Hydrated contact lens

Abstract

This invention relates to a hydrated contact lens, comprising: a structural configuration including two outer surface layers and an inner layer located between the two outer surface layers, wherein the inner layer has a first water content of 10% to 70%, and the outer surface layers have a second water content higher than the first water content, wherein the thickness of each outer surface layer is 30% or less of the center thickness of the hydrated contact lens; a water content gradient from the inner layer to the outer surface layer in the structural configuration, wherein the water content gradient is characterized by having the highest water content in a region close to and including the surface of the hydrated contact lens and the lowest water content in the core of the hydrated contact lens; surface hydrophilicity, characterized by having a water breakup time of at least 10 seconds; and an elastic modulus of 0.3 MPa to 1.8 MPa.

Description

[Technical Field]

[0001] This invention relates to ophthalmic devices, particularly polysiloxane hydrogel contact lenses, which have a lens structure configuration that generates a water content gradient and include: a polysiloxane hydrogel bulk material with a water content (expressed as WCSiHy) of about 10% to about 70% by weight and an outer surface layer, the outer surface layer having a thickness of about 0.1 µm to about 20 µm and completely covering the polysiloxane hydrogel bulk material and being composed of a hydrogel material that is completely or substantially free of polysiloxane and has a high water content, the high water content being characterized in that if WCSiHy ≤ 45%, the water expansion rate is at least about 100% or if WCSiHy > 45%, the water expansion rate is at least about, as measured by AFM using a cross-section of a fully hydrated polysiloxane hydrogel contact lens. [Previous Technology]

[0002] Polysiloxane hydrogel (SiHy) contact lenses are widely used to correct many different types of visual defects. They are composed of a hydrated, cross-linked polymer material containing polysiloxane and a certain amount of water in equilibrium within the lens polymer matrix. According to the FDA's contact lens classification system, hydrogel contact lenses are generally divided into two main categories: low water content contact lenses (containing less than 50% water) and high water content contact lenses (containing more than 50% water). For SiHy contact lenses, high oxygen permeability is achieved by incorporating polysiloxane into the cross-linked polymer material rather than by increasing the water content. High oxygen permeability is required for contact lenses that have minimal adverse effects on corneal health. Therefore, unlike conventional hydrogel contact lenses, SiHy contact lenses can have low water content while still maintaining relatively high oxygen permeability (Dk). Examples include: Focus® Night & Day® from CIBA Vision (approximately 23.5% H2O and Dk of approximately 140 Barrer); Air Optix® from CIBA Vision (approximately 33% H2O and Dk of approximately 110 Barrer); PureVision® from Bausch & Lomb (approximately 36% H2O and Dk of approximately 100 Barrer); Acuvue® Oasys® from Johnson & Johnson (approximately 38% H2O and Dk of approximately 105 Barrer); Acuvue® Advance® from Johnson & Johnson (approximately 47% H2O and Dk of approximately 65 Barrer); and Acuvue® TruEye™ from Johnson & Johnson (approximately 46% H2O and Dk of approximately 100 Barrer). Barrer); Biofinity® from CooperVision (approx. 48% H2O, Dk approximately 128 Barrer); Avaira™ from CooperVision (approx. 46% H2O, Dk approximately 100 Barrer); and PremiOTM from Menicon (approx. 40% H2O, Dk approximately 129 Barrer).

[0003] The water in SiHy contact lenses provides the desired softness for extended wear and offers patients benefits including: adequate initial comfort (i.e., immediately after insertion), a relatively short adaptation time, and / or wearability. Higher water content is desirable to provide biocompatible and comfortable SiHy contact lenses. However, like conventional hydrogel contact lenses, there are limitations on the amount of water SiHy lenses can contain (believed to be 80%) while still maintaining sufficient mechanical strength and rigidity. Furthermore, high water content can have undesirable consequences. For example, increased water content can negatively impact the oxygen permeability of SiHy contact lenses. Additionally, high water content in SiHy lenses can cause significant intraocular dehydration and resulting dehydration-induced discomfort, as high water content in SiHy contact lenses can deplete the limited supply of tears (water) in the eye. It is believed that intraocular dehydration can originate from evaporation (i.e., water loss) on the anterior surface of the contact lens, and that this water loss is mainly controlled by the diffusion of water through the lens from the posterior surface to the anterior surface, and that the diffusion rate is approximately proportional to the water content of the lens bulk material in equilibrium (L. Jones et al., Contact Lens & Anterior Eye 25 (2002) 147-156, the entire contents of which are incorporated herein by reference).

[0004] The incorporation of polysiloxane (PSA) into contact lens materials also has undesirable effects on the biocompatibility of contact lenses, as PSA is hydrophobic and has a greater tendency to migrate to lens surfaces exposed to air. Therefore, SiHy contact lenses typically require surface modification processes to eliminate or minimize PSA exposure and maintain a hydrophilic surface. These surface modification processes include, for example, various plasma treatments (e.g., Focus® Night & Day® and Air Optix® from CIBA Vision; PureVision® from Bausch & Lomb; and PremiOTM from Menicon); and internal wetting agents embedded in the SiHy polymer matrix in a physical and / or chemical manner (e.g., Acuvue® Oasys®, Acuvue® Advance®, and Acuvue® TruEye™ from Johnson & Johnson; and Biofinity® and Avaira™ from CooperVision). Although surface modification techniques used in commercial SiHy lens production can provide fresh (unused) SiHy lenses with suitable hydrophilic surfaces, SiHy lenses worn in the eye may have dry spots and / or hydrophobic surface areas resulting from air exposure, eyelid shear forces, polysiloxane migration, and / or partial failure of protection against polysiloxane exposure. These dry spots and / or hydrophobic surface areas are non-wetting and readily attract lipids or proteins from the ocular environment, which can adhere to the eye and cause patient discomfort.

[0005] Therefore, the industry still needs SiHy contact lenses with hydrophilic surfaces that can maintain long-lasting hydrophilicity, wettability and lubricity in the eye all day long. [Summary of the Invention]

[0006] The present invention can meet the need for SiHy contact lenses with hydrophilic surfaces, that is, such hydrophilic surfaces have durable surface hydrophilicity, surface wettability and surface lubricity in the eye throughout the day.

[0007] In one embodiment, the present invention provides a hydrated polysiloxane hydrogel contact lens, comprising: a front (convex) surface and a corresponding rear (concave) surface; and a layered structure configuration from the front surface to the rear surface, wherein the layered structure configuration includes a front outer hydrogel layer, an inner layer of polysiloxane hydrogel material, and a rear outer hydrogel layer, wherein the oxygen permeability (Dk) of the polysiloxane hydrogel material is at least about 50 barrer, preferably at least about 60 barrer, more preferably at least about 70 barrer, even more preferably at least about 90 barrer, and most preferably at least about 110 barrer. Barrer, and having a first water content (expressed as WCSiHy) of about 10% to about 70%, more preferably about 10% to about 65%, more preferably about 10% to about 60%, even more preferably about 15% to about 55%, and most preferably about 15% to about 50% by weight, wherein the front outer hydrogel layer and the rear outer hydrogel layer are substantially of uniform thickness and merged at the periphery of the contact lens to completely surround the inner layer of the polysiloxane hydrogel material, wherein the front outer hydrogel layer and the rear outer hydrogel layer are adjacent to each other. Independently having a second water content higher than WCSiHy, characterized in that if WCSiHy≤45%, the water swelling rate (expressed as WSR) is at least about 100% (preferably at least about 150%, more preferably at least about 200%, even more preferably at least about 250%, best at least about 300%), or if WCSiHy>45%, the water swelling rate is at least about (preferably, more preferably, even more preferably), wherein the thickness of each of the front outer hydrogel layer and the rear outer hydrogel layer is about 0.1 µm to about 20 µm, preferably about 0.25 µm to about 15 µm, more preferably about 0.5 µm to about 12.5 µm, even more preferably about 1 µm to about 10 µm (as measured using an atomic force microscope across a cross section from the rear surface to the front surface of a fully hydrated polysiloxane hydrogel contact lens).

[0008] In another embodiment, the present invention provides a hydrated polysiloxane hydrogel contact lens. The hydrated polysiloxane hydrogel contact lens of the present invention comprises: a polysiloxane hydrogel material as a bulk material, a front surface, and a corresponding rear surface; wherein the oxygen transmittance of the contact lens is at least about 40 barrer / mm, preferably at least about 60 barrer / mm, more preferably at least about 80 barrer / mm, and even more preferably at least about 110 barrer / mm, and its cross-sectional surface modulus curve along the shortest line between the front and rear surfaces on the cross-sectional surface of the contact lens includes a front outer region (including and close to the front surface), an inner region (including and surrounding the center of the shortest line), and a rear outer region (including and close to the rear surface), wherein the front outer region has an average front surface modulus (denoted as ) and the rear outer region has an average rear surface modulus (denoted as ), wherein the inner region has an average inner surface modulus (denoted as ), wherein at least one of and is at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, and most preferably at least about 40%.

[0009] In another embodiment, the present invention provides a hydrated polysiloxane hydrogel contact lens. The hydrated polysiloxane hydrogel contact lens of the present invention comprises: a polysiloxane hydrogel material as a bulk material, a front surface and a corresponding rear surface; wherein the contact lens (1) has an oxygen permeability of at least about 40 barrer / mm, preferably at least about 60 barrer / mm, more preferably at least about 80 barrer / mm, and even more preferably at least about 110 barrer / mm, and (2) is characterized by a surface lubricity in that its critical coefficient of friction (expressed as CCOF) is about 0.046 or less, preferably about 0.043 or less, and even more preferably about 0.040 or less, wherein the front and rear surfaces have a low surface concentration of negatively charged groups (including carboxylic acid groups), and is characterized by attracting up to about 200, preferably up to about 160, more preferably up to about 120, even more preferably up to about 90, and most preferably up to about 60 positively charged particles in a positively charged particle adhesion test.

[0010] The present invention, including any combination of the various preferred embodiments, and other variations thereof, will become clear from the following description of the present preferred embodiments. The detailed description is merely illustrative and not restrictive of the scope of the invention, which is defined by the appended claims and their equivalents. As will be apparent to those skilled in the art, many variations and modifications can be made to the invention without departing from the spirit and scope of the novel concept disclosed herein.

Implementation Method

[0012] Embodiments of the present invention will now be discussed in detail. Those skilled in the art will readily recognize that various modifications, variations, and combinations can be made to the invention without departing from its scope or spirit. For example, a feature illustrated or described in one embodiment may be used in another embodiment to obtain yet another embodiment. Therefore, the present invention is intended to cover such modifications, variations, and combinations as if they fall within the scope of the appended claims and their equivalents. Other objects, features, and aspects of the invention are disclosed in or may be apparent from the following detailed description. Those skilled in the art should understand that the discussion of the present invention is merely illustrative of exemplary embodiments and is not intended to limit the broader aspects of the invention.

[0013] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Generally, the nomenclature and laboratory procedures used herein are well-known and commonly used in this art. These procedures use conventional methods, for example, those provided in this art and various general references. When a term is provided in the singular, the inventors also intend to cover the plural form of that term. The nomenclature used herein and the laboratory procedures described below are well-known and commonly used in this art.

[0014] As used in this application, the term "polysilicon-oxygen hydrogel contact lens" refers to a contact lens that includes polysilicon-oxygen hydrogel material.

[0015] As used in this application, the term "hydrogel" or "hydrogel material" means a cross-linked polymeric material that is insoluble in water and may contain at least 10% by weight of water in its polymer matrix when fully hydrated.

[0016] As used in this application, the term "non-polysilicon-oxygen hydrogel" refers to a hydrogel that theoretically does not contain silicon.

[0017] As used in this application, the term "polysiloxane hydrogel" refers to a hydrogel containing polysiloxane. Polysiloxane hydrogels are typically obtained by copolymerizing polymerizable compositions comprising at least one polysiloxane-type monomer or at least one polysiloxane-type macromonomer or at least one polysiloxane-containing prepolymer having an olefinic unsaturated group.

[0018] As used in this application, the term "ethylene monomer" refers to a compound having a single olefinic unsaturated group and being capable of photochemical or thermal polymerization.

[0019] As used herein, the term "olefinic unsaturated group" or "olefinic unsaturated group" is used in a broad sense and is intended to cover any group containing at least one >C=C< group. Exemplary olefinic unsaturated groups include, but are not limited to, (meth)acrylic (and / or), allyl, vinyl, styryl, or other C=C groups.

[0020] As used in this application, the term "(meth)acrylamide" refers to methacrylamide and / or acrylamide.

[0021] As used in this application, the term "(meth)acrylate" refers to methacrylate and / or acrylate.

[0022] As used in this application, the term "hydrophilic vinyl monomer" refers to vinyl monomers that typically produce water-soluble polymers or polymers capable of absorbing at least 10% by weight of water in the form of homopolymers.

[0023] As used in this application, the term "hydrophobic vinyl monomer" refers to a vinyl monomer that typically produces a polymer in the form of a homopolymer that is insoluble in water and can absorb less than 10% by weight of water.

[0024] As used in this application, the terms "macromonomer" or "prepolymer" refer to medium and high molecular weight compounds or polymers containing two or more olefinic unsaturated groups. Medium and high molecular weight generally mean an average molecular weight greater than 700 Daltons.

[0025] As used in this application, the term "crosslinking agent" refers to a compound having at least two olefinic unsaturated groups. "Crosslinking agent" refers to a crosslinking agent with a molecular weight of about 700 Daltons or less.

[0026] As used in this application, the term "polymer" means a material formed by polymerizing / crosslinking one or more monomers or macromonomers or prepolymers.

[0027] As used in this application, unless otherwise specifically stated or unless the test conditions indicate otherwise, the term “molecular weight” for polymeric materials (including monomeric or macromolecular monomeric materials) refers to weight average molecular weight.

[0028] As used in this application, unless otherwise specifically stated, 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 straight-chain or branched alkyl group.

[0029] As used in this application, the terms "epoxychloropropane-functionalized polyamine" or "epoxychloropropane-functionalized polyamide" refer to polymers obtained by reacting polyamines or polyamides with epichlorohydrin to convert all or a substantial proportion of the amine groups in the polyamines or polyamides into azacyclobutane groups.

[0030] As used in this application, the term "azacyclobutane group" refers to a positively charged group.

[0031] As used in this application, the term "thermally crosslinkable" in relation to a polymeric material or functional group means that the polymeric material or functional group can undergo a crosslinking (or coupling) reaction with another material or functional group at a relatively high temperature (about 40°C to about 140°C). However, the polymeric material or functional group will not undergo the same crosslinking (or coupling) reaction with another material or functional group at room temperature (i.e., about 22°C to about 28°C, preferably about 24°C to about 26°C, and specifically at about 25°C) to a detectable degree (i.e., greater than about 5%) within about one hour.

