrogen at 1 atm, and this mixture is stirred well. 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 dropwise through a dropping funnel over 10 minutes under gentle stirring. The reaction solution 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 about 55 °C overnight under a blanket of dry nitrogen. The next day, MEK is removed by flash distillation. The reactor is cooled, then 22.7 g of IEM is charged into the reactor, and then about 0.235 g of DBTDL is charged. After about 3 hours, an additional 3.3 g of IEM is added, and the reaction is allowed to proceed overnight. The next day, the terminal methacrylate group-containing CE-PDMS macromer is obtained by cooling the reaction mixture to about 18 °C.

[0141] Example 3 Preparation of lens formulation The lens formulation is prepared by dissolving the components in 1-propanol such that it has 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 (a 5% copper phthalocyanine blue pigment dispersion in methacrylic acid tris(trimethylsiloxy)silylpropyl, TRIS), and 24.5 wt% of 1-propanol.

[0142] Preparation of lens The lens is a reusable molding die similar to the molding dies shown in FIGS. 1-6 of U.S. Patent No. 7,384,590 and FIGS. 1-6 of 7,387,759, and is prepared by a casting method from the lens formulation prepared above. The molding die includes a female half made of quartz (or CaF2) and a male half made of glass (or PMMA). The UV irradiation source is a Hamamatsu lamp equipped with a WG335 + TM297 cut-off filter at an intensity of about 4 mW / cm 2 The lens formulation in the molding die is irradiated with UV light for about 25 seconds. The cast lens is extracted with isopropanol (or methyl ethyl ketone, MEK), rinsed in water, coated with PAA by immersing the lens in a propanol solution of polyacrylic acid (PAA, 0.1 wt%, acidified to pH about 2.5 with formic acid), and hydrated in water. The resulting lens with a reactive PAA-LbL-based coating is determined to have the following properties: an ion permeability about 8.0 to about 9.0 times that of the Alsacon lens material; an apparent Dk of about 90 to 100 (single point); a water content of about 30% to about 33%; and a modulus of elasticity of about 0.60 MPa to about 0.65 MPa.

[0143] Example 4 The in-package coating (IPC) physiological 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 lens from Example 3 is placed in a polypropylene lens packaging shell together with 0.6 mL of IPC physiological saline (half of the IPC physiological saline is added before inserting the lens). The blister is then sealed with aluminum foil and autoclaved at 121 °C for about 30 minutes to form a crosslinked coating (PAA-x-PAE coating) on the lens.

[0145] Next, the lenses are 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 a PAA-x-PAE coating) show no debris adhesion, while the control lenses (packaged / autoclaved in PBS, i.e., lenses with a PAA-LbL-based coating) show severe debris adhesion. The water contact angle (WCA) of the test lenses is low (≈20 degrees), but the WBUT is less than 2 seconds. When observed under a dark-field microscope, severe crack lines can be seen after lens manipulation (lens inversion and rubbing between fingers). The test lenses are much less lubricious (lubricity score of 4) than the control lenses as determined by a qualitative finger-rub test.

[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) is 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 is prepared by dissolving 0.76% NaCl, 0.044% NaH2PO4·H 2O and 0.388% NaH2PO4·2H2O in water.

[0148] Lenses with the PAA-LbL-based coating prepared in Example 3 are placed in a polypropylene lens packaging shell together with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). Next, the blister is sealed with aluminum foil and autoclaved at about 121 °C for about 30 minutes. It is believed that a three-layer cross-linked coating of PAA-x-PAE-x-poly(AAm-co-AA) is formed on the lens during autoclaving.

[0149] The test lenses (IPC physiological saline packaged / autoclaved, i.e., lenses with a PAA-x-PAE-x-poly(AAm-co-AA) coating) are free of debris adhesion and have a WBUT exceeding 10 seconds. When observed under a dark-field microscope, crack lines can be seen after the rubbing test of the test lenses. 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 score of 1 - 2).

[0150] Example 6 IPC physiological 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. Next, the physiological saline is heated to about 70 °C and treated (pre-heat treatment) by heating at this temperature for 4 hours to form a water-soluble and thermally crosslinkable hydrophilic polymer material containing azetidinium groups in this IPC physiological saline. After the pre-heat treatment, the IPC physiological saline is filtered using a 0.22-micron polyethersulfone (PES) membrane filter and cooled back to room temperature.

[0151] The lenses with the PAA-LbL-based coating prepared in Example 3 are placed together with 0.6 mL of IPC physiological saline (half of the physiological saline is added before inserting the lenses) in a polypropylene lens packaging shell. Next, the blister is 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 (lenses that have been packaged in IPC physiological saline before heat treatment, i.e., lenses with a coating of PAA-x-hydrophilic polymer material) show no debris adhesion after being rubbed against a paper towel. On the other hand, the control lenses (lenses that have been packaged in PBS, i.e., lenses with a non-covalent layer of PAA on them) show severe debris adhesion. The test lenses have a WBUT of more than 10 seconds. When observed under a dark-field microscope, no crack lines are visible after the rubbing test of the test lenses. The test lenses are very lubricious in the finger-rubbing test and are equivalent to the control lenses (lubricity score of 0).

[0153] A series of experiments are carried out to test the effect of the conditions (duration and / or temperature) of the heat pretreatment of IPC physiological saline on the surface properties of the resulting lenses coated with IPC physiological saline. Depending on the azetidinium functional group of PAE and the concentration of PAE used, lenses with a sensitivity to debris adhesion similar to that of the control lenses can be obtained with a heat treatment time of about 6 hours or more at about 70 °C. With a heat treatment of only 4 hours at 50 °C, lenses that show crack lines on the surface under a dark-field microscope after being pinched and rubbed with a finger are obtained, similar to the test lenses of Example 5 where the IPC physiological saline was not heat-pretreated.

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

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

[0156] The lens provided with the PAA-LbL base coating prepared in Example 3 and the uncoated Lotrafilcon B lens (manufactured by CIBA VISION CORPORATION), which were immersed in an acidic propanol solution of PAA (about 0.1%, pH ≒ 2.5), were placed together with 0.6 mL of pre-heated IPC physiological saline (half of the IPC physiological saline was added before inserting the lens) in a polypropylene lens packaging shell. Next, the blister was sealed with aluminum foil and autoclaved at 121 °C for about 30 minutes to form a cross-linked coating (PAA-x-hydrophilic polymer material) on the lens.

[0157] The test lenses (both the Lotrafilcon B and the lens of Example 3 provided with the PAA-x-hydrophilic polymer material coating) have no debris adhesion. The test lenses have a WBUT exceeding 10 seconds. When observed under a dark-field microscope, no crack lines are visible after the rubbing test of the lens pinched by fingers. The lens is extremely lubricious (lubricity score of 0) in the qualitative finger-rubbing test.

[0158] Example 8 In the design of experiments (DOE), the IPC physiological saline is prepared to contain about 0.05% - about 0.09% of PAAm-PAA and about 0.075% - about 0.19% of PAE (Kymene) in PBS. The IPC physiological saline is heat-treated at 60 °C for 8 hours, and the lenses from Example 3 are packaged in the pre-heated IPC physiological saline. No difference is observed in the final lens surface characteristics, and all lenses show excellent lubricity, resistance to debris adhesion, excellent wettability, and no evidence of surface cracking.

