HK1207689B - A silicone hydrogel lens with a crosslinked hydrophilic coating - Google Patents

Description

Silicone hydrogel lens with cross-linked hydrophilic coating

This application is a divisional application of the patent application with application number 201180037428.8, application date July 29, 2011, and invention name “Silicone hydrogel lens with cross-linked hydrophilic coating”.

Technical Field

The present invention generally relates to a cost-effective and time-efficient method of applying a cross-linked hydrophilic coating to a silicone hydrogel contact lens to improve its hydrophilicity and lubricity. Additionally, the present invention provides an ophthalmic lens product.

Background Art

Soft silicone hydrogel contact lenses are becoming increasingly popular due to their high oxygen permeability and comfort. However, silicone hydrogel materials are generally hydrophobic (non-wettable) and readily adsorb lipids or proteins from the ocular environment, which can adhere to the surface of the eye or at least some area of its surface. Therefore, silicone hydrogel contact lenses generally require surface modification.

A known approach to improving the hydrophilicity of relatively hydrophobic contact lens materials is through the use of plasma treatment, an approach used, for example, in the production process of commercial lenses such as Focus NIGHT & DAY ^™ and O2OPTIX ^™ (CIBA VISION) and PUREVISION ^™ (Bausch & Lomb). The advantages of a plasma coating, such as that found in Focus NIGHT & DAY ^™ , are its durability, relatively high hydrophilicity/wettability, and low susceptibility to lipid and protein deposition and adsorption. However, plasma treatment of silicone hydrogel contact lenses can be cost-ineffective because the contact lenses typically must be dried prior to plasma treatment and because of the relatively high capital investment associated with plasma treatment equipment.

Another approach to improving the surface hydrophilicity of silicone hydrogel contact lenses is to incorporate a wetting agent (hydrophilic polymer) into the lens formulation used to prepare silicone hydrogel contact lenses, as described in U.S. Patent Nos. 6,367,929, 6,822,016, 7,052,131, and 7,249,848. This approach may obviate the need for additional, subsequent methods of improving the surface hydrophilicity of the lens after cast molding of the silicone hydrogel contact lens. However, the wetting agent may be incompatible with the silicone component of the lens formulation, and this incompatibility may impart haziness to the resulting lens. In addition, such surface treatments may be susceptible to lipid deposition and adsorption. Furthermore, such surface treatments may not provide a durable surface for extended wear.

Another approach to improving the hydrophilicity of relatively hydrophobic contact lens materials is layer-by-layer (LbL) polyionic material deposition technology (see, for example, U.S. Patent Nos. 6,451,871, 6,717,929, 6,793,973, 6,884,457, 6,896,926, 6,926,965, 6,940,580, and 7,297,725, and U.S. Patent Application Publication Nos. US2007/0229758A1, 2008/0174035A1, and 2008/0152800A1). Although LbL deposition technology can provide a cost-effective method for rendering silicone hydrogel lenses wettable, LbL coatings may not be as durable as plasma coatings and may have a relatively high surface charge density; this can interfere with contact lens cleaning and disinfecting solutions. To improve durability, crosslinking of LbL coatings on contact lenses has been proposed in co-pending U.S. Patent Application Publication Nos. 2008/0226922A1 and 2009/0186229A1 (the entire contents of which are incorporated herein by reference). However, the crosslinked LbL coating may have inferior hydrophilicity and/or wettability to the original LbL coating (before crosslinking) and still have a relatively high surface charge density.

Yet another approach to improving the hydrophilicity of relatively hydrophobic contact lens materials is to attach hydrophilic polymers to the contact lens according to various mechanisms (see, e.g., U.S. Patent 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, 6,73 , 6,835,410, 6,878,399, 6,923,978, 6,440,571, and 6,500,481, U.S. Patent Application Publication Nos. 2009/0145086 Al, 2009/0145091 Al, 2008/0142038 Al, and 2007/0122540 Al, the entire disclosures of all of which are incorporated herein by reference). While these techniques can be used to impart wettability to silicone hydrogel lenses, they may not be cost-effective and/or time-efficient for execution in a mass production environment because they generally require a relatively long time and/or involve laborious multiple steps to obtain a hydrophilic coating.

Therefore, there remains a need for methods of producing silicone hydrogel contact lenses having wettable and durable coatings (surfaces) in a cost-effective and time-efficient manner.

Summary of the Invention

In one aspect, the present invention provides a method for producing a silicone hydrogel contact lens, each having a crosslinked hydrophilic coating thereon, the method comprising the steps of: (a) obtaining a silicone hydrogel contact lens and a water-soluble and thermally crosslinkable hydrophilic polymer material, wherein the contact lens comprises amino and/or carboxyl groups on and/or near the surface of the contact lens, wherein the hydrophilic polymer material comprises: (i) from about 20 to about 95 weight percent of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, (ii) from about 5 to about 80 weight percent of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino, carboxyl, thiol, and combinations thereof, wherein the hydrophilic moieties or second polymer chains are each crosslinked by a hydrophilic coating on the surface of the contact lens. The invention further comprises the steps of: (i) covalently attaching to a first polymer chain one or more covalent bonds formed between an azetidine group of the alcohol-functionalized polyamine or polyamidoamine and an amino, carboxyl, or thiol group of the hydrophilicity-enhancing agent, and (ii) an azetidine group that is part of the first polymer chain or covalently attached to a pendant or terminal group of the first polymer chain; and (b) heating the contact lens in an aqueous solution in the presence of the hydrophilic polymeric material to a temperature of about 40 to about 140° C. and maintaining the temperature of about 40 to about 140° C. for a time sufficient to covalently attach the hydrophilic polymeric material to the surface of the contact lens through second covalent bonds each formed between an azetidine group of the hydrophilic polymeric material and an amino and/or carboxyl group on and/or near the surface of the contact lens, thereby forming a cross-linked hydrophilic coating on the contact lens.

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

In another aspect, the present invention provides an ophthalmic product comprising a sterilized and sealed lens package, wherein the lens package comprises: a post-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 cross-linked hydrophilic coating obtained by autoclaving an initial silicone hydrogel contact lens having amino and/or carboxyl groups on and/or near the surface of the initial silicone hydrogel contact lens in a pre-autoclaved packaging solution containing a water-soluble and thermally cross-linkable hydrophilic polymeric material, wherein the hydrophilic polymeric material comprises (i) from about 20 to about 95 weight percent of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, (ii) from about 5 to about 80 weight percent of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino, carboxyl, thiol, and combinations thereof The invention also provides a method for preparing a hydrophilic polymeric lens comprising: (i) a first polymer chain comprising: (i) an azetidinium group on the epichlorohydrin-functionalized polyamine or polyamidoamine and (ii) an azetidinium group on the epichlorohydrin-functionalized polyamine or polyamidoamine and (iii) an azetidinium group that is part of the first polymer chain or is pendant or terminally attached to the first polymer chain, wherein the hydrophilic polymeric material is covalently attached to the silicone hydrogel contact lens through a second covalent bond that is formed between an amino or carboxyl group on and/or near the surface of the silicone hydrogel contact lens and an azetidinium group of the hydrophilic polymeric material, wherein the post-autoclave packaging solution comprises at least one buffering agent in an amount sufficient to maintain a pH of about 6.0 to about 8.5, and a hydrolyzate of the hydrophilic polymeric material and has a tonicity of about 200 to about 450 milliosmoles (mOsm) and a viscosity of about 1 to about 20 centipoise.

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

These and other aspects of the present invention are apparent from the following description of the presently preferred embodiments. The detailed description is intended only to illustrate the present invention and is not intended to limit the scope of the invention as defined by the appended claims and their equivalents. As will be appreciated by those skilled in the art, many variations and modifications of the present invention may be made without departing from the spirit and scope of the novel concepts of this disclosure.

DETAILED DESCRIPTION

Reference will now be made in detail to embodiments of the present invention. Those skilled in the art will appreciate that various modifications, variations, and combinations of the present invention may be made without departing from the scope or spirit of the present invention. For example, features described or illustrated as part of one embodiment may be used in another embodiment to yield yet another embodiment. Therefore, the present invention is intended to encompass such modifications, variations, and combinations within the scope of the appended claims and their equivalents. Other objects, features, and aspects of the present invention are disclosed in or will be learned from the following detailed description. Those skilled in the art will appreciate that this discussion is merely a description of typical embodiments and is not intended to limit the broader scope of the present invention.

Unless otherwise specified, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which the present invention belongs. Generally, the nomenclature used herein and laboratory procedures are well known and commonly used in the art. Conventional methods are used for these procedures, such as those provided in this area and in various general references. If a term is provided in the singular, the inventors also contemplate the plural form of the term. Nomenclature used herein and laboratory procedures described below are those well known and commonly used in the art.

A "silicone hydrogel contact lens" refers to a contact lens comprising a silicone hydrogel material. "Silicone hydrogel" refers to a silicone-containing polymer material that can absorb at least 10% by weight of water when fully hydrated and is obtained by copolymerizing a polymerizable composition comprising at least one silicone-containing vinyl monomer or at least one silicone-containing vinyl macromer or at least one silicone-containing prepolymer having ethylenically unsaturated groups.

As used herein, "vinyl monomer" refers to a compound having one unique ethylenically unsaturated group and which can be polymerized actinically or thermally.

The term "ethylenically unsaturated group" or "ethylenically unsaturated group" is used herein in a broad sense and is intended to include any group containing at least one >C=C< group. Typical ethylenically unsaturated groups include, but are not limited to, (meth)acryloyl (i.e., and/or), allyl, vinylstyrene, or other C=C-containing groups.

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

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

As used herein, "hydrophilic vinyl monomer" refers to a vinyl monomer that as a homopolymer generally yields a polymer that is water-soluble or can absorb at least 10% by weight of water when fully hydrated.

As used herein, "hydrophobic vinyl monomer" refers to a vinyl monomer that as a homopolymer generally yields a polymer that is insoluble in water and can absorb less than 10% by weight of water.

"Macromer" or "prepolymer" refers to medium and high molecular weight compounds or polymers containing two or more ethylenically unsaturated groups. Medium and high molecular weight generally means an average molecular weight greater than 700 Daltons.

"Crosslinking agent" refers to a compound having at least two ethylenically unsaturated groups. "Crosslinking agent" refers to a crosslinking agent having a molecular weight of about 700 Daltons or less.

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

Unless specifically noted otherwise or unless testing conditions indicate otherwise, as used herein, "molecular weight" of a polymeric material (including monomeric or macromeric materials) refers to the weight average molecular weight.

Unless specifically stated otherwise, the term "amino" refers to a primary or secondary amino group of the formula -NHR', wherein R' is hydrogen or a _C1 - _C20 unsubstituted or substituted linear or branched alkyl group.

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

"Azetidyl group" refers to a positively charged group.

The term "thermally cross-linkable" with respect to a polymeric material or functional group means that the polymeric material or functional group can undergo a cross-linking (or coupling) reaction with another material or functional group at a higher temperature (e.g., about 40 to about 140°C), while the polymeric material or functional group cannot undergo the same cross-linking reaction (or coupling reaction) with another material or functional group to a detectable extent at room temperature (i.e., about 22 to about 28°C, preferably about 24 to about 26°C, and especially at about 25°C) for a period of about 1 hour.

The term "phosphocholine" refers to a zwitterionic group, wherein n is an integer from 1 to 5, and R ₁ , R ₂ and R ₃ are independently C ₁ -C ₈ alkyl or C ₁ -C ₈ hydroxyalkyl.

The term "reactive vinyl monomer" refers to a vinyl monomer having a carboxyl group or an amino group (ie, a primary or secondary amino group).

The term "non-reactive hydrophilic vinyl monomer" refers to a hydrophilic vinyl monomer that does not contain any carboxyl or amino groups (ie, primary or secondary amino groups). The non-reactive vinyl monomer may contain tertiary or quaternary amino groups.

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

"Water contact angle" refers to the average water contact angle (ie, the contact angle measured by the sessile drop method) obtained by averaging the contact angles of at least three individual contact lenses.

The term "integrity" in reference to a coating on a silicone hydrogel contact lens is intended to describe the extent to which a contact lens can be stained by Sudan Black in the Sudan Black staining test described in Example 1. Good integrity of a coating on a silicone hydrogel contact lens means that the contact lens is virtually free of Sudan Black staining.

The term "durability" in reference to a coating on a silicone hydrogel contact lens is intended to describe that the coating on the silicone hydrogel contact lens withstands the finger rub test.

As used herein, reference to a coating on a contact lens "withstanding the finger rub test" or "withstanding the durability test" means that after the lens is finger rubbed according to the procedure described in Example 1, the water contact angle on the finger rubbed lens is still about 100 degrees or less, preferably about 90 degrees or less, more preferably about 80 degrees or less, and most preferably about 70 degrees or less.

The intrinsic "oxygen permeability," Dk, of a material is the rate at which oxygen passes through the material. According to the present invention, the term "oxygen permeability (Dk)" in reference to a hydrogel (silicone or non-silicone) or contact lens means the oxygen permeability (Dk) corrected for the surface resistance to oxygen flux due to boundary layer effects according to the procedure set forth in the Examples below. Oxygen permeability is conventionally expressed in Barrer units, where "barrer" is defined as [( ^cm3 oxygen)(mm)/( ^cm2 )(sec)(mm Hg)]× ^10-10 .

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 t (in mm) over a measured area. Oxygen transmission rate is conventionally expressed in units of barrer/mm, where "barrer/mm" is defined as [( ^cm3 oxygen)/( ^cm2 )(sec)(mm Hg)]× ^10-9 .

The "ion permeability" of a lens is related to the ion flux diffusion coefficient. The ion flux diffusion coefficient D (in [mm ² /min]) is determined by applying Fick's law as follows:

D = -n'/(A × dc/dx)

Where n' = ion transport rate [mol/min]; A = exposed lens area [ ^mm2 ]; dc = concentration difference [mol/L]; dx = lens thickness [mm].

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

The term "ophthalmically safe" with respect to packaging solutions for disinfecting and storing contact lenses means that contact lenses stored in the solution are safe for direct placement on the eye without rinsing after autoclaving and that the solution is safe and sufficiently comfortable for daily contact with the eye via contact lenses. The ophthalmically safe packaging solution after autoclaving has a tonicity and pH compatible with the eye and is substantially free of eye irritants or eye cytotoxic materials according to international ISO standards and U.S. FDA regulations.

The present invention generally relates to a cost-effective and time-efficient method for preparing silicone hydrogel contact lenses having a durable hydrophilic coating by using a water-soluble and thermally cross-linkable hydrophilic polymeric material having azetidine groups.

The present invention is based, in part, on the surprising discovery that a water-soluble, thermally cross-linkable, hydrophilic, azetidine-containing polymeric material, which is the partial reaction product of a polyamine-epichlorohydrin or polyamidoamine-epichlorohydrin and at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from amino, carboxyl, thiol, and combinations thereof, can be used to form a cross-linked coating having good surface hydrophilicity and/or wettability, good hydrophilicity, and good integrity on silicone hydrogel contact lenses having carboxylic acid and/or amino groups on or near the surface. At relatively elevated temperatures (defined above), the positively charged azetidine groups react with functional groups such as amino, thiol, and carboxylate ions –COO ⁻ (i.e., the deprotonated form of the carboxyl group) to form neutral, hydroxyl-containing covalent bonds, as depicted in Scheme 1:

wherein R is the remainder of the compound, and L is -NR'-, wherein R' is hydrogen, a _C1 - _C20 unsubstituted or substituted linear or branched alkyl group, or a polymer chain -S-, or -OC(=O)-. Polyamine-epichlorohydrin or polyamidoamine-epichlorohydrin (PAE) is widely used as a wet-strengthening agent due to the thermally controllable reactivity of the azetidine group. However, PAE has not been successfully used to form crosslinked coatings on contact lenses, likely because crosslinked PAE coatings may not impart the desired hydrophilicity, wettability, and lubricity to contact lenses. It has surprisingly been discovered that PAE can be chemically modified with a hydrophilicity-enhancing agent (particularly a hydrophilic polymer) having one or more functional groups each reactive with an azetidine group in a "heat pretreatment" or "pretreatment" process to yield a water-soluble azetidine-containing polymer material. This polymeric material is still thermally cross-linkable (reactive) due to the presence of azetidine groups and can be used to form a cross-linked coating on a silicone hydrogel contact lens having reactive functional groups (e.g., amino groups, carboxyl groups, thiol groups, or combinations thereof) on and/or near the surface. Furthermore, it has been surprisingly discovered that the resulting cross-linked coating on the contact lens derived from the water-soluble azetidine-containing polymeric material has improved surface hydrophilicity, wettability, and/or lubricity relative to a control coating obtained by using unmodified (virgin or virgin) PAE alone or by using a mixture of PAE and a hydrophilicity-enhancing agent that has not been thermally pretreated for use in preparing the water-soluble azetidine-containing polymeric material.

It is believed that the hydrophilicity-enhancing agent plays at least two roles in improving the properties of the resulting cross-linked coating: adding hydrophilic polymer chains to the polyamine or polyamidoamine polymer chains to form a highly branched hydrophilic polymer material with dangling polymer chains and/or segments; and reducing the cross-link density of the cross-linked coating by significantly reducing the number of azetidine groups in the cross-linkable polymer material (coating). It is believed that the coating with a loose structure and dangling polymer chains and/or segments imparts good surface hydrophilicity, wettability, and/or lubricity.