[0032] As used in this application, the term "phosphocholine" refers to a zwitterionic group, wherein n is an integer from 1 to 5, and R1, R2 and R3 are independently C1-C8 alkyl or C1-C8 hydroxyalkyl.

[0033] As used in this application, the term "reactive ethylene monomer" refers to an ethylene monomer having a carboxyl group or an amino group (i.e., a primary or secondary amino group).

[0034] As used in this application, the term "non-reactive hydrophilic vinyl monomer" refers to a hydrophilic vinyl monomer that does not contain any carboxyl or amino group (i.e., primary or secondary amino group). Non-reactive vinyl monomers may contain tertiary or quaternary amino groups.

[0035] As used in this application, the term "water-soluble" in relation to a polymer means that the polymer is soluble in water to the extent that it can form an aqueous solution of polymer (as defined above) at a concentration of up to about 30% by weight at room temperature.

[0036] As used in this application, the term "water contact angle" refers to the average water contact angle (i.e., the contact angle measured by the sessile drop method), which is obtained by averaging the contact angle measurements.

[0037] As used in this application, the term "integrity" in relation to the coating on a SiHy contact lens is intended to describe the degree to which the contact lens can be stained with Sudan Black in the Sudan Black staining test described in Example 1. Good integrity of the coating on a SiHy contact lens means that the contact lens is not actually stained with Sudan Black.

[0038] As used in this application, the term "durability" in relation to the coating on the SiHy contact lens is intended to describe that the coating on the SiHy contact lens can withstand a finger rubbing test.

[0039] As used in this application, the terms “withstands finger rubbing test” or “withstands durability test” regarding the coating on a contact lens mean that after rubbing the lens with a finger according to the procedure described in Example 1, the water contact angle on the 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.

[0040] The inherent "oxygen permeability" Dk of a material refers to the rate at which oxygen passes through the material. As used in this application, the term "oxygen permeability (Dk)" in relation to hydrogels (polysiloxane or non-polysiloxane) or contact lenses means the measured oxygen permeability (Dk) corrected for the surface resistance to oxygen flux caused by the boundary layer effect, according to the procedure shown in the examples below. Oxygen permeability is usually expressed in barrers, where "barrer" is defined as [(cm3 oxygen)(mm) / (cm2)(sec)(mm Hg)]×10-10.

[0041] The “oxygen transmittance” Dk / t of a lens or material refers to the rate at which oxygen passes through a specific lens or material with an average thickness of t [in mm] over the measured area. Oxygen transmittance is usually expressed in barrer / mm, where “barrer / mm” is defined as [(cm3 oxygen) / (cm2) (sec)(mm Hg)]×10-9.

[0042] The "ion permeability" through the lens is related to the Ionoflux diffusion coefficient. The Ionoflux diffusion coefficient D (in [mm2 / min]) is determined by applying the following Fick's Law: D=-n' / (A×dc / dx) where n'=ion transport rate [mol / min]; A=area of ​​the exposed lens [mm2]; dc=concentration difference [mol / L]; dx=thickness of the lens [mm].

[0043] As used in this application, the term "ophthalmic compatibility" refers to a material or material surface that can be in close contact with the ocular environment for a long time without significantly harming the ocular environment and without causing significant discomfort to the user.

[0044] As used in this application, the term "ophthalmic safe" in relation to packaging solutions for sterilizing and storing contact lenses means that contact lenses stored in the solution are safe to be placed directly 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. According to international ISO standards and US FDA regulations, ophthalmic safe packaging solutions, after autoclaving, have eye-compatible surface tension and pH and are substantially free of irritating or ocularly cytotoxic materials.

[0045] As used in this application, the term "cross-section" for a SiHy contact lens refers to a lens cross-section obtained by cutting through the lens at an angle substantially perpendicular to the front and rear surfaces of the lens using a knife or cutting tool. Those skilled in the art are familiar with manually cutting (i.e., hand-cutting), or using a cryostat microtome, or a lathe to obtain the cross-section of a contact lens. The resulting cross-section of the contact lens can be polished using ion etching or a similar technique.

[0046] The terms “surface modulus,” “surface softness,” “surface elastic modulus,” “surface Young’s modulus,” or “surface compressibility modulus” are used interchangeably in this application to refer to nanomechanical properties (elastic properties) measured by atomic force microscopy (AFM) on the surface of a material or on a cross-section of a contact lens in a fully hydrated state (in phosphate buffer solution, pH 7.3 ± 0.2) using contact patterns, nanoindentation methods, Peakforce QNM methods, or tuning force methods known to those skilled in the art. Jan Domke and Manfred Radmacher reported that the elastic properties of thin films can be measured using AMF (Langmuir 1998, 14, 3320-3325, the entire contents of which are incorporated herein by reference). AFM nanoindentation can be performed according to the experimental protocol described by González-Méijome JM, Almeida JB, and Parafita MA in the following document: Microscopy: Science, Technology, Applications and Education, "Analysis of Surface Mechanical Properties of Unworn and Worn Silicone Hydrogel Contact Lenses Using Nanoindentation with AFM", pp. 554-559, A. Méndez-Vilas and J. Díaz (eds.), Formatex Research Center, Badajoz, Spain (2010), the entire contents of which are incorporated herein by reference. It should be noted that AFM is used to analyze the surface cross-section of the contact lens using nanoindentation, rather than the front or back surface of the contact lens (as described by González-Méijome JM, Almeida JB, and Parafita MA in their document). The nanoindentation method, the Peakforce QNM method, and the tuning force method are described in the paper entitled "Nanomechanical properties of a-synuclein amyloid fibrils: a comparative study by nanoindentation, harmonic force microscopy, and Peakforce QNM" by Kim Sweers et al. in Nanoscale Research Letters 2011, 6:270 (the entire contents of which are incorporated herein by reference).It should also be understood that when using AFM to measure the surface modulus across a cross-section of a fully hydrated SiHy contact lens from the front surface to the body or from the body to the rear surface (or vice versa), the surface modulus curve across the lens cross-section can be established along the shortest line between the front and rear surfaces of the contact lens. Furthermore, it should be understood that, as a good approximation, any quantity measured experimentally or directly can be used to represent the surface modulus, provided that the measurement is proportional to the surface modulus.

[0047] As used in this application, the term "front outer hydrogel layer" in relation to the SiHy contact lens of the present invention refers to a hydrogel layer that comprises the front surface of the contact lens, is substantially uniform in thickness (i.e., the thickness variation is no more than about 10% compared to the average thickness of the layer), and has an average thickness of at least about 0.1 µm. In this application, the "average thickness" of the front outer hydrogel layer is simply referred to as the "thickness of the front outer hydrogel layer".

[0048] As used in this application, the term "rear external hydrogel layer" in relation to the SiHy contact lens of the present invention refers to a hydrogel layer that comprises the rear surface of the contact lens, is substantially uniform in thickness (i.e., the thickness variation is no more than about 10% compared to the average thickness of the layer), and has an average thickness of at least about 0.1 µm. In this application, the "average thickness" of the rear external hydrogel layer is simply referred to as the "thickness of the rear external hydrogel layer".

[0049] As used in this application, the term "inner layer" in relation to the SiHy contact lens of the present invention means a layer that includes a central curved surface (which divides the contact lens into two parts, one part containing a front surface and the other part containing a rear surface) and has a variable thickness.

[0050] As used in this application, the terms "crosslinked coating" or "hydrogel coating" are used interchangeably to describe a crosslinked polymeric material having a three-dimensional network that may contain water when fully hydrated. The three-dimensional network of the crosslinked polymeric material may be formed by crosslinking two or more linear or branched polymers via crosslinking bonds.

[0051] As used in this application, the term "water expansion rate" in relation to the front or rear outer hydrogel layer of the hydrogel material of the SiHy contact lens of the present invention means the value measured using AFM, wherein WSR is the water expansion rate of one of the front and rear outer hydrogel layers, L wet is the average thickness of the outer hydrogel layer of the SiHy contact lens in a fully hydrated state, as measured using AFM on a cross-section of the SiHy contact lens in a fully hydrated state (i.e., in a phosphate buffer solution with a pH of about 7.3 ± 0.2), and L dry is the average thickness of the outer hydrogel layer of the SiHy contact lens in a dry state, as measured using AFM on a cross-section of the SiHy contact lens in a dry state (drying without retaining the porosity of the hydrogel material, for example, vacuum drying) and in a substantially dry atmosphere. It is believed that the water expansion rate of each outer hydrogel layer (in relation to the SiHy contact lens of the present invention) is proportional to the water content of each outer hydrogel layer, and a water expansion rate of at least about 100% (however large, WCSiHy is the water content of the body (or inner layer) polysiloxane hydrogel material of the SiHy contact lens of the present invention) can be used as a good indicator of the property that the water content in the SiHy contact lens of the present invention is higher than that of the outer hydrogel layer of the body (or inner layer) polysiloxane hydrogel material.

[0052] As used in this application, the term "reduced surface modulus" in relation to either or both of the front and rear outer hydrogel layers of the SiHy contact lens of the present invention means a value calculated based on the following equation: where RSM is the reduced surface modulus of the front or rear outer hydrogel layer relative to the inner layer, RSM is the average surface modulus of the rear or front outer hydrogel layer, and RSM is the average surface modulus of the inner layer. RSM is obtained from the surface modulus curve of the cross-section of the fully hydrated SiHy contact lens as described above (e.g., measured by analyzing the surface mechanical properties, i.e., the surface modulus, of the cross-section of the fully hydrated SiHy contact lens using AFM). The expected cross-sectional surface modulus curve (i.e., a graph of the surface modulus versus the distance from one of the front and rear surfaces to the other (along the shortest line between the front and rear surfaces in a fully hydrated SiHy lens)) should have at least two outer regions (one containing the front surface and the other containing the rear surface) and one inner region (corresponding to the bulk polysilicon-oxygen hydrogel material). The average surface modulus of the outer region (i.e., the outer hydrogel layer) is obtained by averaging the surface moduli of all surfaces in the outer region, excluding the area of ​​approximately 1 to approximately 2 micrometers between the outer and inner regions (i.e., in the boundary or transition regions and / or near these regions).

[0053] The "critical coefficient of friction" is the tangent of the critical angle, which is the highest tilt angle of the tilting plate at which the lens begins to slide on the tilting plate after being pushed, but stops before reaching the end, or takes more than 10 seconds to reach the end. The procedure for determining the critical coefficient of friction (CCOF) is described in Example 29. It is believed that the critical coefficient of friction (CCOF) of a contact lens is related to the surface lubricity of the contact lens and can be used to quantify the surface lubricity of the contact lens.

[0054] As used in this application, "positively charged particle adhesion test" refers to a test used to characterize the surface concentration of negatively charged groups (e.g., carboxylic acid groups) in hydrated SiHy contact lenses. The positively charged particle adhesion test is performed as follows. A given amount of DOWEXTM 1×4 20-50 mesh resin (which is a spherical type I strong base resin (containing N+(CH3)3Cl- functional groups and 4% divinylbenzene styrene / divinylbenzene copolymer)) is dispersed in phosphate buffered saline (pH about 7.3) to prepare an aqueous dispersion of DOWEXTM 1×4 20-50 mesh resin (which is a spherical type I strong base resin (containing N+(CH3)3Cl- functional groups and 4% divinylbenzene styrene / divinylbenzene copolymer))) is then thoroughly mixed by shaking, stirring or vortexing at about 1000 rpm for 10 seconds. Hydrated polysiloxane hydrogel contact lenses were immersed in an aqueous dispersion of DOWEXTM 1×4 20-50 mesh resin prepared above and vortexed at approximately 1000-1100 rpm for about 1 minute. They were then rinsed with DI water and vortexed in DI water for about 1 minute. Next, the lenses were placed in water in a glass petri dish, and images of the lenses were acquired using a Nikon optical microscope with bottom illumination. The number of positively charged particles adhering to the surface of each lens was counted. The number of positively charged particles adhering to the lens surface is directly proportional to the surface concentration of negatively charged groups in the contact lens.

[0055] As used in this application, the term "carboxylic acid content" in relation to the cross-linked coating or external hydrogel layer of the SiHy contact lens of the present invention refers to the weight percentage of carboxylic acid groups (COOH) based on the weight of the cross-linked coating or external hydrogel layer of the SiHy contact lens. The carboxylic acid content of the cross-linked coating or external hydrogel layer can theoretically be estimated based on the composition of the starting materials used to manufacture the cross-linked coating or external hydrogel layer and the carboxylic acid content of each starting material.

[0056] This invention relates to a SiHy contact lens having a layered structural configuration and a unique water gradient from the inner to the outer side of the SiHy contact lens: a low-water-content polysiloxane hydrogel core (or bulk material) is completely covered by an outer (surface) hydrogel layer having a higher water content and an appropriate thickness (at least about 0.1 µm) and being substantially free of polysiloxane (preferably completely free of polysiloxane); and the water content of the outer hydrogel layer is at least about 1.2 times (or 120%), preferably at least about 1.3 times (or 130%), more preferably at least about 1.4 times (or 140%), even more preferably at least about 1.5 times (150%), and most preferably at least about 2 times (or 200%) the water content of the bulk material. Figure 1 schematically illustrates a preferred embodiment of a SiHy contact lens with a layered structural configuration. According to this preferred embodiment of the invention, the SiHy contact lens 100 has a front surface (or anterior curved or convex surface) 101 and an opposing posterior surface (or posterior curved or concave surface) 102 that rests on the cornea of ​​the eye when worn by a user. The SiHy contact lens 100 includes an inner (or intermediate) layer 110 and two outer layers 120. The inner layer 110 is a bulk material of the SiHy contact lens 100 and has a shape very close to the three-dimensional shape of the SiHy contact lens 100. The inner layer 110 is preferably composed of a low-water-content polysiloxane hydrogel. The two outer layers 120 (substantially identical to each other) are substantially of uniform thickness and are composed of a substantially polysiloxane-free (preferably completely polysiloxane-free) hydrogel material with a higher water content than the inner layer 110. The two outer layers 120 merge at the peripheral edge 103 of the contact lens 100 and completely cover the inner layer 110.