[0159] Example 9 In the design of experiments (DOE), IPC physiological saline is manufactured to contain approximately 0.07% PAAm-PAA and sufficient PAE (≈0.15% PAE) to provide an initial azetidinium content of approximately 9 milliequivalents per liter. The heat pretreatment conditions vary from 50 °C to 70 °C in a central composite design, and the pre-reaction time varies from about 4 to about 12 hours. A pretreatment time of 24 hours at 60 °C is also tested. Next, 10 ppm hydrogen peroxide is added to the physiological saline to prevent bioburden growth, and the IPC physiological saline is filtered using a 0.22 micron polyethersulfone [PES] membrane filter.

[0160] The lenses from Example 3 are packaged in heat-pretreated IPC physiological 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 paper towels 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 or 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%), and add 0.2% PAE (Polycup 3160). Adjust the pH to about 7.3.

[0164] Next, by adding one of several MPC copolymers at 0.25%, IPC physiological saline is formed, and this IPC physiological saline is heat pretreated at 70 °C for 4 hours to form a water-soluble and thermally crosslinkable hydrophilic polymer material containing azetidinium groups. After 4 hours, this heat-pretreated IPC physiological saline 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 based coating prepared in Example 3 are packaged in the heat-pretreated IPC physiological saline and autoclaved at 121 °C for about 30 minutes. Table 2 shows that all lenses have excellent surface properties.

[0166]

Table 2

[0167] Example 11 PAA-coated lenses 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 the following series of baths: 3 MEK baths (22, 78, and 224 seconds); a DI water bath (56 seconds); 2 PAA coating solution baths (prepared by dissolving 3.6 g of PAA (M.W.: 450 kDa, manufactured by Lubrizol) in 975 ml of 1-propanol and 25 ml of formic acid) for 44 and 56 seconds separately; and 3 DI water baths for 56 seconds each.

[0168] PAE / PAA-coated lenses The lenses prepared after applying the PAA-based coating are successively immersed in the following baths: two PAE coating solutions (prepared by dissolving 0.25 wt% of PAE (Polycup 172, manufactured by Hercules) in DI water, adjusting the pH to approximately 5.0 using sodium hydroxide, and finally filtering the resulting solution using a 5 μm filter) for 44 and 56 seconds respectively; 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 One batch of lenses having one layer of PAA and one layer of PAE thereon is packaged in 0.2% sodium carboxymethyl cellulose (CMC, Product# 7H 3SF PH, Ashland Aqualon) in phosphate buffered saline (PBS), and then the pH is adjusted to 7.2 - 7.4. Then this blister is sealed and autoclaved at 121 °C for about 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 having one layer of PAA and one layer of PAE thereon is packaged in 0.2% hyaluronic acid (HA, Product# 6915004, Novozymes) in phosphate buffered saline (PBS), and then the pH is adjusted to 7.2 - 7.4. Then this blister is sealed and autoclaved at 121 °C for about 30 minutes to form a crosslinked coating (PAA-x-PAE-x-HA) on the lenses.

[0171] The resulting lenses with either PAA-x-PAE-x-CMC coating or PAA-x-PAE-x-HA coating show no Sudan black staining, debris attachment, or cracking under microscopy. Lenses with PAA-x-PAE-x-CMC coating have an average contact angle of 30 ± 3 degrees, while lenses with PAA-x-PAE-x-HA coating have an average contact angle of 20 ± 3 degrees.

[0172] Example 12 Preparation of IPC solution A reaction mixture is prepared by dissolving 2.86 wt% methoxy-poly(ethylene glycol)-thiol, average Mw 2000 (Product# MPEG-SH-2000, Laysan Bio Inc.) together with 2 wt% PAE (Kymene) in PBS, and adjusting the final pH to 7.5. This solution is heat-treated at 45 °C for about 4 hours to form a thermally crosslinkable hydrophilic polymer material containing MPEG-SH-2000 groups chemically grafted onto the polymer by reaction with the azetidinium groups in PAE. After heat treatment, the solution is diluted 10-fold with PBS containing 0.25% sodium citrate, the pH is adjusted to 7.2 - 7.4, and then filtered using a 0.22 micron polyethersulfone (PES) membrane filter. This final IPC saline contains 0.286 wt% hydrophilic polymer material (consisting of about 59 wt% MPEG-SH-2000 chains and about 41 wt% 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 crosslinked coating The PAA-coated lenses from Example 11 are packaged in the above IPC saline in a polypropylene lens packaging shell and then autoclaved at about 121 °C for about 30 minutes to form a crosslinked coating on the lenses.

[0174] The final lens shows no signs of debris attachment or crack lines after rubbing the lens. The lens is very lubricious, comparable to the control PAA-coated lens in the finger-rub test.

[0175] A series of experiments are carried out to test the effect of conditions (reaction time and solution concentration of mPEG-SH-2000 (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 the contact angle of the surface is presumably due to the increase in the density of terminal methyl groups on the surface with an increased graft density. At a high graft density, corresponding to a solution concentration of 0.6%, the contact angle approaches the measured value obtained on a flat substrate grafted with a polyethylene glycol (PEG) monolayer (Reference: Langmuir 2008, 24, 10646 - 10653).

[0178] Example 13 A series of experiments are carried out to test the effect of the molecular weight of mPEG-SH. The IPC saline is prepared in the same procedure as described in Example 12, but using one of the following mPEG-SHs: mPEG-SH 1000, mPEG-SH 2000, mPEG-SH 5000, and mPEG-SH 20000. All saline solutions are 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 is prepared by dissolving 2.5% methoxy-poly(ethylene glycol)-thiol, average MW 2000 (Product# MPEG-SH-2000, Laysan Bio Inc.), 10% PAE (Kymene) in PBS and 0.25% sodium citrate dihydrate. Next, the pH of this final solution is adjusted to 7.5 and the solution in the container is degassed by bubbling nitrogen gas through it for 2 hours to minimize thiol oxidation. This solution is then heat-treated at 45 °C for about 6 hours to form a thermally crosslinkable hydrophilic polymer material containing MPEG-SH-2000 groups chemically grafted to the polymer by reaction with azetidinium groups in PAE. After heat treatment, the solution is diluted 50-fold with PBS containing 0.25% sodium citrate, the pH is adjusted to 7.2 - 7.4, and then filtered using a 0.22 micron polyethersulfone (PES) membrane filter. The final IPC saline contains about 0.30 wt% polymer material (consisting of about 17 wt% MPEG-SH-2000 and about 83 wt% PAE) and 0.25% sodium citrate dihydrate.

[0181] The PAA-coated lenses from Example 11 are packaged in the above IPC saline in a polypropylene lens packaging shell 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 signs of debris attachment or crack lines after rubbing the lenses. The test lenses are very lubricious, comparable to the control PAA-coated lenses in the finger rub test.

