Silicone hydrogel lenses with cross-linked hydrophilic coating

Abstract

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

Description

Technical Field

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

[0002] Background [[ID=Z11]]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) and tend to adsorb 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 pre-formed contact lenses typically need to be dried prior to plasma treatment and because of the relatively high capital investment associated with plasma treatment equipment.

[0004] Another approach to modifying the surface hydrophilicity of silicone hydrogel contact lenses is the incorporation of a wetting agent (hydrophilic polymer) into the lens formulation for manufacturing silicone hydrogel contact lenses, as proposed in U.S. Patents 6,367,929, 6,822,016, 7,052,131, and 7,249,848. This method does not require further post-processing to modify the surface hydrophilicity of the lens after casting 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 cause the formed lens to become cloudy. Furthermore, such surface treatments are susceptible to lipid deposition and adsorption. In addition, such surface treatments cannot provide a durable surface intended for long-term wear.

[0005] Another approach to modifying the hydrophilicity of relatively hydrophobic contact lens materials is the layer-by-layer (LbL) polyionic material deposition method (see, for example, U.S. Patents US 6,451,871, US 6,717,929, US 6,793,973, US 6,884,457, US 6,896,926, US 6,926,965, US 6,940,580, and US 7,297,725, as well as U.S. Patent Application Publications US 2007 / 0229758A1, US 2008 / 0174035A1, and US 2008 / 0152800A1). While LbL deposition can provide a cost-effective process for making silicone hydrogel materials wettable, LbL coatings are not as durable as plasma coatings and may have a relatively high surface charge density; this may interfere with contact lens cleaning and disinfecting solutions. To improve durability, crosslinking of LbL coatings on contact lenses is proposed in the jointly owned, concurrently pending U.S. Patent Application Publications 2008 / 0226922 A1 and 2009 / 0186229 A1 (both incorporated as cited references). However, crosslinked LbL coatings 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] Another approach to modifying the hydrophilicity of relatively hydrophobic contact lens materials is to bond hydrophilic polymers to the contact lenses by various mechanisms (e.g., U.S. Patent Applications 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 Publications). See 2009 / 0145086A1, 2009 / 0145091A1, 2008 / 0142038A1, and 2007 / 0122540A1 (all of which are incorporated herein by reference in their entirety). While these methods can be used to wettable silicone hydrogel materials, they typically require relatively long periods of time and / or involve difficult, multi-step processes to obtain a hydrophilic coating, making them uncost-effective and / or time-efficient for mass production environments.

[0007] Therefore, there is still a need for a cost-effective and time-efficient method of producing silicone hydrogel contact lenses with a wettable and durable coating (surface).

[0008] Summary of the Invention In one embodiment, the present invention provides a method for producing a silicone hydrogel contact lens, each comprising a crosslinked hydrophilic coating, comprising: (a) a step of obtaining a silicone hydrogel contact lens and a water-soluble, heat-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) about 20% to about 95% by weight of a first polymer chain derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, and (ii) about 5% to about 80% by weight of a hydrophilic moiety or second polymer chain derived from at least one hydrophilicity enhancer having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof (wherein the hydrophilic moiety or second polymer chain is each an epichlorohydrin-functionalized polyamine (iii) comprising a first polymer chain covalently bonded to a first polymer chain via one or more covalent bonds formed between one azetidinium group of a riamine or polyamidoamine and one amino, carboxyl, or thiol group of a hydrophilicity enhancer; and (b) comprising a part of the first polymer chain, or an azetidinium group that is a pendant or terminal group covalently bonded to the first polymer chain; and (b) heating a contact lens in an aqueous solution in the presence of a hydrophilic polymer material at 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 embodiment, the present invention provides a silicone hydrogel contact lens obtained by the method of the present invention, which has surface wettability characterized by an oxygen permeability of at least about 40 bars, a water contact angle of about 100 degrees or less, and good coating durability characterized by withstanding a finger rubbing test.

[0010] In yet another embodiment, the present invention provides an ophthalmic product comprising a sterile and sealed lens package, wherein the lens package comprises an autoclaved lens packaging solution and a ready-to-use silicone hydrogel contact lens immersed therein, and the ready-to-use silicone hydrogel contact lens comprises a crosslinked hydrophilic coating obtained by autoclaving an original silicone hydrogel contact lens having amino groups and / or carboxyl groups on and / or near the surface of the original silicone hydrogel contact lens in a pre-autoclaved packaging solution containing a water-soluble, thermally crosslinkable hydrophilic polymer material, wherein the hydrophilic polymer material comprises (i) about 20% to about 95% by weight of a first polymer chain derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, and (ii) about 5% to about 80% by weight of a hydrophilic portion derived from at least one hydrophilicity enhancer having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof. (iii) a second polymer chain (wherein this hydrophilic portion 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 an epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl, or thiol group of a hydrophilicity enhancer), and (iii) a portion of the first polymer chain, or an azetidinium group that is a pendant or terminal group covalently bonded to the first polymer chain, and this hydrophilic polymer material is a silicone hydrogel contact lens Each of the silicone hydrogel contact lenses is covalently bonded 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. The autoclaved packaging solution contains at least one buffer and a hydrolysis product of the hydrophilic polymer material in an amount sufficient to maintain a pH of about 6.0 to about 8.5, and has a tensile strength of about 200 to about 450 milliosmoles (mOsm) and a viscosity of about 1 cmpoise to about 20 cmpoise.

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

[0012] These and other aspects of the present invention will become apparent from the following description of currently preferred embodiments. This detailed description is merely illustrative of the invention and does not limit its scope, which is defined by the appended claims and equivalents. As will be obvious to those skilled in the art, many modifications and variations of the present invention can be achieved without losing the essence and scope of the novel concepts of this disclosure.

[0013] Detailed description of the embodiments of the invention Embodiments of the present invention will now be described in detail. Those skilled in the art will see that various modifications, alterations, and combinations can be made in 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 used in another embodiment to produce yet another embodiment. Therefore, the present invention treats such modifications, alterations, 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 or evident therefrom in the following detailed description. As will be obvious to those skilled in the art, this discussion is merely a description of exemplary embodiments and does not limit broader embodiments of the present invention.

[0014] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as those commonly understood by those of the ordinary skill in the art to which this invention pertains. Generally, the nomenclature and laboratory procedures used herein are well known and commonly used in the art. These procedures employ prior art, as provided in the art and various general references. Where a term is provided in the singular form, the inventors also consider the plural form of that term. The nomenclature and laboratory procedures used herein, as described below, are well known and commonly used in the art.

[0015] "Silicone hydrogel contact lenses" refer to contact lenses containing silicone hydrogel material. "Silicone hydrogel" refers to a silicone-containing polymer 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, at least one silicone-containing vinyl macromer, or at least one silicone-containing prepolymer having an ethylenically unsaturated group.

[0016] As used herein, "vinyl monomer" means a compound having a single ethylenically unsaturated group and that can be polymerized by chemical radiation or heat.

[0017] The terms "olefinic unsaturated group" or "ethylenically unsaturated group" are used herein in a broad sense and encompass any group containing at least one >C=C< group. Examples of ethylenically unsaturated groups are, but are not limited to, the following formulas:

[0018] [ka] (Meth)acryloyl, allyl, represented by the following formula:

[0019] [ka] It contains vinyl, styrene, or other C=C-containing groups as indicated by .

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

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

[0022] "Hydrophilic vinyl monomer" as used herein means a vinyl monomer that is water-soluble or, when fully hydrated, typically produces a homopolymer that can absorb at least 10 weight percent of water.

[0023] As used herein, "hydrophobic vinyl monomer" refers to a vinyl monomer that is water-insoluble and typically produces a homopolymer that can absorb less than 10% by weight of water.

[0024] A "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 refers to an average molecular weight exceeding 700 daltons.

[0025] A "crosslinker" is a compound that has at least two ethylenically unsaturated groups. A "crosslinking agent" is a crosslinker with a molecular weight of approximately 700 daltons or less.

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

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

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

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

[0030] The "azetidinium group" is defined by the following formula:

[0031] [ka] This refers to a group that has a positive charge, as indicated by [the symbol].

[0032] The term "thermally crosslinkable" with respect to a polymer material or functional group means that the polymer material or functional group can undergo a crosslinking (or coupling) reaction with another material or functional group at relatively high temperatures (approximately 40°C to approximately 140°C), whereas at room temperature (i.e., approximately 22°C to approximately 28°C, preferably approximately 24°C to approximately 26°C, and particularly approximately 25°C), it cannot undergo the same crosslinking (or coupling) reaction with another material or functional group, even after extending the detectable time to approximately one hour.

[0033] The term "phosphorylcholine" is expressed by the following formula:

[0034] [ka] This refers to an amphoteric ion represented by [wherein n is an integer between 1 and 5, and R1, R2, and R3 are independently 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 that lacks carboxyl groups or amino groups (i.e., primary or secondary amino groups). Non-reactive vinyl monomers may include tertiary or quaternary amino groups.

[0037] With respect to polymers, the term "water-soluble" means that the polymer can dissolve in water to a degree sufficient to form an aqueous solution of the polymer with a maximum concentration of approximately 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 contact angle measurements with at least three individual contact lenses.

[0039] The term "intactness" in relation to coatings on silicone hydrogel contact lenses 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 a coating on a silicone hydrogel contact lens means that there is virtually no Sudan Black staining of the contact lens.

[0040] In relation to coatings on silicone hydrogel contact lenses, the term "durability" is intended to describe whether the coating on the silicone hydrogel contact lens can withstand a finger rubbing test.

[0041] As used herein, with respect to a coating on a contact lens, “withstands finger rubbing test” or “withstands durability test” 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 a 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 inherent "oxygen permeability" (Dk) of a material is the rate at which oxygen passes through the material. In this invention, with respect to hydrogels (silicone or non-silicone) or contact lenses, the term "oxygen permeability (Dk)" means the oxygen permeability (Dk) corrected for surface resistance to oxygen flux due to boundary layer effects, as shown in the examples described below. Oxygen permeability is conventionally expressed in units of bars, where "barrer" is [(cm 3 Oxygen) (mm) / (cm 2 )(sec)(mmHg)]×10 -10 It is defined as follows.

[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 "ion 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 according to 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 for direct placement in 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 using a water-soluble, thermally crosslinkable hydrophilic polymer material having an azetidinium group.

[0048] The present invention is partly based on the remarkable discovery that a water-soluble, azetidinium-containing, and thermally crosslinkable hydrophilic polymer material (which is a partial reaction product of polyamine-epichlorohydrin or polyamidoamine-epichlorohydrin with at least one hydrophilicity enhancer having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof) can be used to form a crosslinked coating on silicone hydrogel contact lenses having carboxylic acid and / or amino groups on or near its surface, exhibiting good surface hydrophilicity and / or wettability, good hydrophilicity, and good scratch resistance. At relatively high temperatures (as described above), the positively charged azetidinium group interacts with amino groups, thiol groups, and carboxylate ions -COO - By reacting with a functional group such as (i.e., a deprotonated carboxyl group), Scheme 1:

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

[0050] Hydrophilicity enhancers are thought to play at least two roles in improving the performance of the resulting crosslinked coatings: by adding hydrophilic polymer chains to polyamine or polyamidoamine polymer chains to form a highly branched hydrophilic polymer material having suspended polymer chains and / or chain segments; and by significantly reducing the number of azetidinium groups in the crosslinkable polymer material (coating material) to lower the crosslink density of the crosslinked coating. Coatings with a loose structure and suspended polymer chains and / or chain segments are thought to provide good surface hydrophilicity, wettability, and / or lubricity.