[0057] The SiHy contact lens with a layered structure of the present invention offers several advantages over prior art contact lenses. First, this SiHy contact lens can still maintain high oxygen permeability, which is necessary to maintain corneal health. Second, because the inner layer (bulk material) provides the necessary bulk mechanical strength and rigidity for the contact lens, the outer hydrogel layer can be unrestricted in terms of water content and can contain as much water as possible. Therefore, the outer hydrogel layer can provide an overly water-rich skin layer to the contact lens or provide a water content gradient in the lens structure configuration (with the highest water content in the region close to and including the lens surface and the lowest water content in the lens core). Third, the SiHy contact lens with a layered structure of the present invention can have lower intraocular dehydration, causing less dryness in the eye, and thus providing enhanced daily wearing comfort. It is believed that the inner layer with low water content (i.e., the bulk material of the lens) controls (limits) the rate at which water diffuses through the lens from the posterior surface to the anterior surface, and consequently controls water evaporation (water loss) at the anterior surface of the lens. Furthermore, it is believed that the layered structural configuration of the present invention can generate an inward water concentration gradient (i.e., the water content gradually decreases as it moves inward from the front surface toward the lens core), which, based on Fick's laws of diffusion, is unfavorable for water diffusion from the rear surface to the front surface through the lens. Fourth, the SiHy contact lens of the present invention with a layered structural configuration can provide high biocompatibility because water is highly biocompatible with tears and because the high water content (e.g., preferably >75% H2O) in the outer hydrogel layer is located and close to the front and rear surfaces, which are in direct contact with the eye and where biocompatibility is considered optimal. Fifth, the high water content in the outer hydrogel layer of appropriate thickness can provide a SiHy contact lens with a highly soft surface (i.e., a "water cushion"). Sixth, the SiHy contact lens of the present invention with a layered structural configuration can have a highly lubricated surface. It is believed that an outer hydrogel layer with extremely high water content and appropriate thickness will provide a "hydrophobic" surface that attracts tears to spread across the lens surface. It is believed that the outer hydrogel layer, with its significantly greater flexibility than the body lens material (inner layer), can be easily deformed under pressure (i.e., shear force on the eyelid) and can provide hydroelastic dynamic lubrication when this SiHy contact lens is worn in the eye. Seventh, the layered structural configuration in the SiHy contact lens of the present invention prevents polysiloxane (PSA) exposure. It is believed that the three-dimensional network (i.e., polymer matrix) of the outer hydrogel layer with appropriate thickness can encapsulate PSA and prevent PSA migration to the lens surface. Eighth, the SiHy contact lens of the present invention can have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups) and is less prone to high debris adhesion during patient handling and high protein adhesion during wear (it is believed that most proteins in tears are positively charged).

[0058] In one embodiment, the present invention provides a hydrated polysiloxane hydrogel contact lens, comprising: a front (convex) surface and an opposite rear (rear) surface; and a layered structure configuration from the front surface to the rear surface, wherein the layered structure configuration includes a front outer hydrogel layer, an inner layer of polysiloxane hydrogel material, and a rear outer hydrogel layer, wherein the oxygen permeability (Dk) of the polysiloxane hydrogel material is at least about 50 barrer, preferably at least about 60 barrer, more preferably at least about 70 barrer, even more preferably at least about 90 barrer, and most preferably at least about 110 barrer. The barrer has a first water content (denoted as WCSiHy) of about 10% to about 70% by weight, preferably about 10% to about 65% by weight, more preferably about 10% to about 60% by weight, even more preferably about 15% to about 55% by weight, and most preferably about 15% to about 50% by weight, wherein the front and rear outer hydrogel layers are substantially of uniform thickness and merge at the periphery of the contact lens to completely surround the inner layer of the polysiloxane hydrogel material. The front and rear external hydrogel layers independently have a second water content higher than WCSiHy, characterized in that if WCSiHy≤45%, the water swelling rate is at least about 100% (preferably at least about 150%, more preferably at least about 200%, even more preferably at least about 250%, most preferably at least about 300%), or if WCSiHy>45%, the water swelling rate is at least about (preferably, more preferably, even more preferably), wherein the thickness of each external hydrogel layer is about 0.1 µm to about 20 µm, preferably about 0.25 µm to about 15 µm, more preferably about 0.5 µm to about 12.5 µm, even more preferably about 1 µm to about 10 µm (as measured using an atomic force microscope across a cross-section from the rear surface to the front surface of a fully hydrated polysiloxane hydrogel contact lens). Preferably, the front and rear surfaces have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups), characterized in that they attract up to about 200, more preferably up to about 160, more preferably up to about 120, even more preferably up to about 90, and most preferably up to about 60 positively charged particles in a positively charged particle adhesion test. Also preferably, the hydrated polysilicon-oxygen hydrogel contact lens has surface lubricity characterized by a critical coefficient of friction (CCOF) of about 0.046 or less, more preferably about 0.043 or less, and more preferably about 0.040 or less.

[0059] According to the present invention, the inner layer of the SiHy contact lens is actually the bulk material of the lens. It can be directly derived from a pre-formed SiHy contact lens during a surface modification process, in which two external hydrogel layers are applied and directly and / or indirectly attached to the pre-formed SiHy contact lens. The pre-formed SiHy contact lens can be any commercially available SiHy lens, for example, any of those described above. Alternatively, the pre-formed SiHy can be prepared according to any method known to those skilled in the art. For example, preformed contact lenses can be produced in conventional "rotational casting molds" (e.g., as described in U.S. Patent No. 3,408,429), or through a static form of full casting molding process (as described in U.S. Patent Nos. 4,347,198, 5,508,317, 5,583,463, 5,789,464, and 5,849,810), or by lathe cutting of polysiloxane hydrogel pellets (buttons) (as used in the manufacture of custom contact lenses). In casting molding, the lens formulation is typically dispensed into a mold and cured (i.e., polymerized and / or crosslinked) within the mold used to manufacture the contact lens. To produce preformed SiHy contact lenses, SiHy lens formulations used for casting or rotational casting or for manufacturing SiHy rods (for lathe-cut contact lenses) typically include at least one component selected from the group consisting of: polysiloxane-type monomers, polysiloxane-type macromonomers, polysiloxane-type prepolymers, hydrophilic vinyl monomers, hydrophobic vinyl monomers, crosslinking agents (compounds with a molecular weight of about 700 Daltons or less and containing at least two olefinic unsaturated groups), free radical initiators (photoinitiators or thermal initiators), hydrophilic vinyl macromonomers / prepolymers, and combinations thereof, as is well known to those skilled in the art. The SiHy contact lens formulation may also include other essential components known to those skilled in the art, such as UV absorbers, visible colorants (e.g., dyes, pigments, or mixtures thereof), antimicrobial agents (e.g., preferably silver nanoparticles), bioactive agents, leachable lubricants, leachable tear stabilizers, and mixtures thereof, as known to those skilled in the art. The resulting preformed SiHy contact lens can then be extracted using an extraction solvent to remove unpolymerized components from the resulting lens and to perform a hydration process, as known to those skilled in the art. Furthermore, the preformed SiHy contact lens may be a tinted contact lens (i.e., the SiHy contact lens is printed with at least one tinted pattern known to those skilled in the art).

[0060] Any suitable polyoxyethylene monomer can be used in this invention. Examples of preferred polyoxyethylene monomers include, but are not limited to, N-[tris(trimethylsiloxy)methalkylpropyl]-(meth)acrylamide, N-[tris(dimethylpropylsiloxy)methalkylpropyl](meth)acrylamide, N-[tris(dimethylphenylsiloxy)methalkylpropyl](meth)acrylamide, N-[tris(dimethylethylsiloxy)methalkylpropyl](meth)acrylamide, N-(2-hydroxy-3-(3-(bis))acrylamide, etc. (trimethylsilyloxy)methylsilyl)propoxy)propyl)-2-methylpropenylamine, N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propoxy)propyl)propenylamine, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propoxy)propyl]-2-methylpropenylamine, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propoxy)propyl]-2-methylpropenylamine, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propoxy]-2-methylpropenylamine [2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propoxy)propyl]-2-methylpropenylamine, N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propoxy)propyl)propyl)propenylamine, N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propoxy)propyl]-2-methyl ... -hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propoxy)propyl]acrylamide, N-[2-hydroxy-3-(3-(tert-butyldimethylsilyl)propoxy)propyl]-2-methylacrylamide, N-[2-hydroxy-3-(3-(tert-butyldimethylsilyl)propoxy)propyl]acrylamide, N,N-bis[2-hydroxy-3-(3-(tert-butyldimethylsilyl)propoxy)propyl]-2-methylacrylamide;N,N-bis[2-hydroxy-3-(3-(tert-butyldimethylsilyl)propoxy)propyl]acrylamide, 3-methacryloxypropylpentamethyldisiloxane, tris(trimethylsilyloxy)methacrylate (TRIS), (3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxane), (3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxane), 3-methacryloxy-2-(2-hydroxyethoxy)propoxy)propylbis(trimethylsiloxane), N-2-methacryloxyethyl-O-( Methyl-bis-trimethylsiloxo-3-propyl)methoxyalkylaminocarbamate, 3-(trimethylsiloxo)propyl vinyl carbonate, 3-(vinyloxycarbonylthio)propyl-tris(trimethyl-siloxo)silane, 3-[tris(trimethylsiloxo)siloxo]propyl vinyl aminocarbamate, 3-[tris(trimethylsiloxo)siloxo]propyl allyl aminocarbamate, 3-[tris(trimethylsiloxo)siloxo]propyl vinyl carbonate, tributyldimethyl-siloxoethyl vinyl carbonate, trimethylsiloxoethyl vinyl carbonate, and trimethylsiloxomethyl vinyl carbonate. The optimal siloxane (meth)acrylamide monosystem of formula (1) is N-[tris(trimethylsiloxy)methoxypropyl]acrylamide, TRIS, N-[2-hydroxy-3-(3-(tert-butyldimethylsiloxy)propoxy)propyl]acrylamide, or a combination thereof.

[0061] Preferably, the type of monomer or macromonomer containing polysiloxane is a polysiloxane-vinyl type monomer or macromonomer. Examples of such polysiloxane-vinyl type monomers or macromonomers are monomethacrylated or monoacrylated polydimethylsiloxanes of different molecular weights (e.g., mono-3-methacryloxypropyl-terminated, mono-butyl-terminated polydimethylsiloxanes or mono-(3-methacryloxy-2-hydroxypropyloxy)propyl-terminated, mono-butyl-terminated polydimethylsiloxanes); dimethacrylated or diacrylated polydimethylsiloxanes of different molecular weights; vinyl carbonate-terminated polydimethylsiloxanes; and vinyl carbamate-terminated polydimethylsiloxanes. Alkane; vinyl-terminated polydimethylsiloxanes of different molecular weights; methacrylamide-terminated polydimethylsiloxanes; acrylamide-terminated polydimethylsiloxanes; acrylate-terminated polydimethylsiloxanes; methacrylate-terminated polydimethylsiloxanes; bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane; N,N,N',N'-tetratetra(3-methacryloxy-2-hydroxypropyl)-α,ω-bis-3-aminopropyl-polydimethylsiloxane; polysiloxane alkyl (meth)acrylic acid monomers; selected from US The following are siloxane-containing macromonomers comprising the group of macromonomers A, B, C, and D as described in 5,760,100 (the entire contents of which are incorporated herein by reference): glycidyl methacrylate and amino-functionalized polydimethylsiloxane; hydroxyl-functionalized siloxane-containing vinyl monomers or macromonomers;The following documents disclose polysiloxane-containing macromonomers: US Patent Nos. 4,136,250, 4,153,641, 4,182,822, 4,189,546, 4,343,927, 4,254,248, 4,355,147, 4,276,402, 4,327,203, and 4... No. 341,889, No. 4,486,577, No. 4,543,398, No. 4,605,712, No. 4,661,575, No. 4,684,538, No. 4,703,097, No. 4,833,218, No. 4,837,289, No. 4,954,586, No. 4,954,587, No. 5,0 No. 10,141, No. 5,034,461, No. 5,070,170, No. 5,079,319, No. 5,039,761, No. 5,346,946, No. 5,358,995, No. 5,387,632, No. 5,416,132, No. 5,451,617, No. 5,486,579, No. 5,9 Polysiloxane-containing macromonomers disclosed in U.S. Patents 62,548, 5,981,675, 6,039,913, and 6,762,264 (the entire contents of which are incorporated herein by reference); and U.S. Patents 4,259,467, 4,260,725, and 4,261,875 (the entire contents of which are incorporated herein by reference). Diblock and triblock macromonomers composed of polydimethylsiloxane and polyalkylene oxides may also be used. For example, methacrylate-terminated polyethylene oxide-block-polydimethylsiloxane-block-polyethylene oxide may be used to enhance oxygen permeability. Suitable monofunctional hydroxyl-functionalized siloxane-containing ethylene monomers / macromonomers and suitable polyfunctional hydroxyl-functionalized siloxane-containing ethylene monomers / macromonomers were purchased from Gelest, Morrisville, PA.

[0062] Another preferred type of polysiloxane macromolecular monopolymer includes silicon-containing prepolymers with hydrophilic and hydrophobic segments. Any suitable polysiloxane prepolymer having hydrophilic and hydrophobic segments can be used in this invention. Examples of such polysiloxane-containing prepolymers include those set forth in the following documents: jointly owned U.S. Patents 6,039,913, 7,091,283, 7,268,189, and 7,238,750 and 7,521,519; jointly owned U.S. Patent Application Publications US 2008-0015315 A1, US 2008-0143958 A1, US 2008-0143003 A1, US 2008-0234457 A1, and US 2008-0231798 A1; and jointly owned U.S. Patent Applications 61 / 180,449 and 61 / 180,453; the entire contents of which are incorporated herein by reference.

[0063] Examples of preferred hydrophilic vinyl monomers are N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA), 2-acrylamide glycolic acid, 3-acrylamide amino-1-propanol, N-hydroxyethylacrylamide, N-[tri(hydroxymethyl)methyl]acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1 5-Methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone 1-n-Butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl methacrylate (HEMA), 2-hydroxyethyl acrylate (HEA), hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), trimethylammonium methacrylate 2-hydroxypropyl hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate (DMAEMA), glycerol methacrylate (GMA), N-vinyl-2-pyrrolidone (NVP), allyl alcohol, vinylpyridine, C1-C4-alkoxy polyethylene glycol (meth)acrylates with a weight average molecular weight of up to 1500, methacrylic acid, N-vinylmethoxyamine, N-vinylacetamide, N-vinylisopropylamine, N-vinyl-N-methylacetamide, allyl alcohol, N-vinylcaprolactam, and mixtures thereof.

[0064] Examples of preferred hydrophobic vinyl monomers include methyl acrylate, ethyl acrylate, propyl acrylate, isopropyl acrylate, cyclohexyl acrylate, 2-ethylhexyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile, 1-butene, butadiene, methacrylonitrile, vinyltoluene, vinyl ethyl ether, perfluorohexylethyl-thio-carbonyl-aminoethyl methacrylate, isocamphenyl methacrylate, trifluoroethyl methacrylate, hexafluoroisopropyl methacrylate, and hexafluorobutyl methacrylate.