[0183] Example 15 The reaction mixture is prepared by dissolving 3.62% methoxy-poly(ethylene glycol)-amine, average MW 550 (Product# MPEG-NH2-550, Laysan Bio Inc.) together with 2% PAE (Kymene) in PBS and adjusting the final pH to 10. This solution is heat-treated at 45 °C for about 4 hours to form a thermally crosslinkable hydrophilic polymer material containing MPEG-NH2-550 groups chemically grafted to the polymer by reaction with azetidinium groups in PAE. After heat treatment, the solution is diluted 10-fold with PBS containing 0.25% sodium citrate, the pH is adjusted to 7.2 - 7.4, and then filtered using a 0.22 micron polyethersulfone (PES) membrane filter. The final IPC physiological saline contains about 0.562 wt% polymer material (consisting of about 64 wt% MPEG-SH-2000 and about 36 wt% 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 physiological saline in a polypropylene lens packaging shell and then autoclaved at about 121 °C for about 30 minutes to form a crosslinked coating on the lenses.

[0185] The final lenses show neither debris attachment nor crack lines after rubbing the lenses.

[0186] Example 16 Use Poloxamer 108 (sample) and Nelfilcon A (CIBA VISION) as they are. 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 formation reaction conditions (Buehler et al., CHIMIA, 53 (1999), 269-274, which is hereby incorporated by reference in its entirety). Approximately 2.5% of the vinyl alcohol units in Nelfilcon A are modified with N-(2,2-dimethoxyethyl)acrylamide.

[0187] IPC physiological saline is prepared by dissolving 0.004% of Poloxamer 108, 0.8% of Nelfilcon A, 0.2% of PAE (Kymene, Polycup 3160), 0.45% of NaCl, and 1.1% of Na2HPO4·2H2O in DI water. This physiological saline is heat-pretreated by stirring at about 65 - 70 °C for 2 hours. After heat pretreatment, the physiological saline is allowed to cool to room temperature and then filtered using a 0.2 μm PES filter.

[0188] The lens prepared in Example 3 is placed in a polypropylene lens packaging shell together with 0.6 mL of IPC physiological saline (half of the physiological saline is added before inserting the lens). Next, the blister is sealed with aluminum foil and autoclaved at 121 °C for about 30 minutes.

[0189] The test lens does not show debris adhesion after rubbing against a paper towel. This lens had a WBUT of more than 10 seconds. When observed under a dark-field microscope, no crack lines are visible after rubbing the lens between fingers. This 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 Polysiloxane Extended with 80% Ethylenically Functionalized Chains 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 separately dried in a one-neck flask under high vacuum at about 60 °C for 12 hours (or overnight). The OH molar equivalents of KF-6001A and KF-6002A are determined by titration of the hydroxyl groups and used to calculate the millimolar equivalents to be used in the synthesis.

[0191] The moisture is removed from a 1-liter reaction vessel by reducing the pressure overnight, and the vacuum is released with dry nitrogen. 75.00 g (75 meq) of dry KF6001A is charged into the reactor, and then 16.68 g (150 meq) of freshly distilled IPDI is added to the reactor. The reactor is purged with nitrogen, heated to 45 °C with stirring, and then 0.30 g of DBTDL is added. The reactor is sealed and a positive nitrogen flow is maintained. Exotherm occurs, and then the reaction mixture is cooled and stirred (at 55 °C for 2 hours). Once exotherm occurs, 248.00 g (150 meq) of dry KF6002A is added to the reactor at 55 °C, and then 100 μL of DBTDL is added. The reactor is stirred for 4 hours. Heating is stopped, and the reactor is allowed to cool overnight. Nitrogen bubbling is stopped, and the reactor is gently stirred and opened to the atmosphere for 30 minutes. A hydroxyl-terminated polysiloxane extended with three polysiloxane segments, HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH (or HO-CE-PDMS-OH) is formed.

[0192] For the 80% ethylenic-functionalized polysiloxane, 18.64 g (120 meq) of IEM is added to the reactor together with 100 μL of DBTDL. The reactor is stirred for 24 hours, and then the product (80% IEM-capped CE-PDMS) is decanted and stored frozen.

[0193] B. Synthesis of Non-UV-Absorbing Amphiphilic Branched Polysiloxane Prepolymer Attach a 500 mL dropping funnel, an overhead stirrer, a reflux condenser with a nitrogen / vacuum inlet adapter, a thermometer, and a sampling adapter to a 1 L jacketed reactor. Charge 45.6 g of the 80% IEM cap CE-PDMS prepared above into this reactor and seal it. Charge a solution of 0.65 g of hydroxyethyl methacrylate (HEMA), 25.80 g of DMA, and 27.80 g of methacrylic acid (tris(trimethylsilyl)-siloxypropyl) (TRIS) in 279 g of ethyl acetate into the dropping funnel. Degas the reactor with a high vacuum pump at <1 mbar for 30 minutes at RT. The monomer solution is degassed for 3 cycles at 100 mbar and RT for 10 minutes while releasing the vacuum with nitrogen during the degassing cycle. Next, charge this monomer solution into the reactor, and then stir this reaction mixture and heat it to 67 °C. While heating, charge 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 into the dropping funnel and deoxygenate it 3 times at 100 mbar and RT for 10 minutes. When the reactor temperature reaches 67 °C, add the initiator / CTA solution to the PDMS / monomer solution in the reactor. Allow the reaction to proceed for 8 hours, then cut off the heating and bring the reactor temperature to room temperature within 15 minutes.

[0194] The resulting reaction mixture is then suctioned into a dry one-neck flask with an airtight lid, and 4.452 g of IEM is added together with 0.21 g of DBTDL. Stir this mixture at room temperature for 24 hours to form a non-UV-absorbing amphiphilic branched polysiloxane prepolymer. Add 100 μL of a hydroxy-tetramethylene piperonyloxy solution (2 g / 20 mL) in ethyl acetate to this mixed solution. Next, this solution is concentrated to 200 g ( ≒50%) at 30 °C using a rotary evaporator and filtered through a filter paper with a 1 μm pore size. After solvent exchange to 1-propanol, this solution is further concentrated to the desired concentration.

[0195] C. Synthesis of UV-absorbing amphiphilic branched polysiloxane prepolymer A 1 L reactor with a jacket is equipped with a 500 mL dropping funnel, an overhead stirrer, nitrogen / reflux condenser with a nitrogen / vacuum inlet adapter, a thermometer, and a sampling adapter. Next, 45.98 g of 80% IEM cap CE-PDMS prepared above is charged into this reactor, and the reactor is sealed. 0.512 g of HEMA, 25.354 g of DMA, 1.38 g of Norbloc methacrylate, and 26.34 g of TRIS in 263 g of ethyl acetate are charged into the dropping funnel. The reactor is degassed at <1 mbar for 30 minutes at RT using a high vacuum pump. The monomer solution is degassed for 3 cycles at 100 mbar and RT for 10 minutes while releasing the vacuum with nitrogen during the degassing cycle. Next, this monomer solution is charged into the reactor, and then the reaction mixture is stirred and heated to 67 °C. While heating, 1.480 g of mercaptoethanol (chain transfer agent, CTA) dissolved in 38 g of ethyl acetate and 0.260 g of azoisobutyronitrile are charged into the dropping funnel, and deoxygenated 3 times at 100 mbar and room temperature for 10 minutes. When 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 stopped, and the reactor temperature is brought to room temperature within 15 minutes. The resulting reaction mixture is then suctioned into a dry one-neck flask with an airtight lid, and 3.841 g of

[0196] acryloyloxyethyl isocyanate is added together with 0.15 g of DBTDL. This mixture is stirred at room temperature for about 24 hours to form a UV-absorbing amphiphilic branched polysiloxane prepolymer. To this mixed solution, a solution of hydroxy-tetramethylene piperonyloxy in ethyl acetate is added. Add 100 μL of (2 g / 20 mL). Next, this solution is concentrated to 200 g (≈50%) at 30 °C using a rotary evaporator and filtered through a filter paper with a pore size of 1 μm.