[0051] The present invention is also partly based on the discovery that the crosslinked coating of the present invention can be advantageously formed directly on a silicone hydrogel contact lens within 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 by either adding the azetidinium-containing polymer material to the lens packaging solution or by physically 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 hydrated in a packaging solution and packaged must be sterilized. Sterilization of 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 approximately 118°C to 125°C for approximately 20 to 40 minutes. It has been found that during autoclaving, water-soluble azetidinium-containing polymer materials can effectively crosslink with functional groups (e.g., amino groups, thiol groups, and / or carboxylic acid groups) on and / or near the surface of silicone hydrogel contact lenses to form a wettable, ophthalmically compatible crosslinked coating. During autoclaving, azetidinium groups 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 be converted into a non-reactive polymer wetting material that, where applicable, can improve the comfort of lens insertion.

[0053] By utilizing the method of the present invention, the coating process can be combined with a sterilization process (autoclave treatment) in the manufacture of silicone hydrogel contact lenses. The resulting contact lenses can have high surface hydrophilicity / wetting properties, minimal surface changes if any, good abrasion resistance, and good durability. Furthermore, because the packaging solution is suitable for ophthalmos, patients can use the lenses directly from the package without washing and / or rinsing.

[0054] In one embodiment, the present invention provides a method for producing a silicone hydrogel contact lens, each comprising a crosslinked hydrophilic coating, comprising: (a) a step of obtaining a silicone hydrogel contact lens and a water-soluble, heat-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) about 20% to about 95% by weight of a first polymer chain derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, and (ii) about 5% to about 80% by weight of a hydrophilic moiety or second polymer chain derived from at least one hydrophilicity enhancer having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof (wherein the hydrophilic moiety or second polymer chain is each epichlorohydrin-functionalized The present invention provides a method comprising the steps of: (iii) a first polymer chain covalently bonded to a first polymer chain via one or more covalent bonds formed between one azetidinium group of a polyamine or polyamidoamine and one amino, carboxyl, or thiol group of a hydrophilicity enhancer; and (iii) a part of the first polymer chain, or an azetidinium group that is a pendant or terminal group covalently bonded to the first polymer chain; and (b) heating a contact lens at a temperature of about 40°C to about 140°C in the presence of a hydrophilic polymer material in an aqueous solution 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 methods for manufacturing contact lenses. For example, contact lenses can be manufactured by conventional “rotational molding molds” as described in U.S. Patent No. 3,408,429, or by static, complete casting methods as described in U.S. Patents No. 4,347,198; 5,508,317; 5,583,463; 5,789,464; and 5,849,810. In casting, the lens formulation is typically poured into a mold and cured (i.e., polymerized and / or crosslinked) in the 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. Silicone hydrogel contact lens formulations may also contain other necessary components known to those skilled in the art, such as crosslinking agents, UV absorbers, visible colorants (e.g., dyes, pigments, or mixtures thereof), antimicrobial agents (e.g., preferably silver nanoparticles), bioactive agents, leaching lubricants, leaching tear fluid stabilizers, and mixtures thereof. The molded silicone hydrogel contact lens can then be subjected to an extraction in an extraction solvent to remove non-polymerized components from the molded lens, as known to those skilled in the art, and then subjected to a hydration process. Numerous silicone hydrogel lens formulations are described in numerous patents and patent applications published up to the filing date of this application.

[0056] According to the present invention, a silicone hydrogel contact lens may essentially contain, or 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 near its surface, this 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 (meth)acrylate amino-C2-C6 alkyl, (meth)acrylate C1-C6 alkylamino-C2-C6 alkyl, allylamine, vinylamine, amino-C2-C6 alkyl(meth)acrylamide, C1-C6 alkylamino-C2-C6 alkyl(meth)acrylamide, acrylic acid, C1-C 12 Alkyl acrylic acid (e.g., methacrylic acid, ethyl acrylic acid, propyl acrylic acid, butyl acrylic acid, etc.), N,N-2-acrylamidoglycolic acid, β-methyl acrylic acid (crotonic acid), α-phenylacrylic acid, β-acrylooxypropionic 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 includes (meth)acrylic acid amino-C2-C6 alkyl, (meth)acrylic acid C1-C6 alkylamino-C2-C6 alkyl, allylamine, vinylamine, amino-C2-C6 alkyl(meth)acrylamide, C1-C6 alkylamino-C2-C6 alkyl(meth)acrylamide, acrylic acid, C1-C 12 The lens is produced from a lens formulation containing at least one reactive vinyl monomer selected from the group consisting of alkylacrylic acid, N,N-2-acrylamidoglycolic acid, and combinations thereof. This lens formulation preferably contains about 0.1% to about 10%, more preferably about 0.25% to about 7%, even more preferably about 0.5% to about 5%, and most preferably about 0.75% to about 3% (by weight) of the reactive vinyl monomer.

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

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

[0061] In this reactive LbL base coating embodiment, the reactive polymer may be a linear or branched polymer having pendant amino groups and / or carboxyl groups. Any polymer having pendant amino groups and / or carboxyl groups can be used as a reactive polymer for forming a base coating on a silicone hydrogel contact lens. Examples of such reactive polymers are, but are not limited to, homopolymers of reactive vinyl monomers; copolymers of two or more reactive vinyl monomers; copolymers of a reactive vinyl monomer 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., carboxymethylcellulose, carboxyethylcellulose, carboxypropylcellulose); hyaluronate; chondroitin sulfate; poly(glutamic acid); poly(aspartic acid); and combinations thereof.

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

[0063] Preferred examples of non-reactive hydrophilic vinyl monomers that do not contain carboxyl or amino groups are, but are not limited to, acrylamide (AAm), methacrylamide, N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA), N-vinylpyrrolidone (NVP), N,N-dimethylaminoethyl methacrylate (DMAEM), N,N-dimethylaminoethyl acrylate (DMAEA), N,N-dimethylaminopropyl methacrylamide (DMAPMAm), N,N-dimethylaminopropylacrylamide (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- This includes 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 copolymers), phosphorylcholine-containing vinyl monomers (including (meth)acryloyloxyethyl phosphorylcholine and those described in U.S. Patent No. 5,461,433 (which is incorporated herein in whole as referenced)), and combinations thereof.

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

[0065] Weight-average molecular weight M of reactive polymers for forming reactive LbL base coatings W This is at least about 10,000 Daltons, preferably at least about 50,000 Daltons, and more preferably about 100,000 Daltons to about 5,000,000 Daltons.

[0066] A solution of a reactive polymer for forming a reactive LbL base coating on a contact lens can be prepared by dissolving one or more reactive polymers in water, a mixture of water and one or more water-miscible organic solvents, an organic solvent, or a mixture of one or more organic solvents. Preferably, the reactive 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 the silicone hydrogel contact lens, and it is believed that a portion of the reactive polymer penetrates the silicone hydrogel contact lens, thereby improving the durability of the reactive base coating.

[0067] Any organic solvent can be used to prepare the solution of the reactive polymer. Examples of preferred organic solvents are not particularly limited, but include 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 L, dipropylene glycol dimethyl ether, polyethylene glycols, polypropylene glycols, ethyl acetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate, i-propyl lactate, methylene chloride, methanol, ethanol, 1- or 2-propanol, 1- or 2-butanol, tert-butanol, tert-amyl alcohol, menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-Dimethyl-3-Octanol, 1-Chloro-2-methyl-2-propanol, 2-Methyl-2-Heptanol, 2-Methyl-2-Octanol, 2-Methyl-2-Nonanol, 2-Methyl-2-Decanol, 3-Methyl-3-Heptanol, 3-Methyl-3-Heptanol, 4-Methyl-4-Heptanol, 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-Methylcyclopene This includes tanol, 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 essentially contains amino groups and / or carboxyl groups on and / or near its surface, and is further subjected to surface treatment to form a reactive LbL base coating containing amino groups and / or carboxyl groups.

[0069] In another preferred embodiment (reactive plasma-based coating), a silicone hydrogel contact lens is subjected to plasma treatment to form a covalently bonded reactive plasma-based coating on the contact lens, that is, one or more reactive vinyl monomers (any of the aforementioned) are polymerized under the influence of plasma generated by discharge (so-called plasma-induced polymerization). The term "plasma" refers to an ionized gas produced by, for example, glow discharge, which may consist of electrons in the ground state or any higher state of any type of excitation, ions of either polarity, gas atoms and molecules, and even photons. This is often called "low-temperature plasma."For a review of plasma polymerization and its use, see: R. Hartmann, "Plasma polymerisation: Grundlagen, Technik und Anwendung, Jahrb. Oberflachentechnik (1993) 49, pp. 283-296, Battelle-Inst. eV Frankfurt / Main Germany"; H. Yasuda, "Glow Discharge 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 This is referenced in 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 "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 in the subsequent step, the activated surface is exposed to a vinyl monomer having amino or carboxyl groups (any of the above reactive vinyl monomers), while the plasma power is turned off. The activation causes plasma-induced radical formation on the surface, which then initiates polymerization of the vinyl monomer in the subsequent step.

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

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

[0072] Any suitable hydrophilicity enhancer can be used in the present invention, provided that 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, glucosamic acid, mannosamine, sugar acid 1,4-lactone, saccharidic acid, ketodeoxynonurosonic acid, N-methyl-D-glucamine, 1-amino-1-deoxy-β-D-galactose, 1-amino-1-deoxysorbitol) This includes 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 the same as above)), carboxyl (-COOH), and / or thiol (-SH) groups in the hydrophilic polymer as a 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% (by weight), based on the total weight of the hydrophilic polymer.

[0075] Another preferred type of hydrophilicity enhancer is a hydrophilic polymer, such as an amino- or carboxyl-containing polysaccharide, e.g., carboxymethylcellulose (repeating unit: -[C6H 10-m O5(CH2CO2H) m Based on the composition of ]-(where m is 1 to 3), it has an estimated carboxyl content of about 40% or less), carboxyethylcellulose (repeating unit:-[C6H 10-m O5(C2H4CO2H) mBased on the composition of ]-(where m is 1 to 3), it has an estimated carboxyl content of approximately 36% or less), carboxypropyl cellulose (repeating unit:-[C6H 10-m O5(C3H6CO2H) m Based on the composition of ]-(where m is 1-3), it is estimated to have a carboxyl content of approximately 32% or less), hyaluronic acid (repeating unit:-(C) 13 H 20 Based on the composition of O9NCO2H), it is estimated to have a carboxyl content of approximately 11%, chondroitin sulfate (repeating unit:-(C) 12 H 18 O 13 Based on the composition of NSCO2H)-, it has an estimated carboxyl content of approximately 9.8%, or a combination thereof.

[0076] Hydrophilic polymers as other preferred types of hydrophilicity enhancers include, but are not limited to, 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-armed PEG having one or more amino, carboxyl, and / or thiol groups; PEG dendrimers having one or more amino, carboxyl, and / or thiol groups. -; homo- or copolymers of diamino- or dicarboxyl-terminated non-reactive hydrophilic vinyl monomers; homo- or copolymers of monoamino- or monocarboxyl-terminated non-reactive hydrophilic vinyl monomers; copolymers which are polymerization products of compositions comprising (1) one or more reactive vinyl monomers in about 50% by weight or less, preferably about 0.1% to about 30%, more preferably about 0.5% to about 20%, and even more preferably about 1% to about 15% (by weight) and (2) at least one non-reactive hydrophilic vinyl monomer and / or at least one phosphorylcholine-containing vinyl monomer; and combinations thereof. The reactive vinyl monomers and non-reactive hydrophilic vinyl monomers are those described above.