[0065] Examples of preferred crosslinking agents include, but are not limited to, tetraethylene glycol diacrylate, triethylene glycol diacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, tetraethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylpropane trimethacrylate, isopentetrol tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethacrylate, ethylenediamine dimethacrylate, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1,3-bis(methacrylamidepropyl)-1,1,3,3- Tetra(trimethylsiloxy)diasiloxane, N,N'-methylenebisacrylamide, N,N'-methylenebisacrylamide, N,N'-ethylbisacrylamide, N,N'-ethylbisacrylamide, 1,3-bis(N-methacrylaminopropyl)-1,1,3,3-tetra-(trimethylsiloxy)diasiloxane, 1,3-bis... (methacrylaminobutyl)-1,1,3,3-tetra(trimethylsiloxy)-diasiloxane, 1,3-bis(acrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane, 1,3-bis(methacryloxyethylureapropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane, and combinations thereof. Preferred crosslinking agents are tetra(ethylene glycol) diacrylate, tri(ethylene glycol) diacrylate, ethylene glycol diacrylate, di(ethylene glycol) diacrylate, methylenebisacrylamide, triallyl isocyanurate, or triallyl cyanurate. The amount of crosslinking agent used is expressed as a percentage of the total polymer by weight, and preferably between about 0.05% and about 4%, and more preferably between about 0.1% and about 2%.

[0066] Examples of suitable thermal initiators include, but are not limited to, 2,2'-azobis(2,4-dimethylvaleronitrile), 2,2'-azobis(2-methylpropionitrile), 2,2'-azobis(2-methylbutyronitrile), peroxides (e.g., benzoyl peroxide), and the like. Preferably, the thermal initiator is 2,2'-azobis(isobutyronitrile) (AIBN).

[0067] Suitable photoinitiators include benzoin methyl ether, diethoxyacetophenone, benzoylphosphine oxide, 1-hydroxycyclohexylphenyl ketone, and Darocur and Irgacur, preferably Darocur 1173® and Darocur 2959®. Examples of benzoylphosphine oxide initiators include 2,4,6-trimethylbenzoyldiphenylphosphine oxide, bis-(2,6-dichlorobenzoyl)-4-N-propylphenylphosphine oxide, and bis-(2,6-dichlorobenzoyl)-4-N-butylphenylphosphine oxide. Reactive photoinitiators that can be incorporated into, for example, macromonomers or used as specific monomers are also suitable. Examples of reactive photoinitiators are those disclosed in EP 632 329, the entire contents of which are incorporated herein by reference. Polymerization can then be triggered by photochemical radiation (e.g., light of a suitable wavelength, specifically UV light). Therefore, if appropriate, the spectral requirements can be controlled by adding a suitable photosensitizer.

[0068] Any suitable polymerizable UV absorber can be used in this invention. Preferably, the polymerizable UV absorber includes a benzotriazole portion or a benzophenone portion. Examples of preferred polymerizable UV absorbers include, but are not limited to, 2-(2-hydroxy-5-vinylphenyl)-2H-benzotriazole, 2-(2-hydroxy-5-propenyloxyphenyl)-2H-benzotriazole, 2-(2-hydroxy-3-methylpropenylaminomethyl-5-tert-octylphenyl)benzotriazole, 2-(2'-hydroxy-5'-methylpropenylaminophenyl)-5-chlorobenzotriazole, 2-(2'-hydroxy-5'-methylpropenylaminophenyl)-5-methoxybenzotriazole, 2- (2'-hydroxy-5'-methacryloxypropyl-3'-tert-butyl-phenyl)-5-chlorobenzotriazole, 2-(2'-hydroxy-5'-methacryloxyethylphenyl)benzotriazole, 2-(2'-hydroxy-5'-methacryloxypropylphenyl)benzotriazole, 2-hydroxy-4-propenyloxyalkoxybenzophenone, 2-hydroxy-4-methacryloxyalkoxybenzophenone, allyl-2-hydroxybenzophenone, 2-hydroxy-4-methacryloxybenzophenone.

[0069] A bioactive agent is any compound that can prevent or reduce eye discomfort. A bioactive agent can be a drug, an amino acid (e.g., taurine, glycine, etc.), a polypeptide, a protein, a nucleic acid, or any combination thereof. Examples of drugs used herein include, but are not limited to, rebamipide, ketotifen, olaptidine, cromoglycolate, cyclosporine, nedocromil, levocabastine, lodoxamide, ketotifen, or pharmaceutically acceptable salts or esters thereof. Other examples of bioactive agents include 2-pyrrolidone-5-carboxylic acid (PCA), α-hydroxy acids (e.g., glycolic acid, lactic acid, malic acid, tartaric acid, mandelic acid, and citric acid and their salts), linoleic acid and γ-linoleic acid, and vitamins (e.g., B5, A, B6, etc.).

[0070] Examples of leachable lubricants include, but are not limited to, mucin-like materials (e.g., polyglycolic acid) and non-crosslinkable hydrophilic polymers (i.e., those without olefinic unsaturated groups). Any hydrophilic polymer or copolymer that does not contain any olefinic unsaturated groups can be used as a leachable lubricant. Preferred examples of non-crosslinkable hydrophilic polymers include, but are not limited to, polyvinyl alcohol (PVA), polyamide, polyimide, polylactone, homopolymers of vinyl lactone, copolymers of at least one vinyl lactone in the presence or absence of one or more hydrophilic vinyl comonomers, homopolymers of acrylamide or methacrylamide, copolymers of acrylamide or methacrylamide with one or more hydrophilic vinyl monomers, polyethylene oxide (i.e., polyethylene glycol (PEG)), polyoxyethylene derivatives, poly-NN-dimethylacrylamide, polyacrylic acid, poly-2-ethyloxazoline, heparin polysaccharide, polysaccharide, and mixtures thereof. The weight-average molecular weight (Mw) of the non-crosslinkable hydrophilic polymer is preferably between 5,000 and 100,000.

[0071] Examples of tear stabilizers include, but are not limited to, phospholipids, monoglycerides, diglycerides, triglycerides, glycolipids, glyceroglycolipids, sphingolipids, sphingo-glycolipids, fatty alcohols, fatty acids, mineral oils, and mixtures thereof. Preferably, the tear stabilizer is a phospholipid, monoglyceride, diglyceride, triglyceride, glycolipid, glyceroglycolipid, sphingolipid, sphingo-glycolipid, fatty acid having 8 to 36 carbon atoms, fatty alcohol having 8 to 36 carbon atoms, or mixtures thereof.

[0072] According to the present invention, the SiHy lens formulation can be a solution or a melt at a temperature of about 20°C to about 85°C. Preferably, the polymerizable composition is a solution of all desired components in a suitable solvent or a mixture of suitable solvents.

[0073] The SiHy lens formulation can be prepared by dissolving all the desired components in any suitable solvent, such solvent as water, a mixture of water and one or more organic solvents miscible with water, an organic solvent, or a mixture of one or more organic solvents, as is known to those skilled in the art.

[0074] Examples of preferred organic solvents include, but are not limited to, tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, ketones (e.g., acetone, methyl ethyl ketone, etc.), diethylene glycol n-butyl ether, diethylene glycol methyl ether, ethylene glycol phenyl ether, propylene glycol methyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether acetate, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, propylene glycol n-butyl ether, dipropylene glycol n-butyl ether, tripropylene glycol n-butyl ether, propylene glycol phenyl ether, dipropylene glycol dimethyl ether, polyethylene glycol, polypropylene glycol, ethyl acetate, butyl acetate, acetic acid. Amyl ester, methyl lactate, ethyl lactate, isopropyl lactate, dichloromethane, 2-butanol, 1-propanol, 2-propanol, menthol, cyclohexanol, cyclopentanol and exo-norbornol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norbornol, tri-butanol, tri-pentanol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol 2-Methyl-2-heptanol, 2-Methyl-2-octanol, 2-Methyl-2-nonanol, 2-Methyl-2-decanol, 3-Methyl-3-hexanol, 3-Methyl-3-heptanol, 4-Methyl-4-heptanol, 3-Methyl-3-octanol, 4-Methyl-4-octanol, 3-Methyl-3-nonanol, 4-Methyl-4-nonanol, 3-Methyl-3-octanol, 3-ethyl-3-hexanol, 3-Methyl-3-heptanol, 4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol 3-Hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol, 2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol, 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl-2-propanol, tri-pentanol, isopropanol, 1-methyl-2-pyrrolidone, N,N-dimethylpropionic acid, dimethylformamide, dimethylacetamide, dimethylpropionic acid, N-methylpyrrolidone, and mixtures thereof.

[0075] Numerous SiHy lens formulations have been described in numerous patents and patent applications published up to the filing date of this application. These SiHy lens formulations can all be used to obtain a pre-formed SiHy lens that subsequently becomes the inner layer of the SiHy contact lens of this invention, provided that it produces a SiHy material having the Dk and water content specified above. SiHy lens formulations used to manufacture commercial SiHy lenses (e.g., lotrafilcon A, lotrafilcon B, balafilcon A, galyfilcon A, senofilcon A, narafilcon A, narafilcon B, comfilcon A, enfilcon A, asmofilcon A, filcon II 3) can also be used to manufacture pre-formed SiHy contact lenses (the inner layer of the SiHy contact lens of this invention).

[0076] Those skilled in the art are familiar with lens molds used in the manufacture of contact lenses and, for example, in casting molding or spin casting. For instance, a mold (for casting molding) typically comprises at least two mold sections (or portions) or mold halves, namely a first mold half and a second mold half. The first mold half defines a first molding (or optical) surface, and the second mold half defines a second molding (or optical) surface. The first and second mold halves are configured to receive each other, thereby forming a cavity for forming the lens between the first molding surface and the second molding surface. The molding surface of the mold half is the surface of the mold forming the cavity and is in direct contact with the material forming the lens.

[0077] Those skilled in the art are generally familiar with methods for manufacturing mold segments for casting molded contact lenses. The method of the present invention is not limited to any particular method of forming a mold. In fact, any method of forming a mold can be used in the present invention. The first and second mold halves can be formed by various techniques, such as injection molding or lathe work. Examples of suitable methods for forming mold halves are disclosed in U.S. Patent No. 4,444,711 to Schad, No. 4,460,534 to Boehm et al., No. 5,843,346 to Morrill, and No. 5,894,002 to Boneberger et al., which are also incorporated herein by reference.

[0078] In fact, all materials known in the industry for manufacturing molds can be used to manufacture molds for contact lenses. For example, polymeric materials such as polyethylene, polypropylene, polystyrene, PMMA, Topas® COC grade 8007-S10 (a clear amorphous copolymer of ethylene and norbornene, from Ticona GmbH of Frankfurt, Germany; and Summit, New Jersey) or similar materials can be used. Other materials that allow UV light to pass through, such as quartz glass and sapphire, can also be used.

[0079] In a preferred embodiment, a reusable mold is used, and the polysilicon-oxygen hydrogel lens forming composition is cured photochemically under spatial confinement of photochemical radiation to form a SiHy contact lens. Examples of preferred reusable molds are disclosed in the following documents: U.S. Patent Application No. 08 / 274,942, filed July 14, 1994; U.S. Patent No. 10 / 732,566, filed December 10, 2003; U.S. Patent No. 10 / 721,913, filed November 25, 2003; and U.S. Patent No. 6,627,124, the entire contents of which are incorporated herein by reference. Reusable molds can be made from the following materials: quartz, glass, sapphire, CaF2, cyclic olefin copolymers (e.g., Topas® COC grade 8007-S10 (a clear amorphous copolymer of ethylene and norbornene), from Ticona GmbH of Frankfurt, Germany and Summit, New Jersey; Zeonex® and Zeonor®, from Zeon Chemicals LP, Louisville, KY), polymethyl methacrylate (PMMA), polyoxymethylene (Delrin) from DuPont, Ultem® (polyetherimide) from GE Plastics, PrimoSpire®, etc.

[0080] According to the present invention, the oxygen permeability of the inner layer polysiloxane hydrogel (bulk material) is at least about 50 barrer, preferably at least about 60 barrer, more preferably at least about 70 barrer, even more preferably at least about 90 barrer, and most preferably at least about 110 barrer. The polysiloxane hydrogel material may also have the following (first) water content WCSiHy: about 10 wt% to about 70 wt%, preferably about 10 wt% to about 65 wt%, more preferably about 10 wt% to about 60 wt%, even more preferably about 15 wt% to about 55 wt%, and most preferably about 15 wt% to about 50 wt%. The polysilicon-oxygen hydrogel material may further have the following bulk modulus of elasticity or bulk Young's modulus (in the following, unless the term is modified by the word "surface," the terms "softness," "modulus of elasticity," and "Young's modulus" are used interchangeably in this application to mean bulk modulus of elasticity): about 0.3 MPa to about 1.8 MPa, preferably 0.4 MPa to about 1.5 MPa, and more preferably about 0.5 MPa to about 1.2 MPa. The oxygen permeability, modulus of elasticity, and water content of the inner layer of the polysilicon-oxygen hydrogel material in the SiHy contact lens of the present invention can be determined by measuring the oxygen permeability, modulus of elasticity, and water content of the pre-formed SiHy lens derived from the inner layer. It should be understood that, as a reasonable approximation, the modulus of elasticity of the SiHy contact lens of the present invention can be regarded as the modulus of elasticity of the inner layer of the polysilicon-oxygen hydrogel material, because the outer hydrogel layer is extremely thin. Those familiar with this technology know how to determine the elastic modulus and water content of polysiloxane hydrogel materials or SiHy contact lenses. For example, all commercial SiHy contact lenses have reported values ​​for elastic modulus and water content.

[0081] Preferably, the two outer hydrogel layers of the SiHy contact lens of the present invention are substantially identical to each other and are cross-linked coatings applied to a pre-formed SiHy contact lens having a desired Dk, water content, and bulk modulus.

[0082] The layered structure configuration of the SiHy contact lens of the present invention can be established by analyzing the cross-section of a fully hydrated SiHy contact lens (i.e., directly in water or buffered saline) using atomic force microscopy (AFM), as described above and in the examples. AFM (e.g., force-volume mode) can be used to characterize the surface modulus of the cross-section (by imaging it) to visually observe any change in surface modulus across the cross-section from the rear surface side to the front surface side. Significant changes in surface modulus observed across the cross-section of the fully hydrated SiHy contact lens at a thickness of approximately 0.04 µm, preferably approximately 0.03 µm, more preferably approximately 0.02 µm, and even more preferably approximately 0.01 µm (by examining the AFM image) within a thickness of approximately 0.04 µm, preferably approximately 20% or greater, more preferably approximately 30% or greater, along the shortest line between the front and rear surfaces (by examining the AFM image) indicate a transition from one layer to different layers. The average thickness of each outer hydrogel layer can be measured using AFM images familiar to those skilled in this technique.