[0197] D-1: Lens formulation containing a non-UV-absorbing polysiloxane prepolymer Add 4.31 g of the synthetic macromer solution (82.39% in 1-propanol) prepared in Example C-2 to a 100 mL brown flask. Dissolve 0.081 g of TPO and 0.045 g of DMPC in 10 g of 1-propanol in a 20 mL vial, and then transfer it to the macromer solution. Concentrate this mixture to 5.64 g at 30 °C using a rotary evaporator, then add 0.36 g of DMA, and homogenize this formulation at room temperature. Obtain 6 g of a clear lens formulation D-1.

[0198] D-2: Lens formulation containing a UV-absorbing polysiloxane prepolymer (4% DMA) Add 24.250 g of the macromer solution (43.92% in ethyl acetate) prepared in Example D-2 to a 100 mL brown flask. Dissolve 0.15 g of TPO and 0.75 g of DMPC in 20 g of 1-propanol in a 50 mL vial, and then transfer it to the macromer solution. Distill off 20 g of the solvent at 30 °C using a rotary evaporator, and then add 20 g of 1-propanol. After 2 cycles, concentrate this mixture to 14.40 g. Add 0.6 g of DMA to this mixture, and homogenize this formulation at room temperature. Obtain 15 g of a clear lens formulation D-2.

[0199] D-3: Lens formulation containing a UV-absorbing polysiloxane prepolymer (2% DMA / 2% HEA) To a 100 mL brown flask, add 24.250 g of the macromer solution (43.92% in ethyl acetate) prepared in Example D-2. In a 50 mL vial, dissolve 0.15 g of TPO and 0.75 g of DMPC in 20 g of 1-propanol, and then transfer it to the macromer solution. Using a rotary evaporator, distill off 20 g of the solvent at 30 °C, and then add 20 g of 1-propanol. After 2 cycles, concentrate this mixture to 14.40 g. Add 0.3 g of DMA and 0.3 g of HEA to this mixture, and then homogenize this formulation at room temperature. Obtain 15 g of a clear lens formulation D-3.

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

[0202] The reactive packaging physiological saline is prepared by dissolving the components listed in Table 5 in DI water together with an appropriate buffer salt. After heat pretreatment, this physiological saline is allowed to cool to room temperature and then filtered using a 0.2 μm PES filter.

[0203]

Table 5

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

[0205] DSM Lenses The female mold of the polypropylene lens molding die is filled with approximately 75 microliters of the lens formulation prepared as described above, and the molding die is closed with the male mold (base curve mold) of the polypropylene lens molding die. The contact lens is obtained by curing the closed molding die with a UV irradiation source (Hamamatsu lamp equipped with a 330 nm cut-off filter) at a strength of approximately 16 mW / cm 2 .

[0206] LS Lenses The LS lenses are prepared by the casting method from the lens formulation prepared as described above using a reusable molding die similar to the molding dies shown in FIGS. 1-6 of U.S. Patent No. 7,384,590 and FIGS. 1-6 of 7,387,759. This molding die includes a half female mold made of quartz (or CaF2) and a half male mold made of glass (or PMMA). The UV irradiation source is a Hamamatsu lamp equipped with a 380 nm cut-off filter at a strength of approximately 4.6 mW / cm 2 . The lens formulation in the molding die is irradiated with UV light for approximately 30 seconds.

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

[0208] The formed lens is extracted in methyl ethyl ketone, hydrated, and packaged in one of the physiological saline solutions described in Table 5. The lens is placed in a polypropylene lens packaging shell together with 0.6 mL of IPC physiological saline (half of the physiological saline is added before inserting the lens). The blister is then sealed with aluminum foil and autoclaved at 121 °C for 30 minutes.

[0209] In the evaluation of the lens surface, no debris adhesion is observed on all test lenses. When observed under a dark-field microscope, no crack lines are visible after the rubbing test of the lens held by fingers.

[0210] The lens surface wettability (WBUT), lubricity, and contact angle are measured, and the results are summarized in Table 6. The lens is manufactured by the DSM method unless otherwise specified. The lubricity is scored according to a qualitative scale of 0 - 4 where a smaller number indicates higher lubricity. Generally, the lens surface characteristics are slightly improved after the application of the in-package coating.

[0211]

Table 6

[0212] Example 19 The lens is manufactured using lens formulation D-2 (Example 17) with the addition of APMAA monomer up to a concentration of 1%. The LS lens is prepared from the lens formulation prepared as described above by the casting method using a reusable molding die similar to the molding dies shown in FIGS. 1 - 6 of U.S. Patent No. 7,384,590 and FIGS. 1 - 6 of 7,387,759. This molding die includes a half female die made of glass and a half male die made of quartz. The UV irradiation source is a Hamamatsu lamp equipped with a 380 nm cut-off filter with an intensity of about 4.6 mW / cm 2 and the lens formulation in the molding die is irradiated with UV rays for about 30 seconds.

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

[0214] IPC physiological saline is prepared according to the composition described in Example 9 under preliminary reaction conditions of about 60 °C for 8 hours. The lens is placed in a polypropylene lens packaging shell together with 0.6 mL of IPC physiological saline (half of the physiological saline is added before inserting the lens). Next, the blister is sealed with aluminum foil and autoclaved at 121 °C for 30 minutes.

[0215] In the evaluation of the lens surface, no debris adhesion is observed on all test lenses. When observed under a dark field microscope, no crack lines are visible after the rubbing test of the lens pinched by fingers. The wettability (WBUT) of the lens surface exceeds 10 seconds, the lubricity is rated as "1", and the contact angle is approximately 20°.

[0216] Example 20 Preparation of lens formulation The lens formulation is prepared by dissolving the components in 1-propanol such that it has the following composition: approximately 32 wt% of the CE-PDMS macromer prepared in Example 2, approximately 21 wt% of TRIS-Am, approximately 23 wt% of DMA, approximately 0.6 wt% of L-PEG, approximately 1 wt% of DC 1173, approximately 0.1 wt% of visitint (a 5% copper phthalocyanine blue pigment dispersion in TRIS), approximately 0.8 wt% of DMPC, approximately 200 ppm of H-TEMPO, and approximately 22 wt% of 1-propanol.

[0217] Preparation of lens The lens is prepared by a casting method from the lens formulation prepared above using a reusable molding die (a quartz female half and a glass male half) similar to the molding die shown in FIGS. 1-6 of U.S. Patent No. 7,384,590 and FIGS. 1-6 of 7,387,759. The lens formulation in the molding die is irradiated with UV light (13.0 mW / cm 2) is irradiated.