[0077] More preferably, the hydrophilic polymer as a 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-armed PEG having one or more amino, carboxyl, or thiol groups; PEG dendrimers having one or more amino, carboxyl, or thiol groups; acrylamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, or a weight-average molecule of 400 daltons or less. (1) (meth)acrylic acid, C2-C4 alkoxy polyethylene glycol (meth)acrylate having an amount of C1-C4-alkoxy polyethylene glycol (meth)acrylate, 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 combinations thereof, selected from the group consisting of monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymers of nonreactive hydrophilic vinyl monomers; (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 12The copolymer is a polymerization product of a composition comprising (2) alkylacrylic acid, vinylamine, allylamine and / or amino-C2-C4 alkyl (meth)acrylic acid, and (2) (meth)acryloyloxyethyl phosphorylcholine and / or at least one nonreactive hydrophilic vinyl monomer [selected from the group consisting of acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, (meth)acrylic acid glycerol, (meth)acrylic acid hydroxyethyl, 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 a hydrophilicity enhancer is PEG-NH2; PEG-SH; PEG-COOH; monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated polyvinylpyrrolidone; monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated polyacrylamide; monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly(DMA); monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly(DMA-co-NVP); monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly(NVP-co-(meth)acrylate N,N-dimethylaminoethyl); monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly(vinyl alcohol); monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly[(meth)acryloyloxyethyl phosphorylcholine] homopolymer or copolymer Poly(NVP-co-vinyl alcohol) with monoamino-, monocarboxyl-, diamino-, or dicarboxyl terminators; poly(DMA-co-vinyl alcohol) with monoamino-, monocarboxyl-, diamino-, or dicarboxyl terminators; 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; about 0.1% to about 30%, preferably Poly[(meth)acrylic acid-co-NVP] containing about 0.5% to about 20%, more preferably about 1% to about 15% (by weight) of (meth)acrylic acid; copolymers which are polymerization products of compositions containing (1) (meth)acryloyloxyethyl phosphorylcholine and (2) carboxylic acid-containing vinyl monomer and / or amino acid-containing vinyl monomer in amounts of about 0.1% to about 30%, preferably about 0.5% to about 20%, more preferably about 1% to about 15% (by weight); and combinations thereof.

[0079] Functionalized PEGs and functionalized multi-armed PEGs can be obtained from various suppliers, such as Polyscience and Shearwater Polymers, Inc.

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

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

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

[0083] In the present invention, the reaction between the hydrophilicity enhancer and the epichlorohydrin-functionalized polyamine or polyamidoamine is carried out at a temperature of about 40°C to about 100°C for a sufficient amount of time (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) to form a water-soluble, thermally crosslinkable hydrophilic polymer material containing azetidinium groups.

[0084] In the present invention, the concentration of the hydrophilicity enhancer for epichlorohydrin-functionalized polyamines or polyamidoamines must be selected so as not to result in a water-insoluble hydrophilic polymer material (i.e., a solubility of less than 0.005 g per 100 ml of water at room temperature), and so as not to exhaust more than about 99%, preferably about 98%, more preferably about 97%, and even more preferably about 96% of the azetidinium groups of the epichlorohydrin-functionalized polyamine or polyamidoamine.

[0085] In this 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 approximately 118°C to approximately 125°C for approximately 20 to 90 minutes. In this embodiment of the invention, the packaging solution is a buffered aqueous solution that is safe for eye use after autoclaving.

[0086] Lens packages (or containers) for autoclaving and storing soft contact lenses are well known to those skilled in the art. 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 the cover is removably sealed to the base, and the base contains a cavity for receiving a sterile packaging solution and the contact lens).

[0087] The lenses are packaged in individual packages, sealed, and sterilized (for example, by autoclaving at approximately 120°C or above for at least 30 minutes) before being supplied to the user. Those skilled in the art will have a good understanding of 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 the other components are not particularly limited, but include isotonic agents, surfactants, antimicrobial agents, preservatives, and lubricants (or water-soluble thickeners) (e.g., cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone).

[0089] The packaging solution contains a buffer in an amount sufficient to maintain the pH of the packaging solution within a desirable range, preferably within a physiologically acceptable range of about 6 to about 8.5. Any known physiologically compatible buffer can be used. Buffers suitable as components of the contact lens care composition of the present invention are known to those skilled in the art. Examples include boric acid, borates, e.g., sodium borate; citric acid, citrates, e.g., potassium citrate; bicarbonates, e.g., 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) These include 1,3-bis(tris[hydroxymethyl]-methylamino)propane (bis-TRIS-propane), 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), their salts, 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 buffer in the packaging solution is preferably 0.001% to 2%, preferably 0.01% to 1%, most preferably about 0.05% to about 0.30% (by weight).

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

[0092] In a preferred embodiment, the 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, thermally crosslinkable hydrophilic polymer material of the present invention.

[0093] The packaging solution of the present invention may contain a thickening polymer. This thickening polymer is preferably nonionic. Increasing the viscosity of the solution creates a film on the lens, which can facilitate the comfortable wearing of the contact lens. This thickening component also acts to reduce the impact on the surface of the eyeball during insertion and reduces 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 over about 2,000 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 with at least one dialkylaminoalkyl (meth)acrylate having 7 to 20 carbon atoms, and combinations thereof. Water-soluble cellulose ethers and copolymers of vinylpyrrolidone with dimethylaminoethyl methacrylate are the most preferred thickening polymers. Copolymers of N-vinylpyrrolidone with dimethylaminoethyl methacrylate are commercially available (e.g., Copolymer 845 and Copolymer 937 from ISP).

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

[0096] The packaging solution may 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 crosslinked coating and packaging solution contains a polymer material having polyethylene glycol segments, the packaging solution preferably contains an α-oxo-polybasic acid or a salt thereof in an amount sufficient to reduce the susceptibility of the polyethylene glycol segments to oxidative degradation. A jointly owned concurrent patent application (U.S. Patent Application Publication 2004 / 0116564 A1, which is incorporated herein by reference in its entirety) discloses that oxo-polybasic acids or salts thereof can reduce the susceptibility of PEG-containing polymer materials to oxidative degradation.

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

[0099] In the present invention, the packaging solution may further contain a mucin-like substance, a substance beneficial to the eyes, and / or a surfactant.

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

[0101] Examples of substances beneficial to the eye include, but are not limited to, 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-linoleic acid, and vitamins (e.g., B5, A, B6, etc.).

[0102] The surfactant may be virtually any ophthalmally acceptable surfactant, encompassing nonionic, anionic, and amphoteric surfactants. Examples of preferred surfactants are, but are not limited to, poloxamers (e.g., Pluronic® F108, F88, F68, F68LF, F127, F87, F77, P85, P75, P104, and P84), poloamines (e.g., Tetronic® 707, 1107, and 1307), polyethylene glycol esters of fatty acids (e.g., Tween® 20, Tween® 80), C 12 -C 18 This includes alkanes such as polyoxyethylene or polyoxypropylene ethers (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 lenses obtained by the method of the present invention are characterized by having an average water contact angle of preferably 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, and thus possess surface hydrophilicity / wetting properties.

[0104] In another preferred embodiment, the method of the present invention may further include the steps of: contacting a silicone hydrogel contact lens with an aqueous solution of a thermocrosslinkable hydrophilic polymer material at room temperature before the heating step to form a thermocrosslinkable hydrophilic polymer top layer (i.e., LbL coating) on ​​the surface of the silicone hydrogel contact lens; immersing the silicone hydrogel contact lens having this thermocrosslinkable hydrophilic polymer top layer in a packaging solution in a lens package; sealing the lens package; and autoclaving the lens package containing the silicone hydrogel contact lens to form a crosslinked hydrophilic coating on the silicone hydrogel contact lens. Because it is positively charged, the thermocrosslinkable hydrophilic polymer material is thought to be able to form a non-covalent LbL coating on the surface of the silicone hydrogel contact lens (i.e., via physical interaction) (especially in contact lenses having negatively charged carboxyl groups on their surface).

[0105] Various embodiments encompassing preferred embodiments of the present invention are described separately, but naturally, these can be used in any desired combination and / or together in the method of the present invention for producing silicone hydrogel contact lenses having a crosslinked hydrophilic coating.

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

[0107] In yet another embodiment, the present invention provides an ophthalmic product comprising a sterile and sealed lens package, wherein the lens package comprises an autoclaved lens packaging solution and a ready-to-use silicone hydrogel contact lens immersed therein, wherein the ready-to-use silicone hydrogel contact lens comprises a crosslinked hydrophilic coating obtained by autoclaving an original silicone hydrogel contact lens having amino groups and / or carboxyl groups on and / or near the surface of the original silicone hydrogel contact lens in a pre-autoclaved packaging solution containing a water-soluble, thermally crosslinkable hydrophilic polymer material, wherein the hydrophilic polymer material comprises (i) a first polymer chain in about 20% to about 95%, preferably about 35% to about 90%, more preferably about 50% to about 85% (by weight) of epichlorohydrin-functionalized polyamines or polyamidoamines, and (ii) at least one antagonist selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof. A hydrophilic moiety or second polymer chain comprising about 5% to about 80%, preferably about 10% to about 65%, and more preferably about 15% to about 50% (by weight) of a hydrophilic moiety or second polymer chain derived from at least one hydrophilicity enhancer having a responsive functional group (wherein this 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 hydrophilicity enhancer), and (ii i) The hydrophilic polymer material comprises a portion of the first polymer chain, or an azetidinium group which is a pendant or terminal group covalently bonded to the first polymer chain, and this 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 thermally crosslinkable hydrophilic polymer material, and the autoclave-treated packaging solution is approximately 6.0 to approximately 8.The autoclaved packaging solution contains at least one buffer in an amount sufficient to maintain a pH of 5, has a tonicity of about 200 to about 450 milliosmoles (mOsm), preferably about 250 to about 350 mOsm, and a viscosity of about 1 cmpoise to about 20 cmpoise at 25°C, preferably about 1.2 cmpoise to about 10 cmpoise, more preferably about 1.5 cmpoise to about 5 cmpoise, and the autoclaved packaging solution contains a polymer wetting material which is a hydrolysis product of a heat-crosslinkable hydrophilic polymer material after autoclaving, and the ready-to-use silicone hydrogel contact lens has surface hydrophilicity / wetting properties 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.

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

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

[0110] The ready-to-use silicone hydrogel contact lenses of the present invention have an oxygen permeability of at least about 40 bars, preferably at least about 50 bars, more preferably at least about 60 bars, and even more preferably about 70 bars; 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; an elastic modulus of about 1.5 MPa or less, preferably about 1.2 MPa or less, more preferably about 1.0 MPa or less, and even more preferably about 0.3 MPa to about 1.0 MPa; and preferably at least about 1.5 × 10⁻¹⁶ -6 mm 2 / min, more preferably at least about 2.6 × 10 -6 mm 2 / min, more preferably at least about 6.4 × 10 -6 mm 2 Ionoflux diffusion coefficient D / min; water content preferably about 18% to about 70%, more preferably about 20% to about 60% (by weight) when fully hydrated; or a combination thereof. It holds.

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

[0112] In a further embodiment, the present invention relates to a water-soluble, thermally crosslinkable hydrophilic polymer material comprising: (a) a first polymer chain comprising about 20% to about 95%, preferably about 35% to about 90%, more preferably about 50% to about 85% (by weight) of a first polymer chain derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; and (b) a hydrophilicity-enhancing polymer agent comprising about 5% to about 80%, preferably about 1% of a first polymer chain derived from at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof. The present invention provides a material comprising (c) a second polymer chain in an amount of 0% to approximately 65%, more preferably approximately 15% to approximately 50% (by weight) (wherein this second polymer chain is covalently bonded to the first polymer chain via one or more covalent bonds formed between one azetidinium group of an epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl, or thiol group of a hydrophilicity-enhancing polymer agent), and (c) a part of the first polymer chain or an azetidinium group that is a pendant group covalently bonded to the first polymer chain.