[0083] The two outer hydrogel layers of the SiHy contact lens of the present invention are substantially uniform in thickness. They merge at the periphery of the contact lens to completely surround the inner layer of the polysilicon-oxygen hydrogel material. The thickness of each outer hydrogel layer is about 0.1 µm to about 20 µm, preferably about 0.25 µm to about 15 µm, even more preferably about 0.5 µm to about 12.5 µm, and most preferably about 1 µm to about 10 µm. As described above, the thickness of the outer hydrogel layer (or cross-linked coating) of the SiHy contact lens of the present invention is determined by AFM analysis of the cross-section of a fully hydrated SiHy contact lens. In another preferred embodiment, the thickness of each outer hydrogel layer is preferably at most about 30% (i.e., 30% or less) of the center thickness of the fully hydrated SiHy contact lens, preferably at most about 20% (20% or less), and more preferably at most about 10% (10% or less).

[0084] It should be understood that the layered structural configuration of the SiHy contact lens of the present invention can also be qualitatively established by scanning electron microscopy (SEM) analysis of the cross-section of the freeze-dried SiHy contact lens shown in the example. SEM can show the different composition and / or structure of each layer in the cross-section of the freeze-dried SiHy contact lens. Significant compositional changes (e.g., about 20% or more, more preferably about 30% or more) and / or significant (visually visible) structural changes (by examining SEM images) observed across the cross-section of the freeze-dried SiHy contact lens within a thickness of about 0.04 µm, preferably about 0.03 µm, more preferably about 0.02 µm, and even more preferably about 0.01 µm indicate the transition from one layer to different layers. However, the thickness values ​​based on SEM analysis of the cross-section of the freeze-dried SiHy lens are usually lower than the actual values ​​because the outer hydrogel layer, transition layer (if applicable), and inner layer collapse after freeze-drying.

[0085] According to this embodiment of the invention, the two outer hydrogel layers (front outer hydrogel layer and rear outer hydrogel layer) of the SiHy contact lens of the present invention include a (second) water content that must be higher than the (first) water content (WCSiHy) of the inner layer of the polysiloxane hydrogel material, and more specifically, must be at least about 1.2 times (i.e., 120%) the (first) water content (WCSiHy) of the inner layer of the polysiloxane hydrogel material. It is believed that the water expansion rate of each outer hydrogel layer is related to its water content and can be suitably represented by a good approximation of the water content of the outer hydrogel layer. In alternative preferred embodiments, if the water content (WCSiHy) of the inner layer of the polysiloxane hydrogel material is about 55% or less, the water swelling rate of each outer hydrogel layer is at least about 150%; if the water content (WCSiHy) of the inner layer of the polysiloxane hydrogel material is about 60% or less, the water swelling rate of each outer hydrogel layer is at least about 200%; if the water content (WCSiHy) of the inner layer of the polysiloxane hydrogel material is about 65% or less, the water swelling rate of each outer hydrogel layer is at least about 250%; and if the water content (WCSiHy) of the inner layer of the polysiloxane hydrogel material is about 70% or less, the water swelling rate of each outer hydrogel layer is at least about 300%.

[0086] It should be understood that the water content of the front and rear outer hydrogel layers (crosslinked coatings) can be measured more accurately according to the procedure described in Example 23. Alternatively, the water content of the two outer hydrogel layers (crosslinked coatings) can be measured using an object comprising a non-absorbent thin substrate and the crosslinked coating thereon, wherein the crosslinked coating is applied to the non-absorbent thin substrate under substantially the same conditions according to the same coating process used for SiHy contact lenses. The water content of each outer hydrogel layer can then be determined based on the difference between the dry weight and the hydrated weight of the object having the crosslinked coating.

[0087] According to the invention, each of the two outer hydrogel layers is substantially free of polysiloxane, preferably completely free of polysiloxane. However, it is well known that when using X-ray photoelectron spectrometry (XPS) to determine the presence or absence of silicon in the outer hydrogel layer (typically, at a detection depth of 1.5 nm to 6 nm), the sample is inevitably contaminated by environmental silicon, as shown by XPS detection of silicon on the surface of a sample that is theoretically free of any silicon atoms, such samples being, for example, polyethylene sheets, DAILIES® AquaComfortPlus™ contact lenses from CIBA VISION, or ACUVUE® Moist from Johnson & Johnson (see Example 21 below). Therefore, the term "substantially silicon-free" is used in this application to mean that the percentage of surface silicon atoms on the SiHy contact lens, as measured by XPS, is less than about 200%, preferably less than about 175%, more preferably less than about 150%, and even more preferably less than about 125% of the percentage of silicon atoms in a known inherently (theoretically) silicon-free control sample (e.g., polyethylene sheet, DAILIES® AquaComfortPlus™ contact lens from CIBA VISION, or ACUVUE® Moist from Johnson & Johnson). Alternatively, each outer hydrogel layer of the SiHy contact lens of the present invention is substantially silicon-free, characterized by a silicon atom percentage of about 5% or less, preferably about 4% or less, and even more preferably about 3% or less of the total elemental percentage, as measured by XPS analysis of the contact lens in a dry state. It should be understood that a smaller percentage of polysiloxane may be incorporated into the polymer network of the outer hydrogel layer as needed (but not necessarily preferred), provided that it does not significantly impair the surface properties (hydrophilicity, wettability, and / or lubricity) of the SiHy contact lens.

[0088] In a preferred embodiment, the crosslinking density (or crosslink density) of the front and rear external hydrogel layers (crosslinked coatings) is sufficiently low to provide a crosslinked coating or external hydrogel layer (i.e., SiHy contact lens) with high resistance to finger rubbing, as characterized by the absence of visible surface cracks in a dark field after rubbing the SiHy contact lens between fingers. It is believed that surface cracking caused by finger rubbing can reduce surface lubricity and / or may fail to prevent polysiloxane migration to the surface (exposure). Surface cracking can also indicate the presence of excessive crosslinking density in the surface layer, which can affect the surface elastic modulus. Preferably, the non-polysiloxane hydrogel material in the external hydrogel layer (crosslinked coating) comprises crosslinks derived from nitrogen-containing heterocyclic butyronitrile groups in a thermally induced coupling reaction.

[0089] In another preferred embodiment, the front and rear surfaces have a low surface concentration of negatively charged groups (including carboxylic acid groups), characterized by attracting up to about 200, preferably up to about 160, more preferably up to about 120, even more preferably up to about 90, and most preferably up to about 60 positively charged particles in a positively charged particle adhesion test. It is desirable to have a minimum surface concentration of negatively charged groups (e.g., carboxylic acid groups) on the SiHy contact lens of the present invention, as contact lenses with a high surface concentration of negatively charged groups (e.g., carboxylic acid groups) are prone to high debris adhesion (during patient handling), high protein adhesion (during wear) (it is believed that most proteins in tears are positively charged), and high deposition and accumulation of antimicrobial agents (e.g., polyhexamethylene biguanide (PHMB)) present in contact lens care solutions. To have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups), the front and rear outer hydrogel layers should have a relatively low carboxylic acid content. Preferably, the carboxylic acid content of the front and rear outer hydrogel layers is about 20% by weight or less, more preferably about 15% by weight or less, even more preferably about 10% by weight or less, and most preferably about 5% by weight or less.

[0090] In another preferred embodiment, the SiHy contact lens of the present invention has good surface lubricity, characterized by having a critical coefficient of friction (CCOF) of about 0.046 or less, preferably about 0.043 or less, and more preferably about 0.040 or less. Alternatively, the SiHy contact lens of the present invention preferably has lubricity superior to ACUVUE OASYS or ACUVUE TruEye, as measured in a blind eye test according to the lubricity evaluation procedure described in Example 1.

[0091] In another preferred embodiment, the SiHy contact lens of the present invention further includes two transition layers of polymeric material in its layered structural configuration, as schematically shown in FIG2. Each of the two transition layers 115 is located between the inner layer 110 and one of the two outer hydrogel layers 120. Each transition layer is substantially uniform in thickness. The thickness of each transition layer is at least about 0.05 µm, preferably about 0.05 µm to about 10 µm, more preferably about 0.1 µm to about 7.5 µm, and even more preferably about 0.15 µm to about 5 µm. The transition layers merge at the peripheral edge of the contact lens to completely surround the inner layer of polysilicon-oxygen hydrogel material. The presence and thickness of the transition layers can preferably be determined by AFM analysis of the cross-section of a fully hydrated SiHy contact lens, as described above for the outer hydrogel layers and the inner layer.

[0092] The two transition layers of the SiHy contact lens of the present invention are essentially a base (or bottom) coating, which is applied to a pre-formed SiHy contact lens having a desired Dk, water content, and bulk modulus, and then a cross-linked coating (outer hydrogel layer) is applied on top. The transition layer (base coating) is used to anchor / attach the outer hydrogel layer. Preferably, the transition layer comprises a carboxyl-containing (COOH) polymer, preferably a homopolymer or copolymer of acrylic acid, methacrylic acid, or C2-C12 alkyl acrylic acid. It should be understood that the carboxyl-containing polymer can permeate into the bulk material and extend into the outer hydrogel layer. When this permeation occurs in the inner layer of the polysiloxane hydrogel material, each transition layer will comprise carboxyl-containing polymer and polysiloxane hydrogel entangled together. It is also believed that the presence of a transition layer, especially when it includes a carboxyl-containing polymer, can provide a relatively high water content on a thicker layer and / or provide a water reservoir for the outer hydrogel layer, due to the high water-binding properties of carboxyl groups. Furthermore, even if the transition layer contains a high concentration of carboxylic acid groups, it has minimal adverse effect on the surface concentration of carboxylic acid groups in the SiHy contact lens. This is because the surface concentration of carboxylic acid groups is primarily determined by the outer hydrogel layer that completely covers the transition layer. An outer hydrogel layer with a low surface concentration of carboxylic acid groups prevents the deposition of positively charged proteins from the tears of the lens wearer.

[0093] In another preferred embodiment, the front outer hydrogel layer and the rear outer hydrogel layer have a reduced surface modulus of at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, and most preferably at least about 40% relative to the inner layer.

[0094] The front and rear outer hydrogel layers are preferably made of the same or substantially the same material (preferably completely free of polysiloxane) and can be formed by applying a water-soluble and crosslinkable hydrophilic polymeric material to a pre-formed SiHy contact lens (which includes amine and / or carboxyl groups on and / or near the surface of the contact lens, or includes a base coating containing amine and / or carboxyl groups) and crosslinking it, wherein the pre-formed SiHy contact lens becomes an inner layer after crosslinking.

[0095] According to the present invention, the preformed SiHy contact lens may inherently include or be modified to include amine and / or carboxyl groups on and / or near its surface.

[0096] If the pre-formed SiHy hydrogel contact lens inherently includes amine and / or carboxyl groups on and / or near its surface, it is obtained by polymerizing a polysiloxane hydrogel lens formulation including reactive vinyl monomers.

[0097] Examples of preferred reactive vinyl monomers include, but are not limited to, (meth)acrylate amino-C2-C6 alkyl ester, (meth)acrylate C1-C6 alkylamino-C2-C6 alkyl ester, allylamine, vinylamine, amino-C2-C6 alkyl(meth)acrylamide, C1-C6 alkylamino-C2-C6 alkyl(meth)acrylamide, acrylic acid, C1-C12 alkylacrylic acid (e.g., methacrylic acid, ethylacrylic acid, propylacrylic acid, butylacrylic acid, pentylacrylic acid, etc.), N,N-2-acrylamide glycolic acid, β-methacrylic acid (crotonic acid), α-phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenylbutadiene-1,3, itaconic acid, citraconic acid, mesoconic acid, pentenediaic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof. Preferably, the SiHy contact lens is prepared from a lens formulation comprising at least one of the following groups: (meth)acrylate amino-C2-C6 alkyl ester, (meth)acrylate C1-C6 alkylamino-C2-C6 alkyl ester, allylamine, vinylamine, amino-C1-C6 alkyl(meth)acrylamide, C1-C6 alkylamino-C2-C6 alkyl(meth)acrylamide, acrylic acid, C1-C12 alkylacrylic acid, N,N-2-acrylamide glycolic acid, and combinations thereof.

[0098] The lens formulation preferably includes about 0.1% to about 10% by weight, more preferably about 0.25% to about 7% by weight, even more preferably about 0.5% to about 5% by weight, and most preferably about 0.75% to about 3% by weight of the above-mentioned reactive vinyl monomer.

[0099] The pre-formed SiHy contact lens may also undergo surface treatment to form a reactive base coating having amine and / or carboxyl groups on the surface of the contact lens. Examples of surface treatment include, but are not limited to, surface treatment performed by energy (e.g., plasma, static charge, irradiation, or other energy sources), chemical treatment, chemical vapor deposition, grafting of hydrophilic vinyl monomers or macromonomers onto the surface of an object, and layer-by-layer coating (“LbL coating”) (obtained according to the methods described in the following documents: 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 covalently attached to the polymer matrix of the contact lens and is obtained by depositing charged or chargeable (by protonation or deprotonation) and / or uncharged materials layer by layer ("LbL") on the lens. An LbL coating may consist of one or more layers.

[0100] Preferably, the surface treatment is an LbL coating process. In this preferred embodiment (i.e., the reactive LbL base coating embodiment), the resulting polysiloxane hydrogel contact lens includes a reactive LbL base coating (i.e., two transition layers) containing at least one reactive polymer layer (i.e., a polymer having side-chain amine groups and / or carboxyl groups), wherein the reactive LbL base coating is obtained by contacting the contact lens with a solution of the reactive polymer. Contact between the contact lens and the coating solution of the reactive polymer can be carried out by immersing it in the coating solution or by spraying it with the coating solution. One contact process involves simply immersing the contact lens in a bath of coating solution for a period of time, or another option is to successively immerse the contact lens in a series of baths of coating solutions, each bath lasting a short, fixed time. Another contact process involves simply spraying the coating solution. However, numerous alternatives involve various combinations of spray-and-immersion steps that can be designed by those skilled in the art. The contact time between the contact lens and the coating solution of the reactive polymer can last up to about 10 minutes, preferably about 5 seconds to about 360 seconds, more preferably about 5 seconds to about 250 seconds, or even more preferably about 5 seconds to about 200 seconds.