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

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

By using the method of the present invention, the coating process can be combined with the sterilization step (autoclaving) in the production of silicone hydrogel contact lenses. The resulting contact lenses can not only have high surface hydrophilicity/wettability, no or minimal surface changes, good integrity and good durability, but also can be used by patients directly from the lens packaging without washing and/or rinsing due to the ophthalmic compatibility of the packaging solution.

In one aspect, the present invention provides a method for producing silicone hydrogel contact lenses each having a crosslinked hydrophilic coating thereon, the method comprising the steps of: (a) obtaining a silicone hydrogel contact lens and a water-soluble and thermally crosslinkable hydrophilic polymer material, wherein the contact lens comprises amino and/or carboxyl groups on and/or near the surface of the contact lens, wherein the hydrophilic polymer material comprises: (i) from about 20 to about 95 weight percent of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, (ii) from about 5 to about 80 weight percent of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino, carboxyl, thiol, and combinations thereof, wherein the hydrophilic moieties or second polymer chains are each crosslinked by a hydrophilic coating on the surface of the contact lens. The invention further comprises the steps of: (i) forming a cross-linked hydrophilic coating on the contact lens by heating the contact lens in an aqueous solution in the presence of a hydrophilic polymeric material to a temperature of about 40 to about 140° C. and maintaining the contact lens at a temperature of about 40 to about 140° C. for a sufficient time to covalently attach the hydrophilic polymeric material to the surface of the contact lens through second covalent bonds each formed between an azetidine group of the hydrophilic polymeric material and an amino and/or carboxyl group on and/or near the surface of the contact lens, thereby forming a cross-linked hydrophilic coating on the contact lens.

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

According to the present invention, silicone hydrogel contact lenses may inherently contain or be modified to contain amino and/or carboxyl groups on and/or near their surface.

If the silicone hydrogel contact lens inherently contains amino and/or carboxyl groups on and/or near its surface, it is obtained by polymerizing a silicone hydrogel lens formulation containing a reactive vinyl monomer.

Examples of preferred reactive vinyl monomers include, but are not limited to, amino-C ₂ -C ₆ alkyl(meth)acrylates, C ₁ -C ₆ alkylamino-C ₂ -C ₆ alkyl(meth)acrylates, 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 alkylacrylic acid (e.g., methacrylic acid, ethylacrylic acid, propylacrylic acid, butylacrylic acid, etc.), N,N-2-acrylamidoglycolic acid, β-methyl-acrylic acid (crotonic acid), α-phenylacrylic acid, β-acryloyloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof. Preferably, the silicone hydrogel contact lens is prepared from a lens formulation comprising at least one reactive vinyl monomer selected from the group consisting of amino- _C2 - _C6 alkyl (meth)acrylates, _C1 - _C6 alkylamino- _C2 - _C6 alkyl (meth)acrylates, allylamines, vinylamines, amino- _C2 - _C6 alkyl (meth)acrylamides, _C1 - _C6 alkylamino- _C2 - _C6 alkyl (meth)acrylamides, acrylic acid, _C1 - _C12 alkyl acrylic acid, N,N-2-acrylamidoglycolic acid, and combinations thereof. The lens formulation preferably comprises from about 0.1 to about 10%, more preferably from about 0.25 to about 7%, even more preferably from about 0.5 to about 5%, and most preferably from about 0.75 to about 3% by weight of the reactive vinyl monomer.

Silicone hydrogel contact lenses can also be subjected to surface treatment to form a reactive primer coating having amino and/or carboxyl groups on the surface of the contact lens. Examples of surface treatments include, but are not limited to, surface treatment by energy (e.g., plasma, electrostatic charge, radiation, or other energy sources), chemical treatment, chemical vapor deposition, grafting of hydrophilic vinyl monomers or macromers onto the surface of the article, layer-by-layer coating ("LbL coating") according to the methods described in U.S. Patent Nos. 6,451,871, 6,719,929, 6,793,973, 6,811,805, and 6,896,926, and U.S. Patent Application Publication Nos. 2007/0229758A1, 2008/0152800A1, and 2008/0226922A1, the entire contents of which are incorporated herein by reference. As used herein, "LbL coating" refers to a coating that is not co-constructively attached to the polymer matrix of a contact lens and is deposited layer-by-layer ("LbL") of charged or chargeable (by protonation or deprotonation) and/or uncharged materials onto the lens. An LbL coating may consist of one or more layers.

Preferably, the surface treatment is an LbL coating method. In this preferred embodiment (i.e., a reactive LbL primer embodiment), the resulting silicone hydrogel contact lens comprises a reactive LbL primer coating comprising at least one layer of a reactive polymer (i.e., a polymer having pendant amino and/or carboxyl groups), wherein the reactive LbL primer coating is obtained by contacting the contact lens with a reactive polymer solution. The contact lens can be contacted with the reactive polymer coating solution by immersing it in the coating solution or by spraying it with the coating solution. One contacting method involves simply immersing the contact lens in a coating solution bath for a period of time, or alternatively, sequentially immersing the contact lens in a series of coating solution baths for a fixed, short period of time for each bath. Another contacting method involves simply spraying the coating solution. However, numerous alternatives involve various combinations of spraying and immersing steps that can be designed by one skilled in the art. The contact lens can be contacted with the reactive polymer coating solution for a period of up to about 10 minutes, preferably from about 5 to about 360 seconds, more preferably from about 5 to about 250 seconds, and even more preferably from about 5 to about 200 seconds.

According to the reactive LbL primer embodiment, the reactive polymer can 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 to form a primer on a silicone hydrogel contact lens. Examples of such reactive polymers include, but are not limited to: homopolymers of reactive vinyl monomers; copolymers of two or more reactive vinyl monomers; copolymers of reactive vinyl monomers and one or more non-reactive hydrophilic vinyl monomers (i.e., hydrophilic vinyl monomers that do not contain any carboxyl groups or (primary or secondary) amino groups); polyethyleneimine (PEI); polyvinyl alcohol having pendant amino groups; carboxyl-containing cellulose (e.g., carboxymethyl cellulose, carboxyethyl cellulose, carboxypropyl cellulose); hyaluronate; chondroitin sulfate; poly(glutamic acid); poly(aspartic acid); and combinations thereof.

Examples of preferred reactive vinyl monomers are those described above, with carboxylic acid-containing vinyl monomers being the most preferred reactive vinyl monomers to prepare the reactive polymer for forming the reactive LbL primer layer.

Preferred examples of non-reactive hydrophilic vinyl monomers containing no carboxyl or amino groups include, but are not limited to, acrylamide (AAm), methacrylamide, N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA), N-vinylpyrrolidone (NVP), N,N,-dimethylaminoethyl methacrylate (DMAEM), N,N-dimethylaminoethyl acrylate (DMAEA), N,N-dimethylaminopropyl methacrylamide (DMAPMAm), N,N-dimethylaminopropyl acrylamide (DMAPAAm), methyl Glyceryl acrylate, 3-acrylamido-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-1-6-hydroxybenzoate having a weight average molecular weight of up to 1500 Daltons ₁ - _C4 alkoxy polyethylene glycol (meth)acrylates, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (the hydrolyzed form of vinyl acetate in the copolymer), phosphorylcholine-containing vinyl monomers (including (meth)acryloyloxyethylphosphocholine and those described in U.S. Patent No. 5,461,433, the entire contents of which are incorporated herein by reference), and combinations thereof.

Preferred reactive polymers for forming the reactive LbL primer layer are polyacrylic acid, polymethacrylic acid, poly(C ₂ -C ₁₂ alkyl acrylic acid), poly[acrylic acid-co-methacrylic acid], poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone], poly[C ₂ -C ₁₂ alkyl acrylic acid-co-acrylamide], poly[C ₂ -C ₁₂ alkyl acrylic acid-co-vinylpyrrolidone], hydrolyzed poly[(meth)acrylic acid-co-vinyl acetate], hydrolyzed poly[C ₂ -C ₁₂ alkyl acrylic acid-co-vinyl acetate], polyethyleneimine (PEI), polyallylamine hydrochloride (PAH) homopolymer or copolymer, polyethyleneamine homopolymer or copolymer, or a combination thereof.

The reactive polymer used to form the reactive LbL primer layer has a weight average molecular weight, Mw, of at least about 10,000 Daltons, preferably at least about 50,000 Daltons, and more preferably from about 100,000 to about 5,000,000 Daltons.

The reactive polymer solution used to form the reactive LbL primer coating on the 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. It is believed that a solvent system containing at least one organic solvent can cause the silicone hydrogel contact lens to swell, allowing a portion of the reactive polymer to penetrate into the silicone hydrogel contact lens and improve the durability of the reactive primer coating.

Any organic solvent can be used for preparing the reactive polymer solution. The example of preferred organic solvent includes but is not limited to tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, ketone (such as acetone, methyl ethyl ketone etc.), diethylene glycol n-butyl ether, diethylene glycol methyl ether, ethylene glycol phenyl ether, propylene glycol methyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether acetate, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, propylene glycol n-butyl ether, dipropylene glycol n-butyl ether, tripropylene glycol n-butyl ether, propylene glycol phenyl ether, dipropylene glycol dimethyl ether, polyethylene glycol, polypropylene glycol, ethyl acetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate Esters, isopropyl lactate, dichloromethane, methanol, ethanol, 1- or 2-propanol, 1- or 2-butanol, tert-butanol, tert-amyl alcohol, menthol, cyclohexanol, cyclopentanol and norborneol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol, 2 2-Methyl-2-heptanol, 2-methyl-2-octanol, 2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol Pentanol, 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-methylpyrrolidone and mixtures thereof.

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

In another preferred embodiment (reactive plasma primer), a silicone hydrogel contact lens is subjected to a plasma treatment to form a covalently attached reactive plasma primer on the contact lens, i.e., one or more reactive vinyl monomers (any of those described above) are polymerized under the action of a plasma generated by an electrical discharge (so-called plasma-induced polymerization). The term "plasma" refers to an ionized gas, such as that generated by a glow discharge, which may be composed of electrons, ions of any polarity, gas atoms and molecules in any excited form, in the ground state or in any higher order states, and protons. It is often referred to as "low-temperature plasma." For plasma polymerization and its uses, reference is made to R. Hartmann "Plasma polymerisation": Grundlagen, Technika and Anwendung, Jahrb. (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. T. Mort and F. Jansen, CRC Press Boca Raton (19); O. Auciello et al. (eds.) "Plasma-Surface Interactions and Processing of Materials", Kluwer Academic Publishers, Inc., NATO ASI Series Publications; Series E: Applied Sciences, Vol. 176 (1990), pp. 377-399; and N. Dilsiz and G. Akovali, "Plasma Polymerization of Selected Organic Compounds," Polymer, Vol. 37 (1996), pp. 333-341. Preferably, the plasma-induced polymerization is "afterglow" plasma-induced polymerization as described in WO98028026 (the entire contents of which are incorporated herein by reference). For "afterglow" plasma-induced polymerization, the surface of the contact lens is first treated with a non-polymerizable plasma (e.g., H ₂ , He, or Ar), and then, in a subsequent step, the thus activated surface is exposed to a vinyl monomer having an amino or carboxyl group (any of the reactive vinyl monomers described above) while the plasma power is turned off. This activation results in the plasma-induced formation of radicals on the surface, which, in a subsequent step, initiate polymerization of the vinyl monomer thereon.

According to the present invention, the water-soluble and thermally cross-linkable hydrophilic polymeric material containing azetidine groups comprises (i.e., has a composition 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 about 5 to about 80%, preferably about 10 to about 65%, even more preferably about 15 to about 50% by weight of a hydrophilic moiety or second polymer chain derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from an amino group, a carboxyl group, a thiol group, and combinations thereof. The composition of the hydrophilic polymeric material is determined by the composition of the reactant mixture (based on the total weight of the reactants) used to prepare the thermally cross-linkable hydrophilic polymeric material according to the cross-linking reaction shown in Scheme 1 above. For example, if the reactant mixture comprises about 75 weight percent of an epichlorohydrin-functionalized polyamine or polyamidoamine and about 25 weight percent of at least one hydrophilicity-enhancing agent, based on the total weight of the reactants, the resulting hydrophilic polymeric material comprises about 75 weight percent of first polymer chains derived from the epichlorohydrin-functionalized polyamine or polyamidoamine and about 25 weight percent of hydrophilic moieties or second polymer chains derived from the at least one hydrophilicity-enhancing agent. The azetidine groups of the thermally cross-linkable hydrophilic polymeric material are those azetidine groups (of the epichlorohydrin-functionalized polyamine or polyamidoamine) that do not participate in the cross-linking reaction to prepare the thermally cross-linkable hydrophilic polymeric material.

Epichlorohydrin functionalized polyamines or polyamidoamines can be obtained by reacting epichlorohydrin with a polyamine polymer or a polymer containing primary or secondary amino groups. For example, poly(alkylene imines) or poly(amidoamines) derived from polyamine and dicarboxylic acid condensation polymers (e.g., adipic acid-diethylenetriamine copolymers) can react 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 react with epichlorohydrin to form epichlorohydrin functionalized polyamines. The reaction conditions for the epichlorohydrin functionalization of polyamines or polyamidoamine polymers are described in EP1465931 (incorporated herein in its entirety by reference). Preferred epichlorohydrin functionalized polymers are polyaminoamide-epichlorohydrin (PAE) (or polyamide-polyamine-epichlorohydrin or polyamide-epichlorohydrin), such as the GLUTAMIDE® or GLUTAMIDE® resins (epichlorohydrin functionalized adipic acid-diethylenetriamine copolymer) from Hercules or the GLUTAMIDE® or GLUTAMIDE® resins from Servo/Delden.

Any suitable hydrophilicity-enhancing agents may be used in the present invention, provided they contain at least one amino group, at least one carboxyl group, and/or at least one thiol group.

A preferred class of hydrophilicity enhancers includes, but is not limited to, amino-, carboxyl-, or thiol-containing monosaccharides (e.g., 3-amino-1,2-propanediol, 1-thioglycerol, 5-keto-D-gluconic acid, galactosamine, glucosamine, galacturonic acid, gluconic acid, glucosamine, mannosamine, saccharic acid 1,4-lactone, sugar acid, ketodeoxynonulosonicacid, N-methyl-D-glucosamine, 1-amino-1-deoxy-β-D- galactose, 1-amino-1-deoxysorbitol, 1-methylamino-1-deoxysorbitol, N-aminoethylglucamide); 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.

Another preferred class of hydrophilicity-enhancing agents is a hydrophilic polymer having one or more amino, carboxyl, and/or thiol groups. More preferably, the content of monomeric units having amino (-NHR', wherein R' is as defined above), carboxyl (-COOH), and/or thiol (-SH) groups in the hydrophilic polymer as a hydrophilicity-enhancing agent 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.

A class of preferred hydrophilic polymers as hydrophilicity-enhancing agents are amino- or carboxyl-containing polysaccharides, such as carboxymethyl cellulose (having a carboxyl content of about 40% or less, estimated based on the composition of the repeating unit ─[C ₆ H _10-m O ₅ (CH ₂ CO ₂ H) _m ]─, wherein m is 1-3), carboxyethyl cellulose (having a carboxyl content of about 36% or less, estimated based on the composition of the repeating unit ─[C ₆ H _10-m O ₅ (C ₂ H ₄ CO ₂ H) _m ]─, wherein m is 1-3), carboxypropyl cellulose (having a carboxyl content of about 32% or less, estimated based on the composition of the repeating unit ─[C ₆ H _10-m O ₅ (C ₃ H ₆ CO ₂ H) _m ]─, wherein m is 1-3), hyaluronic acid (having a carboxyl content of about 11%, estimated based on the composition of the repeating unit ─(C ₁₃ H ₂₀ O ₉ NCO ₂ H)─), chondroitin sulfate (having a carboxyl content of about 9.8%, which is estimated based on the composition of the repeating unit ─(C ₁₂ H ₁₈ O ₁₃ NS CO ₂ H)─), or a combination thereof.

Another class of preferred hydrophilic polymers as hydrophilicity-enhancing agents includes, but is not limited to, poly(ethylene glycol) (PEG) having a sole amino, carboxyl, or thiol group (e.g., PEG-NH ₂ , PEG-SH, PEG-COOH); H ₂ N-PEG-NH ₂ ; HOOC-PEG-COOH; HS-PEG-SH; H ₂ N-PEG-COOH; HOOC-PEG-SH; H ₂ N-PEG-SH; multi-arm PEG having one or more amino, carboxyl or thiol groups; PEG dendrimers having one or more amino, carboxyl or thiol groups; diamino- or dicarboxyl-terminated homopolymers or copolymers of non-reactive hydrophilic vinyl monomers; monoamino- or monocarboxyl-terminated homopolymers or copolymers of non-reactive hydrophilic vinyl monomers; copolymers that are the polymerization product of a composition comprising: (1) about 50% by weight or less, preferably about 0.1 to about 30%, more preferably about 0.5 to about 20%, even more preferably about 1 to about 15% by weight of one or more reactive vinyl monomers and (2) at least one non-reactive hydrophilic vinyl monomer and/or at least one phosphorylcholine-containing vinyl monomer; and combinations thereof. The reactive vinyl monomers and non-reactive hydrophilic vinyl monomers are those described above.