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

[0219] PAA-coated lens The above-mentioned cast contact lens is extracted and coated by immersing it in the following series of baths: DI water bath (about 56 seconds); 6 MEK baths (about 44, 56, 56, 56, 56, and 56 seconds each); DI water bath (about 56 seconds); 1 bath of PAA coating solution in 100% 1-propanol (about 0.36 to 0.44% by weight, acidified to about pH 1.7 to 2.3 with formic acid) (about 44 seconds); 1 bath of 50% / 50% mixture of water / 1-propanol (about 56 seconds); 4 DI water baths, each about 56 seconds; 1 PBS bath, about 56 seconds; and 1 DI water bath, about 56 seconds.

[0220] IPC physiological 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, azetidinium content of 0.46 as evaluated by NMR) was purchased from Ashland as an aqueous solution and used as received. IPC saline was prepared by dissolving approximately 0.07 wt% of Poly(AAm-co-AA)(90 / 10) and approximately 0.15% of 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. Next, the IPC saline was heat-pretreated at approximately 70 °C for approximately 4 hours (heat pretreatment). During this heat pretreatment, Poly(AAm-co-AA) and PAE partially crosslink with each other (i.e., not all azetidinium groups of PAE are used up), thereby forming a water-soluble and heat-crosslinkable hydrophilic polymer material containing azetidinium groups within a branched polymer network in the IPC saline. After heat pretreatment, the IPC saline was filtered using a 0.22 micron polyethersulfone [PES] membrane filter and cooled back to room temperature. Next, to prevent bioburden growth, 10 ppm of hydrogen peroxide was added to the final IPC saline, and the IPC saline was filtered using a 0.22 micron PES membrane filter.

[0221] Application of the crosslinked coating Lenses equipped with the PAA-LbL-based coating prepared above are placed in a polypropylene lens packaging shell (one lens per shell) together with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). Next, the blister is sealed with aluminum foil and autoclaved at approximately 121 °C for approximately 30 minutes to form a SiHy contact lens with a crosslinked coating (PAA-x-hydrophilic polymer material).

[0222] Characterization of the SiHy lens The resulting SiHy contact lens with a crosslinked coating (PAA-x-hydrophilic polymer material) shows no debris adhesion after rubbing against a paper towel, while the control lens (packaged in PBS, i.e., the lens with a non-covalent layer of PAA on it) shows severe debris adhesion. The lens has an oxygen permeability (Dk c or estimated intrinsic Dk) of about 146 barrer, a bulk elastic modulus of about 0.76 MPa, a water content of about 32 wt%, a relative ionic permeability of about 6 (compared to the Alsacon lens), a contact angle of about 34 - 47 degrees, and a WBUT of more than 10 seconds. When observed under a dark field microscope, no crack lines are visible after rubbing the test lens. The lens is very lubricious in the finger rubbing test and is equivalent to the control lens.

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

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

[0225] In vivo test ISO Systemic Toxicity in the Mouse indicates that there is no evidence of systemic toxicity in mice due to the lens extract. ISO Ocular Irritation Study in the Rabbit indicates that the lens extract is not considered an irritant to rabbit eye tissue. ISO Ocular Irritation Study in the Rabbit indicates that the IPC saline in the package after autoclaving is not considered an irritant to rabbit eye tissue. Lenses worn continuously for 22 days in a one-day disposable wearing modality were not irritating in the rabbit model, and the eyes treated with the test lenses were similar to those treated with the control lenses. ISO Sensitization Study (Guinea Pig Maximization Testing of Packaging Solutions) indicates that the IPC saline after autoclaving does not cause any delay in skin contact sensitization in guinea pigs. ISO Sensitization Study (Guinea Pig Maximization Testing of Lens Extracts) indicates that sodium chloride and the sesame oil extract of the lens do not cause a delay in skin contact sensitization in guinea pigs.

[0226] Genotoxicity test When the IPC physiological saline and SiHy lens extracts from the lens package are tested in the Bacterial Reverse Mutation Assay (Ames Test), it was found that the lens extracts and IPC physiological saline are considered non-mutagenic against the test strains TA98, TA100, TA1535, and TA1537 of Salmonella typhimurium, and furthermore against Escherichia coli WPuvrA. When the SiHy lens extracts are tested in the Mammalian Erythrocyte Micronucleus Assay, they were negative for inducing chromosomal abnormalities in the mouse bone marrow micronucleus test. When the IPC physiological saline from the lens package is tested by the Chromosome Aberration Test in Chinese Hamster Ovary, the IPC physiological saline is negative for the assay of inducing structural and numerical chromosomal abnormalities using CHO cells in both the inactivation and S9 activation test systems. When the SiHy lens extracts are tested by the Cell Gene Mutation Test (Mouse Lymphoma Mutagenesis Assay), the lens extracts were shown to be negative in the Mouse Lymphoma Mutagenesis Assay.

[0227] Example 22 The surface compositions of pre-formed SiHy contact lenses (i.e., SiHy contact lenses without any coating and before applying a PAA-based coating), PAA-coated SiHy contact lenses (i.e., these lenses before being sealed and autoclaved in a lens package containing IPC physiological saline), and SiHy contact lenses with a crosslinked coating (all of which are prepared by the procedure described in Example 20) are determined by characterizing the vacuum-dried contact lenses by X-ray photoelectron spectroscopy (XPS). XPS is a method for measuring the surface composition of the lens with a sampling depth of about 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 (pre-formed without coating), the carbon and oxygen atomic composition approaches that of PAA (60% C and 40% O), and the silicon atomic composition substantially decreases (from 12.1% to 4.5%). When a cross-linked coating is further applied on top of the PAA coating, the surface composition is dominated by carbon, nitrogen, and oxygen, which are a three-atom composition (hydrogen is excluded because XPS does not count hydrogen in surface composition). Such results indicate that the outermost layer of the cross-linked coated SiHy contact lens is most likely composed of a hydrophilic polymer material that is essentially 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 are 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 lens of the present invention has 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™) and also lower than that of PureVision® (plasma oxidation) and Premio™ (unknown plasma treatment), and further lower than that of SiHy lenses with a plasma vapor deposition coating having a thickness of about 25 nm (N&D® Aqua™ and Air Optix® Aqua™). This very low Si% value is comparable to the proportion of silicon atoms in a control sample of polyethylene from Goodfellow (LDPE, d = 0.015 mm; LS356526 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 would be due to contaminants introduced during the preparation process involving the vacuum drying process and XPS analysis, like the fluorine content in fluorine-free lenses. In the SiHy contact lenses of the present invention, silicon is well shielded from exposure.

[0233] The 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)), a polyethylene sheet manufactured by Goodfellow (LDPE, d = 0.015 mm; LS356526 SDS; ET31111512; 3004622910), DAILIES® (a polyvinyl alcohol hydrogel lens, i.e., a non-silicone hydrogel lens), and XPS analysis of ACUVUE® Moist (a polyhydroxyethyl methacrylate hydrogel lens, i.e., a non-silicone hydrogel lens) are also performed. All lenses are dried in vacuo. The polyethylene sheet, DAILIES® and ACUVUE® Moist do not contain silicone and are used as controls. The silicon atom 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 the conventional hydrogels and closer to those of the silicone hydrogels.