[0101] According to this reactive LbL substrate coating embodiment, the reactive polymer can be a linear or branched polymer having side-chain amine groups and / or carboxyl groups. Any polymer having side-chain amine groups and / or carboxyl groups can be used as a reactive polymer for forming a substrate coating on polysilicon-oxygen hydrogel contact lenses. Examples of such reactive polymers include, but are not limited to: homopolymers of reactive vinyl monomers, copolymers of two or more reactive vinyl monomers, copolymers of reactive vinyl monomers with one or more non-reactive hydrophilic vinyl monomers (i.e., hydrophilic vinyl monomers without any carboxyl or (primary or secondary) amine groups), polyethyleneimine (PEI), polyvinyl alcohol having side-chain amine groups, cellulose containing carboxyl groups (e.g., carboxymethyl cellulose, carboxyethyl cellulose, carboxypropyl cellulose), hyaluronic acid esters, chondroitin sulfate, poly(glutamate), poly(aspartic acid), and combinations thereof.

[0102] Any of the preferred reactive vinyl monomers described above can be used in this embodiment to form a reactive polymer for forming a reactive LbL substrate coating.

[0103] Preferred examples of non-reactive hydrophilic vinyl monomers without 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-dimethylaminopropylmethacrylamide (DMAPMAm), N,N-dimethylaminopropylacrylamide (DMAPAAm), glycerol methacrylate, 3-acrylamide amino-1-propanol, N-hydroxyethylacrylamide, N-[tri(hydroxymethyl)methyl]acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-propanol - 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 methacrylate, hydroxypropyl methacrylate, C1-C4-alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 1500 Daltons, N-vinylmethoxyamine, N-vinylacetamide, N-vinylisopropylamine, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in copolymers), vinyl monomers containing phosphocholine (including (meth)acryloxyethyl phosphocholine and those set forth in U.S. Patent No. 5,461,433, the entire contents of which are incorporated herein by reference), and combinations thereof.

[0104] Preferably, the reactive polymer used to form the reactive LbL substrate coating 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-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], polyethyleneimine (PEI), polyallylamine hydrochloride (PAH) homopolymer or copolymer, polyvinylamine homopolymer or copolymer, or a combination thereof.

[0105] The weight average molecular weight Mw of the reactive polymer used to form the reactive LbL base coating is at least about 10,000 Daltons, preferably at least about 50,000 Daltons, and more preferably from about 100,000 Daltons to 5,000,000 Daltons.

[0106] A solution of the reactive polymer used to form a reactive LbL base coating on a contact lens can be prepared by dissolving one or more reactive polymers in water, a mixture of water and one or more organic solvents miscible with water, an organic solvent, or a mixture of one or more organic solvents. Preferably, the reactive polymer is dissolved in water and a mixture of 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 pre-formed SiHy contact lens to swell, thereby allowing a portion of the reactive polymer to penetrate into the pre-formed SiHy contact lens and increase the durability of the reactive base coating. Any of the aforementioned organic solvents can be used to prepare a solution of the reactive polymer, provided that it can dissolve the reactive polymer.

[0107] In another preferred embodiment, the pre-formed SiHy contact lens inherently includes amine and / or carboxyl groups on and / or near its surface, and is further subjected to surface treatment to form a reactive LbL substrate coating having amine and / or carboxyl groups therein.

[0108] In another preferred embodiment (reactive plasma substrate coating), the pre-formed SiHy contact lens is subjected to plasma treatment to form a covalently attached reactive plasma substrate coating on the contact lens, that is, one or more reactive vinyl monomers (any of those described above) are polymerized under the influence of plasma generated by discharge (so-called plasma-induced polymerization). The term "plasma" refers to, for example, an ionized gas generated by glow discharge, which may consist of electrons, ions of any polarity, gas atoms and molecules in the ground state or any higher state of any excited form, and photons. It is commonly referred to as "cryoplasma". For reviews on plasma polymerization and its applications, see R. Hartmann, "Plasma polymerisation": Grundlagen, Technik und Anwendung, Jahrb. Oberflächentechnik (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 (1985); Frank Jansen, "Plasma Deposition Processes", "Plasma Deposited Thin Films", T. Mort and F. Jansen, eds., CRC Press Boca Raton (19); O. Auciello et al., (eds.) "Plasma-Surface Interactions and Processing of Materials", Kluwer Academic Publishers in NATO ASI Series publication; Series E: Applied Sciences, 176th edition (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 a "afterglow" plasma-induced polymerization, as described in WO 98028026 (the entire contents of which are incorporated herein by reference). For "afterglow" plasma polymerization, the surface of the contact lens is first treated with a non-polymerizable plasma gas (e.g., H2, He, or Ar), and then in a subsequent step, the thus activated surface is exposed to an ethylene monomer having amine or carboxyl groups (any of the aforementioned reactive ethylene monomers), while the plasma power supply is turned off. Activation causes the formation of free radicals on the surface in a plasma-induced manner, which initiate the polymerization of the ethylene monomer in the subsequent step.

[0109] According to the present invention, the water-soluble and crosslinkable hydrophilic polymeric material used to form an external hydrogel layer (or a crosslinked coating) includes crosslinkable groups, preferably thermally crosslinkable groups, and more preferably aziridine groups. Preferably, the water-soluble and crosslinkable hydrophilic polymeric material used to form an external hydrogel layer (or a crosslinked coating) is a partially crosslinked polymeric material, which includes a three-dimensional network and crosslinkable (preferably thermally crosslinkable) groups and more preferably aziridine groups located within the network. The term "partially crosslinked" in relation to polymeric materials means that the crosslinkable groups of the starting material used to prepare the polymeric material in the crosslinking reaction are not completely consumed. Examples of crosslinkable groups include, but are not limited to, aziridine groups, epoxy groups, isocyanate groups, aziridine groups, acrylonitrile groups, and combinations thereof.

[0110] In a preferred embodiment, the water-soluble and crosslinkable hydrophilic polymeric material for forming the external hydrogel layer (or crosslinked coating) comprises: (i) about 20% to about 95% by weight of a first polymer chain derived from epichlorohydrin-functionalized polyamine or polyamide; (ii) about 5% to about 80% by weight of a hydrophilic portion or a second polymer chain derived from at least one hydrophilic reinforcing agent having at least one group selected from amino, carboxyl, thiol groups, The reactive functional groups of the group and their combinations, wherein the hydrophilic portions or second polymer chains are covalently attached to the first polymer chains via one or more covalent links, each covalent link being formed between an azacyclobutane group of the epichlorohydrin-functionalized polyamine or polyamide and an amine, carboxyl, or thiol group of the hydrophilic reinforcing agent; and (iii) azacyclobutane groups, which are part of or covalently attached to the side chains or terminal groups of the first polymer chains.

[0111] Using this water-soluble and crosslinkable hydrophilic polymeric material, the outer hydrogel layer (or crosslinked coating) can be easily formed by heating a pre-formed SiHy contact lens (having amine and / or carboxyl groups on and / or near the surface of the contact lens, or having a base coating including amine and / or carboxyl groups) in an aqueous solution in the presence of the hydrophilic polymeric material to a temperature of about 40°C to about 140°C, and holding it at that temperature for a sufficient period of time to covalently attach the hydrophilic polymeric material to the surface of the contact lens via covalent links, each covalent link being formed between a nitrogen-containing butyronitrile group of the hydrophilic polymeric material and one of the amine and / or carboxyl groups on and / or near the surface of the contact lens, thereby forming a crosslinked hydrophilic coating on the contact lens. It should be understood that any water-soluble and crosslinkable hydrophilic polymeric material containing crosslinkable groups (e.g., those described above) can be used in this invention to form the outer hydrogel layer before and after the SiHy contact lens.

[0112] A water-soluble and thermally crosslinkable hydrophilic polymeric material containing a nitrogen-containing heterocyclic butyronitrile group comprises (i.e., having a composition including) about 20% to about 95% by weight, preferably about 35% to about 90% by weight, more preferably about 50% to about 85% by weight, of a first polymer chain derived from an epichlorohydrin-functionalized polyamine or polyamide; and about 5% to about 80% by weight, preferably about 10% to about 65% by weight, and even more preferably about 15% to about 50% by weight, of a hydrophilic portion or a second polymer chain derived from at least one hydrophilic reinforcing agent having at least one reactive functional group selected from the group consisting of amine, carboxyl, thiol, and combinations thereof. The composition of the hydrophilic polymeric material is determined by the composition of the reactant mixture used to prepare the thermally crosslinkable hydrophilic polymeric material according to the crosslinking reaction shown in the reaction diagram I above (based on the total weight of the reactants). For example, if the reactant mixture comprises about 75% by weight of epichlorohydrin-functionalized polyamine or polyamide and about 25% by weight of at least one hydrophilic reinforcing agent (based on the total weight of the reactants), the resulting hydrophilic polymeric material comprises about 75% by weight of a first polymer chain derived from the epichlorohydrin-functionalized polyamine or polyamide and about 25% by weight of a hydrophilic portion or second polymer chain derived from the at least one hydrophilic reinforcing agent. The azahexacyclobutane groups in the thermally crosslinkable hydrophilic polymeric material are azahexacyclobutane groups (groups of epichlorohydrin-functionalized polyamine or polyamide) that do not participate in the crosslinking reaction used to prepare the thermally crosslinkable hydrophilic polymeric material.

[0113] Epichlorohydrin-functionalized polyamines or polyamides can be obtained by reacting epichlorohydrin with a polyamine polymer or a polymer containing primary or secondary amine groups. For example, poly(alkylimide) or poly(amide) (which is a condensation polymer derived from a polyamine and a dicarboxylic acid (e.g., adipic acid-diethyltriamine copolymer)) can be reacted with epichlorohydrin to form epichlorohydrin-functionalized polymers. Similarly, homopolymers or copolymers of (meth)acrylate aminoalkyl esters, (meth)acrylate monoalkylaminoalkyl esters, aminoalkyl (meth)acrylamide, or monoalkylaminoalkyl (meth)acrylamide can also be reacted with epichlorohydrin to form epichlorohydrin-functionalized polyamines. The reaction conditions for epichlorohydrin functionalization of polyamines or polyamide polymers are taught in EP1465931 (the entire contents of which are incorporated herein by reference). Preferred epichlorohydrin-functionalized polymer systems include polyamine-epoxychlorohydrin (PAE) (or polyamine-polyamine-epoxychlorohydrin or polyamine-epoxychlorohydrin), for example, Kymene® or Polycup® resins (epoxychlorohydrin-functionalized adipic acid-diethyltriamine copolymer) from Hercules or Polycup® or Servamine® resins from Servo / Delden.

[0114] Any suitable hydrophilicity enhancer may be used in this invention, as long as it contains at least one amine group, at least one carboxyl group, and / or at least one thiol group.

[0115] Preferred types of hydrophilicity enhancers include, but are not limited to, monosaccharides containing amino, carboxyl, or thiols (e.g., 3-amino-1,2-propanediol, 1-thioglycerol, 5-keto-D-gluconic acid, galactosamine, glucosamine, galacturonic acid, gluconic acid, aminogluconic acid, mannosamine, sucralose 1,4-lactone, sugar acid, 2-keto-3-deoxynonulosonic acid). (acid), N-methyl-D-glucosamine, 1-amino-1-deoxy-β-D-galactose, 1-amino-1-deoxysorbitol, 1-methylamino-1-deoxysorbitol, N-aminoethylglucosamine); disaccharides containing amino, carboxyl or thiol (e.g., sodium chondroitin disaccharide, di(β-D-xylopyranosyl)amine, lacturonic acid, heparin disaccharide, hyaluronic acid disaccharide, lactobionic acid); and oligosaccharides containing amino, carboxyl or thiol (e.g., sodium carboxymethyl-β-cyclodextrin, galacturonic acid); and combinations thereof.

[0116] Another preferred type of hydrophilicity enhancer is a hydrophilic polymer having one or more amine, carboxyl, and / or thiol groups. More preferably, based on the total weight of the hydrophilic polymer, the content of monomer units having amine (-NHR', where R' is as defined above), carboxyl (-COOH), and / or thiol (-SH) groups in the hydrophilic polymer serving as the hydrophilic enhancer is less than about 40% by weight, more preferably less than about 30% by weight, more preferably less than about 20% by weight, and even more preferably less than about 10% by weight.

[0117] A preferred type of hydrophilic polymer as a hydrophilicity enhancer is a polysaccharide containing amino or carboxyl groups, such as carboxymethyl cellulose (carboxyl content of about 40% or less, estimated based on the composition of the repeating unit -[C6H10-mO5(CH2CO2H)m]-, where m is 1 to 3), carboxyethyl cellulose (carboxyl content of about 36% or less, estimated based on the composition of the repeating unit -[C6H10-mO5(C2H4CO2H)m]-, where m is 1 to 3), and carboxypropyl cellulose (carboxyl content of about 32% or less, estimated based on the composition of the repeating unit -[C6H10-mO5(CH2CO2H)m]-, where m is 1 to 3), etc. The composition of [(C3H6CO2H)m]- is estimated, where m is 1 to 3), hyaluronic acid (carboxyl content of about 11%, which is estimated based on the composition of the repeating unit -(C13H20O9NCO2H)-), chondroitin sulfate (carboxyl content of about 9.8%, which is estimated based on the composition of the repeating unit -(C12H18O13NSCO2H)-), or combinations thereof.

[0118] Another preferred type of hydrophilic polymer as a hydrophilicity enhancer includes, but is not limited to: polyethylene glycol (PEG) having mono-amine, carboxyl, or thiol groups (e.g., PEG-NH2, PEG-SH, PEG-COOH); H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; multi-arm PEG having one or more amine, carboxyl, or thiol groups; PEG dendritic polymers having one or more amine, carboxyl, or thiol groups; and homopolymers of non-reactive hydrophilic vinyl monomers terminated with diamine or dicarboxyl groups. or copolymers; homopolymers or copolymers of non-reactive hydrophilic vinyl monomers with monoamine- or monocarboxyl-terminated ends; copolymers as polymeric products comprising compositions including: (1) about 60% by weight or less, preferably about 0.1% by weight to about 30% by weight, more preferably about 0.5% by weight to about 20% by weight, and even more preferably about 1% by weight 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 vinyl monomer containing phosphocholine; and combinations thereof. The reactive vinyl monomers and non-reactive hydrophilic vinyl monomers are described above.