More preferably, the hydrophilic polymer as the hydrophilicity-enhancing agent is PEG-NH ₂ ; PEG-SH; PEG-COOH; H ₂ N-PEG-NH ₂ ; HOOC-PEG-COOH; HS-PEG-SH; H ₂ N-PEG-COOH; HOOC-PEG-SH; H ₂ N-PEG-SH; a multi-arm PEG having one or more amino, carboxyl or thiol groups; a PEG dendrimer having one or more amino, carboxyl or thiol groups; a monoamino-, monocarboxyl-, diamino-, dicarboxyl-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer selected from the group consisting of acrylamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C ₁ -C 2-hydroxyethyl (meth)acrylamide having a weight average molecular weight of up to 400 Daltons; _4- 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, (meth)acryloyloxyethyl phosphorylcholine and combinations thereof; a copolymer which is the polymerization product of a composition comprising: (1) from about 0.1 to about 30%, preferably from about 0.5 to about 20%, more preferably from about 1 to about 15% by weight of (meth)acrylic acid, C ₂ -C ₁₂ alkyl acrylic acid, vinylamine, allylamine and/or (meth)acrylic acid amino-C ₂ -C 12 ₄ alkyl esters, and (2) (meth)acryloyloxyethyl phosphorylcholine and/or at least one non-reactive hydrophilic vinyl monomer selected from the group consisting of acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C ₁ -C ₄ alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of up to 400 Daltons, vinyl alcohol, and combinations thereof.

Most preferably, the hydrophilicity enhancer is PEG-NH ₂ ; 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- or monocarboxyl-, diamino- or dicarboxyl-terminated poly(DMA-co-NVP); monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly(NVP-co-N,N-dimethylaminoethyl (meth)acrylate); monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly(vinyl alcohol); monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly[(meth)acryloyloxyethyl phosphorylcholine] homopolymer or copolymer; monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated end-capped poly(NVP-co-vinyl alcohol); monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated poly(DMA-co-vinyl alcohol); poly[(meth)acrylic acid-co-acrylamide] having from about 0.1 to about 30%, preferably from about 0.5 to about 20%, more preferably from about 1 to about 15% by weight of (meth)acrylic acid; poly[(meth)acrylic acid-co-NVP) having from about 0.1 to about 30%, preferably from about 0.5 to about 20%, more preferably from about 1 to about 15% by weight of (meth)acrylic acid; a copolymer which is the polymerization product of a composition comprising: (1) (meth)acryloyloxyethylphosphocholine and (2) from about 0.1 to about 30%, preferably from about 0.5 to about 20%, more preferably from about 1 to about 15% by weight of a carboxylic acid-containing vinyl monomer and/or an amino-containing vinyl monomer; and combinations thereof.

PEG with functional groups and multi-arm PEG with functional groups are available from various commercial suppliers such as Polyscience and Shearwater Polymers, Inc., among others.

Monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated homopolymers or copolymers of one or more non-reactive hydrophilic vinyl monomers or phosphorylcholine-containing vinyl monomers can be prepared according to the procedures described in U.S. Patent No. 6,218,508, the entire contents of which are incorporated herein by reference. For example, to prepare diamino- or dicarboxyl-terminated homopolymers or copolymers of non-reactive hydrophilic vinyl monomers, a non-reactive vinyl monomer, a chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid, or other hydroxythiols, aminothiols, or carboxyl-containing thiols), and optionally other vinyl monomers are copolymerized (thermally or photochemically) with a reactive vinyl monomer (having an amino or carboxyl group) in the presence of a free radical initiator. Typically, the molar ratio of the chain transfer agent to all vinyl monomers other than the reactive vinyl monomer is from about 1:5 to about 1:100, while the molar ratio of the chain transfer agent to the reactive vinyl monomer is 1:1. In this preparation, a chain transfer agent having an amino group or a carboxyl group is used to control the molecular weight of the resulting hydrophilic polymer and to form the terminal of the resulting hydrophilic polymer, thereby providing the resulting hydrophilic polymer with one terminal amino group or carboxyl group, while the reactive vinyl monomer provides the resulting hydrophilic polymer with the other terminal carboxyl group or amino group. Similarly, to prepare a monoamino- or monocarboxyl-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer, a non-reactive vinyl monomer, a chain transfer agent having an amino group or a carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid or other hydroxythiols, aminothiols or carboxyl-containing thiols) and optionally other vinyl monomers are copolymerized (thermally or photochemically) in the absence of any reactive vinyl monomer.

As used herein, a copolymer of a non-reactive hydrophilic vinyl monomer refers to a polymerization product of a non-reactive hydrophilic vinyl monomer and one or more other vinyl monomers. Copolymers comprising a non-reactive hydrophilic vinyl monomer and a reactive vinyl monomer (e.g., a carboxyl-containing vinyl monomer) can be prepared according to any well-known free radical polymerization method or obtained from commercial suppliers. Copolymers comprising methacryloxyethylphosphocholine and a carboxyl-containing vinyl monomer can be obtained from NOP Corporation (e.g., -A and -AF).

The weight average molecular weight Mw of the hydrophilic polymer having at least one amino group, carboxyl group, or thiol group (as the hydrophilicity-enhancing agent) is preferably about 500 to about 1,000,000, more preferably about 1,000 to about 500,000.

According to the present invention, the reaction between the hydrophilicity-enhancing agent and the epichlorohydrin-functionalized polyamine or polyamidoamine is carried out at a temperature of about 40 to about 100° C. for a sufficient time (about 0.3 to about 24 hours, preferably about 1 to about 12 hours, even more preferably about 2 to about 8 hours) to form a water-soluble and thermally cross-linkable hydrophilic polymeric material containing azetidine groups.

According to the present invention, the concentration of the hydrophilicity-enhancing agent relative to the epichlorohydrin-functionalized polyamine or polyamidoamine must be selected so as not to render the resulting hydrophilic polymeric material water-insoluble (i.e., having a solubility of less than 0.005 g/100 mL of water at room temperature) and not to consume more than about 99%, preferably about 98%, more preferably about 97%, and even more preferably about 96% of the azetidine groups of the epichlorohydrin-functionalized polyamine or polyamidoamine.

According to the present invention, the heating step is preferably performed by autoclaving the silicone hydrogel contact lenses immersed in a packaging solution (i.e., a buffered aqueous solution) in a sealed lens package at a temperature of about 118 to about 125° C. for about 20-90 minutes. According to this embodiment of the invention, the packaging solution is an ophthalmically safe buffered aqueous solution after autoclaving.

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

The lenses are packaged in individual packages, sealed, and sterilized (eg, autoclaved at about 120° C. or higher for at least 30 minutes) prior to distribution to users. One skilled in the art will understand how to seal and sterilize lens packages.

According to the present invention, the packaging solution contains at least one buffer and one or more other ingredients known to those skilled in the art. Examples of other ingredients include, but are not limited to, tonicity agents, surfactants, antimicrobial agents, preservatives, and lubricants (or water-soluble viscosity increasing agents) (e.g., cellulose derivatives, polyvinyl alcohol, polyvinyl pyrrolidone).

The packaging solution contains a buffer in an amount sufficient to maintain the pH of the packaging solution within the desired range, preferably within the physiologically acceptable range of about 6 to about 8.5. Any known physiologically compatible buffer can be used. Suitable buffers as components of the contact lens care compositions of the present invention are known to those skilled in the art. Examples are boric acid, borates such as sodium borate, citric acid, citrates such as potassium citrate, bicarbonates such as sodium bicarbonate, TRIS (2-amino-2-hydroxymethyl-1,3-propanediol), bis-tris(bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane), bisaminopolyols, triethanolamine, ACES (N-(2-hydroxyethyl)-2-aminoethanesulfonic acid), BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), MOPS (3-[N-morpholino]-propanesulfonic acid), PIPES (piperazine-N,N'-bis(2-ethanesulfonic acid), TES (N-[tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid), salts thereof, phosphate buffers such _{as Na2HPO4} , _{NaH2PO4 4} and KH ₂ PO ₄ or a mixture thereof. A preferred bisamino polyol is 1,3-bis(tris[hydroxymethyl]-methylamino)propane (bis-TRIS-propane). The amount of each buffer in the packaging solution is preferably 0.001-2%, preferably 0.01-1%; most preferably about 0.05 to about 0.30% by weight.

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

The packaging solutions of the present invention have a viscosity at 25°C of from about 1 to about 20 centipoise, preferably from about 1.2 to about 10 centipoise, and more preferably from about 1.5 to about 5 centipoise.

In a preferred embodiment, the packaging solution comprises preferably from about 0.01 to about 2%, more preferably from about 0.05 to about 1.5%, even more preferably from about 0.1 to about 1%, and most preferably from about 0.2 to about 0.5% by weight of the water-soluble and thermally cross-linkable hydrophilic polymeric material of the present invention.

The packaging solutions of the present invention may contain a viscosity-increasing polymer. The viscosity-increasing polymer is preferably nonionic. Increasing the viscosity of the solution provides a film on the lens that promotes comfortable wearing of the contact lens. The viscosity-increasing component may also be used to cushion the eye surface during insertion and to reduce eye irritation.

Preferred viscosity-increasing polymers include, but are not limited to, water-soluble cellulose ethers (e.g., methylcellulose (MC), ethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), or mixtures thereof), water-soluble polyvinyl alcohol (PVA), high molecular weight poly(ethylene oxide) having a molecular weight greater than about 2000 (up to 10,000,000 Daltons), polyvinyl pyrrolidone having a molecular weight of about 30,000 to about 1,000,000 Daltons, copolymers of N-vinyl pyrrolidone and at least one dialkylaminoalkyl (meth)acrylate having 7 to 20 carbon atoms, and combinations thereof. Copolymers of water-soluble cellulose ethers and vinyl pyrrolidone with dimethylaminoethyl methacrylate are the most preferred viscosity-increasing polymers. N-vinyl pyrrolidone with dimethylaminoethyl methacrylate is commercially available, for example, as Copolymer 845 and Copolymer 937 from ISP.

The viscosity-building polymer is present in the packaging solution in an amount of about 0.01 to about 5 weight percent, preferably about 0.05 to about 3 weight percent, even more preferably about 0.1 to about 1 weight percent, based on the total amount of the packaging solution.

The packaging solution may further comprise 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.

If at least one of the cross-linked coating and the packaging solution contains a polymeric material having polyethylene glycol segments, the packaging solution preferably contains an α-oxypolyacid or salt thereof in an amount sufficient to reduce susceptibility to oxidative degradation of the polyethylene glycol segments. Co-pending patent application (U.S. Application Publication No. 2004/0116564A1, incorporated herein in its entirety) discloses that oxypolyacids or salts thereof can reduce susceptibility to oxidative degradation of PEG-containing polymeric materials.

Typical α-oxypolyacids or biocompatible salts thereof include, but are not limited to, citric acid, 2-oxoglutaric acid, or malic acid, or biocompatible (preferably ophthalmically compatible) salts thereof. More preferably, the α-oxypolyacid is citric acid or malic acid, or biocompatible (preferably ophthalmically compatible) salts thereof (e.g., sodium, potassium, etc.).

According to the present invention, the packaging solution may further comprise a mucinous material, an ophthalmically beneficial material and/or a surfactant.

Typical mucin-like materials include, but are not limited to, polyglycolic acid, polylactide, and the like. Mucin-like materials can be used as guest materials that can be continuously and slowly released onto the ocular surface of the eye over an extended period of time to treat dry eye. The mucin-like material is preferably present in an effective amount.

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

The surfactant can be essentially any eye-compatible surfactant, including nonionic, anionic and amphoteric surfactants. Examples of preferred surfactants include, but are not limited to, poloxamers (e.g., F108, F88, F68, F68LF, F127, F87, F77, P85, P75, P104 and P84), poloamines (e.g., 707, 1107 and 1307), polyethylene glycol esters of fatty acids (e.g., 20, 80), polyethylene oxide or polypropylene oxide ethers of _C12 - _C18 paraffins (e.g., 35), polyoxyethylene stearate (52), polyoxyethylene propylene glycol stearate (G 2612), and amphoteric surfactants under the trade names PTFE® and PTFE®.

The silicone hydrogel contact lenses obtained according to the process of the present invention have a surface hydrophilicity/wettability 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.

In another preferred embodiment, the method of the present invention may further comprise the steps of: contacting the silicone hydrogel contact lens with an aqueous solution of a heat-crosslinkable hydrophilic polymer material at room temperature to form a top layer of the heat-crosslinkable hydrophilic polymer material (i.e., an LbL coating) on the surface of the silicone hydrogel contact lens; immersing the silicone hydrogel contact lens having the top layer of the heat-crosslinkable hydrophilic polymer material in a packaging solution in a lens package; and sealing the lens package; and autoclaving the lens package with the silicone hydrogel contact lens therein to form a crosslinked hydrophilic coating on the silicone hydrogel contact lens. Due to its positive charge, it is believed that the heat-crosslinkable hydrophilic polymer material can form an LbL coating on a silicone hydrogel contact lens that is not covalently bonded to the surface of the silicone hydrogel contact lens (i.e., through physical interaction), particularly a contact lens having negatively charged carboxyl groups on its surface.

It should be understood that although various embodiments of the present invention, including preferred embodiments, may be described above separately, they may be combined in any desired manner and/or used together to obtain the present method for producing silicone hydrogel contact lenses having a cross-linked hydrophilic coating thereon.

In another aspect, the present invention provides a silicone hydrogel contact lens obtained according to the above-described method of the present invention.

In another aspect, the present invention provides an ophthalmic product comprising a sterilized and sealed lens package, wherein the lens package comprises a post-autoclave 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 cross-linked hydrophilic coating obtained by autoclaving an initial silicone hydrogel contact lens having amino and/or carboxyl groups on and/or near the surface of the initial silicone hydrogel contact lens in a pre-autoclave packaging solution comprising a water-soluble and thermally cross-linkable hydrophilic polymeric material, wherein the hydrophilic polymeric material comprises: (i) from about 20 to about 95%, preferably from about 35 to about 90%, More preferably, from about 50 to about 85 weight percent of first polymer chains derived from epichlorohydrin-functionalized polyamines or polyamidoamines, (ii) from about 5 to about 80%, preferably from about 10 to about 65%, even more preferably from about 15 to about 50 weight percent of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino, carboxyl, thiol, and combinations thereof, wherein the hydrophilic moieties or second polymer chains are each formed between an azetidinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and an amino, carboxyl, or thiol group of the hydrophilicity-enhancing agent. The invention further comprises: (i) an azetidine group covalently attached to the first polymer chain by one or more covalent bonds covalently attached to the first polymer chain, and (ii) an azetidine group that is part of the first polymer chain or is covalently attached to the first polymer chain or is a pendant or terminal group, wherein the hydrophilic polymeric material is covalently attached to the silicone hydrogel contact lens via a first covalent bond formed between one amino group or carboxyl group, each on and/or near the surface of the silicone hydrogel contact lens, and one azetidine group of the thermally cross-linkable hydrophilic polymeric material, wherein the post-autoclave packaging solution comprises at least one buffering agent in an amount sufficient to maintain a pH of about 6.0 to about 8.5 and has a pH of about 200 to about 450 mOsm. The invention also provides a method for preparing a silicone hydrogel contact lens having a surface hydrophilicity/wettability characterized by a mean 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.

"Ready-to-use silicone hydrogel contact lens" refers to a silicone hydrogel contact lens that is ophthalmically compatible and sterilized by autoclaving. "Naive silicone hydrogel contact lens" refers to a silicone hydrogel contact lens that lacks a cross-linked hydrophilic coating and has not been sterilized by autoclaving.

Silicone hydrogel contact lenses inherently having amino and/or carboxyl groups, silicone hydrogel contact lenses having a reactive primer coating, reactive vinyl monomers, non-reactive vinyl monomers, reactive polymers for forming reactive LbL primer coatings, plasma coatings, epichlorohydrin-functionalized polyamines or polyamidoamines, hydrophilicity-enhancing agents, water-soluble hydrophilic polymeric materials having azetidine groups, a heating step, a packaging solution, and various embodiments of the surface wettability of silicone hydrogel contact lenses having a cross-linked hydrophilic coating of the present invention, including preferred embodiments, are described above and can be combined and/or used together in both aspects of the present invention.

The ready-to-use silicone hydrogel contact lenses of the present invention have an oxygen permeability of at least about 40 barrers, preferably at least about 50 barrers, more preferably at least about 60 barrers, even more preferably at least about 70 barrers; a center thickness of about 30 to about 200 μm, more preferably about 40 to about 150 μm, even more preferably about 50 to about 120 μm, and most preferably about 60 to about 110 μm; an elastic modulus of about 1.5 MPa or less, preferably about 1.2 MPa or less, more preferably about 1.0 or less, even more preferably about 0.3 to about 1.0 MPa; an iontophoresis diffusion coefficient, D, preferably at least about 1.5×10 ⁻⁶ mm ² /min, more preferably at least about 2.6×10 ⁻⁶ mm ² /min, even more preferably at least about 6.4×10 ⁻⁶ mm ² /min; a water content when fully hydrated, preferably from about 18 to about 70%, more preferably from about 20 to about 60% by weight; or combinations thereof.

The water content of silicone hydrogel contact lenses can be determined according to the Bulk Technique as disclosed in US 5,849,811.