[0234] Example 23 Synthesis of UV-absorbing amphiphilic branched copolymer Attach a 500 mL dropping funnel, an overhead stirrer, a reflux condenser with a nitrogen / vacuum inlet adapter, a thermometer, and a sampling adapter to a 1 L jacketed reactor. Charge 89.95 g of the 80% partially ethylenically functionalized polysiloxane prepared in Example 17, A into this reactor, and then degas at room temperature under a vacuum of less than 1 mbar for about 30 minutes. Charge a monomer solution prepared by mixing 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 into a 500 mL dropping funnel, then degas at room temperature under a vacuum of 100 mbar for 10 minutes, and then fill with nitrogen gas. The monomer solution is degassed for two more cycles under the same conditions. Next, charge the monomer solution into the reactor. Heat this reaction mixture to 67 °C while stirring moderately. While heating, charge a solution consisting of 2.96 g of mercaptoethanol (chain transfer agent, CTA), 0.72 g of 2,2'-azobis(2-methylpropionic acid) dimethyl (V-601, initiator), and 76.90 g of ethyl acetate into the dropping funnel, and then subject it to the same degassing process as the monomer solution. When the reactor temperature reaches 67 °C, add the initiator / CTA solution to the reactor as well. Carry out the reaction at 67 °C for 8 hours. After completion of the copolymerization, cool the reactor temperature to room temperature.

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

[0236] Preparation of lens formulation The lens formulation is prepared to have the following composition: prepolymer prepared above 71 wt%; 4 wt% DMA; 1 wt% TPO; 1 wt% DMPC; 1 wt% Brij 52 (from); and 22 wt% 1-PrOH.

[0237] Preparation of the lens The lens is manufactured by casting the lens formulation prepared above under spatial confinement of UV irradiation using a reusable molding die similar to the molding dies shown in FIGS. 1-6 of U.S. Patent No. 7,384,590 and 7,387,759 (FIGS. 1-6). This molding die includes a female half made of glass and a male half made of quartz. The UV irradiation source is a Hamamatsu lamp equipped with a 380 nm cut-off filter at an intensity of about 4.6 mW / cm 2 The lens formulation in the molding die is irradiated with UV light for about 30 seconds.

[0238] The cast lens is extracted with methyl ethyl ketone (MEK), rinsed in water, coated with PAA by immersing the lens in a propanol solution of polyacrylic acid (PAA) (0.004 wt%, acidified to about pH 2.0 with formic acid), and hydrated in water.

[0239] IPC physiological saline is prepared from a composition containing about 0.07% PAAm-PAA and sufficient PAE (≈0.15% PAE) to provide an initial azetidinium content of approximately 8.8 milliequivalents / liter under pre-reaction conditions of about 60 °C for 6 hours. Next, 5 ppm hydrogen peroxide is added to the IPC physiological saline to prevent bioburden growth, and the IPC physiological saline is filtered using a 0.22 micron polyethersulfone [PES] membrane filter. The lens is placed in a polypropylene lens packaging shell together with 0.6 mL of IPC physiological saline (half of the physiological saline is added before inserting the lens). The blister is then sealed with aluminum foil and autoclaved at 121 °C for 30 minutes.

[0240] Characterization of the lens The resulting lens has the following properties: E’ ≈ 0.82 MPa; Dk c ≈ 159.4 (using Rotofilcon B as the control lens, 80 μm average center thickness and intrinsic Dk 110); IP ≈ 2.3; water % ≈ 26.9; and UVA / UVB %T ≈ 4.6 / 0.1. When observed under a dark field microscope, no crack lines are visible after rubbing the test lens. The lens is very lubricious in the finger rub test and is equivalent to the control lens.

[0241] Example 24 Preparation of the lens formulation Formulation I is prepared by dissolving the components in 1-propanol such that it has 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 Vistint (tris(trimethylsiloxy)silylpropyl methacrylate, 5% copper phthalocyanine blue pigment dispersion in TRIS), and 24.5 wt% of 1-propanol.

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

[0243] Preparation of the lens The lens is prepared by a casting method from the lens formulation prepared above using a reusable molding die (a female die for half of the quartz and a male die for half of the glass) similar to the molding dies shown in FIGS. 1-6 of U.S. Patent No. 7,384,590 and FIGS. 1-6 of 7,387,759. The UV irradiation source is a Hamamatsu lamp equipped with a cut-off filter of WG335+TM297 at an intensity of about 4 mW / cm 2 The lens formulation in the molding die is irradiated with UV light for about 25 seconds. The cast lens is extracted with methyl ethyl ketone (MEK) (or propanol or isopropanol).

[0244] Application of a PAA prime coating to the SiHy contact lens A polyacrylic acid coating solution (PAA-1) is prepared by dissolving a certain amount of PAA (M.W.: 450 kDa, manufactured by Lubrizol) in a predetermined volume of 1-propanol so as to have a concentration of about 0.39 wt%, and adjusting the pH to about 2.0 with formic acid.

[0245] Another PAA coating solution (PAA-2) is prepared by dissolving a certain amount of PAA (M.W.: 450 kDa, manufactured by Lubrizol) in a predetermined volume of an organic solvent (50 / 50, 1-propanol / H2O) so as to have a concentration of about 0.39 wt%, and adjusting the pH to about 2.0 with formic acid.

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

[0247]

Table 9

[0248]

Table 10

[0249] Application of a crosslinked 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 evaluated by NMR) was purchased from Ashland as an aqueous solution and used as received. Package internal cross-linked (IPC) physiological saline was prepared by dissolving approximately 0.07 wt% of poly(AAm-co-AA)(90 / 10) and approximately 0.15% of 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. Next, the IPC physiological saline was heat pretreated at approximately 70 °C for approximately 4 hours (heat pretreatment). During this heat pretreatment, poly(AAm-co-AA) and PAE cross-link partially with each other (i.e., not all azetidinium groups of PAE are used up), thereby forming a water-soluble and thermally cross-linkable hydrophilic polymer material containing azetidinium groups within a branched polymer network in the IPC physiological saline. After heat pretreatment, the IPC physiological saline was filtered using a 0.22 micron polyethersulfone [PES] membrane filter and cooled back to room temperature. Next, 10 ppm of hydrogen peroxide was added to the final IPC physiological saline to prevent bioburden growth, and the IPC physiological saline was filtered using a 0.22 micron polyethersulfone [PES] membrane filter.

[0250] Lenses with the PAA prime coating prepared above are placed into polypropylene lens packaging shells (one lens per shell) together with 0.6 mL of IPC physiological saline (half of the physiological saline is added before inserting the lens). Next, the blisters are sealed with aluminum foil and autoclaved at approximately 121 °C for approximately 30 minutes to form SiHy lenses with a cross-linked hydrophilic coating.

[0251] Characterization of SiHy Lenses The resulting SiHy contact lens, with a crosslinked hydrophilic coating and a center thickness of about 0.95 microns, has an oxygen permeability (Dk c or estimated intrinsic Dk) of about 142 to about 150 barrer, 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 an Alsacon lens), and a contact angle of about 34 to about 47 degrees.