[0119] More preferably, the hydrophilic polymer system used as the hydrophilicity enhancer is PEG-NH2; PEG-SH; PEG-COOH; H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; multi-arm PEG having one or more amino, carboxyl, or thiol groups; PEG dendritic polymer having one or more amino, carboxyl, or thiol groups; or a non-reactive hydrophilic vinyl type selected from the group consisting of the following components. Homopolymers or copolymers of monomers with monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated groups: acrylamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C1-C4-alkoxy polyethylene glycol (meth)acrylate 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 Methyl-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminopropyl (meth)acrylamide, (meth)acryloxyethyl phosphocholine, and combinations thereof; as copolymers of a polymeric product comprising a composition including: (1) about 0.1% to about 30% by weight, preferably about 0.5% to about 20% by weight, more preferably about 1% to about 15% by weight of (meth)acrylic acid, C2-C12 alkylacrylic acid, vinylamine, allylamine, and / or (2) (meth)acrylate amino-C2-C4 alkyl ester; and (3) (meth)acryloxyethyl phosphocholine 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, (meth)acrylate hydroxyethyl ester, N-hydroxyethyl (meth)acrylamide, C1-C4-alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 400 Daltons, vinyl alcohol, and combinations thereof.

[0120] Preferably, the hydrophilicity enhancing agent is PEG-NH2; PEG-SH; PEG-COOH; polyvinylpyrrolidone with monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated groups; polyacrylamide with monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated groups; poly(DMA) with monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated groups; or poly(D) with monoamine- or monocarboxyl-, diamine-, or dicarboxyl-terminated groups. MA-co-NVP); monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated poly(NVP-co-(meth)acrylate N,N-dimethylaminoethyl ester); monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated poly(vinyl alcohol); monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated poly[(meth)acryloxyethyl phosphocholine] homopolymer or copolymer; monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated poly(NVP-co-(meth)acrylate ethyl phosphocholine] homopolymer or copolymer; monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated poly(NVP-co-(meth)acrylate ethyl phosphocholine) homopolymer or copolymer. P-co-vinyl alcohol; monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated poly(DMA-co-vinyl alcohol); poly((meth)acrylic acid-co-acrylamide) having about 0.1 wt% to about 30 wt%, preferably about 0.5 wt% to about 20 wt%, more preferably about 1 wt% to about 15 wt% of (meth)acrylic acid; poly((meth)acrylic acid-co-NVP) having about 0.1 wt% to about 30 wt%, preferably about 0.5 wt% to about 20 wt%, more preferably about 1 wt% to about 15 wt% of (meth)acrylic acid; copolymers as polymers of compositions comprising: (1) (meth)acryloxyethyl phosphocholine and (2) about 0.1 wt% to about 30 wt%, preferably about 0.5 wt% to about 20 wt%, more preferably about 1 wt% to about 15 wt% of carboxylic acid-containing vinyl monomers and / or amino-containing vinyl monomers; and combinations thereof.

[0121] PEG with functional groups and multi-arm PEG with functional groups are available from various commercial suppliers, such as Polyscience and Shearwater Polymers.

[0122] Homopolymers or copolymers of one or more non-reactive hydrophilic vinyl monomers or vinyl monomers containing phosphocholine, characterized by monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated groups, can be prepared according to the procedure described in U.S. Patent No. 6,218,508 (the entire contents of which are incorporated herein by reference). For example, to prepare a non-reactive hydrophilic vinyl monomer characterized by diamine- or dicarboxyl-terminated groups, the non-reactive vinyl monomer, a chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, mercaptoacetic acid, thiolactic acid, or other hydroxythiols, aminothiols, or carboxyl-containing thiols), and, if desired, other vinyl monomers, are copolymerized with the reactive vinyl monomer (having an amino or carboxyl group) in the presence of a free radical initiator (thermally or photochemically). Typically, the molar ratio of the chain transfer agent to all vinyl monomers except 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, the chain transfer agent having an amino or carboxyl group is used to control the molecular weight of the resulting hydrophilic polymer and to form the end of the resulting hydrophilic polymer to provide a terminal amino or carboxyl group, while the reactive vinyl monomer provides other terminal carboxyl or amino groups to the resulting hydrophilic polymer. Similarly, to prepare homopolymers or copolymers of non-reactive hydrophilic vinyl monomers with monoamine- or monocarboxyl-terminated ends, the non-reactive vinyl monomer, a chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, mercaptoacetic acid, thiolactic acid, or other hydroxythiols, aminothiols, or carboxyl-containing thiols), and other vinyl monomers (thermally or photochemically) as needed are copolymerized in the absence of any reactive vinyl monomer.

[0123] As used in this application, a copolymer of a non-reactive hydrophilic vinyl monomer refers to a polymerization product of a non-reactive hydrophilic vinyl monomer and one or more additional vinyl monomers. Copolymers comprising a non-reactive hydrophilic vinyl monomer and a reactive vinyl monomer (e.g., a carboxyl-containing vinyl monomer) can be prepared by any known free radical polymerization method or obtained from commercial suppliers. Copolymers containing methacryloyloxyethyl phosphocholine and a carboxyl-containing vinyl monomer can be obtained from NOP (e.g., LIPIDURE®-A and LIPIDURE®-AF).

[0124] The weight average molecular weight Mw of the hydrophilic polymer (as a hydrophilicity enhancer) having at least one amine, carboxyl or thiol group is preferably about 500 to about 1,000,000, more preferably about 1,000 to about 500,000.

[0125] According to the present invention, the reaction between the hydrophilic reinforcing agent and the epichlorohydrin or polyamide is carried out at a temperature of about 40°C to about 100°C for a time (about 0.3 hours to about 24 hours, more preferably about 1 hour to about 12 hours, and even more preferably about 2 hours to about 8 hours) sufficient to form a water-soluble and thermally crosslinkable hydrophilic polymeric material containing a nitrogen-containing heterocyclic butyronitrile groups.

[0126] According to the present invention, the concentration of the hydrophilic reinforcing agent relative to the epichlorohydrin-functionalized polyamine or polyamide must be selected so that the resulting hydrophilic polymeric material is not water-insoluble (i.e., at room temperature, the solubility is less than 0.005 g / 100 ml water) and does not consume more than about 99%, preferably about 98%, more preferably about 97%, and even more preferably about 96% of the azacyclobutane groups in the epichlorohydrin-functionalized polyamine or polyamide.

[0127] According to the present invention, it is preferred to perform heating by autoclaving a pre-formed SiHy contact lens comprising amine and / or carboxyl groups on and / or near the surface of the contact lens, or comprising a base coating containing amine and / or carboxyl groups, and immersing it in a packaging solution (i.e., a buffer aqueous solution) containing a water-soluble thermocrosslinkable hydrophilic polymeric material in a sealed lens package at a temperature of about 118°C to about 125°C for about 20-90 minutes. According to this embodiment of the present invention, the packaging solution is an eye-safe buffer aqueous solution after autoclaving. Alternatively, it is preferred to perform heating by autoclaving a pre-formed SiHy contact lens comprising a base coating and a layer of water-soluble thermocrosslinkable hydrophilic polymeric material on top of the base coating, and immersing it in a packaging solution (i.e., a buffer aqueous solution) in a sealed lens package at a temperature of about 118°C to about 125°C for about 20-90 minutes.

[0128] Those skilled in the art are familiar with the autoclaving and storage of soft contact lenses in lens packaging (or containers). Any lens packaging can be used in this invention. Preferably, the lens packaging is a blister pack comprising a base and a cap, wherein the cap is detachably sealed to the base, wherein the base includes a cavity for containing a sterile packaging solution and the contact lens.

[0129] The lenses are packaged individually, sealed, and sterilized (e.g., by autoclaving at approximately 120°C or higher for at least 30 minutes) and then distributed to the user. Those skilled in this technique should have a full understanding of how to seal and sterilize the lens packaging.

[0130] According to the present invention, the packaging solution contains at least one buffer and one or more other components known to those skilled in the art. Examples of other components include, but are not limited to, permeability modifiers, surfactants, antibacterial agents, preservatives, and lubricants (or water-soluble thickeners) (e.g., cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone).

[0131] The packaging solution contains a buffer in an amount sufficient to maintain the pH of the packaging solution within a desired range (e.g., preferably, a physiologically acceptable range of about 6 to about 8.5). Any known physiologically compatible buffer can be used. Those skilled in the art know of suitable buffers as components of the contact lens care composition of the present invention. Examples include boric acid, borates (e.g., sodium borate), citric acid, citrates (e.g., potassium citrate), bicarbonates (e.g., sodium bicarbonate), and TRIS. (2-amino-2-hydroxymethyl-1,3-propanediol), Bis-Tris (bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane), bis-amino polyol, triethanolamine, ACES (N-(2-hydroxyethyl)-2-aminoethanesulfonic acid), BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), HEPES (4-(2-hydroxyethyl)-1-hexahydropyrazine ethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), MOPS (3-[N-morpholino]-propanesulfonic acid), PIPES (hexahydropyrazine ethanesulfonic acid) Pyrazine-N,N'-bis(2-ethanesulfonic acid), TES (N-[tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid), its salts, phosphate buffers (e.g., Na2HPO4, NaH2PO4, and KH2PO4), or mixtures thereof. Preferred bis-amino polyol is 1,3-bis(tris(hydroxymethyl)-methylamino)propane (bis-TRIS-propane). The amount of each buffer in the packaged solution is preferably from 0.001% to 2% by weight, more preferably from 0.01% to 1% by weight; most preferably from about 0.05% to about 0.30% by weight.

[0132] The tonicity of the packaging solution is approximately 200 mOsm to approximately 450 mOsm, preferably approximately 250 mOsm to approximately 350 mOsm. The tonicity of the packaging solution can be adjusted by adding organic or inorganic substances that affect the tonicity. Suitable ocularly acceptable osmotic regulators include, but are not limited to, sodium chloride, potassium chloride, glycerol, propylene glycol, polyols, mannitol, sorbitol, xylitol, and mixtures thereof.

[0133] The viscosity of the packaging solution of the present invention at 25°C is about 1 centipoise to about 20 centipoise, more preferably about 1.2 centipoise to about 10 centipoise, and even more preferably about 1.5 centipoise to about 5 centipoise.

[0134] In a preferred embodiment, the packaging solution preferably includes about 0.01% to about 2% by weight, more preferably about 0.05% to about 1.5% by weight, even more preferably about 0.1% to about 1% by weight, and most preferably about 0.2% to about 0.5% by weight of the water-soluble and thermally crosslinkable hydrophilic polymeric material of the present invention.

[0135] The packaging solution of the present invention may contain a thickening polymer. The thickening polymer is preferably nonionic. Increasing the solution viscosity provides a film on the lens that facilitates comfortable wearing of the contact lens. The thickening component can also be used to reduce the impact on the ocular surface during insertion and to reduce eye irritation.

[0136] Preferred tackifying polymers include, but are not limited to, water-soluble cellulose ethers (e.g., methylcellulose (MC), ethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropyl methylcellulose (HPMC), or mixtures thereof), water-soluble polyvinyl alcohol (PVA), high molecular weight poly(ethylene oxide) with a molecular weight greater than about 2,000 (up to 10,000,000 Daltons), polyvinylpyrrolidone with a molecular weight of about 30,000 Daltons to about 1,000,000 Daltons, N-vinylpyrrolidone, and at least one copolymer of a dialkylaminoalkyl ester of (meth)acrylate having 7-20 carbon atoms, and combinations thereof. Copolymers of water-soluble cellulose ethers and vinylpyrrolidone with dimethylaminoethyl methacrylate are preferred tackifying polymers. N-vinylpyrrolidone and dimethylaminoethyl methacrylate are commercially available, for example, Copolymer 845 and Copolymer 937 from ISP.

[0137] Based on the total amount of the packaging solution, the thickening polymer is present in the packaging solution in an amount of about 0.01% by weight to about 5% by weight, preferably about 0.05% by weight to about 3% by weight, or even more preferably about 0.1% by weight to about 1% by weight.

[0138] The packaging solution may further comprise polyethylene glycol with a molecular weight of about 1200 Daltons or less, more preferably 600 Daltons or less, most preferably about 100 Daltons to about 500 Daltons.

[0139] If at least one of the crosslinked coating and the packaging solution contains a polymeric material having a polyethylene glycol segment, the packaging solution preferably includes an amount sufficient to reduce susceptibility to oxidative degradation of the polyethylene glycol segment including α-side-hydroxy polyacids or salts thereof. A jointly owned, pending patent application (U.S. Patent Application Publication No. 2004 / 0116564 A1, the entire contents of which are incorporated herein by reference) discloses side-hydroxy polyacids or salts thereof that can reduce susceptibility to oxidative degradation of PEG-containing polymeric materials.

[0140] Exemplary α-side-oxy-polyacids or their biocompatible salts include, but are not limited to, citric acid, 2-ketoglutaric acid, or malic acid or their biocompatible (preferably ophthalmic compatible) salts. More preferably, the α-side-oxy-polyacids are citric acid or malic acid or their biocompatible (preferably ophthalmic compatible) salts (e.g., sodium salts, potassium salts, or the like).

[0141] According to the present invention, the packaging solution may further include a mucin-like material, an ophthalmologically beneficial material, and / or a surfactant. The aforementioned exemplary mucin-like material, the aforementioned exemplary ophthalmologically beneficial material, and the aforementioned exemplary surfactant can all be used in this embodiment.

[0142] In a preferred embodiment, the SiHy contact lens of the present invention has a relatively long water breakup time (WBUT). WBUT is the time required for the water film to break up (dehydrate) and expose the underlying lens material as observed by the naked eye. A SiHy contact lens with a longer WBUT can maintain a water (tear) film on its surface for a relatively long period when worn on the eye. Dry spots are less likely to occur during eyelid blinking and enhanced wearing comfort is provided. WBUT can be measured according to the procedure described in the examples below. Preferably, the SiHy contact lens of the present invention is characterized by surface hydrophilicity having a water breakup time of at least about 10 seconds.

[0143] In a preferred embodiment, the SiHy contact lens of the present invention is characterized by surface wettability with an average water contact angle of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, even more preferably about 60 degrees or less, and most preferably about 50 degrees or less.

[0144] In a preferred embodiment, the oxygen permeability of the SiHy contact lens is at least about 40 barrer / mm, more preferably at least about 60 barrer / mm, more preferably at least about 80 barrer / mm, even more preferably at least about 100 barrer / mm, and most preferably at least about 120 barrer / mm.

[0145] It should be understood that although various embodiments comprising preferred embodiments of the present invention may be set forth above in this embodiment of the present invention, such embodiments may be combined and / or used together in any desired form to achieve different embodiments of the polysilicon-oxygen hydrogel contact lenses of the present invention.