In yet another aspect, the present invention provides a water-soluble and thermally cross-linkable hydrophilic polymeric material comprising: (a) from about 20 to about 95%, preferably from about 35 to about 90%, more preferably from about 50 to about 85% by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine; (b) from about 5 to about 80%, preferably from about 10 to about 65%, even more preferably from about 15 to about 50% by weight of second polymer chains derived from at least one hydrophilicity-boosting polymeric agent having at least one reactive functional group selected from the group consisting of amino, carboxyl, thiol, and combinations thereof, wherein the second polymer chains are covalently attached to the first polymer chains via one or more covalent bonds each formed between one azetidine group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl, or thiol group of the hydrophilicity-boosting polymeric agent; and (c) azetidine groups that are part of or pendant to the first polymer chains.

The various embodiments, including preferred embodiments, of the reactive vinyl monomers, non-reactive vinyl monomers, epichlorohydrin-functionalized polyamines or polyamidoamines, and hydrophilic polymers as hydrophilicity-enhancing agents may be combined in any manner and/or used together in this aspect of the invention.

The foregoing disclosure will enable those skilled in the art to practice the present invention. Various modifications, variations, and combinations of the various embodiments described herein may be made. In order to better facilitate the reader's understanding of the specific embodiments and their advantages, reference is made to the following examples. The description and examples are intended to be exemplary.

Although specific terms, devices, and methods have been used to describe various embodiments of the present invention, such descriptions are for illustrative purposes only. The terms used are descriptive and not restrictive. It should be understood that those skilled in the art may make changes and variations without departing from the spirit or scope of the present invention as set forth in the following claims. In addition, it should be understood that aspects of the various embodiments may be interchangeable in whole or in part or may be combined and/or used together in any manner. Therefore, the spirit and scope of the appended claims should not be limited to the description of the preferred variations contained herein.

Example 1

Oxygen permeability measurement

The apparent oxygen permeability of the lens and the oxygen permeability of the lens material are determined according to techniques similar to those described in U.S. Patent No. 5,760,100 and Winterton et al. (The Cornea: Transactions of the World Congress on the Cornea 111, HD Cavanagh Ed., Raven Press: New York 1988, pp. 273-280), both of which are incorporated herein by reference in their entireties. Oxygen flux (J) is measured in a wet cell (i.e., an air stream maintained at approximately 100% relative humidity) at 34° C. using a Dk1000 instrument (available from Applied Design and Development Co., Norcross, GA) or similar analytical instrument. An air stream having a known percentage of oxygen (e.g., 21%) is passed through one side of the lens at a rate of approximately 10-20 cm ³ /min, while a nitrogen stream is passed through the opposite side of the lens at a rate of approximately 10-20 cm ³ /min. The specimen is equilibrated in the test medium (i.e., saline or distilled water) at the specified test temperature for at least 30 minutes but not more than 45 minutes prior to measurement. Any test medium used as an overlay is equilibrated at the specified test temperature for at least 30 minutes but not more than 45 minutes prior to measurement. The stirring motor speed is set to 1200 ± 50 rpm, which is equivalent to a specified setting of 400 ± 15 on the stepper motor controller. The atmospheric pressure surrounding the system is measured, P _measured . The thickness (t) of the lens in the area exposed to the test is determined by measuring approximately 10 locations with a Mitotoya micrometer VL-50 or similar instrument and averaging the measurements. The oxygen concentration in the nitrogen stream (i.e., the oxygen that diffuses through the lens) is measured using a DK1000 instrument. The apparent oxygen permeability, Dk _app, of the lens material is determined by the following formula:

Dk _app = Jt/(P _oxygen )

Where J = oxygen flux [μL O ₂ /cm ² –min]

P _oxygen = (P _measured - P _{water vapor} ) = (% O ₂ in air stream) [mm Hg] = partial pressure of oxygen in air stream

P _measured = atmospheric pressure (mm Hg)

P _{water vapor} = 0 mm Hg at 34°C (in a dry cell) (mm Hg)

P _{water vapor} = 40 mm Hg at 34°C (in a wet cell) (mm Hg)

t = average thickness of the lens over the exposed test area (mm)

Dk _app is expressed in Barrer.

The apparent oxygen transmission rate (Dk/t) of a material can be calculated by dividing the apparent oxygen permeability (Dk _app ) by the average thickness (t) of the lens.

The above measurements do not correct for the so-called boundary layer effect, which can be attributed to the use of a water or saline bath on top of the contact lens during oxygen flux measurements. Boundary layer effects cause the reported values for the apparent Dk of silicone hydrogel materials to be lower than the actual intrinsic Dk value. Additionally, the relative impact of the boundary layer effect is greater for thinner lenses than for thicker lenses. The net effect is that the reported Dk appears to vary as a function of lens thickness, when it should remain constant.

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

The apparent oxygen permeability values (single point) of reference lotrafilcon A (from CIBA VISION CORPORATION) or lotrafilcon B (AirOptix ^™ from CIBA VISION CORPORATION) lenses were measured using the same equipment.The reference lenses had similar optical power to the test lenses and were measured simultaneously with the test lenses.

The intrinsic Dk values (Dk _i ) of the reference lenses are obtained by measuring the oxygen flux through a thickness series of lotrafilcon A or lotrafilcon B (reference) lenses using the same equipment as described above for the apparent Dk measurement. The thickness series should cover a thickness range of approximately 100 μm or greater. Preferably, the range of reference lens thicknesses includes the experimental lens thicknesses. The Dk _app of these reference lenses must be measured on the same equipment as the test lenses and ideally should be measured simultaneously with the test lenses. The equipment settings and measurement parameters should be kept constant throughout the experiment. If necessary, each sample can be measured multiple times.

The residual oxygen resistance value, R _r , was determined from the reference lens results using Equation 1 in the calculations.

Where t is the thickness of the test lens (also referred to as the reference lens), and n is the number of reference lenses measured. The residual oxygen resistance value R _r is plotted against the t data and a curve of the form Y = a + bX is fitted, where for the jth lens, Y _j = (ΔP/J) _j and X = t _j . The residual oxygen resistance R _r is equal to a.

The corrected oxygen permeability Dk _c (estimated intrinsic Dk) of the test lenses was calculated based on Equation 2 using the residual oxygen resistance values determined above.

Dk _c =t/[(t/Dk _a )–R _r ] (2)

The estimated intrinsic Dk of the test lens can be used to calculate the apparent Dk ( _{Dka_std} ) of a standard thickness lens in the same test environment based on Equation 3. Standard thickness of lotrafilcon A ( _tstd ) = 85 μm. Standard thickness of lotrafilcon B = 60 μm.

Dk _{a_std} =t _std/ [(t _std/ Dk _c )+R _{r_std} ] (3)

Ion permeability measurements

The ion permeability of the lens was measured according to the procedure described in U.S. Patent No. 5,760,100 (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/ _Dref ) of the lens material Alsacon as a reference material. Alsacon has an ion flux diffusion coefficient of 0.314× ^{10-3 mm2} /min.

Lubricity evaluation

Lubricity is assessed using a qualitative rating scale of 0-5, with 0 or lower indicating better lubricity, 1 being assigned to commercial Oasys ^™ /TruEye ^™ lenses, and 5 to commercial Air Optix ^™ lenses. Before evaluation, the specimens were rinsed at least three times with excess DI water and then transferred to PBS. Before evaluation, hands were rinsed with a soap solution, rinsed extensively with DI water, and then towel-dried. The specimens were handled between the fingers, and each was assigned a numerical value relative to the standard lens described above. For example, if a lens was determined to be only slightly better than an Air Optix ^™ lens, it was assigned a number of 4. For consistency, all ratings were collected independently by the same two operators to avoid bias, and the data to date demonstrate very good qualitative agreement and compatibility in the evaluations.

Surface Hydrophilicity/Wettability Test. The water contact angle on a contact lens is a general measure of the surface hydrophilicity (or wettability) of the contact lens. In particular, a low water contact angle corresponds to a more hydrophilic surface. The average contact angle (sessile drop method) of the contact lens was measured using a VCA 2500XE contact angle measurement instrument from AST, Inc., located in Boston, Massachusetts. This instrument can measure advancing or receding contact angles, or sessile (static) contact angles. The measurement was performed as follows on a fully hydrated contact lens immediately after staining and drying. The contact lens was removed from the vial and washed three times in ~200 ml of fresh DI water to remove loosely bound packaging additives from the lens surface. The lens was then placed on a lint-free cleaning cloth (Alpha Wipe TX1009), patted thoroughly to remove surface water, mounted on a contact angle measurement stand, blown dry with a dry air blast, and finally the sessile drop contact angle was automatically measured using the manufacturer's software. The DI water used for contact angle measurements has a resistivity of >18 MΩcm, and the drop volume used is 2 μl. Typically, uncoated silicone hydrogel lenses (after autoclaving) have a sessile drop contact angle of approximately 120 degrees. The tweezers and holder were thoroughly cleaned with isopropyl alcohol and rinsed with DI water before contact with the contact lens.

Water Breakup Time (WBUT) Test. The wettability of the lens (after autoclaving) is also assessed by measuring the time required for the water film on the lens surface to begin to break. Briefly, the lens is removed from the vial and washed three times in ~200 ml of fresh DI water to remove loosely bound packaging additives from the lens surface. The lens is removed from the solution and held facing away from a bright light source. The time required for the water film to break (dehumidify), exposing the underlying lens material, is recorded visually. Uncoated lenses typically break immediately upon removal from the DI water and are assigned a WBUT of 0 seconds. Lenses that exhibit a WBUT ≥ 5 seconds are considered good wettability and are expected to exhibit adequate wettability (ability to support a tear film) on the eye.

Coating Integrity Test. The integrity of the coating on the contact lens surface can be tested according to 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 dye solution (Sudan Black in Vitamin E oil). Sudan Black dye is hydrophobic and has the tendency to be absorbed by hydrophobic materials or onto hydrophobic spots on a hydrophobic lens surface or a partially coated surface of a hydrophobic lens (e.g., SiHy contact lens). If the coating on a hydrophobic lens is intact, no spots should be observed on or in the lens. All test lenses were fully hydrated.

Coating Durability Test. The lens was finger-rubbed 30 times with a multi-purpose lens care solution and then rinsed with saline. The above procedure was repeated a given number of times, e.g., 1-30 times (i.e., the number of consecutive finger-rub tests to simulate a cleaning and soaking cycle). The lens was then subjected to the Sudan Black test (i.e., the coating integrity test described above) to check whether the coating remained intact. To survive the finger-rub test, there should be no significantly elevated stain (e.g., the stain covering no more than about 5% of the total lens surface area). Water contact angle was measured to determine coating durability.

Debris Adhesion Test. Contact lenses with highly charged surfaces may be susceptible to increased debris adhesion during patient handling. Rub a gloved hand with a paper towel, then rub both sides of the lens with your fingers to transfer any debris to the lens surface. Rinse the lens briefly and then observe under a microscope. A qualitative rating scale of 0 (no debris adhesion) to 4 (debris adhesion equivalent to that of a PAA-coated control lens) is used to rate each lens. Lenses with a score of "0" or "1" are considered acceptable.

Surface Crack Test. Excessive cross-linking of the coating can result in surface cracks visible under a darkfield microscope after rubbing the lens. The lens is turned over, rubbed, and any crack lines noted. A qualitative rating of 0 (no cracks) to 2 (severe cracks) is used to evaluate the lens. Any severe crack lines are considered unacceptable.

Determination of Azetidine Content. The azetidine content in PAE can be determined according to one of the following tests.

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

PES-Na Assay. The PES-Na assay is another colorimetric titration assay used to determine the charge density (azetidine content) of PAE. In this assay, the titrant is sodium polyvinyl sulfonate (PES-Na) rather than PPVS. This assay is identical to the PPVS assay described above.

PCD Test. The PCD test is a potentiometric titration test used to determine the charge density (azetidine content) of PAEs. The titrant is sodium polyethylene sulfonate (PES-Na), PPVS, or other titrants. The PAE charge is measured using electrodes, such as the Mütek PCD-04 particle charge detector from BTG. The measurement principle of this detector can be found on BTG's website at http://www.btg.com/products.asp?langage=1&appli=5&numProd=357&cat=prod).

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

Example 2

Preparation of CE-PDMS macromonomer

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

Optional preparation of CE-PDMS macromers

240.43g of KF-6001 was added to a 1-L reactor equipped with a stirrer, thermometer, cryostat, dropping funnel, and nitrogen/vacuum inlet adapter, and then dried by applying high vacuum (2× ^10-2 mbar). Then, under a dry nitrogen atmosphere, 320g of distilled MEK was added to the reactor, and the mixture was thoroughly stirred. 0.235g of DBTDL was added to the reactor. After heating the reactor to 45°C, 45.86g of IPDI was added to the reactor via an addition funnel over 10 minutes under gentle stirring. The reaction was maintained at 60°C for 2 hours. 630g of KF-6002 dissolved in 452g of distilled MEK was then added and stirred until a homogeneous solution was formed. 0.235g of DBTDL was added, and the reactor was maintained at approximately 55°C overnight under a dry nitrogen blanket. The next day, the MEK was removed by flash evaporation. The reactor was cooled, and then 22.7 g of IEM was added to the reactor, followed by approximately 0.235 g of DBTDL. After approximately 3 hours, another 3.3 g of IEM was added, and the reaction was allowed to proceed overnight. The next day, the reaction mixture was cooled to approximately 18° C. to yield a CE-PDMS macromonomer having terminal methacrylate groups.

Example 3

Preparation of lens formulations

A lens formulation was prepared by dissolving the components in 1-propanol to have the following composition: 33 wt% of the CE-PDMS macromer prepared in Example 2, 17 wt% 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 (5% copper phthalocyanine blue pigment dispersion in tris(trimethylsiloxy)silylpropyl methacrylate, TRIS), and 24.5 wt% 1-propanol.

Lens preparation

Lenses were prepared by cast molding the lens formulation prepared above in a reusable mold similar to the mold shown in Figures 1-6 of U.S. Patent Nos. 7,384,590 and 7,387,759 (Figures 1-6). The mold comprised a female mold half composed of quartz (or _CaF2 ) and a male mold half composed of glass (or PMMA). The UV radiation source was a Hamamatsu lamp with a WG335+TM297 cutoff filter and an intensity of approximately 4 mW/ ^cm2 . The lens formulation in the mold was irradiated with UV radiation for approximately 25 seconds. The cast-molded lenses were extracted with isopropyl alcohol (or methyl ethyl ketone, MEK), rinsed with water, coated with polyacrylic acid (PAA) by immersing the lenses in a propanol solution of PAA (0.1 wt %, acidified to approximately pH 2.5 with formic acid), and hydrated in water. The resulting lenses having the reactive PAA-LbL primer coating thereon were determined to have the following properties: an ion permeability of about 8.0 to about 9.0 relative to Alsacon lens material; an apparent Dk (single point) of about 90-100; a water content of about 30 to about 33%; and an elastic modulus of about 0.60 to about 0.65 MPa.

Example 4

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

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

The lenses were then evaluated for debris adhesion, surface cracking, lubricity, contact angle, and water breakup time (WBUT). The test lenses (packaged/autoclaved in IPC saline, i.e., lenses having a PAA-x-PAE coating thereon) showed no debris adhesion, while the control lenses (packaged/autoclaved in PBS, i.e., lenses having a PAA-LbL primer thereon) showed severe debris adhesion. The water contact angle (WCA) of the test lenses was low (~20 degrees), but the WBUT was less than 2 seconds. When observed under a darkfield microscope, severe crack lines were visible after handling of the lenses (inversion of the lenses and rubbing between fingers). As judged by a qualitative finger rub test, the test lenses were less smooth than the control lenses (lubricity rating of 4).

Example 5

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

IPC saline was prepared by dissolving 0.02% poly(AAm-co-AA) (80/20) and 0.2% PAE (Kymene) in PBS. _The pH was adjusted to 7.2-7.4. _PBS was prepared by dissolving 0.76% NaCl, 0.044% _NaH2PO4 · _H2O , and 0.388% _Na2HPO4 · _2H2O in water.

The lens prepared in Example 3, having a PAA-LbL primer thereon, was placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline was added before inserting the lens). The bubble was then sealed with foil and autoclaved at approximately 121° C. for approximately 30 minutes. It is believed that a cross-linked coating consisting of three layers of PAA-x-PAE-x-poly(AAm-co-AA) was formed on the lens during the autoclaving process.

The test lenses (encapsulated/autoclaved in IPC saline, i.e., lenses having a PAA-x-PAE-x-poly(AAm-co-AA) coating thereon) had no debris attached and had a WBUT longer than 10 seconds. When observed under a darkfield microscope, crack lines were visible after rubbing the test lenses. The test lenses were much smoother than the test lenses from Example 4, but still not as smooth as the control lenses encapsulated in PBS (lubricity rating of 1-2).

Example 6

IPC saline was prepared by dissolving 0.02% poly(AAm-co-AA) (80/20) and 0.2% PAE (Kymene) in PBS and adjusting the pH to 7.2-7.4. The saline was then treated by heating to approximately 70°C for 4 hours (heat pretreatment) to form a water-soluble and heat-crosslinkable hydrophilic polymer material containing azetidine groups in the IPC saline. After heat pretreatment, the IPC saline was filtered using a 0.22 μm polyethersulfone (PES) membrane filter and cooled back to room temperature.