[0113] Various embodiments encompassing preferred embodiments of reactive vinyl monomers, non-reactive vinyl monomers, epichlorohydrin-functionalized polyamines or polyamidoamines, and hydrophilic polymers as hydrophilicity enhancers are described above, and these can be used in any way in this embodiment of the present invention.

[0114] With the foregoing disclosure, a person with ordinary skill in the art will be able to carry out the present invention. Various modifications, alterations, and combinations can be made to the various embodiments described herein. References to the following examples are proposed so that the reader may better understand the particular embodiments and their advantages. This specification and examples are intended to be considered illustrative.

[0115] Various embodiments of the present invention are described using specific terms, apparatus, and methods, but such descriptions are solely for illustrative purposes. The terms used are more descriptive than restrictive. Naturally, those skilled in the art can make modifications and alterations without departing from the essence or scope of the invention as set forth in the following claims. Furthermore, naturally, the aspects of the various embodiments can be replaced in whole or in part, or used in any way combined and / or together. Thus, the essence and scope of the appended claims are not limited to the description of the preferred views contained herein.

[0116] Example 1 Oxygen permeability measurement The apparent oxygen permeability of the lens and the oxygen transfer coefficient of the lens material are measured by the same method as described in the U.S. paper 5,760,100 and the paper by Winterton et al. (The Cornea: Transactions of the World Congress on the Cornea 111, HD Cavanagh Ed., Raven Press: New York 1988, pp273-280) (both of which are incorporated herein by reference in their entirety). The oxygen flux (J) is measured at 34°C in a wet cell (i.e., the gas flow is maintained at approximately 100% relative humidity) using a Dk1000 instrument (available from Applied Design and Development Co., Norcross, GA) or a similar analytical instrument. An airflow with a known percentage of oxygen (e.g., 21%) is measured for approximately 10–20 cm 3 The nitrogen stream passes through one side of the lens at a speed of 1 / min, while the nitrogen stream flows approximately 10-20cm. 3Pass the sample through the other side of the lens at a rate of / min. Allow the sample to equilibrate in the test medium (i.e., physiological saline or distilled water) at the specified test temperature for at least 30 minutes (but not exceeding 45 minutes) before measurement. Any test medium used as a coating layer should be equilibrated at the specified test temperature for at least 30 minutes (but not exceeding 45 minutes) before measurement. Set the speed of the stirring motor to 1200±50 rpm, corresponding to the display setting of 400±15 on the stepping motor controller. Ambient pressure, P 測定値 The following is measured. The lens thickness (t) in the area exposed for testing is determined by measuring at approximately 10 points using a Mitotoya micrometer VL-50 or a similar device, and then averaging the measurements. The oxygen concentration in the nitrogen stream (i.e., oxygen diffusing through the lens) is measured using a DK1000 device. The apparent oxygen permeability of the lens material, Dk app It can be calculated from the following formula. ru: Dk app =Jt / (P 酸素 ) (In the formula, J = Oxygen flux [microliter O2 / cm³] 2 -min] P 酸素 =(P 測定値 -P 水蒸気 ) = (O2% in airflow) [mmHg] = Partial pressure of oxygen in airflow 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 a wet cell) (mmHg) t = Average thickness of the lens in the exposed test area (mm) Dk app (It is expressed in units of bars.)

[0117] The apparent oxygen transfer coefficient (Dk / t) of a material is the apparent oxygen permeability (Dk app This can be calculated by dividing ) by the average thickness (t) of the lens.

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

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

[0120] The apparent oxygen permeability value (single point) of a control Lotrafilcon A (Focus® N&D®, manufactured by CIBA VISION CORPORATION) or Lotrafilcon B (AirOptix®, manufactured by CIBA VISION CORPORATION) lens is measured 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] The intrinsic Dk value (Dk) of the reference lens is determined by measuring the oxygen flux through a series of Rotrafilcon A or Rotrafilcon B (control) lenses of the same thickness using the same apparatus as described above for apparent Dk measurement. i ) is obtained. The series of thicknesses should cover a thickness range of approximately 100 μm or more. Preferably, the thickness range of the reference lens includes the thickness of the test lens in between. Dk of these reference lenses app The measurement must be performed using the same apparatus as the test lens, and ideally, it should be performed simultaneously with the test lens. The apparatus settings and measurement parameters should remain constant throughout the experiment. Individual samples may be measured multiple times if necessary.

[0122] The residual oxygen resistance value, R, was calculated using formula (1) from the results of the control lens.r We seek.

[0123]

number

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

[0125] The estimated intrinsic Dk of the test lens is the apparent Dk (Dk a_std ) can be used to calculate, based on formula (3), how a lens of standard thickness behaves in the same test environment. The standard thickness (t) of the Rotrafilcon A std ) = 85 μm. Standard thickness of Rotrafilcon 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 incorporated herein by reference in its entirety). The ion permeability values ​​reported in the following examples are relative to the ion flux diffusion coefficient (D / D) of the lens material, Alsacon, as a control material.ref ) is. Alsacon is 0.314 × 10 -3 mm 2 It has an ionoflux diffusion coefficient of / min.

[0127] Lubricity evaluation The lubricity rating method is a qualitative ranking scheme using a scale of 0 to 5, where 0 or a small number indicates good lubricity, with 1 assigned to commercially available Oasys® / TruEye® lenses and 5 assigned to commercially available Air Optix® lenses. Samples are rinsed at least three times with excess DI water and then transferred to PBS before evaluation. Before evaluation, hands are washed with soapy water, rinsed extensively with DI water, and then dried with a KimWipe® towel. Samples are handled between fingers and each sample is assigned a numerical value in comparison to the standard lenses mentioned above. For example, if a lens is judged to be only slightly better than an Air Optix® lens, it is assigned a number of 4. For consistency, all ratings are collected independently by the same two operators to avoid bias, and this data so far demonstrates very good qualitative agreement and consistency in this evaluation.

[0128] Surface hydrophilicity / wetness test The water contact angle of a contact lens is a general measure of the surface hydrophilicity (or wetting properties) of the contact lens. Specifically, a low water contact angle corresponds to a highly hydrophilic surface. The average contact angle of a contact lens (static drop method) is measured using a VCA 2500 XE contact angle measuring instrument manufactured by AST, Inc., located in Boston, Massachusetts. This instrument can measure advancing or receding contact angles or fixed (static) contact angles. The measurement is performed on a fully hydrated contact lens immediately after wiping and drying as follows: The contact lens is removed from the vial and rinsed three times in approximately 200 ml of fresh DI water to remove any loosely bound packaging additives from the lens surface. Next, the lens is placed on a clean, lint-free cloth (Alpha Wipe TX1009), pressed firmly to remove surface water, placed on the contact angle measuring stand, air-dried with a burst of dry air, and finally the static drop contact angle is automatically measured using the software provided by the manufacturer. The DI water used to measure the contact angle had a resistivity of >18 MΩcm, and the droplet volume used was 2 μl. Typically, an uncoated silicone hydrogel lens (after autoclaving) has a stationary droplet contact angle of approximately 120 degrees. The tweezers and measuring stand were thoroughly cleaned with isopropanol and rinsed with DI water before contact with the contact lens.

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

[0130] Coating integrity test The integrity of the coating on the surface of a contact lens can be tested by the Sudan Black staining test as follows: A contact lens with a coating (LbL coating, plasma coating, or any other coating) is immersed in a Sudan Black staining solution (Sudan Black in vitamin E oil). The Sudan Black dye is hydrophobic and has a strong tendency to adsorb onto hydrophobic materials or onto hydrophobic spots on the hydrophobic lens surface or on the partially coated surface of 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 inside the lens. All lenses under test are fully hydrated.

[0131] Coating durability test The lens is rubbed 30 times with a finger using Solo-care® multipurpose lens care solution, and then rinsed with saline solution. The above procedure is repeated a predetermined number of times, for example, 1 to 30 times (i.e., the number of times in a continuous finger-rubbing test that simulates a washing and immersion cycle). The lens is then subjected to a Sudan Black test (i.e., the coating integrity test described above) to check whether the coating is still intact. To withstand the finger-rubbing test, there should be no significant increase in stained spots (e.g., stained spots should not cover more than approximately 5% of the total lens surface). The water contact angle is measured to determine the coating durability.

[0132] Debris adhesion test Contact lenses with high-charge surfaces are more susceptible to increased debris accumulation during patient handling. Rub a paper towel onto a gloved hand, then rub both sides of the lens with your fingers to transfer debris to the lens surface. Lightly rinse the lens, then observe it under a microscope. Rate each lens using a qualitative rating scale from 0 (no debris) to 4 (debris accumulation equivalent to a PAA-coated control lens). Lenses with a score of "0" or "1" are considered acceptable.

[0133] Surface cracking test Excessive crosslinking of the coating layer can cause surface cracks visible under a dark-field microscope after rubbing the lens. Rub the lens inverted and record any crack lines. Rate the lens using a qualitative scoring system from 0 (no cracks) to 2 (severe cracks). Any severe crack lines should be 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 vinyl potassium sulfate (PPVS) as the titrant and toluidine blue as the indicator. See SK Kam and J. Gregory, "Charge determination of synthetic cationic polyelectrolytes by colloid titration," in Colloid & Surface A: Physicochem. Eng. Aspect, 159: 165-179 (1999). PPVS binds to positively charged species, such as toluidine blue and the azetidinium groups of PAE. A decrease in toluidine blue absorbance indicates a proportional decrease in PAE charge density (azetidinium content).

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

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

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

[0139] Example 2 Preparation of CE-PDMS macromers In the first step, α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn=2000, Shin-Etsu, KF-6001a) is capped with IPDI by reacting 49.85 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane with 11.1 g of isophorone diisocyanate (IPDI) and 150 g of anhydrous methyl ethyl ketone (MEK) in the presence of 0.063 g of dibutyltin dilaurate (DBTDL). This reaction is maintained 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 an IPDI-PDMS-IPDI solution to which 0.063 g of DBTDL has been further added. The reactor is maintained at approximately 40°C for 4.5 hours to form HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. Next, the MEK is removed under reduced pressure. In the third step, by adding 7.77 g of isocyanatoethyl methacrylate (IEM) and 0.063 g of DBTDL, the terminal hydroxyl groups are capped with methacryloyloxyethyl groups in the third step to form IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM (CE-PDMS macromer).

[0140] Alternative preparation of CE-PDMS macromers Add 240.43g of KF-6001 to a 1L reactor equipped with a stirrer, thermometer, cryostat, dropping funnel, and nitrogen / reduced pressure inlet adapter, then apply a high vacuum (2 × 10⁻⁶). -2Dry the mixture by applying mBar. Next, add 320g of distilled MEK to the reactor under dry nitrogen at 1 atmosphere and stir the mixture thoroughly. Add 0.235g of DBTDL to the reactor. After warming the reactor to 45°C, add 45.86g of IPDI to the reactor over 10 minutes using a dropping funnel under gentle stirring. Maintain the reaction mixture at 60°C for 2 hours. Next, add 630g of KF-6002 dissolved in 452g of distilled MEK and stir until a homogeneous solution is formed. Add 0.235g of DBTDL and maintain the reactor at approximately 55°C overnight under a blanket of dry nitrogen. The next day, remove the MEK by flash distillation. Cool the reactor, then charge 22.7g of IEM into the reactor, followed by approximately 0.235g of DBTDL. After about 3 hours, add another 3.3g of IEM and allow the reaction to proceed overnight. The following day, the reaction mixture was cooled to approximately 18°C ​​to obtain a CE-PDMS macromer with terminal methacrylate groups.