[0252] Characterization of the Nanotextured Surface of Contact Lenses Transmission - Differential - Interference - Contrast (TDIC) method The contact lens is placed on a slide glass and flattened by pressing the lens between the slide and a glass coverslip. The contact lens surface is positioned and inspected by focusing through the lens using a Nikon ME600 microscope with a transmission - differential - interference optical unit and a 40× objective lens. The resulting TDIC images are then evaluated to determine the presence of a wrinkled surface pattern (e.g., random and / or ordered worm - like patterns, etc.).

[0253] Reflection - Differential - Interference - Contrast (RDIC) method The lens is placed on a slide glass and flattened by making four radial cuts at ≒90 - degree intervals. Excess physiological saline is blown off the surface using compressed air. Next, the lens surface is inspected for the presence of a wrinkled surface pattern on the contact lens surface using a Nikon Optiphot - 2 with a reflection - differential - interference optical unit and 10×, 20×, and 50× objective lenses. Representative images on each side are acquired using the 50× objective lens. The contact lens is then flipped over, excess physiological saline is removed, and the other side of the contact lens is investigated in the same way. The resulting RDIC images are then evaluated to determine the presence of a wrinkled surface pattern (e.g., random and / or ordered worm - like patterns, etc.).

[0254] Dark field light microscopy (DFLM) DFLM is generally based on dark field illumination, a method of enhancing the contrast of an observation sample. This technique consists of a light source outside or blocked from the observer's field of view for illuminating the sample at an angle with respect to normal transmitted light. Since the non-scattered light from the light source does not converge by the objective lens, this is not part of the image and the background of the image appears dark. Since the light source illuminates the sample at an angle, the light observed in the sample image is the light scattered by the sample towards the observer, and a contrast is created between this scattered light from the sample and the dark background of the image. Due to this contrast mechanism, dark field illumination is particularly useful for observing scattering phenomena such as haze.

[0255] DFLM is used to evaluate the haziness of contact lenses as follows. Since the dark field setting involves scattered light, it is considered that dark field data may provide an estimate of the worst-case scenario of haziness. In an 8-bit grayscale digital image, each image pixel is assigned a grayscale intensity (GSI) value in the range of 0 to 255. Zero represents a pixel that is completely black, and 255 represents a pixel that is completely white. An increase in 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 the area of interest (AOI) (e.g., the entire lens, or the lenticular or optical part 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 / arranged such that the entire contact lens to be observed fills the field of view (typically a field of view of ≈15 mm × 20 mm). The illumination is set to an appropriate level to observe the desired changes in the sample. The light intensity is adjusted / calibrated to the same level for each set of samples using density / light scattering standards known to those skilled in the art. For example, a certain standard consists of two overlapping plastic coverslips (identical and slightly or moderately matte). Such a standard consists of three regions with three different average GSI values, including two regions of intermediate grayscale level and saturated white (edges). The black region represents an empty dark field. The black and saturated white regions can be used to verify the gain and offset (contrast and brightness) settings of the camera. The intermediate gray level can provide three points for verifying the linear response of the camera. The light intensity is adjusted such that the average GSI of the empty dark field approaches 0, and that of the defined AOI in a standard digital image is the same each time within ±5 GSI units. After calibration of the light intensity, the contact lens is immersed in 0.2 μm filtered phosphate buffered saline in a quartz Petri dish or similar transparent dish placed on the DFLM stand.Next, acquire an 8-bit grayscale digital image of the lens when viewed using the calibrated illumination, and determine the average GSI of the defined AOI within a portion of the image containing the lens. Repeat this for the contact lenses of the sample set. The light intensity calibration is re-evaluated periodically throughout the test to ensure consistency. The level of turbidity under DFLM inspection refers to DFLM turbidity = (GSI / 255) × 100%.

[0256] SiHy contact lenses (whose PAA prime coating is obtained by either immersion process 20-0 or 80-0) are determined to have an average DFLM turbidity of approximately 73%, and the hydrated contact lenses show a wrinkled surface pattern (a random worm-like pattern) that can be visually observed by inspecting using either of the above RDIC or TDIC methods. However, this wrinkled surface pattern has virtually no detrimental effect on the light transmittance of the contact lens.

[0257] SiHy contact lenses (whose PAA prime coating is obtained by either immersion process 20-1 to 20-4) are determined to have a low average DFLM turbidity of approximately 26% (presumably due to the presence of visitint pigment particles), and when inspected under either of the above RDIC or TDIC, they do not show a prominent wrinkled surface pattern (a random worm-like pattern).

[0258] A high percentage of SiHy contact lenses (whose PAA prime coating is obtained by immersion process 20-5) are determined to have an average DFLM turbidity of approximately 45%, and when inspected under either of the above RDIC or TDIC, they show a slightly prominent wrinkled surface pattern. However, this wrinkled surface pattern has virtually no detrimental effect on the light transmittance of the contact lens.

[0259] The SiHy contact lens (the PAA prime coating of which is obtained by any of dipping processes 80-1, 80-2, 80-3, 80-5 and 80-6) does not show an obvious wrinkled surface pattern when inspected under any of the above RDIC or TDIC. However, the SiHy contact lens (the PAA prime coating of which is obtained by either dipping process 80-0 or 80-4) shows an obvious wrinkled surface pattern when inspected under any of the above RDIC or TDIC. However, this wrinkled surface pattern has virtually no harmful effect on the light transmittance of the contact lens.

Claims

1. A silicone hydrogel contact lens for ophthalmic use, comprising a silicone hydrogel material and a crosslinked hydrophilic coating on the silicone hydrogel material, wherein the crosslinked hydrophilic coating comprises (I) a first polymer chain, and (II) 5 to 80% by weight of a second polymer chain derived from at least one hydrophilic enhancer having at least one reactive functional group selected from the group consisting of a carboxylic acid group, a primary amino group, a secondary amino group, and combinations thereof, and wherein the at least one hydrophilic enhancer is (i) a monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymer of a first hydrophilic vinyl monomer having no carboxylic acid group or primary or secondary amino group, wherein the first hydrophilic vinyl monomer is 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, C having a weight average molecular weight of 400 daltons or less １ -C ４ -alkoxypolyethylene glycol (meth)acrylate, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, and combinations thereof; or (ii) 0.1 to 30% by weight of at least one reactive vinyl monomer which is a vinyl monomer having a carboxylic acid group or a primary or secondary amino group, and at least one second hydrophilic vinyl monomer having no carboxylic acid group or primary or secondary amino group A copolymer which is a polymerization product of a composition containing At least one of the reactive vinyl monomers is Amino-C １ -C ６ Alkyl, acrylic acid C １ -C ６ Alkylamino-C １ -C ６ Alkyl, allylamine, 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 Alkyl acrylic acid, N-2-acrylamidoglycolic acid, and combinations thereof; The second hydrophilic vinyl monomer is Acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, glycerol methacrylate, 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, 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 -Alkoxypolyethylene glycol (meth) acrylate, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol, and combinations thereof; the silicone hydrogel contact lens has (1) a water break-up time ("WBUT") of at least 5 seconds, (2) an average water contact angle of 80 degrees or less; (3) an oxygen permeability of at least 40 barrers; (4) a modulus of elasticity of 1.5 MPa or less; and (5) a water content of 18 to 70% by weight when fully hydrated, and after inverting the silicone hydrogel contact lens and pinching and rubbing it between fingers, there are no cracks on the surface of the crosslinked hydrophilic coating visible under a dark field microscope. A silicone hydrogel contact lens.