The lens having the PAA-LbL primer coating thereon prepared in Example 3 was placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline was added before inserting the lens). The bubble was then sealed with foil and autoclaved at about 121° C. for about 30 minutes to form a cross-linked coating (PAA-x-hydrophilic polymer material) on the lens.

The test lens (encapsulated in heat-preconditioned IPC saline, i.e., a lens having a PAA-x-hydrophilic polymer material thereon) showed no debris adhesion after rubbing with a paper towel, while the control lens (encapsulated in PBS, i.e., a lens having a non-covalently attached PAA layer thereon) showed severe debris adhesion. The test lens had a WBUT longer than 10 seconds. When observed under a darkfield microscope, no crack lines were visible after rubbing the test lens. The test lens was very smooth in the finger rub test and was equivalent to the control lens (lubricity rating of 0).

A series of experiments were conducted to investigate the effect of the IPC saline heat pretreatment conditions (duration and/or temperature) on the surface properties of the resulting lenses coated with IPC saline. Depending on the azetidine functionality of the PAE and the concentration of the PAE used, heat treatment times of about 6 hours or longer at about 70°C produced lenses that were similar to the control lenses in their sensitivity to debris adhesion. Heat treatment at 50°C for only 4 hours produced lenses that exhibited surface crack lines under dark field microscopy after rubbing between fingers, similar to the test lenses in Example 5 in which the IPC saline was not heat pretreated.

Example 7

Poly(acrylamide-co-acrylic acid) partial sodium salt (-90% solids content, poly(AAm-co-AA) 90/10, Mw 200,000) was purchased from Polysciences, Inc. and used as received.

IPC saline was prepared by dissolving 0.07% PAAm-PAA (90/10) and 0.2% PAE (Kymene) in PBS and adjusting the pH to 7.2-7.4. The saline was then preheated at approximately 70°C for approximately 4 hours (heat pretreatment) to form a water-soluble and heat-crosslinkable hydrophilic polymer material containing azetidine groups. After heat pretreatment, the IPC saline was filtered using a 0.22 μm polyethersulfone (PES) membrane filter and cooled back to room temperature.

The lens having the PAA-LbL primer coating thereon, prepared in Example 3, and an uncoated Lotrafilcon B lens immersed in an acidic propanol solution of PAA (approximately 0.1%, pH 2.5) were placed in a polypropylene lens packaging shell containing 0.6 mL of preheated IPC saline (half of the IPC saline was added prior to lens insertion). The bubble was then sealed with foil and autoclaved at 121° C. for approximately 30 minutes to form a crosslinked coating (PAA-x-hydrophilic polymer material) on the lens.

The test lenses (Lotrafilcon B and Example 3 lenses with PAA-x-hydrophilic polymer thereon) had no debris attached. The test lenses had a WBUT greater than 10 seconds. When observed under a darkfield microscope, no crack lines were visible after rubbing the lenses between fingers. In a qualitative finger rub test, the lenses were extremely smooth (lubricity rating of 0).

Example 8

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

Example 9

In a design of experiments (DOE), IPC saline was prepared to contain approximately 0.07% PAAm-PAA and sufficient PAE to provide an initial azetidine content of approximately 9 mmol/L (~0.15% PAE). Thermal pretreatment conditions were varied from 50 to 70°C in a central composite design, and pre-reaction times were varied from about 4 to about 12 hours. A 24-hour pre-treatment time at 60°C was also tested. 10 ppm hydrogen peroxide was then added to the saline to prevent bioburden growth and the IPC saline was filtered using a 0.22 μm polyethersulfone [PES] membrane filter.

The lenses from Example 3 were packaged in heat-pretreated IPC saline and then autoclaved at 121°C for 45 minutes. All lenses had excellent lubricity, wettability, and resistance to surface cracking. Some lenses showed attachment of debris from the tissue, as shown in Table 1.

Table 1

Example 10

A copolymer of methacryloxyethylphosphorylcholine ( _MPC ) and a carboxyl-containing vinyl monomer ( _CH2 =CH( _CH3 )C(O) _OC2H4OC (O) _C2H4COOH (MS), methacrylic acid (MA)) was evaluated in combination with _PAE in an in-pack coating system.

PBS containing NaCl (0.75 wt%), _NaH2PO4.H2O (0.0536 wt%), _Na2HPO4.2H2O ( _{0.3576 wt} %) and DI water (97.59 wt _% ) was prepared and 0.2% PAE (polycup 3160) was added. The pH was adjusted to about 7.3.

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

The lenses prepared in Example 3 with the PAA-LbL primer thereon were packaged in heat-preconditioned IPC saline and autoclaved for approximately 30 minutes at 121° C. Table 2 shows that all lenses had excellent surface properties.

Table 2

MPC Copolymer* D.A. crack Lubricity Poly(MPC/MA)90/10 qualified qualified Excellent Excellent Poly(MPC/BMA/MA)40/40/20 qualified qualified Excellent Excellent Poly(MPC/BMA/MA)70/20/10 qualified qualified Excellent Excellent Poly(MPC/BMA/MS)70/20/10 qualified qualified Excellent Excellent

*Numbers are mole percentages of monomer units in the copolymer. D.A. = Debris Attachment

1. "Excellent" means a WBUT of 10 seconds or longer.

Example 11

PAA-coated lenses. Lenses cast molded from the lens formulation prepared in Example 3 according to the molding method described in Example 3 were extracted and coated by immersion in the following series of baths: 3 MEK baths (22, 78, and 224 seconds); a DI water bath (56 seconds); 2 PAA coating solution baths (prepared by dissolving 3.6 g PAA (M.W.: 450 kDa, from Lubrizol) in 975 ml of 1-propanol and 25 ml of formic acid) for 44 and 56 seconds, respectively; and 3 DI water baths for 56 seconds each.

PAE/PAA-coated lenses. The lenses prepared above, having a PAA primer coating thereon, were sequentially immersed in the following baths: two baths of a PAE coating solution prepared by dissolving 0.25 wt% PAE (Polycup 172, from Hercules) in DI water and adjusting the pH to approximately 5.0 using sodium hydroxide, and finally filtering the resulting solution using a 5 μm filter; and three baths of DI water for 56 seconds each. After this treatment, the lenses had one PAA layer and one PAE layer.

Lenses with PAA-x-PAE-x-CMC coatings thereon. A batch of lenses having one PAA layer and one PAE layer thereon were packaged in 0.2% sodium carboxymethylcellulose (CMC, product number 7H 3SF PH, Ashland Aqualon) in phosphate buffered saline (PBS), and the pH was adjusted to 7.2-7.4. The bubbles were then sealed and autoclaved at 121° C. for approximately 30 minutes to form a crosslinked coating (PAA-x-PAE-x-CMC) on the lenses.

Lenses with PAA-x-PAE-x-HA coatings thereon. Another batch of lenses having one PAA layer and one PAE layer thereon were packaged in 0.2% hyaluronic acid (HA, product number 6915004, Novozymes) in phosphate buffered saline (PBS), and the pH was adjusted to 7.2-7.4. The bubbles were then sealed and autoclaved at 121° C. for approximately 30 minutes to form a cross-linked coating (PAA-x-PAE-x-HA) on the lenses.

The resulting lenses having either the PAA-x-PAE-x-CMC coating or the PAA-x-PAE-x-HA coating thereon showed no Sudan Black staining, no debris attachment, and no cracks under microscopic examination. The lenses having the PAA-x-PAE-x-CMC coating thereon had an average contact angle of 30±3 degrees, while the lenses having the PAA-x-PAE-x-HA coating thereon had an average contact angle of 20±3 degrees.

Example 12

IPC Solution Preparation. A reaction mixture was prepared by dissolving 2.86 wt% methoxy-poly(ethylene glycol)-thiol (product number MPEG-SH-2000, Laysan Bio Inc.) with an average MW of 2000, along with 2 wt% PAE (Kymene) in PBS and adjusting the final pH to 7.5. The solution was heat-treated at 45°C for approximately 4 hours to form a thermally cross-linkable hydrophilic polymer material containing MPEG-SH-2000 groups chemically grafted onto the polymer via reaction with the azetidine groups in the PAE. Following heat treatment, the solution was diluted 10-fold with PBS containing 0.25% sodium citrate, the pH adjusted to 7.2-7.4, and then filtered through a 0.22 μm polyethersulfone (PES) membrane filter. The final IPC saline contained 0.286 wt% hydrophilic polymer material (composed of approximately 59 wt% MPEG-SH-2000 chains and approximately 41 wt% PAE chains) and 0.25% sodium citrate. PBS was prepared by dissolving 0.74% NaCl, _0.053 % _{NaH2PO4.H2O , and} 0.353% _{Na2HPO4.2H2O in} water.

Lenses having a cross-linked coating thereon. The PAA-coated lenses from Example 11 were packaged in the above IPC saline in a polypropylene lens packaging shell and then autoclaved at about 121° C. for about 30 minutes to form a cross-linked coating on the lens.

After rubbing the lens, the final lens showed no debris adhesion, no crack lines, and was very smooth in the finger rub test compared to the control PAA coated lens.

A series of experiments were conducted to investigate the effect of conditions (reaction time and solution concentration of mPEG-SH2000 (at a constant PAE concentration of 2%)) on the surface properties of the resulting IPC saline-coated lenses. The results are shown in Table 3.

Table 3

D.A. = Debris Adhesion; WCA = Water Contact Angle.

1.PAE concentration: 2 wt%.

As the solution concentration of mPEG-SH 2000 increases, lens lubricity improves. The increased contact angle is believed to be due to an increased density of terminal methyl groups on the surface as the grafting density increases. Contact angle measurements were performed on a grafted polyethylene glycol (PEG) monolayer on a planar substrate at a high grafting density, equivalent to a 0.6% solution concentration (Langmuir 2008, 24, 10646-10653).

Example 13

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

Table 4

D.A. = Debris Adhesion; WCA = Water Contact Angle. * Initial concentration of MPEG-SH in IPC saline with 2% PAE before heat pretreatment and 10-fold dilution.

Example 14

The reaction mixture was prepared by dissolving 2.5% methoxy-poly(ethylene glycol)-thiol (product number MPEG-SH-2000, Laysan Bio Inc.) with an average MW of 2000, 10% PAE (Kymene) in PBS and 0.25% sodium citrate dihydrate. The pH of the final solution was then adjusted to 7.5 and degassed by bubbling nitrogen through the container for 2 hours to minimize thiol oxidation. The solution was then heat-treated at 45°C for approximately 6 hours to form a thermally cross-linkable hydrophilic polymer material containing MPEG-SH-2000 groups chemically grafted onto the polymer by reaction with the azetidine groups in the PAE. Following the heat treatment, the solution was diluted 50-fold with PBS containing 0.25% sodium citrate, the pH adjusted to 7.2-7.4, and then filtered using a 0.22 μm polyethersulfone (PES) membrane filter. The final IPC saline contained approximately 0.30 wt% polymeric material (consisting of approximately 17 wt% MPEG-SH-2000 and approximately 83 wt% PAE) and 0.25% sodium citrate dihydrate.

The PAA coated lenses from Example 11 were packaged in the above IPC saline in a polypropylene lens packaging shell and then autoclaved at about 121°C for about 30 minutes to form a cross-linked coating on the lens.

After rubbing the lens, the final lens showed no debris attached, no crack lines. The test lens was very smooth in the finger rub test compared to the control PAA coated lens.

Example 15

A reaction mixture was prepared by dissolving 3.62% methoxy-poly(glycol)-amine (product number MPEG-NH2-550, Laysan Bio Inc.) with an average MW of 550 in PBS along with 2% PAE (Kymene) and adjusting the final pH to 10. The solution was heat-treated at 45°C for approximately 4 hours to form a thermally cross-linkable hydrophilic polymer material containing MPEG-NH2-550 groups chemically grafted onto the polymer via reaction with the azetidine groups in the PAE. Following heat treatment, the solution was diluted 10-fold with PBS containing 0.25% sodium citrate, the pH adjusted to 7.2-7.4, and then filtered through a 0.22 μm polyethersulfone (PES) membrane filter. The final IPC saline contained approximately 0.562% by weight of the polymer material (composed of 64% by weight MPEG-SH-2000 and approximately 36% by weight PAE) and 0.25% sodium citrate dihydrate. PBS was prepared by dissolving 0.74% _sodium chloride, _0.053 % _NaH2PO4.H2O , _and 0.353% _{Na2HPO4.2H2O in} water.

The PAA coated lenses from Example 11 were packaged in the above IPC saline in a polypropylene lens packaging shell and then autoclaved at about 121°C for about 30 minutes to form a cross-linked coating on the lens.

After rubbing the lens the final lens showed no debris attached and no crack lines.

Example 16

Poloxamer 108 (sample) and nelfilcon A (CIBA VISION) were used directly. 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-forming reaction conditions (Bühler et al., CHIMIA, 53 (1999), 269-274, the entire contents of which are incorporated herein by reference). Approximately 2.5% of the vinyl alcohol units in nelfilcon A were modified with N-(2,2-dimethoxyethyl)acrylamide.

IPC saline was prepared by dissolving 0.004% poloxamer 108, 0.8% nelfilcon A, 0.2% PAE (Kymene, Polycup 3160), 0.45% NaCl, and 1.1% Na ₂ HPO ₄ .2H ₂ O in DI water. The saline was heat pretreated by stirring at approximately 65-70° C. for 2 hours. After heat pretreatment, the saline was cooled to room temperature and then filtered using a 0.2 μm PES filter.

The lens prepared in Example 3 was placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline was added before inserting the lens). The bubble was then sealed with foil and autoclaved at 121°C for approximately 30 minutes.

The test lens showed no debris adhered after rubbing with a paper towel. The lens had a WBUT of more than 10 seconds. When observed under a darkfield microscope, no crack lines were visible after rubbing the lens between fingers. The lens was much smoother than the lens from Example 4, but still not as smooth as the control lens encapsulated in PBS.

Example 17

A. Synthesis of 80% Olefinically Functionalized Chain-Extended Polysiloxane

KF-6001A (α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane, Mn=2000, from Shin-Etsu) and KF-6002A (α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane, Mn=3400, from Shin-Etsu) were dried in a single-necked flask under high vacuum at about 60° C. for 12 hours (or overnight). The OH molar equivalents of KF-6001A and KF-6002A were determined by titration of the hydroxyl groups and used to calculate the millimole equivalents to be used in the synthesis.

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

For the 80% ethylenically functionalized polysiloxane, 18.64 g (120 meq) of IEM was added to the reactor along with 100 μL of DBTDL. The reactor was stirred for 24 hours and then the product (80% IEM-capped CE-PDMS) was poured out and stored frozen.

B. Synthesis of Non-UV Absorbing Amphiphilic Branched Polysiloxane Prepolymers

A 1-L jacketed reactor was equipped with a 500-mL addition funnel, an overhead stirrer, a reflux condenser with a nitrogen/vacuum inlet adapter, a thermometer, and a sampling adapter. The reactor was charged with 45.6 g of the 80% IEM-terminated CE-PDMS prepared above and sealed. A solution of 0.65 g of hydroxyethyl methacrylate (HEMA), 25.80 g of DMA, and 27.80 g of (tris(trimethylsilyl))-siloxypropyl) methacrylate (TRIS) in 279 g of ethyl acetate was charged to the addition funnel. The reactor was degassed at <1 mbar at RT using a high vacuum pump for 30 minutes. The monomer solution was degassed at 100 mbar and RT for three cycles of 10 minutes, breaking the vacuum with nitrogen between degassing cycles. The monomer solution was then charged to the reactor, and the reaction mixture was then stirred and heated to 67°C. While heating, a solution of 1.50 g of mercaptoethanol (chain transfer agent, CTA) and 0.26 g of azoisobutyronitrile dissolved in 39 g of ethyl acetate was charged to the addition funnel and deoxygenated three times at 100 mbar and RT for 10 minutes. When the reactor temperature reached 67°C, the initiator/CTA solution was added to the PDMS/monomer solution in the reactor. The reaction was allowed to proceed for 8 hours, after which heating was stopped and the reactor temperature was allowed to reach room temperature over 15 minutes.

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

C. Synthesis of UV-absorbing amphoteric branched polysiloxane prepolymers

A 1-L jacketed reactor was equipped with a 500-mL addition funnel, an overhead stirrer, a reflux condenser with a nitrogen/vacuum inlet adapter, a thermometer, and a sampling adapter. The reactor was then charged with 45.98 g of the 80% IEM-terminated CE-PDMS prepared above and sealed. A solution of 0.512 g HEMA, 25.354 g DMA, 1.38 g Norbloc methacrylate, and 26.034 g TRIS in 263 g ethyl acetate was added to the addition funnel. The reactor was degassed at <1 mbar for 30 minutes at room temperature using a high vacuum pump. The monomer solution was degassed at 100 mbar and room temperature for three cycles of 10 minutes, with nitrogen breaking the vacuum between degassing cycles. The monomer solution was then charged into the reactor, and the reaction mixture was stirred and heated to 67°C. While heating, a solution of 1.480 g of mercaptoethanol (chain transfer agent, CTA) and 0.260 g of azoisobutyronitrile dissolved in 38 g of ethyl acetate was charged to the addition funnel and deoxygenated three times at 100 mbar and room temperature for 10 minutes. When the reactor temperature reached 67°C, the initiator/CTA solution was added to the PDMS/monomer solution in the reactor. The reaction was allowed to proceed for 8 hours, after which heating was stopped and the reactor temperature was allowed to reach room temperature over 15 minutes.