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

[0142] Lens preparation The lenses are prepared by casting from the lens formulation prepared on a reusable mold similar to the molds shown in Figures 1-6 of U.S. Patent No. 7,384,590 and Figures 1-6 of Patent No. 7,387,759. The mold 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 approximately 4 mW / cm². 2 This is a Hamamatsu lamp equipped with a WG335+TM297 cutoff filter at a specific intensity. The lens formulation in the molding mold is irradiated with UV light for approximately 25 seconds. The cast lens is extracted with isopropanol (or methyl ethyl ketone, MEK), rinsed in water, coated with polyacrylic acid (PAA) by immersing the lens in a propanol solution of PAA (0.1 wt%, acidified to pH approximately 2.5 with formic acid), and hydrated in water. The resulting lens with a reactive PAA-LbL base coating is determined to have the following properties: ion permeability approximately 8.0 to 9.0 times greater than Alsacon lens material; apparent Dk (point) of approximately 90 to 100; water content of approximately 30% to 33%; and elastic modulus of approximately 0.60 MPa to 0.65 MPa.

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

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

[0145] Next, the lenses are evaluated for debris adhesion, surface cracking, lubricity, contact angle, and water breakup time (WBUT). The test lens (packaged / autoclaved in IPC saline, i.e., a lens with PAA-x-PAE coating) shows no debris adhesion, while the control lens (packaged / autoclaved in PBS, i.e., a lens with PAA-LbL base coating) shows severe debris adhesion. The water contact angle (WCA) of the test lens is low (≒20 degrees), but the WBUT is less than 2 seconds. When observed under a dark-field microscope, severe crack lines are visible after lens manipulation (lens inversion and rubbing between fingers). The test lens is judged to be far less lubricated than the control lens by a qualitative finger-rubbing test (lubricity score of 4).

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

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

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

[0149] The test lens (packaged and autoclaved in IPC saline, i.e., a lens with a PAA-x-PAE-x-poly(AAm-co-AA) coating) showed no debris adhesion and had a WBUT of more than 10 seconds. When observed under a dark-field microscope, crack lines were visible after the abrasion test of the test lens. The test lens was much more lubricated than the test lens from Example 4, but still not as lubricated as the control lens packaged in PBS (lubricity rating of 1-2).

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

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

[0152] The test lens (packaged in heat-pretreated IPC saline, i.e., a lens with a PAA-x-hydrophilic polymer coating) showed no debris adhesion after being rubbed against a paper towel, while the control lens (packaged in PBS, i.e., a lens with a non-covalent layer of PAA on top) showed severe debris adhesion. The test lens had a WBUT of more than 10 seconds. Under dark-field microscopy, no crack lines were visible on the test lens after the rubbing test. The test lens exhibited very high lubricity in the finger rubbing test, comparable to the control lens (lubricity score of 0).

[0153] A series of experiments are conducted to test the effect of the conditions (duration and / or temperature) of the heat pretreatment with IPC saline on the surface properties of the resulting lenses coated with IPC saline. Depending on the azetidinium functional group of the PAE and the concentration of the PAE used, a heat treatment time of about 6 hours or more at about 70°C yields lenses with similar susceptibility to debris adhesion as the control lens. A heat treatment of only 4 hours at 50°C yields lenses that show surface crack lines under a dark-field microscope after being rubbed between fingers, similar to the test lens in Example 5 which was not heat pretreated with IPC saline.

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

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

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

[0157] The test lenses (both the Lotrafilcon B lens and the lens from Example 3 with PAA-x hydrophilic polymer coating) showed no debris adhesion. The test lenses had a WBUT of more than 10 seconds. Under dark-field microscopy, no crack lines were visible after the finger-rubbing test of the lens. The lenses exhibited extremely high lubricity in the qualitative finger-rubbing test (lubricity score of 0).

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

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

[0160] The lenses from Example 3 were packaged in heat pre-treated IPC saline, and this blister was then autoclaved at 121°C for 45 minutes. All lenses exhibited excellent lubricity, wettability, and resistance to surface cracking. Some of the lenses showed 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, either in the absence or in the 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 approximately 7.3.

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

[0165] The lenses with the PAA-LbL base coating prepared in Example 3 were packaged in heat-pretreated IPC saline and autoclaved at 121°C for approximately 30 minutes. Table 2 shows that all lenses exhibited excellent surface properties.

[0166] [Table 2]

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

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

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

[0170] Lenses with PAA-x-PAE-x-HA coating Another batch of lenses, each having one layer of PAA and one layer of PAE on top of it, 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. The blister is then sealed and autoclaved at 121°C for approximately 30 minutes to form a cross-linked coating (PAA-x-PAE-x-HA) on the lens.

[0171] Lenses with either the PAA-x-PAE-x-CMC coating or the PAA-x-PAE-x-HA coating exhibit no Sudan Black staining, debris adhesion, or cracking under microscopic examination. Lenses with the PAA-x-PAE-x-CMC coating have an average contact angle of 30 ± 3 degrees, while lenses with the 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 Mw2000 (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 approximately 4 hours to form a thermo-crosslinkable hydrophilic polymer material containing MPEG-SH-2000 groups chemically grafted onto the polymer by reaction with azetidinium groups in the PAE. After heat treatment, this solution is diluted 10-fold with PBS containing 0.25% sodium citrate to adjust the pH to 7.2-7.4, and then filtered using a 0.22 micron polyethersulfone (PES) membrane filter. This final IPC saline solution contains 0.286 wt% hydrophilic polymer material (consisting of approximately 59 wt% MPEG-SH-2000 chains and approximately 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 cross-linked coatings The PAA-coated lenses from Example 11 are packaged in the above-mentioned IPC saline solution within a polypropylene lens packaging shell, and then autoclaved at approximately 121°C for approximately 30 minutes to form a cross-linked coating on the lenses.

[0174] The final lens shows no debris adhesion or crack lines from rubbing. The lens exhibits very high lubricity, comparable to the control PAA-coated lens in finger rubbing tests.

[0175] A series of experiments are conducted to test the effects of various conditions (reaction time and mPEG-SH-2000 solution concentration (at a constant PAE concentration of 2%)) on the surface properties of 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 also increases accordingly. The increase in the surface contact angle is thought to be due to the increased density of terminal methyl groups on the surface as the graft density increases. At high graft densities, corresponding to a solution concentration of 0.6%, the contact angle approaches the measurement 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 conducted to test the effect of the molecular weight of mPEG-SH. IPC saline is prepared in the same manner as described in Example 12, but using one of the following mPEG-SH: mPEG-SH 1000, mPEG-SH 2000, mPEG-SH 5000, and mPEG-SH 20000. All saline solutions are heat-treated at 45°C for 4 hours and then diluted 10-fold. 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 MW2000 (Product# MPEG-SH-2000, Laysan Bio Inc.), and 10% PAE (Kymene) in PBS and 0.25% sodium citrate dihydrate. The pH of this final solution is then adjusted to 7.5, and the container is degassed by bubbling with nitrogen gas for 2 hours to minimize thiol oxidation. This solution is then heat-treated at 45°C for approximately 6 hours to form a thermo-crosslinkable hydrophilic polymer material containing MPEG-SH-2000 groups chemically grafted onto the polymer by reaction with the azetidinium groups in the PAE. After heat treatment, the solution 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 physiological saline contains approximately 0.30% by weight of polymer material (consisting of approximately 17% by weight of MPEG-SH-2000 and approximately 83% by weight of PAE) and 0.25% of sodium citrate dihydrate.

[0181] The PAA-coated lenses from Example 11 are packaged in the above-mentioned IPC saline solution within a polypropylene lens packaging shell, and then autoclaved at approximately 121°C for approximately 30 minutes to form a cross-linked coating on the lenses.

[0182] The final lens showed no debris adhesion or crack lines after rubbing. The test lens exhibited very high lubricity in the finger-rubbing test, comparable to the control PAA-coated lens.

[0183] Example 15 The reaction mixture is prepared by dissolving 3.62% methoxy-poly(ethylene glycol)-amine, average MW550 (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 approximately 4 hours to form a thermo-crosslinkable hydrophilic polymer material containing MPEG-NH2-550 groups chemically grafted onto the polymer by reaction with azetidinium groups in the PAE. After heat treatment, this 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 approximately 0.562% by weight of polymer material (consisting of approximately 64% by weight of MPEG-SH-2000 and approximately 36% by weight of PAE) and 0.25% sodium citrate dihydrate. This PBS is prepared by dissolving 0.74% sodium chloride, 0.053% NaH2PO4·H2O, and 0.353% NaH2PO4·2H2O in water.

[0184] The PAA-coated lenses from Example 11 are packaged in the above-mentioned IPC saline solution within a polypropylene lens packaging shell, and then autoclaved at approximately 121°C for approximately 30 minutes to form a cross-linked coating on the lenses.

[0185] The final lens shows neither debris adhesion nor crack lines from rubbing the lens.

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

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

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

[0189] The test lens showed no debris adhesion after being rubbed against a paper towel. This lens had a WBUT of more than 10 seconds. When observed under a dark-field microscope, no crack lines were visible after rubbing the lens between fingers. This lens is much more lubricated than the lens from Example 4, but still not as lubricated as the control lens packaged in PBS.

[0190] Example 17 A. Synthesis of polysiloxanes 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 dried separately in single-neck flasks under high vacuum at approximately 60°C for 12 hours (or overnight). The OH molar equivalents of KF-6001A and KF-6002A are determined by titration of the hydroxyl groups and used to calculate the millimolar equivalents to be used in the synthesis.

[0191] Remove moisture from a 1-liter reaction vessel by reducing the pressure overnight, then release the vacuum with dry nitrogen. Charge 75.00g (75meq) of dry KF6001A into the reactor, then add 16.68g (150meq) of freshly distilled IPDI. Purge the reactor with nitrogen and heat to 45°C while stirring, then add 0.30g of DBTDL. Seal the reactor and maintain a positive nitrogen flow. Exothermic reaction will occur, after which the reaction mixture will be cooled and stirred (55°C for 2 hours). Once exothermic reaction has occurred, add 248.00g (150meq) of dry KF6002A to the reactor at 55°C, then add 100μL of DBTDL. Stir the reactor for 4 hours. Stop heating and allow the reactor to cool overnight. Stop nitrogen bubbling and open the reactor to the atmosphere for 30 minutes while gently stirring. A polysiloxane, HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH (or HO-CE-PDMS-OH), is formed by extending a hydroxyl terminal chain having three polysiloxane segments.

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

[0193] B. Synthesis of non-UV absorbing amphoteric branched polysiloxane prepolymers A 1 L jacketed reactor is fitted with a 500 mL dropping funnel, overhead stirrer, reflux condenser with nitrogen / reduced pressure adapter, thermometer, and sampling adapter. 45.6 g of the 80% IEM cap CE-PDMS prepared above is charged into the reactor and sealed. A solution of 0.65 g of hydroxyethyl methacrylate (HEMA), 25.80 g of DMA, and 27.80 g of tris(trimethylsilyl)-siloxypropyl methacrylic acid (TRIS) in 279 g of ethyl acetate is charged into the dropping funnel. The reactor is degassed at <1 mbar for 30 minutes using a high vacuum pump. The monomer solution is degassed for 3 cycles of 10 minutes each at 100 mbar and RT, with the vacuum being released with nitrogen during the degassing cycle. This monomer solution is then charged into the reactor, and the reaction mixture is stirred and heated to 67°C. While heating, a solution of 1.50 g of mercaptoethanol (chain transfer agent, CTA) dissolved in 39 g of ethyl acetate and 0.26 g of azoisobutyronitrile is added to a dropper funnel and deoxygenated three times for 10 minutes at 100 mbar and RT. 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 allowed to return to room temperature within 15 minutes.