2. The silicone hydrogel contact lens according to claim 1, having a WBUT of at least 10 seconds and / or an average water contact angle of 70 degrees or less.

3. The silicone hydrogel contact lens according to claim 1, wherein at least one of the reactive vinyl monomers is selected from the group consisting of acrylic acid, methacrylic acid, ethylacrylic acid, propylacrylic acid, N-2-acrylamidoglycolic acid, and combinations thereof.

4. The silicone hydrogel contact lens according to claim 2, wherein at least one of the reactive vinyl monomers is selected from the group consisting of acrylic acid, methacrylic acid, ethylacrylic acid, propylacrylic acid, N-2-acrylamidoglycolic acid, and combinations thereof.

5. The silicone hydrogel contact lens according to claim 1, wherein at least one of the reactive vinyl monomers is selected from the group consisting of vinylamine, allylamine, amino-C ２ -C ４ alkyl, amino-C ２ -C ４ alkyl (meth)acrylamide, and combinations thereof.

6. At least one of the reactive vinyl monomers is selected from the group consisting of vinylamine, allylamine, amino-C ２ -C ４ alkyl, amino-C ２ -C ４ alkyl (meth)acrylamide, and combinations thereof, the silicone hydrogel contact lens according to claim 2.

7. The at least one hydrophilic enhancer is a monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymer of a first hydrophilic vinyl monomer having no carboxylic acid group or primary or secondary amino group, and The first hydrophilic vinyl monomer is 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, C having a weight average molecular weight of 400 daltons or less １ -C ４ -alkoxypolyethylene glycol (meth)acrylate, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, and combinations thereof, the silicone hydrogel contact lens according to claim 1 or 2.

8. The at least one hydrophilic enhancer is 0.1 to 30% by weight of the at least one of the reactive vinyl monomers, and The at least one second hydrophilic vinyl monomer having no carboxylic acid group or primary or secondary amino group, is a copolymer which is a polymerization product of a composition containing, the silicone hydrogel contact lens according to any one of claims 1 to 6.

9. The at least one second hydrophilic vinyl monomer having no carboxylic acid group or primary or secondary amino group is Acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, C having a weight average molecular weight of 1500 daltons or less １ -C ４ -alkoxypolyethylene glycol (meth)acrylate, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, and combinations thereof, the silicone hydrogel contact lens according to claim 8.

10. A silicone hydrogel contact lens suitable for ophthalmic use, comprising a silicone hydrogel material and a crosslinked hydrophilic coating on the silicone hydrogel material, wherein the crosslinked hydrophilic coating is (I) a first polymer chain, (II) 5 to 80% by weight of a second polymer chain derived from at least one hydrophilic enhancer having at least one reactive functional group selected from the group consisting of carboxylic acid groups, primary amino groups, secondary amino groups, and combinations thereof, and wherein the at least one hydrophilic enhancer is (i) a monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymer of a first hydrophilic vinyl monomer having no carboxylic acid group or primary or secondary amino group, The first hydrophilic vinyl monomer is 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, C having a weight average molecular weight of 400 daltons or less １ -C ４ -alkoxypolyethylene glycol (meth)acrylate, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, and combinations thereof, a homo- or copolymer; Or, (ii) A copolymer which is a polymerization product of a composition containing 0.1 to 30% by weight of at least one reactive vinyl monomer which is a vinyl monomer having a carboxylic acid group or a primary or secondary amino group, And at least one second hydrophilic vinyl monomer having no carboxylic acid group or primary or secondary amino group Wherein at least one of the reactive vinyl monomers is (meth)acrylic acid amino-C -C １ -C ６ alkyl, (meth)acrylic acid C １ -C ６ alkylamino-C １ -C ６ alkyl, allylamine, 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-2-acrylamidoglycolic acid, and combinations thereof; Wherein at least one of the second hydrophilic vinyl monomers is Acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, glycerol methacrylate, 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, 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 -alkoxypolyethylene glycol (meth)acrylate, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol, and combinations thereof; The silicone hydrogel contact lens has (1) an oxygen permeability of at least 40 barrer; (2) a modulus of elasticity of 1.5 MPa or less; (3) a water content of 18 to 70% by weight when fully hydrated; (4) an average water contact angle of 90 degrees or less; and (5) has good coating durability to withstand a finger rubbing test, Here, being able to withstand the finger rubbing test means that after the silicone hydrogel contact lens is rubbed 30 times with a multi-purpose lens care solution by finger and then rinsed with physiological saline, the average water contact angle of the silicone hydrogel contact lens rubbed by the finger is still 90 degrees or less, A silicone hydrogel contact lens having no cracks on the surface of the crosslinked hydrophilic coating visible under a dark field microscope after the silicone hydrogel contact lens is inverted and rubbed between fingers.

11. The silicone hydrogel contact lens according to claim 10, having a WBut of at least 10 seconds and an average water contact angle of 70 degrees or less.

12. The silicone hydrogel contact lens according to claim 10, wherein at least one of the reactive vinyl monomers is selected from the group consisting of acrylic acid, methacrylic acid, ethylacrylic acid, propylacrylic acid, N-2-acrylamidoglycolic acid, and combinations thereof.

13. The silicone hydrogel contact lens according to claim 11, wherein at least one of the reactive vinyl monomers is selected from the group consisting of acrylic acid, methacrylic acid, ethylacrylic acid, propylacrylic acid, N-2-acrylamidoglycolic acid, and combinations thereof.

14. The silicone hydrogel contact lens according to claim 10, wherein at least one of the reactive vinyl monomers is selected from the group consisting of vinylamine, allylamine, amino-C ２ -C ４ alkyl, amino-C ２ -C ４ alkyl (meth)acrylamide, and combinations thereof.

15. The silicone hydrogel contact lens according to claim 11, wherein at least one of the reactive vinyl monomers is selected from the group consisting of vinylamine, allylamine, amino-C ２ -C ４ alkyl, amino-C ２ -C ４ alkyl (meth)acrylamide, and combinations thereof.

16. The at least one hydrophilic enhancer is a monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymer of a first hydrophilic vinyl monomer having no carboxylic acid group or primary or secondary amino group, The first hydrophilic vinyl monomer is 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, C having a weight average molecular weight of 400 daltons or less １ -C ４ -alkoxypolyethylene glycol (meth)acrylate, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, and combinations thereof. The silicone hydrogel contact lens according to claim 10 or 11.

17. The at least one hydrophilic enhancer is 0.1 to 30% by weight of the at least one reactive vinyl monomer, and A copolymer which is a polymerization product of a composition containing the at least one second hydrophilic vinyl monomer having no carboxylic acid group or primary or secondary amino group. The silicone hydrogel contact lens according to any one of claims 10 to 15.

18. The at least one second hydrophilic vinyl monomer has no carboxylic acid group or primary or secondary amino group, acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, C having a weight average molecular weight of 1500 daltons or less １ -C ４The silicone hydrogel contact lens according to claim 17, selected from the group consisting of -alkoxypolyethylene glycol (meth)acrylate, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, and combinations thereof.

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