The resulting reaction mixture was then siphoned into a dry, single-necked flask with an airtight lid, and 3.841 g of isocyanatoethyl acrylate was added along with 0.15 g of DBTDL. The mixture was stirred at room temperature for 24 hours to form a UV-absorbing, amphoteric, branched polysiloxane prepolymer. To this mixture was added 100 μL of a solution of hydroxy-tetramethylenepiperidyloxy in ethyl acetate (2 g/20 mL). The solution was then concentrated to 200 g (~50%) using a rotary evaporator at 30°C and filtered through a 1 μm pore size filter paper.

D-1: Lens formulation with non-UV absorbing polysiloxane prepolymer

In a 100 mL amber flask, 4.31 g of the synthetic macromer solution prepared in Example C-2 (82.39% in 1-propanol) was added. In a 20 mL vial, 0.081 g of TPO and 0.045 g of DMPC were dissolved in 10 g of 1-propanol and then transferred to the macromer solution. After the mixture was concentrated to 5.64 g using a rotary evaporator at 30°C, 0.36 g of DMA was added, and the formulation was homogenized at room temperature. This yielded 6 g of clear lens formulation D-1.

D-2: Lens formulation with UV absorbing polysiloxane prepolymer (4% DMA)

In a 100 mL amber flask, 24.250 g of the macromer solution prepared in Example D-2 (43.92% in ethyl acetate) was added. In a 50 mL vial, 0.15 g of TPO and 0.75 g of DMPC were dissolved in 20 g of 1-propanol and then transferred to the macromer solution. 20 g of solvent was removed using a rotary evaporator at 30° C., followed by the addition of 20 g of 1-propanol. After two cycles, the mixture was concentrated to 14.40 g. 0.6 g of DMA was added to the mixture, and the formulation was homogenized at room temperature. This yielded 15 g of clear lens formulation D-2.

D-3: Lens formulation with UV absorbing silicone prepolymer (2% DMA/2% HEA)

In a 100 mL amber flask, 24.250 g of the macromer solution prepared in Example D-2 (43.92% in ethyl acetate) was added. In a 50 mL vial, 0.15 g of TPO and 0.75 g of DMPC were dissolved in 20 g of 1-propanol and then transferred to the macromer solution. 20 g of solvent was removed using a rotary evaporator at 30° C., followed by the addition of 20 g of 1-propanol. After two cycles, the mixture was concentrated to 14.40 g. 0.3 g of DMA and 0.3 g of HEA were added to this mixture, and the formulation was homogenized at room temperature. This yielded 15 g of clear lens formulation D-3.

Example 18

Example E: Covalent attachment of modified PAE coating polymers

Monomers containing amine groups: N-(3-aminopropyl)methacrylamide hydrochloride (APMAA-HCl) or N-(2-aminoethyl)methacrylamide hydrochloride (AEMAA-HCl) were purchased from Polysciences and used directly. Poly(amidoamine epichlorohydrin) (PAE) was obtained from Ashland as an aqueous solution and used directly. Poly(acrylamide-co-acrylic acid) (poly(AAm-co-AA) (90/10) from Polysciences, mPEG-SH from Laysan Bio, and poly(MPC-co-AeMA) (i.e., a copolymer of methacryloyloxyethylphosphocholine (MPC) and aminoethyl methacrylate (AeMA)) from NOF were used directly.

APMAA-HCl monomer was dissolved in methanol and added to lens formulations D-1, D-2, and D-3 (prepared in Example 17) to achieve a 1 wt% concentration.

Reactive packaging saline was prepared by dissolving the components listed in Table 5 along with the appropriate buffer salts in DI water. Following heat pretreatment, the brine was allowed to cool to room temperature and then filtered using a 0.2 μm PES filter.

Table 5

Lens formulations D-1, D-2, and D3 prepared in Example 17 were modified by the addition of APMMAA-HCl monomer (stock solution of APMMA-HCl in methanol). The DSM lenses were cured at 16 mW/cm ² using a 330 nm filter, while the LS lenses were cured at 4.6 mW/cm ² using a 380 nm filter.

DSM Lenses. The female portion of a polypropylene lens mold was filled with approximately 75 μl of the lens formulation prepared above, and the mold was sealed with the male portion of a polypropylene lens mold (baseline mold). Contact lenses were obtained by curing the sealed mold with a UV radiation source (Hamamatsu lamp with a 330 nm cutoff filter and an intensity of approximately 16 mW/ ^cm2 ) for approximately 5 minutes.

LS Lenses. LS lenses were prepared by cast molding the lens formulation prepared above in a reusable mold similar to the mold shown in Figures 1-6 of U.S. Patent Nos. 7,384,590 and 7,387,759 (Figures 1-6). The mold comprised a female mold half composed of quartz (or _CaF2 ) and a male mold half composed of glass (or PMMA). The UV radiation source was a Hamamatsu lamp with a 380 nm cutoff filter and an intensity of approximately 4.6 mW/ ^cm2 . The lens formulation in the mold was irradiated with UV radiation for approximately 30 seconds.

Lens formulation D-1 modified with APMAA-HCl was cured according to the DSM and LS methods described above, while lens formulation D-2 or D-3 was cured according to the LS method described above.

The molded lenses were extracted with methyl ethyl ketone, hydrated, and packaged in one of the saline solutions described in Table 5. The lenses were placed in polypropylene lens packaging shells with 0.6 mL of IPC saline (half of the saline was added before inserting the lens). The bubble was then sealed with foil and autoclaved at 121° C. for 30 minutes.

Evaluation of the lens surface showed that all test lenses had no debris attached. When observed under a dark field microscope, no crack lines were visible after rubbing the lenses between fingers.

The lens surface wettability (WBUT), lubricity, and contact angle were measured, and the results are summarized in Table 6. Unless otherwise specified, lenses were prepared according to the DSM method. Lubricity was rated on a qualitative scale of 0-4, with lower numbers indicating greater lubricity. Generally, lens surface properties improved slightly after application of the inner coating.

Table 6

1. The numbers are the numbers of the packaged brine shown in Table 5.

2.LS lens

Example 19

Lenses were made using lens formulation D-2 (Example 17) to which APMAA monomer was added to a concentration of 1%. LS lenses were made by cast molding the lens formulation prepared above in a reusable mold similar to the molds shown in Figures 1-6 of U.S. Patent Nos. 7,384,590 and 7,387,759 (Figures ^1-6 ). The mold comprised a female mold half constructed of glass and a male mold half constructed of quartz. The UV radiation source was a Hamamatsu lamp with a 380 nm cutoff filter and an intensity of approximately 4.6 mW/cm2. The lens formulation in the mold was irradiated with UV radiation for approximately 30 seconds.

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

IPC saline was prepared according to the composition described in Example 9 using a pre-reaction condition of approximately 60°C for 8 hours. The lens was placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline was added before inserting the lens). The bubble was then sealed with foil and autoclaved at 121°C for 30 minutes.

Evaluation of the lens surface showed that all test lenses had no debris attached. When observed under a dark field microscope, no crack lines were visible after rubbing the lens between fingers. The lens surface wettability (WBUT) was greater than 10 seconds, the lubricity was rated "1", and the contact angle was approximately 20°.

Example 20

Preparation of lens formulations

A lens formulation was prepared by dissolving the components in 1-propanol to have the following composition: approximately 32 wt% of the CE-PDMS macromer prepared in Example 2, approximately 21 wt% TRIS-Am, approximately 23 wt% DMA, approximately 0.6 wt% L-PEG, approximately 1 wt% DC1173, approximately 0.1 wt% visitint (5% copper phthalocyanine blue pigment dispersion in TRIS), approximately 0.8 wt% DMPC, approximately 200 ppm H-tempo, and approximately 22 wt% 1-propanol.

Lens Preparation. Lenses were prepared by cast molding the lens formulation prepared above in a reusable mold (quartz female mold half and glass male mold half) similar to the mold shown in Figures 1-6 of U.S. Patent Nos. 7,384,590 and 7,387,759 (Figures 1-6). The lens formulation in the mold was irradiated with UV radiation (13.0 mW/ ^cm2 ) for about 24 seconds.

PAA coating solution. The PAA coating solution was prepared by dissolving a certain amount of PAA (M.W.: 450 kDa, from Lubrizol) in a given volume of 1-propanol to have a concentration of about 0.36-0.44 wt % and adjusting the pH to about 1.7-2.3 with formic acid.

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

IPC saline. Poly(AAm-co-AA) (90/10) partial sodium salt (~90% solids, poly(AAm-co-AA) 90/10, Mw 200,000) was purchased from Polysciences, Inc. and used as received. PAE (Kymene, azetidine content 0.46 by NMR) was purchased from Ashland as an aqueous solution and used as received. IPC saline was prepared by dissolving approximately 0.07% w/w poly(AAm-co-AA) (90/10) and approximately 0.15% PAE (initial azetidine millimole equivalent was approximately 8.8 mmol) in PBS (approximately 0.044 _w /w% _{NaH2PO4 · H2O} , approximately 0.388 w/w/% _Na2HPO4 · _2H2O , approximately 0.79 w/w% NaCl) and adjusting the pH to 7.2-7.4. The IPC saline was then heat-pretreated at approximately 70°C for approximately 4 hours (heat pretreatment). During this heat pretreatment, poly(AAm-co-AA) and PAE partially crosslinked with each other (i.e., without consuming all of the azetidinium groups of PAE) to form a water-soluble and heat-crosslinkable hydrophilic polymer material containing azetidinium groups within the branched polymer network in the IPC saline. After the heat pretreatment, the IPC saline was filtered using a 0.22 μm polyethersulfone [PES] membrane filter and cooled back to room temperature. 10 ppm of hydrogen peroxide was then added to the final IPC saline to prevent bioburden growth and filtered using a 0.22 μm PES membrane filter.

Application of Cross-Linked Coating. The lens having the PAA-LbL primer coating thereon prepared above was placed in a polypropylene lens packaging shell (one lens per shell) with 0.6 mL of LPC saline (half of the saline was added before lens insertion). The bubble was then sealed with foil and autoclaved at approximately 121° C. for approximately 30 minutes to form a SiHy contact lens having a cross-linked coating (PAA-x-hydrophilic polymer material) thereon.

Characterization of SiHy Lenses. The resulting SiHy contact lenses having a crosslinked coating (PAA-x-hydrophilic polymer material) thereon showed no debris adhesion after rubbing with a paper towel, whereas control lenses (encapsulated in PBS, i.e., lenses having a non-covalently attached PAA layer thereon) showed severe debris adhesion. The lenses had an oxygen permeability (Dk _c or estimated intrinsic Dk) of approximately 146 barrers, a bulk modulus of approximately 0.76 MPa, a water content of approximately 32 wt%, a relative ion permeability of approximately 6 (relative to Alsacon lenses), a contact angle of approximately 34-47 degrees, and a WBUT greater than 10 seconds. When observed under a darkfield microscope, no crack lines were visible after rubbing the test lenses. The lenses were very smooth in a finger rub test and were equivalent to the control lenses.

Example 21

The SiHy lenses and IPC saline in post-autoclaved lens packages prepared in Examples 6, 14, and 20 were subjected to the following biocompatibility studies.

In vitro cytotoxicity assessment. SiHy lenses were evaluated by the USP direct contact material test. Lens extracts were evaluated by the USP MEM elution and ISO CEN cytotoxicity inhibition tests, and IPC saline in packaging after autoclaving was evaluated by the modified elution test. All lenses and lens extracts evaluated were well within the acceptance criteria for each test, and no unacceptable cytotoxicity was observed.

In vivo studies. ISO systemic toxicity in mice showed no evidence of systemic toxicity of lens extracts to mice. ISO eye irritation studies in rabbits showed that lens extracts were not considered irritants to rabbit eye tissue. ISO eye irritation studies in rabbits showed that IPC saline in the packaging after autoclaving was not considered an irritant to rabbit eye tissue. Wearing the lenses in a daily disposable wear mode for 22 consecutive days was non-irritating to the rabbit model, and eyes treated with the test lenses were similar to eyes treated with the control lenses. ISO allergy studies (Guinea Pig Maximization Testing of Packaging Solutions) showed that IPC saline after autoclaving did not cause any delayed skin contact sensitization in guinea pigs. ISO allergy studies (Guinea Pig Maximization Testing of Lens Extracts) showed that sodium chloride and sesame oil extracts of the lenses did not cause delayed skin contact sensitization in guinea pigs.

Genotoxicity Testing. When IPC saline and SiHy lens extracts from lens packaging were tested in a bacterial reverse mutation assay (Ames Test), the lens extracts and IPC saline were found to be non-mutagenic against Salmonella typhimurium test strains TA98, TA100, TA1535, and TA1537 and Escherichia coli WPuvrA. When SiHy lens extracts were tested in a mammalian erythrocyte micronucleus assay, they had no clastogenic activity and were negative in a mouse bone marrow micronucleus assay. When IPC saline from lens packaging was tested in a chromosome aberration assay in Chinese hamster ovaries, IPC saline was negative for inducing structural and quantitative chromosome aberrations using CHO cells in both the non-activated and S9 activated assay systems. When SiHy lens extracts were tested in a cellular gene mutation assay (mouse lymphoma gene mutation assay), the lens extracts were negative in the mouse lymphoma gene mutation assay.

Example 22

The surface composition of preformed SiHy contact lenses (i.e., SiHy contact lenses without any coating and before application of the PAA primer coating), SiHy contact lenses with PAA coatings (i.e., those lenses before being sealed and autoclaved in a lens package with IPC saline), and SiHy contact lenses with crosslinked coatings thereon, all prepared according to the procedure described in Example 20, was determined by characterizing vacuum-dried contact lenses using X-ray photoelectron spectroscopy (XPS). XPS is a method for measuring the surface composition of lenses at a sampling depth of approximately 10 nm. The surface compositions of the three types of lenses are reported in Table 7.

Table 7

*: Fluorine was most likely detected from surface contaminants during vacuum drying method XPS analysis.

Table 7 shows that when a PAA coating is applied to a SiHy lens (preformed without a coating), the carbon and oxygen atomic compositions approach those of PAA (60% C and 40% O), and the silicon atomic composition decreases substantially (from 12.1% to 4.5%). When a crosslinked coating is further applied to the PAA coating, the surface composition is dominated by carbon, nitrogen, and oxygen, which are the three atomic compositions (excluding hydrogen, as XPS does not count hydrogen in the surface composition). These results suggest that the outermost layer of the SiHy contact lens with a crosslinked coating may be essentially composed of a hydrophilic polymer material that is the reaction product of poly(AAm-co-AA) (90/10) (60% C, 22% O, and 18% N) and PAE.

The following commercial SiHy lenses that were vacuum dried were also subjected to XPS analysis. The surface compositions of those commercial SiHy contact lenses are reported in Table 8.

Table 8

*: Fluorine was also detected in Advance, Oasys, and TruEye lenses, likely from surface contaminants during vacuum dry method XPS analysis.

The SiHy contact lenses of the present invention were found to have a nominal silicone content of approximately 1.4% in the surface layer, which is much lower than those of commercial SiHy lenses without plasma coating (TruEye ^™ , Avaira ^™ ) and (with plasma oxidation) and Premio ^™ (with unknown plasma treatment), and even lower than SiHy lenses with plasma-deposited coatings having a thickness of approximately 25 nm (Aqua ^™ and AirAqua ^™ ). This very low Si% value is comparable to the silicon atomic percentage of a control sample of polyethylene from Goodfellow (LDPE, d=0.015 mm; LS356526SDS; ET31111512; 3004622910). These results suggest that the very low values in the XPS analysis of the vacuum-dried SiHy contact lenses of the present invention may be due to contaminants introduced during the preparation process, including the vacuum drying process and XPS analysis, similar to the fluorine content observed in lenses without fluorine. The silicone in the SiHy contact lenses of the present invention was successfully shielded from exposure.

XPS analysis was also performed on SiHy contact lenses of the present invention (prepared according to the procedure described in Example 20), commercial SiHy contact lenses (CLARITI ^™ 1 Day, TruEye ^™ (narafilcon A and narafilcon B)), polyethylene sheets from Goodfellow (LDPE, d = 0.015 mm; LS356526SDS; ET31111512; 3004622910), (polyvinyl alcohol hydrogel lenses, i.e., non-silicone hydrogel lenses), and Moist (polyhydroxyethyl methacrylate hydrogel lenses, i.e., non-silicone hydrogel lenses). All lenses were vacuum dried. The polyethylene sheets, and Moist were used as controls because they do not contain silicone. The silicon atomic composition in the surface layer of the specimens was as follows: 1.3±0.2 (polyethylene sheet); 1.7±0.9 and 2.8±0.9 (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 (TruEye ^™ (narafilcon A)); and 6.5±0.1 (TruEye ^™ (narafilcon B)). The results for the SiHy contact lenses of the present invention were closer to those of conventional hydrogels than to those of silicone hydrogels.