[0194] The resulting reaction mixture is then drawn up into a dry, single-necked flask with an airtight lid, and 4.452 g of IEM is added along with 0.21 g of DBTDL. This mixture is stirred at room temperature for 24 hours to form a non-UV absorbing amphoteric branched polysiloxane prepolymer. To this mixed solution, 100 ml of hydroxytetramethylenepiperonyloxy solution (2 g / 20 mL) in ethyl acetate is added. Add μL. Next, this solution is heated to 200g at 30°C using a rotary evaporator. It is concentrated to approximately 50% and filtered through filter paper with a pore size of 1 μm. After solvent exchange, this solution is further concentrated to the desired concentration.

[0195] C. Synthesis of UV-absorbing amphoteric branched polysiloxane prepolymers A 1L jacketed reactor, a 500mL dropping funnel, an overhead stirrer, and nitrogen / Reflux condenser with vacuum introduction adapter, thermometer, and sampling adapter attached. Next, add the 80% IEM cap CE-PDMS 45 prepared above to this reactor. Add 98g and seal the reactor. HEMA 0.512 in 263g of ethyl acetate. g, DMA 25.354g, Norbloc methacrylate 1.38g, TRIS 26.0 Place 34g of the solution into a dropping funnel. Maintain the reactor under high vacuum pump at <1mbar for 30 minutes. Degass at T. The monomer solution is released from the vacuum with nitrogen during the degassing cycle. The monomer solution is then degassed for 3 cycles of 10 minutes at 00 mbar and RT. Next, this monomer solution is placed in the reactor. Next, stir the reaction mixture and heat it to 67°C. While heating, add ethyl acetate 38 1.480g of mercaptoethanol (chain transfer agent, CTA) and azoisobub dissolved in g Place 0.260 g of tyronitrile solution into a dropper funnel and inflate to 100 mbar at room temperature for 10 minutes. Deoxygenate the mixture twice. When the reactor temperature reaches 67°C, add the initiator / CTA solution to the reactor. Add to the DMS / monomer solution. Allow the reaction to proceed for 8 hours, then stop heating and wait 15 minutes. The reactor temperature is brought to room temperature.

[0196] The resulting reaction mixture is then drawn up into a dry, single-necked flask with an airtight lid, and acrylic acid Add 3.841 g of isocyanatoethyl along with 0.15 g of DBTDL. Mix this mixture Stir at room temperature for approximately 24 hours to form a UV-absorbing amphoteric branched polysiloxane prepolymer. To this mixed solution, add hydroxytetramethylenepiperonyloxy solution in ethyl acetate ( Add 100 μL of (2 g / 20 mL). Next, use a rotary evaporator to evaporate this solution. It is concentrated to 200g (approximately 50%) at 30°C and filtered through filter paper with a pore size of 1μm.

[0197] D-1: Lens formulation containing 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, then transfer 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 the formulation at room temperature. Obtain 6 g of a clear lens formulation D-1.

[0198] D-2: Lens formulation containing 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, then transfer to the macromer solution. Remove 20 g of solvent at 30°C using a rotary evaporator, followed by the addition of 20 g of 1-propanol. After two cycles, concentrate the mixture to 14.40 g. Add 0.6 g of DMA to the mixture, and homogenize the formulation at room temperature. Obtain 15 g of clarified lens formulation D-2.

[0199] D-3: Lens formulation containing UV-absorbing polysiloxane prepolymer (2% DMA / 2% HEA) 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, then transfer to the macromer solution. Remove 20 g of solvent at 30°C using a rotary evaporator, then add 20 g of 1-propanol. After two cycles, concentrate the mixture to 14.40 g. Add 0.3 g of DMA and 0.3 g of HEA to the mixture, and homogenize the formulation at room temperature. Obtain 15 g of a clear lens formulation D-3.

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

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

[0202] Reactive packaging saline was prepared by dissolving the components listed in Table 5 in DI water along with appropriate buffer salts. After heat pretreatment, the saline was 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 adding APMAA-HCl monomer (stock solution of APMMA-HCl in methanol). The DSM lens is tested using a 330 nm filter at 16 mW / cm². 2 While the LS lens is cured using a 380nm filter at 4.6mW / cm² 2 Then harden it.

[0205] DSM lens Approximately 75 microliters of the lens compound prepared as described above are filled into the female mold of the polypropylene lens molding mold, and the mold is closed with the male mold (base curve type) of the polypropylene lens molding mold. The contact lens is then exposed to UV light (Hamamatsu lamp with a 330nm cutoff filter) for approximately 5 minutes at approximately 16 mW / cm². 2 It is obtained by hardening to a certain strength.

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

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

[0208] The molded lenses are extracted in methyl ethyl ketone, hydrated, and packaged in one of the saline solutions listed in Table 5. The lenses are placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the 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 was observed in any of the test lenses. When observed under a dark-field microscope, no crack lines were visible after the friction test of the lens held between fingers.

[0210] Lens surface wettability (WBUT), lubricity, and contact angle were measured, and the results are summarized in Table 6. Unless otherwise specified, lenses were manufactured using the DSM method. Lubricity was scored on a qualitative scale from 0 to 4, with lower numbers indicating higher lubricity. Generally, lens surface properties improved slightly after the application of in-package coatings.

[0211] [Table 6]

[0212] Example 19 The lens is manufactured using lens formulation D-2 (Example 17), to which APMAA monomer is added to a concentration of 1%. The LS lens is prepared from the lens formulation prepared as described above by casting using a reusable mold similar to the molds shown in Figures 1-6 of U.S. Patent No. 7,384,590 and Figures 1-6 of Patent No. 7,387,759. This mold includes a half-female mold made of glass and a half-male mold made of quartz. The UV irradiation source is approximately 4.6 mW / cm². 2 This is a Hamamatsu lamp with a 380nm cutoff filter at a certain intensity. The lens compound in the molding mold is irradiated with UV rays for approximately 30 seconds.

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

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

[0215] In the evaluation of the lens surface, no debris adhesion was observed in any of the test lenses. When observed under a dark-field microscope, no crack lines were visible after the friction test of the lens held between fingers. The wettability (WBUT) of the lens surface exceeded 10 seconds, the lubricity was rated as "1", and the contact angle was approximately 20°.

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

[0217] Lens preparation The lenses are prepared from the lens compound prepared above by casting using reusable molds (half quartz female mold and half glass male mold) similar to those shown in Figures 1-6 of U.S. Patent No. 7,384,590 and Figures 1-6 of Patent No. 7,387,759. The lens compound in the mold is exposed to UV light (13.0 mW / cm²) for approximately 24 seconds. 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 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 (each about 44, 56, 56, 56, 56, and 56 seconds); 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 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 consumed) to form a water-soluble and thermally 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, 10 ppm of hydrogen peroxide was added to the final IPC saline to prevent bioburden growth, 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 base 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 SiHy lenses The resulting SiHy contact lens, equipped with a cross-linked coating (PAA-x-hydrophilic polymer material), shows no debris adhesion after being rubbed on a paper towel, whereas the control lens (packaged in PBS, i.e., a lens with a non-covalent layer of PAA on top) shows severe debris adhesion. The lens has an oxygen permeability of approximately 146 bars (Dk). c It has an estimated intrinsic Dk, a bulk modulus of approximately 0.76 MPa, a water content of approximately 32% by weight, a relative ion permeability of approximately 6 (compared to Alsacon lenses), a contact angle of approximately 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 exhibits very high lubricity in the finger-rubbing test, comparable to the control lens.

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

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

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

[0226] Genotoxicity testing When tested using the Bacterial Reverse Mutation Assay (Ames Test) on IPC saline and SiHy lens extracts from lens packages, they were found to be non-mutagenic against Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, as well as Escherichia coli WPuvrA. When SiHy lens extracts were tested using the Mammalian Erythrocyte Micronucleus Assay, they showed no chromosomal aberration induction and were negative in the mouse bone marrow micronucleus test. When tested using the Chromosome Aberration Test in Chinese Hamster Ovary, IPC saline from lens packages was negative in both inactivation and S9 activation assays using CHO cells for structural and numerical chromosomal aberration induction. When the SiHy lens extract was tested using the Cell Gene Mutation Test (Mouse Lymphoma Mutagenesis Assay), it showed a negative result 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 the application of the PAA base coating), PAA-coated SiHy contact lenses (i.e., these lenses before sealing and autoclaving in a lens package containing IPC saline), and SiHy contact lenses with cross-linked coatings (all of which are prepared according to 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 lenses with a sampling depth of approximately 10 nm. The surface compositions of the three types of lenses are reported in Table 7.

[0228] [Table 7]

[0229] Table 7 shows that when a PAA coating is applied to a SiHy lens (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 becomes predominantly carbon, nitrogen, and oxygen, which are triatomic compositions (hydrogen is excluded because XPS does not count hydrogen in the surface composition). These results suggest that the outermost layer of a cross-linked SiHy contact lens is likely to consist essentially of a hydrophilic polymer material which is a reaction product of poly(AAm-co-AA)(90 / 10)(60% C, 22% O, and 18% N) and PAE.

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

[0231] [Table 8]

[0232] The SiHy contact lens of the present invention has a nominal silicon content of approximately 1.4% in its surface layer, which is far lower than that of commercially available SiHy lenses without plasma coating (Acuvue® Advance®, Acuvue® Oasys®, TruEye®, Biofinity®, Avaira®), as well as PureVision® (plasma oxidation) and Premio® (unknown plasma treatment). Furthermore, it is even lower than that of SiHy lenses with a plasma deposition coating of approximately 25 nm thickness (N&D® Aqua® and Air Optix® Aqua®). This extremely low Si% value is comparable to that of Goodfellow polyethylene (LDPE, d=0.015 mm; LS356526) used as a control sample. The proportion of silicon atoms is comparable to that of 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 likely be due to contaminants introduced during the preparation process, including the vacuum drying process and XPS analysis, similar to 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 according to the procedure described in Example 20), commercially available SiHy contact lenses (CLARITI® 1 Day, ACUVUE® TruEye® (narafilcon A and narafilcon B)), and a polyethylene sheet manufactured by Goodfellow (LDPE, d=0.015mm; LS356526). XPS analysis will also be performed on SDS;ET31111512;3004622910), DAILIES® (polyvinyl alcohol hydrogel lens, i.e., non-silicone hydrogel lens), and ACUVUE® Moist (polyhydroxyethyl methacrylate hydrogel lens, i.e., non-silicone hydrogel lens). All lenses will be vacuum dried. Polyethylene sheets, DAILIES®, and ACUVUE® Moist will be used as controls as they do not contain silicone. 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 according to 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 the results of conventional hydrogels and closer to silicone hydrogels.

[0234] Example 23 Synthesis of UV-absorbing amphoteric branched copolymers Attach a 500 mL dropping funnel, an overhead stirring device, 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. Prepare a monomer solution 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, charge it 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, prepare 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, charge it 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 of 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 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: 71% by weight of a prepolymer prepared on top of; 4% by weight of DMA; 1% by weight of TPO; 1% by weight of DMPC; 1% by weight of Brij 52 (from); and 22% by weight of 1-PrOH.

[0237] Lens preparation The lenses are manufactured by casting the lens formulation prepared above under spatially restricted UV irradiation using a reusable mold similar to the molds shown in Figures 1-6 of U.S. Patent No. 7,384,590 and Figures 1-6 of Patent No. 7,387,759. This mold includes a half-female mold made of glass and a half-male mold made of quartz. The UV irradiation source is approximately 4.6 mW / cm². 2 This is a Hamamatsu lamp with a 380nm cutoff filter at a certain intensity. The lens compound in the molding mold is irradiated with UV rays for approximately 30 seconds.