Example 23

Synthesis of UV-absorbing amphiphilic branched copolymers

A 1-L jacketed reactor was equipped with a 500-mL addition funnel, an overhead stirrer, a reflux condenser with a nitrogen/vacuum inlet adapter, a thermometer, and a sampling adapter. 89.95 g of the 80% partially olefinically functionalized polysiloxane prepared in Example 17A was charged to the reactor and then degassed at room temperature under a vacuum of less than 1 mbar for approximately 30 minutes. A monomer solution prepared by mixing 1.03 g HEMA, 50.73 g DMA, 2.76 g Norbloc methacrylate, 52.07 g TRIS, and 526.05 g ethyl acetate was charged to a 500-mL addition funnel and then degassed at room temperature under a vacuum of 100 mbar for 10 minutes before refilling with nitrogen. The monomer solution was degassed under the same conditions for two additional cycles. The monomer solution was then charged to the reactor. The reaction mixture was heated to 67°C with appropriate stirring. While heating, a solution consisting of 2.96 g of mercaptoethanol (chain transfer agent, CTA), 0.72 g of dimethyl 2,2'-azobis(2-methylpropionate) (V-601 - initiator), and 76.90 g of ethyl acetate was charged to the addition funnel, followed by the same degassing method as the monomer solution. When the reactor temperature reached 67°C, the initiator/CTA solution was also added to the reactor. The reaction was carried out at 67°C for 8 hours. After the copolymerization was complete, the reactor temperature was cooled to room temperature.

Synthesis of UV-absorbing amphoteric branched prepolymers

The copolymer solution prepared above was olefinically functionalized by adding 8.44 g of IEM (or the desired molar equivalent of 2-isocyanatoethyl methacrylate) in the presence of 0.50 g of DBTDL to form an amphiphilic branched prepolymer. The mixture was stirred at room temperature under sealed conditions for 24 hours. The prepolymer was then stabilized with 100 ppm of hydroxytetramethylenepiperonyloxy groups, and the solution was concentrated to 200 g (~50%) and filtered through 1 μm pore size filter paper. After the reaction solvent was exchanged for 1-propanol by repeated evaporation and dilution cycles, the solution was used for formulation. Solids content was measured by removing the solvent in a vacuum oven at 80°C.

Preparation of lens formulations

A lens formulation was prepared to have the following composition: 71 wt% of the prepolymer prepared above; 4 wt% DMA; 1 wt% TPO; 1 wt% DMPC; 1 wt% Brij 52 (from GLUTAM®), and 22 wt% 1-PrOH.

Lens preparation

The lens was made by cast molding the lens formulation prepared above in a reusable mold similar to the molds shown in Figures 1-6 of U.S. Patent Nos. 7,384,590 and 7,387,759 (Figures 1-6) under spatial confinement of UV radiation. The mold comprised a female mold half made of glass and a male mold half made of quartz. The UV radiation source was a Hamamatsu lamp with a 380 nm cutoff filter and an intensity of approximately 4.6 mW/ ^cm2 . The lens formulation in the mold was irradiated with UV radiation for approximately 30 seconds.

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

IPC saline was prepared from a composition containing approximately 0.07% PAAm-PAA and sufficient PAE (~0.15% PAE) to provide an initial azetidine content of approximately 8.8 mmol/L under pre-reaction conditions at approximately 60°C for 6 hours. 5 ppm hydrogen peroxide was then added to the IPC saline to prevent bioburden growth and the IPC saline was filtered using a 0.22 μm polyethersulfone [PES] membrane filter. The lens was placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline was added prior to lens insertion). The bubble was then sealed with foil and autoclaved at 121°C for 30 minutes.

Lens characterization

The resulting lens had the following properties: E' ~0.82 MPa; DK _c ~159.4 (using lotrafilcon B as a reference lens, with an average center thickness of 80 μm and an intrinsic Dk of 110); IP ~2.3; % water ~26.9; and UVA/UVB %T ~4.6/0.1. When observed under a darkfield microscope, no crack lines were visible after rubbing the test lens. The lens was very lubricated and equivalent to the control lens in a finger rub test.

Example 24

Preparation of lens formulations

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

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

Lens preparation

Lenses were prepared by cast molding the lens formulation prepared above in a reusable mold (quartz female mold half and glass male mold half) similar to the molds shown in Figures 1-6 of U.S. Patent Nos. 7,384,590 and 7,387,759 (Figures 1-6). The UV radiation source was a Hamamatsu lamp with a WG335+TM297 cutoff filter and an intensity of approximately 4 mW/ ^cm2 . The lens formulation in the mold was irradiated with UV radiation for approximately 25 seconds. The cast-molded lenses were extracted with methyl ethyl ketone (MEK) (or propanol or isopropanol).

Application of PAA Primer Coating on SiHy Contact Lenses

A polyacrylic acid coating solution (PAA-1) was prepared by dissolving a certain amount of PAA (M.W.: 450 kDa, from Lubrizol) in a given volume of 1-propanol to have a concentration of about 0.39 wt% and adjusting the pH to about 2.0 with formic acid.

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

The SiHy contact lenses obtained above were subjected to one of the dipping methods shown in Tables 9 and 10.

Table 9

PrOH indicates 100% 1-propanol; PBS indicates phosphate-buffered saline; MEK indicates methyl ethyl ketone; and 50/50 indicates a 50/50 solvent mixture of 1-PrOH/H ₂ O.

Table 10

PrOH indicates 100% 1-propanol; PBS indicates phosphate-buffered saline; MEK indicates methyl ethyl ketone; and 50/50 indicates a 50/50 solvent mixture of 1-PrOH/H ₂ O.

Application of cross-linked hydrophilic coating

Poly(acrylamide-co-acrylic acid) partial sodium salt, poly(AAm-co-AA) (90/10) (~90% solids, poly(AAm-co-AA) 90/10, Mw 200,000) was purchased from Polysciences, Inc. and used as received. PAE (Kymene, azetidine content 0.46 by NMR) was purchased from Ashland as an aqueous solution and used as received. In-package crosslinking (IPC) saline was prepared by dissolving approximately 0.07% w/w poly(AAm-co-AA) (90/10) and approximately 0.15% PAE (approximately 8.8 mmol of initial azetidine millimolar equivalent) in phosphate buffered saline (PBS) (approximately 0.044 _w /w% _NaH2PO4 · _H2O , approximately 0.388 w/w/% _Na2HPO4 · _2H2O , approximately 0.79 _w /w% NaCl) and adjusting the pH to 7.2-7.4. The IPC saline was then heat-pretreated at approximately 70°C for approximately 4 hours (heat pretreatment). During this heat pretreatment, poly(AAm-co-AA) and PAE partially crosslinked with each other (i.e., without consuming all of the azetidine groups of PAE) to form a water-soluble and heat-crosslinkable hydrophilic polymer material containing azetidine groups within a branched polymer network in the IPC saline. After heat pretreatment, the IPC saline was filtered using a 0.22 μm polyethersulfone [PES] membrane filter and cooled back to room temperature. 10 ppm hydrogen peroxide was then added to the final IPC saline to prevent bioburden growth and the IPC saline was filtered using a 0.22 μm polyethersulfone [PES] membrane filter.

The lens having the PAA primer coating thereon prepared above was placed in a polypropylene lens packaging shell (one lens per shell) with 0.6 mL of IPC saline (half of the saline was added before inserting the lens). The bubble was then sealed with foil and autoclaved at about 121° C. for about 30 minutes to form a SiHy contact lens having a cross-linked hydrophilic coating thereon.

Characterization of SiHy lenses

The resulting SiHy contact lens having a cross-linked hydrophilic coating thereon and a center thickness of about 0.95 μm has an oxygen permeability (Dk _c or estimated intrinsic Dk) of about 142 to about 150 barrers, a bulk modulus of about 0.72 to about 0.79 MPa, a water content of about 30 to about 33 weight percent, a relative ion permeability of about 6 (relative to an Alsacon lens), and a contact angle of about 34 to about 47 degrees.

Characterization of Nanostructured Surfaces of Contact Lenses

Transmission differential interference contrast method. A contact lens is placed on a glass slide and flattened by pressing the lens between the slide and a cover glass. The contact lens surface is positioned and examined by focusing the lens using a Nikon ME600 microscope with transmission differential interference contrast goggles using a 40x objective. The resulting TDIC image is then evaluated to determine the presence of scintillating surface patterns (e.g., random and/or ordered worm-like patterns, etc.).

Reflection Differential Interference Contrast (RDIC) Method. The lens is placed on a glass slide and flattened by making four radial sections every ~90 degrees. Excess saline is blown off the surface using compressed air. The lens surface is then examined using a Nikon Optiphot-2 with reflection differential interference contrast goggles using 10x, 20x, and 50x objectives to determine the presence of scintillating surface patterns on the contact lens surface. Representative images of each side are obtained using a 50x objective. The contact lens is then flipped over, excess saline removed, and the other side of the contact lens examined in the same manner. The resulting RDIC images are then evaluated to determine the presence of scintillating surface patterns (e.g., random and/or ordered worm-like patterns, etc.).

Darkfield optical microscopy (DFLM). DFLM is typically based on darkfield illumination, a method for enhancing contrast in observed specimens. The technique consists of a light source that is external to the observer's field of view or blocked out, illuminating the specimen at an angle relative to standard transmitted light. Since the non-diffuse 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 specimen at an angle, the light observed in the specimen image is scattered by the specimen toward the observer, creating contrast between this scattered light from the specimen and the dark background of the image. This contrast mechanism makes darkfield illumination particularly useful for observing scattered phenomena such as haze.

DFLM is used to assess the haze of contact lenses as follows. It is believed that because the darkfield setting involves scattered light, darkfield data provides a worst-case estimate of haze. In an 8-bit grayscale digital image, each image pixel is assigned a grayscale intensity (GSI) value from 0 to 255. 0 represents a completely black pixel, and 255 represents a completely white pixel. Increasing the amount of scattered light captured in the image produces pixels with higher GSI values. This GSI value can then be used as a mechanism to quantify the amount of scattered light observed in the darkfield image. Haze is expressed by averaging the GSI values of all pixels within an area of interest (AOI) (e.g., the entire lens or the lenticular or optical zone of the lens). The experimental setup consists of a microscope or equivalent optics, an attached digital camera, and a darkfield setup with an annular light and a variable-intensity light source. The optics are set up/arranged so that the contact lens to be observed fully fills the field of view (typically ~15 mm × 20 mm). Illumination is set to a level appropriate for observing the desired changes in the specimen of interest. Light intensity is adjusted/calibrated to the same level for each set of samples using a density/light scattering standard, as known to those skilled in the art. For example, a standard consists of two overlapping plastic coverslips (identical and lightly or moderately matte). This standard consists of areas with three different average GSIs, including two areas with intermediate gray levels and a saturated white (edge). The black area represents the empty dark field. The black and saturated white areas can be used to verify the camera's gain and offset (contrast and brightness) settings. The intermediate gray levels provide three points for verifying the camera's linear response. Light intensity is adjusted so that the average GSI of the empty dark field reaches 0, and the designated AOI in the digital image of the standard is identical within ±5 GSI units. After light intensity calibration, the contact lens is immersed in 0.2 μm filtered phosphate-buffered saline in a quartz petri dish or a dish of similar transparency placed on a DFLM stage. An 8-bit grayscale digital image of the lens is then acquired, as observed using the calibrated illumination, and the average GSI of the designated AOI within a portion of the image containing the lens is measured. This was repeated for the contact lens sample set. Light intensity calibration was tested and reassessed periodically to ensure consistency. The haze level under DFLM inspection refers to the DFLM haze level.

SiHy contact lenses whose PAA primer coatings were obtained according to the dipping methods 20-0 and 80-0 were measured to have an average DFLM haze of about 73% and to exhibit a shimmering surface pattern (random worm-like pattern) that can be visually observed by examining the contact lenses in a hydrated state according to the RDIC or TDIC method described above. However, the shimmering surface pattern does not actually have a negative effect on the light transmittance of the contact lenses.

SiHy contact lenses having PAA primers obtained according to any of the dipping methods 20-1 to 20-4 were determined to have a low average DFLM haze of approximately 26% (possibly due to the presence of visitint pigment particles) and did not show a distinct glittering surface pattern (random worm-like pattern) when examined under RDIC or TDIC as described above.

The high percentage SiHy contact lenses whose PAA primer coatings were obtained according to Dip Method 20-5 were determined to have a moderate average DFLM of about 45% and exhibited a slightly noticeable glittering surface pattern when examined under RDIC or TDIC as described above. However, the glittering surface pattern did not actually have a negative impact on the light transmission of the contact lenses.

SiHy contact lenses having PAA primers obtained according to any of the dipping methods 80-1, 80-2, 80-3, 80-5, and 80-6 exhibited no apparent glittering surface pattern when examined under RDIC or TDIC as described above. However, SiHy contact lenses having PAA primers obtained according to the dipping methods 80-0 and 80-4 exhibited apparent glittering surface pattern when examined under RDIC or TDIC as described above. However, the glittering surface pattern did not actually adversely affect the light transmittance of the contact lenses.

Claims (42)

1. An easy-to-use silicone hydrogel contact lens, comprising: Pre-formed silicone hydrogel contact lenses containing amino and/or carboxyl groups on or near the surface of the contact lens; and Its cross-linked hydrophilic coating, The preformed siloxane hydrogel contact lens is obtained by casting and molding a lens formulation, wherein the lens formulation comprises at least one component selected from the following: siloxane-containing vinyl monomers, siloxane-containing prepolymers, hydrophilic vinyl monomers, hydrophobic vinyl monomers, and combinations thereof. The cross-linked hydrophilic coating is formed by the cross-linking reaction of a water-soluble and thermally cross-linkable hydrophilic polymer material with a pre-formed siloxane hydrogel contact lens at a temperature of 40-140℃. The water-soluble and thermally crosslinkable hydrophilic polymer materials include: (i) 20 to 95% by weight of a first polymer chain derived from epichlorohydrin-functionalized polyamines or polyamide-type amines. (ii) 5 to 80% by weight of a hydrophilic structural portion or second polymer chain derived from at least one hydrophilic reinforcing agent, said hydrophilic reinforcing agent having at least one reactive functional group selected from amino, carboxyl, thiol groups and combinations thereof, wherein the hydrophilic structural portion or second polymer chain is covalently attached to the first polymer chain via one or more covalent bonds formed between each of an azo-butyryl group of an epichlorohydrin-functionalized polyamine or polyamide-type amine and an amino, carboxyl, or thiol group of the hydrophilic reinforcing agent, and (iii) A positively charged nitrogen-containing heterocyclic butyl group, which is part of the first polymer chain or a side group or end group covalently attached to the first polymer chain. In the crosslinking reaction, a positively charged nitrogen-containing heterocyclic butyl group of a water-soluble and thermally crosslinkable hydrophilic polymer material reacts with an amino or carboxyl group on or near the surface of a pre-formed siloxane hydrogel contact lens to form a neutral hydroxyl-containing covalent bond. The readily usable siloxane hydrogel contact lens is characterized by surface hydrophilicity/wetting properties with an average water contact angle of 90 degrees or less. 2. The easy-to-use silicone hydrogel contact lens of claim 1, wherein the easy-to-use silicone hydrogel contact lens is characterized by surface hydrophilicity/wetting properties having an average water contact angle of 80 degrees or less. 3. The easy-to-use silicone hydrogel contact lens of claim 1, wherein the easy-to-use silicone hydrogel contact lens is characterized by surface hydrophilicity/wetting properties having an average water contact angle of 70 degrees or less. 4. The easy-to-use silicone hydrogel contact lens of claim 1, wherein the easy-to-use silicone hydrogel contact lens is characterized by surface hydrophilicity/wetting properties having an average water contact angle of 60 degrees or less. 5. The easy-to-use siloxane hydrogel contact lens of claim 1, wherein the water-soluble and thermally crosslinkable hydrophilic polymer material comprises 35 to 90% by weight of a first polymer chain. 6. The easy-to-use silicone hydrogel contact lens according to any one of claims 1-5, wherein the pre-formed silicone hydrogel contact lens is prepared by polymerizing a silicone hydrogel lens formulation, said formulation comprising 0.1 to 10% by weight of a reactive vinyl monomer selected from amino- _C2 - _C6 alkyl methacrylate, _C1 -C6 alkylamino- _C2 - _{C6 alkyl} methacrylate, allylamine, ethyleneamine, amino- _C2 - _C6 alkyl(meth)acrylamide, _C1 - _C6 alkylamino- _C2 - _C6 alkyl(meth)acrylamide, acrylic acid, _C1 -C6... _12- alkyl acrylic acid, N,N-2-acryloylaminohydroxyacetic acid, β-methacrylic acid, α-phenylacrylic acid, β-acryloyloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesocarboxylic acid, pentenoic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof. 7. An easy-to-use siloxane hydrogel contact lens according to any one of claims 1-5, wherein the hydrophilicity enhancer is a hydrophilic polymer having one or more amino, carboxyl, and/or thiol groups, wherein the content of monomer units having amino, carboxyl, or thiol groups in the hydrophilic polymer as the hydrophilicity enhancer is less than 40% by weight based on the total weight of the hydrophilic polymer. 8. The easy-to-use siloxane hydrogel contact lens according to claim 7, wherein the hydrophilic polymer as a hydrophilicity enhancer is: polyethylene glycol having a single amino, carboxyl, or thiol group; polyethylene glycol having two terminal amino, carboxyl, and/or thiol groups; multi-arm polyethylene glycol having one or more amino, carboxyl, and/or thiol groups; polyethylene glycol dendritic polymer having one or more amino, carboxyl, and/or thiol groups; or a combination thereof. 9. The easy-to-use siloxane hydrogel contact lens according to claim 7, wherein the hydrophilic polymer as a hydrophilicity enhancer is a copolymer, said copolymer being a polymeric product of a composition comprising: (1) 60% by weight or less of at least one reactive vinyl monomer and (2) at least one non-reactive hydrophilic vinyl monomer and/or at least one phosphocholine-containing vinyl monomer; or a combination thereof; The reactive vinyl monomers are selected from amino- _C1 - _C6 alkyl esters of (meth)acrylate, _C1 - _C6 alkylamino- _C1 - _C6 alkyl esters of (meth)acrylate, allylamine, ethyleneamine, amino- _C1 - _C6 alkyl(meth)acrylamide, _C1 - _C6 alkylamino- _C1 - _C6 alkyl(meth)acrylamide, acrylic acid, _C1 - _C12 alkylacrylic acid, N,N-2-acryloylaminohydroxyacetic acid, β-methacrylic acid, α-phenylacrylic acid, β-acryloyloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesocarboxylic acid, penteneic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof; The non-reactive hydrophilic vinyl monomers are selected from acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminopropylmethacrylamide, N,N-dimethylaminopropylacrylamide, glyceryl methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[trimethylaminopropylacrylamide], etc. [(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, _C1 - _C4 alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 1500 Daltons, N-vinylformamide, N-vinylacetamide, N-vinylisopropionamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymers), and combinations thereof. 10. The easy-to-use siloxane hydrogel contact lens according to claim 7, wherein the hydrophilic polymer as a hydrophilicity enhancer is a homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer that is monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated: acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glyceryl (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, (meth)acryloyloxyethyl phosphocholine, _C1 - _C4 alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 400 Daltons, 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. 11. The easy-to-use siloxane hydrogel contact lens according to claim 7, wherein the hydrophilic polymer as a hydrophilicity enhancer is a polysaccharide containing amino or carboxyl groups, hyaluronic acid, chondroitin sulfate, or a combination thereof. 12. The easy-to-use siloxane hydrogel contact lens according to claim 7, wherein the weight-average molecular weight _Mw of the hydrophilic polymer as a hydrophilicity enhancer is 500-1,000,000. 13. The easy-to-use siloxane hydrogel contact lens according to any one of claims 1-5, wherein the hydrophilicity enhancer is: a monosaccharide containing amino, carboxyl, or thiol groups; an oligosaccharide containing amino, carboxyl, or thiol groups; or a combination thereof. 14. An easy-to-use silicone hydrogel contact lens according to any one of claims 1-5, wherein the easy-to-use silicone hydrogel contact lens has at least one property selected from the following: oxygen permeability of at least 40 barrer; elastic modulus of 1.5 MPa or less; and water content of 18-70% by weight when fully hydrated; and combinations thereof. 15. An easy-to-use siloxane hydrogel contact lens according to any one of claims 1-5, wherein the hydrophilicity enhancer is a hydrophilic polymer having one or more amino, carboxyl, and/or thiol groups, wherein the content of monomer units having amino, carboxyl, or thiol groups in the hydrophilic polymer as the hydrophilicity enhancer is less than 40% by weight based on the total weight of the hydrophilic polymer. 16. The easy-to-use siloxane hydrogel contact lens of claim 15, wherein the hydrophilic polymer as a hydrophilicity enhancer is: polyethylene glycol having a single amino, carboxyl, or thiol group; polyethylene glycol having two terminal amino, carboxyl, and/or thiol groups; multi-arm polyethylene glycol having one or more amino, carboxyl, and/or thiol groups; polyethylene glycol dendritic polymer having one or more amino, carboxyl, and/or thiol groups; or a combination thereof. 17. The easy-to-use siloxane hydrogel contact lens according to claim 15, wherein the hydrophilic polymer as a hydrophilicity enhancer is a copolymer, said copolymer being a polymeric product of a composition comprising: (1) 60% by weight or less of at least one reactive vinyl monomer and (2) at least one non-reactive hydrophilic vinyl monomer and/or at least one phosphocholine-containing vinyl monomer; or a combination thereof; The reactive vinyl monomers are selected from amino- _C1 - _C6 alkyl esters of (meth)acrylate, _C1 - _C6 alkylamino- _C1 - _C6 alkyl esters of (meth)acrylate, allylamine, ethyleneamine, amino- _C1 - _C6 alkyl(meth)acrylamide, _C1 - _C6 alkylamino- _C1 - _C6 alkyl(meth)acrylamide, acrylic acid, _C1 - _C12 alkylacrylic acid, N,N-2-acryloylaminohydroxyacetic acid, β-methacrylic acid, α-phenylacrylic acid, β-acryloyloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesocarboxylic acid, penteneic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof; The non-reactive hydrophilic vinyl monomers are selected from acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminopropylmethacrylamide, N,N-dimethylaminopropylacrylamide, glyceryl methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[trimethylaminopropylacrylamide], etc. [(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, _C1 - _C4 alkoxy polyethylene glycol (meth)acrylates with a weight average molecular weight of up to 1500 Daltons, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol, and combinations thereof. 18. The easy-to-use siloxane hydrogel contact lens according to claim 15, wherein the hydrophilic polymer as a hydrophilicity enhancer is a homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer that is monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated: acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glyceryl (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, (meth)acryloyloxyethyl phosphocholine, _C1 - _C4 alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 400 Daltons, 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, or combinations thereof. 19. The easy-to-use siloxane hydrogel contact lens according to claim 15, wherein the hydrophilic polymer as a hydrophilicity enhancer is a polysaccharide containing amino or carboxyl groups, hyaluronic acid, chondroitin sulfate, or a combination thereof. 20. The easy-to-use siloxane hydrogel contact lens of claim 15, wherein the weight-average molecular weight _Mw of the hydrophilic polymer as a hydrophilicity enhancer is 500-1,000,000. 21. The easy-to-use siloxane hydrogel contact lens according to any one of claims 1-5, wherein the hydrophilicity enhancer is: a monosaccharide containing amino, carboxyl, or thiol groups; or an oligosaccharide containing amino, carboxyl, or thiol groups. 22. An easy-to-use silicone hydrogel contact lens according to any one of claims 1-5, wherein the easy-to-use silicone hydrogel contact lens has at least one property selected from the following: oxygen permeability of at least 40 barrer; elastic modulus of 1.5 MPa or less; and water content of 18-70% by weight when fully hydrated; and combinations thereof. 23. An easy-to-use silicone hydrogel contact lens, comprising: Preformed siloxane hydrogel contact lenses; A reactive undercoat on a preformed silicone hydrogel contact lens, wherein the reactive undercoat comprises amino and/or carboxyl groups; and Crosslinked hydrophilic coatings are formed by a crosslinking reaction between a water-soluble and thermally crosslinkable hydrophilic polymer material and a reactive primer at a temperature of 40-140°C. The water-soluble and thermally crosslinkable hydrophilic polymer materials include: (i) 20 to 95% by weight of a first polymer chain derived from epichlorohydrin-functionalized polyamines or polyamide-type amines. (ii) 5 to 80% by weight of a hydrophilic structural portion or second polymer chain derived from at least one hydrophilic reinforcing agent, said hydrophilic reinforcing agent having at least one reactive functional group selected from amino, carboxyl, thiol groups and combinations thereof, wherein the hydrophilic structural portion or second polymer chain is covalently attached to the first polymer chain via one or more covalent bonds formed between each of an azo-butyryl group of an epichlorohydrin-functionalized polyamine or polyamide-type amine and an amino, carboxyl, or thiol group of the hydrophilic reinforcing agent, and (iii) A positively charged nitrogen-containing heterocyclic butyl group, which is part of the first polymer chain or a side group or end group covalently attached to the first polymer chain. In the crosslinking reaction, a positively charged nitrogen-containing heterocyclic butyl group of the water-soluble and thermally crosslinkable hydrophilic polymer material reacts with an amino or carboxyl group of the reactive primer to form a neutral hydroxyl-containing covalent bond. The easy-to-use siloxane hydrogel contact lens has (1) an average water contact angle of 80 degrees or less; (2) oxygen permeability of at least 40 barrer; (3) an elastic modulus of 1.5 MPa or less; and (4) a water content of 18-70% by weight when fully hydrated. 24. The easy-to-use silicone hydrogel contact lens of claim 23, wherein the reactive undercoat comprises at least one layer of a reactive polymer having side amino and/or carboxyl groups, wherein the reactive polymer is: a homopolymer of amino- _C1 - _C4 alkyl(meth)acrylamide, amino- _C1 - _C4 alkyl ester of (meth)acrylate, _C1 - _C4 alkylamino-C1- _C4 alkyl(meth)acrylamide, _C1 -C4 alkylamino- _C1 - _C4 alkyl ester of (meth)acrylate, allylamine, or vinylamine; polyethyleneimine; polyvinyl alcohol having side amino groups; linear or branched polyacrylic acid; a homopolymer of _C1 - _C12 alkylacrylic acid; amino- _C2 - _C4 alkyl(meth)acrylamide, amino- _C2 - _C4 alkyl ester of (meth)acrylate, C1-C4 alkylamino-C2-C4 alkyl(meth)acrylamide, _C1 -C4 alkylamino-C2-C4 alkyl ₍ meth)acrylamide, _C1 - _C4 alkylamino- _C2 - _C4 alkyl(meth)acrylamide, or _C1 -C4 alkylamino-C2 _{-C12 alkylacrylic} acid. ₄ -alkyl esters, acrylic acid, _C1 - _C12 alkyl acrylic acid, maleic acid and/or fumaric acid, copolymers with at least one non-reactive hydrophilic vinyl monomer; carboxylated cellulose; hyaluronic acid salts; chondroitin sulfate; poly(glutamic acid); poly(aspartic acid); or combinations thereof. 25. The easy-to-use siloxane hydrogel contact lens of claim 24, wherein the reactive polymer is polyacrylic acid, polymethacrylic acid, poly( _C2 - _C12 alkylacrylic acid), poly[acrylic acid-co-methacrylic acid], poly[ _C2 - _C12 alkylacrylic acid-co-(meth)acrylic acid], poly(N,N-2-acryloylaminohydroxyacetic acid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone], poly[ _C2 - _C12 alkylacrylic acid-co-acrylamide], poly[ _C2 - _C12 alkylacrylic acid-co-vinylpyrrolidone], hydrolyzed poly[(meth)acrylic acid-co-vinyl acetate], hydrolyzed poly[ _C2 - _C12 alkylacrylic acid-co-vinyl acetate], or a combination thereof. 26. The easy-to-use siloxane hydrogel contact lens of claim 24, wherein the reactive polymer is polyacrylic acid, polymethacrylic acid, poly( _C2 - _C12 alkylacrylic acid), poly[acrylic acid-co-methacrylic acid], or a combination thereof. 27. The easy-to-use siloxane hydrogel contact lens of claim 23, wherein the reactive undercoat comprises a plasma undercoat. 28. The easy-to-use siloxane hydrogel contact lens of claim 23, wherein the water-soluble and thermally crosslinkable hydrophilic polymer material comprises 35 to 90% by weight of a first polymer chain. 29. An easy-to-use siloxane hydrogel contact lens according to any one of claims 23-28, wherein the hydrophilicity enhancer is a hydrophilic polymer having one or more amino, carboxyl, and/or thiol groups, wherein the content of monomer units having amino, carboxyl, or thiol groups in the hydrophilic polymer as the hydrophilicity enhancer is less than 40% by weight based on the total weight of the hydrophilic polymer. 30. The easy-to-use siloxane hydrogel contact lens of claim 29, wherein the hydrophilic polymer as a hydrophilicity enhancer is: polyethylene glycol having a single amino, carboxyl, or thiol group; polyethylene glycol having two terminal amino, carboxyl, and/or thiol groups; multi-arm polyethylene glycol having one or more amino, carboxyl, and/or thiol groups; polyethylene glycol dendritic polymer having one or more amino, carboxyl, and/or thiol groups; or a combination thereof. 31. The easy-to-use siloxane hydrogel contact lens according to claim 29, wherein the hydrophilic polymer as a hydrophilicity enhancer is a copolymer, said copolymer being a polymeric product of a composition comprising: (1) 60% by weight or less of at least one reactive vinyl monomer and (2) at least one non-reactive hydrophilic vinyl monomer and/or at least one phosphocholine-containing vinyl monomer; or a combination thereof; The reactive vinyl monomers are selected from amino- _C1 - _C6 alkyl esters of (meth)acrylate, _C1 - _C6 alkylamino- _C1 - _C6 alkyl esters of (meth)acrylate, allylamine, ethyleneamine, amino- _C1 - _C6 alkyl(meth)acrylamide, _C1 - _C6 alkylamino- _C1 - _C6 alkyl(meth)acrylamide, acrylic acid, _C1 - _C12 alkylacrylic acid, N,N-2-acryloylaminohydroxyacetic acid, β-methacrylic acid, α-phenylacrylic acid, β-acryloyloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesocarboxylic acid, penteneic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof; The non-reactive hydrophilic vinyl monomers are selected from acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminopropylmethacrylamide, N,N-dimethylaminopropylacrylamide, glyceryl methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[trimethylaminopropylacrylamide], etc. [(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, _C1 - _C4 alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 1500 Daltons, N-vinylformamide, N-vinylacetamide, N-vinylisopropionamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymers), and combinations thereof. 32. The easy-to-use siloxane hydrogel contact lens according to claim 29, wherein the hydrophilic polymer as a hydrophilicity enhancer is a homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer that is monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated: acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glyceryl (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, (meth)acryloyloxyethyl phosphocholine, _C1 - _C4 alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 400 Daltons, 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, or combinations thereof. 33. The easy-to-use siloxane hydrogel contact lens according to claim 29, wherein the hydrophilic polymer as a hydrophilicity enhancer is a polysaccharide containing amino or carboxyl groups, hyaluronic acid, chondroitin sulfate, or a combination thereof. 34. The easy-to-use siloxane hydrogel contact lens according to claim 29, wherein the weight-average molecular weight _Mw of the hydrophilic polymer as a hydrophilicity enhancer is 500-1,000,000. 35. The easy-to-use siloxane hydrogel contact lens according to any one of claims 23-28, wherein the hydrophilicity enhancer is: a monosaccharide containing amino, carboxyl, or thiol groups; an oligosaccharide containing amino, carboxyl, or thiol groups; or a combination thereof. 36. An easy-to-use siloxane hydrogel contact lens according to any one of claims 23-28, wherein the hydrophilicity enhancer is a hydrophilic polymer having one or more amino, carboxyl, and/or thiol groups, wherein the content of monomer units having amino, carboxyl, or thiol groups in the hydrophilic polymer as the hydrophilicity enhancer is less than 40% by weight based on the total weight of the hydrophilic polymer. 37. The easy-to-use siloxane hydrogel contact lens of claim 36, wherein the hydrophilic polymer as a hydrophilicity enhancer is: polyethylene glycol having a single 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 dendritic polymer having one or more amino, carboxyl, and/or thiol groups. 38. The easy-to-use siloxane hydrogel contact lens according to claim 36, wherein the hydrophilic polymer as a hydrophilicity enhancer is a copolymer, said copolymer being a polymeric product of a composition comprising: (1) 60% by weight or less of at least one reactive vinyl monomer and (2) at least one non-reactive hydrophilic vinyl monomer and/or at least one phosphocholine-containing vinyl monomer; or a combination thereof; The reactive vinyl monomers are selected from amino- _C1 - _C6 alkyl esters of (meth)acrylate, _C1 - _C6 alkylamino- _C1 - _C6 alkyl esters of (meth)acrylate, allylamine, ethyleneamine, amino- _C1 - _C6 alkyl(meth)acrylamide, _C1 - _C6 alkylamino- _C1 - _C6 alkyl(meth)acrylamide, acrylic acid, _C1 - _C12 alkylacrylic acid, N,N-2-acryloylaminohydroxyacetic acid, β-methacrylic acid, α-phenylacrylic acid, β-acryloyloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesocarboxylic acid, penteneic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof; The non-reactive hydrophilic vinyl monomers are selected from acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminopropylmethacrylamide, N,N-dimethylaminopropylacrylamide, glyceryl methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[trimethylaminopropylacrylamide], etc. [(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, _C1 - _C4 alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 1500 Daltons, N-vinylformamide, N-vinylacetamide, N-vinylisopropionamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymers), and combinations thereof. 39. The easy-to-use siloxane hydrogel contact lens according to claim 36, wherein the hydrophilic polymer as a hydrophilicity enhancer is a homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer that is monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated: acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glyceryl (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, (meth)acryloyloxyethyl phosphocholine, _C1 - _C4 alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 400 Daltons, 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, or combinations thereof. 40. The easy-to-use siloxane hydrogel contact lens of claim 36, wherein the hydrophilic polymer as a hydrophilicity enhancer is a polysaccharide containing amino or carboxyl groups, hyaluronic acid, chondroitin sulfate, or a combination thereof. 41. The easy-to-use siloxane hydrogel contact lens according to claim 36, wherein the weight-average molecular weight _Mw of the hydrophilic polymer as a hydrophilicity enhancer is 500-1,000,000. 42. The easy-to-use siloxane hydrogel contact lens according to any one of claims 23-28, wherein the hydrophilicity enhancer is: a monosaccharide containing amino, carboxyl, or thiol groups; or an oligosaccharide containing amino, carboxyl, or thiol groups.