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

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

[0240] Lens characteristic evaluation The resulting lens has the following characteristics: E' ≈ 0.82 MPa; Dk c ≈159.4 (average center thickness of 80 μm and intrinsic Dk 110, using Rotrafilcon B as the reference lens); IP ≈ 2.3; water % ≈ 26.9; and UVA / UVB %T ≈ 4.6 / 0.1. Under dark-field microscopy, no crack lines were visible after rubbing the test lens. The lens exhibited very high lubricity in the finger-rub test, comparable to the reference lens.

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

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

[0243] Lens preparation The lenses are prepared from the lens formulation prepared above by casting using reusable molds (half quartz female mold and half glass male mold) similar to those shown in Figures 1-6 of U.S. Patent No. 7,384,590 and Figures 1-6 of Patent No. 7,387,759. The UV irradiation source is approximately 4 mW / cm². 2 This is a Hamamatsu lamp with a WG335+TM297 cutoff filter at this intensity. The lens mixture in the molding mold is irradiated with UV light for approximately 25 seconds. The cast lens is extracted with methyl ethyl ketone (MEK) (or propanol or isopropanol).

[0244] Application of PAA primer coating to SiHy contact lenses The polyacrylic acid coating solution (PAA-1) is prepared by dissolving a certain amount of PAA (MW: 450 kDa, manufactured by Lubrizol) in a predetermined volume of 1-propanol to have a concentration of approximately 0.39% by weight, and then adjusting the pH to approximately 2.0 with formic acid.

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

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

[0247] [Table 9]

[0248] [Table 10]

[0249] Application of crosslinked hydrophilic coatings Poly(acrylamide-co-acrylic acid) partial sodium salt, poly(AAm-co-AA)(90 / 10) (≒90% solids content, poly(AAm-co-AA)(90 / 10), Mw 200,000) is purchased from Polysciences, Inc. and used as is. PAE (Kymene, azetidinium content of 0.46 as evaluated by NMR) is purchased as an aqueous solution from Ashland and used as is. In-package crosslinking (IPC) saline is prepared by dissolving approximately 0.07 wt% poly(AAm-co-AA)(90 / 10) and approximately 0.15% PAE (millimolecular 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 saline is 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, heat-crosslinkable hydrophilic polymer material containing azetidinium groups within a branched polymer network in the IPC saline. After heat pretreatment, the IPC saline is filtered using a 0.22 micron polyethersulfone [PES] membrane filter and cooled back to room temperature. Next, to prevent bioburden growth, 10 ppm hydrogen peroxide is added to the final IPC saline, and the IPC saline is filtered using a 0.22 micron polyethersulfone [PES] membrane filter.

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

[0251] Characterization of SiHy lenses The resulting SiHy contact lens, which has a cross-linked hydrophilic coating and a central thickness of approximately 0.95 microns, has an oxygen permeability of approximately 142 to 150 bars (Dk). c It has an estimated intrinsic Dk, a bulk modulus of approximately 0.72 to 0.79 MPa, a water content of approximately 30% to 33% by weight, a relative ion permeability of approximately 6 (compared to Alsacon lenses), and a contact angle of approximately 34 to 47 degrees.

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

[0253] Reflection-Differential-Interference-Contrast (RDIC) Method: The lens is placed on a glass slide and flattened by making four radial cuts approximately every 90 degrees. Excess saline solution is blown off the surface using compressed air. The lens surface is then examined for the presence of wrinkled surface patterns on the contact lens surface using a Nikon Optiphot-2 with a reflection-differential-interference optics unit, with 10×, 20×, and 50× objective lenses. Representative images of each side are obtained using a 50× objective lens. The contact lens is then flipped over, the excess saline solution is removed, and the other side of the contact lens is examined in the same manner. The resulting RDIC images are then evaluated to determine the presence of wrinkled surface patterns (e.g., random and / or ordered worm-like patterns).

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

[0255] DFLM is used to evaluate the haziness of contact lenses as follows. Because the darkfield setting involves scattered light, darkfield 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 ranging from 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 results in 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 darkfield image. Haziness is expressed by averaging the GSI values ​​of all pixels in the area of ​​interest (AOI) (e.g., the entire lens, or the lens-like or optical part of the lens). The experimental setup consists of a microscope or equivalent optical apparatus, an accompanying digital camera, and a darkfield stand with an annular light and a variable intensity light source. The optical apparatus is designed / positioned so that the entire contact lens to be observed fills the field of view (typically ≈ 15 mm × 20 mm). Illumination is set to an appropriate level for observing the desired changes in the sample. 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, one standard consists of two overlapping plastic coverslips (identical and slightly or moderately matte). Such a standard consists of three regions with different average GSIs, encompassing two regions: an intermediate grayscale level and saturated white (edge). The black region represents the dark field of view of the sky. The black and saturated white regions can be used to verify the camera's gain and offset (contrast and brightness) settings. The intermediate gray level can provide three points for verifying the camera's linear response. Light intensity is adjusted so that the average GSI of the dark field of view of the sky approaches 0, and that of the specified AOI in a standard digital image is the same each time within ±5 GSI units. After light intensity calibration, the contact lenses are immersed in phosphate-buffered saline filtered through a 0.2 μm filtration meter in a quartz petri dish or a similar clear dish placed on a DFLM stand.Next, an 8-bit grayscale digital image of the lens is obtained using calibrated illumination, and the average GSI of the specified AOI within a portion of the image containing the lens is determined. This is repeated for the contact lenses in the sample set. Light intensity calibration is periodically re-evaluated throughout the test to ensure consistency. The level of turbidity under DFLM testing is defined as DFLM turbidity = (GSI / 255) × 100%.

[0256] SiHy contact lenses (whose PAA prime coating is obtained by either the 20-0 or 80-0 immersion process) have been determined to have an average DFLM turbidity of approximately 73% and exhibit a wrinkled surface pattern (a random worm-like pattern) that can be visually observed by examining the hydrated contact lenses by either the RDIC or TDIC method described above. However, this wrinkled surface pattern does not have any detrimental effect on the light transmittance of the contact lenses.

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

[0258] A high percentage of SiHy contact lenses (whose PAA prime coating is obtained by immersion process 20-5) are determined to have a moderate average DFLM turbidity of approximately 45%, and exhibit a slightly noticeable wrinkled surface pattern when examined under either RDIC or TDIC as described above. However, this wrinkled surface pattern does not have any detrimental effect on the light transmittance of the contact lenses.

[0259] SiHy contact lenses (whose PAA primer coating is obtained by any of the immersion processes 80-1, 80-2, 80-3, 80-5, and 80-6) do not exhibit a noticeable wrinkled surface pattern when inspected under either the RDIC or TDIC described above. However, SiHy contact lenses (whose PAA primer coating is obtained by any of the immersion processes 80-0 and 80-4) exhibit a noticeable wrinkled surface pattern when inspected under either the RDIC or TDIC described above. However, this wrinkled surface pattern does not have a detrimental effect on the light transmittance of the contact lenses.

Claims

1. A method for manufacturing a silicone hydrogel contact lens having a crosslinked hydrophilic coating thereon, (a) A step to obtain a silicone hydrogel contact lens having amino groups and / or carboxyl groups on and / or near the surface of the contact lens, and a water-soluble, heat-crosslinkable hydrophilic polymer material [wherein the silicone hydrogel contact lens contains amino groups or carboxyl groups or both on and / or near the surface of the contact lens, and the hydrophilic polymer material is (i) a first polymer chain of 20% to 95%, preferably 35% to 90%, more preferably 50% to 85% (by weight) derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, and (ii) selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof. (iii) comprising a hydrophilic moiety or second polymer chain in an amount of 5% to 80%, preferably 10% to 65%, more preferably 15% to 50% (by weight) of a hydrophilic moiety or second polymer chain derived from at least one hydrophilicity enhancer having at least one reactive functional group, and a positively charged azetidinium group which is part of the first polymer chain or a pendant or terminal group covalently bonded to the first polymer chain, 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 hydrophilicity enhancer; and (b) A manufacturing method comprising the steps of: heating the silicone hydrogel contact lens in an aqueous solution in the presence of a hydrophilic polymer material at a temperature of 40°C to 140°C and at this temperature for a time sufficient to covalently bond the hydrophilic polymer material to the surface of the silicone hydrogel contact lens via a second covalent bond formed between one azetidinium group of the hydrophilic polymer material and one reactive functional group on and / or near the surface of the contact lens, thereby forming a crosslinked hydrophilic coating on the silicone hydrogel contact lens [wherein the silicone hydrogel contact lens having this crosslinked hydrophilic coating is characterized by having an average water contact angle of preferably 90 degrees or less, more preferably 80 degrees or less, even more preferably 70 degrees or less, and most preferably 60 degrees or less, and having surface wetting properties].

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

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

4. The method according to claim 1 or 2, wherein the hydrophilic polymer as a hydrophilicity enhancer is a copolymer which is a polymerization product of a composition comprising (1) 60% by weight or less, preferably 0.1% to 30%, more preferably 0.5% to 20%, and even more preferably 1% to 15% (by weight) of at least one reactive vinyl monomer and (2) at least one non-reactive hydrophilic vinyl monomer and / or at least one phosphorylcholine-containing vinyl monomer; or a combination thereof [where, The reactive vinyl monomer is amino-C (meth)acrylate １ -C ６ alkyl, C (meth)acrylate 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,N-2-acrylamidoglycolic acid, β-methyl-acrylic acid, α-phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof, preferably selected from the group consisting of (meth)acrylic acid, C ２ -C １２ alkylacrylic acid, vinylamine, allylamine, amino-C (meth)acrylate ２ -C ４ alkyl, amino-C ２ -C ４ alkyl (meth)acrylamide, and combinations thereof; Non-reactive hydrophilic vinyl monomers include acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminopropyl methacrylamide, N,N-dimethylaminopropyl acrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, N-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 - Selected from the group consisting of alkoxy polyethylene glycol (meth)acrylate, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymers), and combinations thereof, preferably acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, and C having a weight-average molecular weight of 400 daltons or less. １ -C ４ - Selected from the group consisting of alkoxy polyethylene glycol (meth)acrylate, vinyl alcohol, and combinations thereof.

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

6. The method according to claim 1 or 2, wherein the hydrophilic polymer used as a hydrophilicity enhancer is an amino- or carboxyl-containing polysaccharide, hyaluronic acid, chondroitin sulfate, or a combination thereof.

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

8. The method according to claim 1 or 2, wherein the hydrophilicity enhancer is an amino-, carboxyl-, or thiol-containing monosaccharide; an amino-, carboxyl-, or thiol-containing disaccharide; and an amino-, carboxyl-, or thiol-containing oligosaccharide.

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

10. The method according to claim 9, wherein the packaging solution contains 0.01% to 2%, preferably 0.05% to 1.5%, more preferably 0.1% to 1%, and even more preferably 0.2% to 0.5% (by weight) of a thermocrosslinkable hydrophilic polymer material.

11. The method according to claim 9, further comprising: contacting a silicone hydrogel contact lens with an aqueous solution of a thermocrosslinkable hydrophilic polymer material at room temperature prior to the heating step to form a thermocrosslinkable hydrophilic polymer material top layer on the surface of the silicone hydrogel contact lens; immersing the silicone hydrogel contact lens having this thermocrosslinkable hydrophilic polymer material top layer in a packaging solution within a lens package; and sealing the lens package.

12. The silicone hydrogel contact lens contains 0.1% to 10%, more preferably 0.25% to 7%, even more preferably 0.5% to 5%, and most preferably 0.75% to 3% (by weight) of reactive vinyl monomer [(meth)acrylate amino-C ２ -C ６ Alkyl, (meth)acrylate C １ -C ６ Alkylamino-C ２ -C ６ Alkylamine, allylamine, vinylamine, amino-C ２ -C ６ Alkyl (meth)acrylamide, C １ -C ６ Alkylamino-C ２ -C ６ Alkyl (meth)acrylamide, acrylic acid, C １ -C １２ The reactive vinyl monomer is selected from the group consisting of alkylacrylic acid, N,N-2-acrylamidoglycolic acid, β-methylacrylic acid, α-phenylacrylic acid, β-acrylooxypropionic 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, and preferably the reactive vinyl monomer is (meth)acrylic acid amino-C ２ -C ６ Alkyl, (meth)acrylate C １ -C ６ Alkylamino-C ２ -C ６ Alkyl, vinylamine, allylamine, amino-C ２ -C ６ Alkyl (meth)acrylamide, C １ -C ６ Alkylamino-C ２ -C ６ Alkyl (meth)acrylamide, acrylic acid, C １ -C １２ The method according to any one of claims 1 to 11, which is produced by polymerizing a silicone hydrogel lens formulation containing alkylacrylic acid and a combination thereof selected from the group consisting of these.

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

14. The method according to claim 13, wherein the reactive base coating comprises a reactive polymer having at least one layer of pendant amino groups and / or carboxyl groups, and is obtained by contacting a silicone hydrogel contact lens with a solution of the reactive polymer [wherein the reactive polymer is amino-C １ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid amino-C １ ~C ４ Alkyl, C １ ~C ４ Alkylamino-C １ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid C １ ~C ４ Alkylamino-C １ ~C ４ Alkylamine, allylamine, or vinylamine homopolymers; polyethyleneimines; polyvinyl alcohols with pendant amino groups; linear or branched polyacrylic acids; C １ ~C １２ Alkyl acrylic acid homopolymer; amino-C ２ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid amino-C ２ ~C ４ Alkyl, C １ ~C ４ Alkylamino-C ２ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid C １ ~C ４ Alkylamino-C ２ ~C ４ Alkyl, acrylic acid, C １ ~C １２ Alkyl acrylic acid, maleic acid, and / or fumaric acid, and at least one non-reactive hydrophilic vinyl monomer (preferably acrylamide, N,N-dimethyl(meth)acrylamide, N-vinylpyrrolidone, glycerol methacrylate, N,N-2-acrylamidoglycolic acid, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone) C10, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, (meth)acryloyloxyethyl phosphorylcholine, C10 having a weight-average molecular weight of 1500 daltons or less. １ -C ４ - Copolymers selected from the group consisting of alkoxy polyethylene glycol (meth)acrylate, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymers), and combinations thereof; carboxyl-containing cellulose; hyaluronate; chondroitin sulfate; poly(glutamic acid); poly(aspartic acid); or combinations thereof.

15. The reactive polymer for forming the base coating is polyacrylic acid, polymethacrylic acid, poly(C ２ -C １２ -alkylacrylic acid), poly[acrylic acid-co-methacrylic acid], poly[C ２ -C １２ -alkylacrylic acid-co-(meth)acrylic acid], poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone], poly[C ２ -C １２ -alkylacrylic acid-co-acrylamide], poly[C ２ -C １２ -alkylacrylic acid-co-vinylpyrrolidone], hydrolyzed poly[(meth)acrylic acid-co-vinyl acetate], hydrolyzed poly[C ２ -C １２ -alkylacrylic acid-co-vinyl acetate], polyethyleneimine (PEI), polyallylamine hydrochloride (PAH) homo- or copolymers, polyvinylamine homo- or copolymers, or combinations thereof, the method according to claim 13.

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

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

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

19. An ophthalmic lens product comprising a sterile and sealed lens package, wherein, The lens package contains a lens packaging solution after autoclaving and ready-to-use silicone hydrogel contact lenses immersed therein. A ready-to-use silicone hydrogel contact lens includes a crosslinked hydrophilic coating obtained by autoclaving the original silicone hydrogel contact lens, which has amino groups and / or carboxyl groups on and / or near the surface of the original silicone hydrogel contact lens, in a pre-autoclave packaging solution containing a water-soluble, thermally crosslinkable hydrophilic polymer material. The thermally crosslinkable hydrophilic polymer material comprises (i) 20% to 95%, preferably 35% to 90%, more preferably 50% to 85% (by weight) of a first polymer chain derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; (ii) 5% to 80%, preferably 10% to 65%, more preferably 15% to 50% (by weight) of a hydrophilic moiety or second polymer chain derived from at least one hydrophilicity enhancer having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof; 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. The thermally crosslinkable 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 original silicone hydrogel contact lens and one azetidinium group of the thermally crosslinkable hydrophilic polymer material, and This autoclaved packaging solution contains at least one buffer in an amount sufficient to maintain a pH of 6.0 to 8.5, has a tonicity of 200 to 450 milliosmoles (mOsm), preferably 250 to 350 mOsm, and a viscosity of 1 cmpoise to 20 cmpoise, preferably 1.2 cmpoise to 10 cmpoise, and more preferably 1.5 cmpoise to 5 cmpoise. The post-autoclave packaging solution contains a polymer wetting material which is a hydrolysis product of a thermally crosslinkable hydrophilic polymer material after autoclave treatment. A ready-to-use silicone hydrogel contact lens is a product characterized by having an average water contact angle of 90 degrees or less, preferably 80 degrees or less, more preferably 70 degrees or less, and even more preferably 60 degrees or less, and possessing surface hydrophilicity / wetting properties.

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

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

22. The hydrophilic polymer as a hydrophilicity enhancer is a copolymer which is a polymerization product of a composition comprising (1) 60% by weight or less, preferably 0.1% to 30%, more preferably 0.5% to 20%, and even more preferably 1% to 15% (by weight) of at least one reactive vinyl monomer and (2) at least one non-reactive hydrophilic vinyl monomer and / or at least one phosphorylcholine-containing vinyl monomer; or a combination thereof, for the ophthalmic lens product according to claim 19 or 20 [where, The reactive vinyl monomer is amino-C (meth)acrylate １ -C ６ alkyl, C (meth)acrylate 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,N-2-acrylamidoglycolic acid, β-methyl-acrylic acid, α-phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof, preferably selected from the group consisting of (meth)acrylic acid, C ２ -C １２ alkylacrylic acid, vinylamine, allylamine, amino-C (meth)acrylate ２ -C ４ alkyl, amino-C ２ -C ４ alkyl (meth)acrylamide, and combinations thereof; Non-reactive hydrophilic vinyl monomers include acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminopropyl methacrylamide, N,N-dimethylaminopropyl acrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, N-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 - Selected from the group consisting of alkoxy polyethylene glycol (meth)acrylate, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymers), and combinations thereof, preferably acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, and C having a weight-average molecular weight of 400 daltons or less. １ -C ４ - Alkoxy polyethylene glycol (meth)acrylate, vinyl alcohol, [Selected from the group consisting of combinations thereof.]

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

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

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

26. Weight-average molecular weight M of hydrophilic polymers used as hydrophilicity enhancers Ｗ The ophthalmic lens product according to any one of claims 20 to 24, wherein the amount is 500 to 1,000,000, preferably 1,000 to 500,000.

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

28. The original silicone hydrogel contact lens contains 0.1% to 10%, more preferably 0.25% to 7%, even more preferably 0.5% to 5%, and most preferably 0.75% to 3% (by weight) of reactive vinyl monomer [(meth)acrylate amino-C １ -C ６ Alkyl, (meth)acrylate C １ -C ６ Alkylamino-C １ -C ６ Alkylamine, 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 An ophthalmic lens product according to any one of claims 19 to 27, produced by polymerizing a silicone hydrogel lens formulation containing [selected from the group consisting of alkylacrylic acid, N,N-2-acrylamidoglycolic acid, β-methylacrylic acid, α-phenylacrylic acid, β-acrylooxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof].

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

30. The ophthalmic lens product according to claim 29, wherein the reactive base coating comprises a reactive polymer having at least one layer of pendant amino groups and / or carboxyl groups, and the reactive base coating is obtained by contacting a silicone hydrogel contact lens with a solution of the reactive polymer [wherein the reactive polymer is amino-C １ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid amino-C １ ~C ４ Alkyl, C １ ~C ４ Alkylamino-C １ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid C １ ~C ４ Alkylamino-C １ ~C ４ Alkylamine, allylamine, or vinylamine homopolymers; polyethyleneimines; polyvinyl alcohols with pendant amino groups; linear or branched polyacrylic acids; C １ ~C １２ Alkyl acrylic acid homopolymer; amino-C １ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid amino-C １ ~C ４ Alkyl, C １ ~C ４ Alkylamino-C １ ~C ４ Alkyl (meth)acrylamide, (meth)acrylic acid C １ ~C ４ Alkylamino-C １ ~C ４ Alkyl, acrylic acid, C １ ~C １２ Alkyl acrylic acid, maleic acid, and / or fumaric acid, and at least one hydrophilic vinyl monomer (preferably acrylamide, N,N-dimethyl(meth)acrylamide, N-vinylpyrrolidone, glycerol methacrylate, N,N-2-acrylamidoglycolic acid, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone) Roridone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, phosphorylcholine-containing vinyl monomer, C having a weight-average molecular weight of 1500 daltons or less. １ -C ４ - Copolymers selected from the group consisting of alkoxy polyethylene glycol (meth)acrylate, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymers), and combinations thereof; carboxyl-containing cellulose; hyaluronate; chondroitin sulfate; poly(glutamic acid); poly(aspartic acid); or combinations thereof.

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

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

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

34. A water-soluble, thermally crosslinkable hydrophilic polymer material, (a) A first polymer chain comprising 20% ​​to 95%, preferably 35% to 90%, more preferably 50% to 85% (by weight) of an epichlorohydrin-functionalized polyamine or polyamidoamine; (b) A second polymer chain in an amount of 5% to 80%, preferably 10% to 65%, more preferably 15% to 50% (by weight) of a hydrophilicity 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 (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 hydrophilicity enhancer); and (c) A material comprising an azetidinium group which is a pendant group covalently bonded to a first polymer chain or to the first polymer chain.

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

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

37. The hydrophilic polymer material according to claim 34 or 35, wherein the hydrophilic polymer as a hydrophilicity enhancer is a copolymer which is a polymerization product of a composition comprising (1) 60% by weight or less, preferably 0.1% to 30%, more preferably 0.5% to 20%, and even more preferably 1% to 15% (by weight) of at least one reactive vinyl monomer and (2) at least one non-reactive hydrophilic vinyl monomer and / or at least one phosphorylcholine-containing vinyl monomer; or a combination thereof [where, This reactive vinyl monomer is (meth)acrylate amino-C １ -C ６ Alkyl, (meth)acrylate C １ -C ６ Alkylamino-C １ -C ６ Alkylamine, 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 Selected from the group consisting of alkylacrylic acid, N,N-2-acrylamidoglycolic acid, β-methylacrylic acid, α-phenylacrylic acid, β-acrylooxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof, preferably (meth)acrylic acid, C ２ -C １２ Alkyl acrylic acid, vinylamine, allylamine, (meth)acrylic acid amino-C ２ -C ４ Alkyl, amino-C ２ -C ４ Selected from the group consisting of alkyl(meth)acrylamides and combinations thereof; These non-reactive hydrophilic vinyl monomers include acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminopropyl methacrylamide, N,N-dimethylaminopropyl acrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, and N-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 - Selected from the group consisting of alkoxy polyethylene glycol (meth)acrylate, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymers), and combinations thereof, preferably acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, and C having a weight-average molecular weight of 400 daltons or less. １ -C ４ - Selected from the group consisting of alkoxy polyethylene glycol (meth)acrylate, vinyl alcohol, and combinations thereof.

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

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