[0146] In another embodiment, the present invention provides a hydrated polysilicon-oxygen hydrogel contact lens. The hydrated polysilicon-oxygen hydrogel contact lens of the present invention comprises: a polysilicon-oxygen hydrogel material as a bulk material, a front surface, and a corresponding rear surface; wherein the oxygen transmittance of the contact lens is at least about 40 barrer / mm, preferably at least about 60 barrer / mm, more preferably at least about 80 barrer / mm, and even more preferably at least about 110 barrer / mm. The barrer / mm, and its cross-sectional surface modulus curve along the shortest line between the front and rear surfaces on the cross-sectional surface of the contact lens includes an anterior outer region (containing and close to the front surface), an inner region (containing and surrounding the center of the shortest line), and a rear outer region (containing and close to the rear surface), wherein the anterior outer region has an average anterior surface modulus (denoted as ) and the rear outer region has an average rear surface modulus (denoted as ), wherein the inner region has an average inner surface modulus (denoted as ), wherein at least one of and is at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, and most preferably at least about 40%. Preferably, the front and rear outer regions cover a span of at least about 0.1 µm, more preferably about 0.1 µm to about 20 µm, more preferably about 0.25 µm to about 15 µm, even more preferably about 0.5 µm to about 12.5 µm, and most preferably about 1 µm to about 10 µm.

[0147] In a preferred embodiment, the hydrated polysiloxane hydrogel contact lens may have the following characteristics: an elastic modulus (or Young's modulus) of about 0.3 MPa to about 1.8 MPa, preferably about 0.4 MPa to about 1.5 MPa, more preferably about 0.5 MPa to about 1.2 MPa; a water content of about 10% to about 75%, preferably about 10% to about 70%, more preferably about 15% to about 65%, even more preferably about 20% to about 60%, best about 25% to about 55% by weight; surface wettability characterized by having an average water contact angle of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, even more preferably about 60 degrees or less, best about 50 degrees or less; surface hydrophilicity characterized by having a WBUT of at least about 10 seconds; or combinations thereof.

[0148] In another preferred embodiment, the front and rear surfaces have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups), characterized in that they attract up to about 200, more preferably up to about 160, more preferably up to about 120, even more preferably up to about 90, and most preferably up to about 60 positively charged particles in a positively charged particle adhesion test. To have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups), the front and rear outer hydrogel layers should have a relatively low carboxylic acid content. Preferably, the carboxylic acid content of the front and rear outer hydrogel layers is about 20% by weight or less, more preferably about 15% by weight or less, even more preferably about 10% by weight or less, and most preferably about 5% by weight or less.

[0149] In another preferred embodiment, the SiHy contact lens of the present invention has good surface lubricity, characterized by having a critical coefficient of friction (CCOF) of about 0.046 or less, preferably about 0.043 or less, and more preferably about 0.040 or less. Alternatively, the SiHy contact lens of the present invention preferably has lubricity superior to ACUVUE OASYS or ACUVUE TruEye, as measured in a blind eye test according to the lubricity evaluation procedure described in Example 1.

[0150] In another preferred embodiment, the hydrated SiHy contact lens preferably has high resistance to finger rubbing, as characterized by the absence of visible surface crack lines in a dark field after rubbing the SiHy contact lens between fingers. It is believed that surface cracking caused by finger rubbing can reduce surface lubricity and / or may not prevent polysiloxane migration to the surface (exposure).

[0151] In another preferred embodiment, the hydrated SiHy contact lens of the present invention includes an inner layer of polysilicon-oxygen hydrogel material, a front outer hydrogel layer, and a rear outer hydrogel layer, wherein the front and rear outer hydrogel layers are substantially uniform in thickness and merge at the peripheral edge of the contact lens to completely surround the inner layer of polysilicon-oxygen hydrogel material. It should be understood that the first and second outer regions in the cross-sectional surface modulus curve correspond to the two outer hydrogel layers, while the inner region corresponds to the inner layer of polysilicon-oxygen hydrogel material. All embodiments of the aforementioned outer hydrogel layer (with cross-linked coating) used in other embodiments of the present invention can be used alone or in any combination as the outer hydrogel layer in this embodiment of the present invention. All embodiments of the aforementioned inner layer of polysilicon-oxygen hydrogel material used in other embodiments of the present invention can be used alone or in any combination as the inner layer of polysilicon-oxygen hydrogel material in this embodiment of the present invention.

[0152] According to this embodiment of the invention, the outer hydrogel layer is substantially uniform in thickness and has a thickness of at least about 0.1 µm, preferably about 0.1 µm to about 20 µm, more preferably about 0.25 µm to about 15 µm, even more preferably about 0.5 µm to about 12.5 µm, and most preferably about 1 µm to about 10 µm. The thickness of each outer hydrogel layer of the SiHy contact lens of the present invention is determined by AFM analysis of the cross-section of the fully hydrated SiHy contact lens described above. In another preferred embodiment, the thickness of each outer hydrogel layer is at most about 30% (i.e., 30% or less) of the center thickness of the fully hydrated SiHy contact lens, preferably at most about 20% (20% or less), and more preferably at most about 10% (10% or less). Furthermore, each of the two outer hydrogel layers is substantially free of polysiloxane (as characterized by a silicon atomic percentage of about 5% or less of the total elemental percentage, preferably about 4% or less, or even more preferably about 3% or less, as measured by XPS analysis of the contact lens in a dry state), and preferably completely free of polysiloxane. It should be understood that a smaller percentage of polysiloxane may be incorporated into the polymer network of the outer hydrogel layer as needed (but not necessarily preferred), provided that it does not significantly impair the surface properties (hydrophilicity, wettability, and / or lubricity) of the SiHy contact lens.

[0153] In another preferred embodiment, the two outer hydrogel layers of the hydrated SiHy contact lens of the present invention comprise a higher water content than that of the hydrated polysiloxane hydrogel contact lens (referred to as a WC lens), and more specifically, must be at least about 1.2 times (i.e., 120%) that of the WC lens. It is believed that the water expansion rate of each outer hydrogel layer can approximately represent the water content of the outer hydrogel layer as discussed above. If the WC lens is about 45% or less, the water expansion rate of each outer hydrogel layer is preferably at least about 150%, more preferably at least about 200%, more preferably at least about 250%, and even more preferably at least about 300%. If the WC lens is above 45%, the water expansion rate of each outer hydrogel layer is at least about, preferably about, more preferably about, and even more preferably about. In an alternative preferred embodiment, if the WC lens is about 55% or less, the water swelling rate of each outer hydrogel layer is at least about 150%; if the WC lens is about 60% or less, the water swelling rate of each outer hydrogel layer is at least about 200%; if the WC lens is about 65% or less, the water swelling rate of each outer hydrogel layer is at least about 250%; and if the WC lens is about 70% or less, the water swelling rate of each outer hydrogel layer is at least about 300%.

[0154] Preferably, the SiHy contact lens further includes a transition layer located between the polysilicon-oxygen hydrogel material and the outer hydrogel layer. All embodiments of the transition layer described in the previous embodiments of the present invention can be used alone or in any combination in this embodiment of the present invention.

[0155] The hydrated SiHy contact lens of the present invention can be prepared according to the above method. All embodiments of the above-described inner layer (i.e., the polysilicon-oxygen hydrogel material) can be used alone or in any combination in this embodiment of the present invention as the polysilicon-oxygen hydrogel core. All embodiments described in the preceding embodiments of the present invention can be used alone or in any combination in this embodiment of the present invention.

[0156] It should be understood that although various embodiments comprising preferred embodiments of the present invention may be individually described above in this embodiment of the invention, such embodiments may be combined and / or used in any desired form to achieve different embodiments of the polysilicon-oxygen hydrogel contact lenses of the present invention. All various embodiments described in the preceding embodiments of the present invention may be used in any desired form, alone or in combination, in this embodiment of the present invention.

[0157] In another embodiment, the present invention provides a hydrated polysiloxane hydrogel contact lens. The hydrated polysiloxane hydrogel contact lens of the present invention comprises: a polysiloxane hydrogel material as a bulk material, a front surface and a corresponding rear surface; wherein the contact lens (1) has an oxygen permeability of at least about 40 barrer / mm, preferably at least about 60 barrer / mm, more preferably at least about 80 barrer / mm, and even more preferably at least about 110 barrer / mm, and (2) is characterized by a surface lubricity in that its critical coefficient of friction (expressed as CCOF) is about 0.046 or less, preferably about 0.043 or less, and even more preferably about 0.040 or less, wherein the front and rear surfaces have a low surface concentration of negatively charged groups (including carboxylic acid groups), and is characterized by attracting up to about 200, preferably up to about 160, more preferably up to about 120, even more preferably up to about 90, and most preferably up to about 60 positively charged particles in a positively charged particle adhesion test.

[0158] In a preferred embodiment, the hydrated polysiloxane hydrogel contact lens has the following characteristics: an elastic modulus (or Young's modulus) of about 0.3 MPa to about 1.8 MPa, preferably about 0.4 MPa to about 1.5 MPa, more preferably about 0.5 MPa to about 1.2 MPa; a water content of about 10% to about 75%, preferably about 10% to about 70%, more preferably about 15% to about 65%, even more preferably about 20% to about 60%, best about 25% to about 55% by weight; surface wettability characterized by having an average water contact angle of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, even more preferably about 60 degrees or less, best about 50 degrees or less; surface hydrophilicity characterized by having a WBUT of at least about 10 seconds; or a combination thereof.

[0159] In another preferred embodiment, the hydrated SiHy contact lens preferably has high resistance to finger rubbing, as characterized by the absence of visible surface crack lines in a dark field after rubbing the SiHy contact lens between fingers. It is believed that surface cracking caused by finger rubbing can reduce surface lubricity and / or may not prevent polysiloxane migration to the surface (exposure).

[0160] In another preferred embodiment, the hydrated SiHy contact lens of the present invention includes an inner layer of polysilicon-oxygen hydrogel material, a front outer hydrogel layer, and a rear outer hydrogel layer, wherein the front and rear outer hydrogel layers are substantially uniform in thickness and merge at the peripheral edge of the contact lens to completely surround the inner layer of polysilicon-oxygen hydrogel material. It should be understood that the first and second outer regions in the cross-sectional surface modulus curve correspond to the two outer hydrogel layers, while the inner region corresponds to the inner layer of polysilicon-oxygen hydrogel material. All embodiments of the aforementioned outer hydrogel layer (with cross-linked coating) used in other embodiments of the present invention can be used alone or in any combination as the outer hydrogel layer in this embodiment of the present invention. All embodiments of the aforementioned inner layer of polysilicon-oxygen hydrogel material used in other embodiments of the present invention can be used alone or in any combination as the inner layer of polysilicon-oxygen hydrogel material in this embodiment of the present invention.

[0161] According to this embodiment of the invention, the outer hydrogel layer is substantially uniform in thickness and has a thickness of at least about 0.1 µm, preferably about 0.1 µm to about 20 µm, more preferably about 0.25 µm to about 15 µm, even more preferably about 0.5 µm to about 12.5 µm, and most preferably about 1 µm to about 10 µm. The thickness of each outer hydrogel layer of the SiHy contact lens of the present invention is determined by AFM analysis of the cross-section of the fully hydrated SiHy contact lens described above. In another preferred embodiment, the thickness of each outer hydrogel layer is preferably at most about 30% (i.e., 30% or less) of the center thickness of the fully hydrated SiHy contact lens, preferably at most about 20% (20% or less), and more preferably at most about 10% (10% or less). Furthermore, each of the two outer hydrogel layers is substantially free of polysiloxane (e.g., characterized by a silicon atomic percentage of about 5% or less, preferably about 4% or less, or even more preferably about 3% or less of the total elemental percentage, as measured by XPS analysis of the contact lens in a dry state), and preferably completely free of polysiloxane. It should be understood that a smaller percentage of polysiloxane may be incorporated into the polymer network of the outer hydrogel layer as needed (but not preferably), provided that it does not significantly impair the surface properties (hydrophilicity, wettability, and / or lubricity) of the SiHy contact lens. To have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups), the front and rear outer hydrogel layers should have relatively low carboxylic acid content. Preferably, the carboxylic acid content of the front and rear outer hydrogel layers is about 20% by weight or less, preferably about 15% by weight or less, even more preferably about 10% by weight or less, and most preferably about 5% by weight or less.

[0162] In another preferred embodiment, the two outer hydrogel layers of the hydrated SiHy contact lens of the present invention comprise a water content higher than that of the hydrated polysiloxane hydrogel contact lens (referred to as the WC lens), and more specifically, must be at least about 1.2 times (i.e., 120%) the water content of the hydrated polysiloxane hydrogel contact lens (referred to as the WC lens). It is believed that the water expansion rate of each outer hydrogel layer can approximately represent the water content of the outer hydrogel layer as discussed above. If the WC lens is about 45% or less, the water expansion rate of each outer hydrogel layer is preferably at least about 150%, more preferably at least about 200%, more preferably at least about 250%, and even more preferably at least about 300%. If the WC lens is higher than 45%, the water expansion rate of each outer hydrogel layer is at least about, preferably about, more preferably about, and even more preferably about. In an alternative preferred embodiment, if the WC lens is about 55% or less, the water swelling rate of each outer hydrogel layer is at least about 150%; if the WC lens is about 60% or less, the water swelling rate of each outer hydrogel layer is at least about 200%; if the WC lens is about 65% or less, the water swelling rate of each outer hydrogel layer is at least about 250%; and if the WC lens is about 70% or less, the water swelling rate of each outer hydrogel layer is at least about 300%.

[0163] In another preferred embodiment, the front outer hydrogel layer and the rear outer hydrogel layer have a reduced surface modulus of at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, and most preferably at least about 40% of the inner layer, independently of each other.

[0164] Preferably, the SiHy contact lens further includes a transition layer located between the polysilicon-oxygen hydrogel material and the outer hydrogel layer. All embodiments of the transition layer described in the previous embodiments of the present invention can be used alone or in any combination in this embodiment of the present invention.

[0165] The hydrated SiHy contact lens of the present invention can be prepared according to the above method. All embodiments of the above-described inner layer (i.e., the polysilicon-oxygen hydrogel material) can be used alone or in any combination in this embodiment of the present invention as the polysilicon-oxygen hydrogel core. All embodiments described in the preceding embodiments of the present invention can be used alone or in any combination in this embodiment of the present invention.

[0166] It should be understood that although various embodiments comprising preferred embodiments of the present invention may be individually described above in this embodiment of the invention, such embodiments may be combined and / or used in any desired form to achieve different embodiments of the polysilicon-oxygen hydrogel contact lenses of the present invention. All various embodiments described in the preceding embodiments of the present invention may be used alone or in combination in any desired form in this embodiment of the present invention.

[0167] The foregoing disclosure will enable those skilled in the art to practice the present invention. Various modifications, changes, and combinations can be made to the various embodiments described herein. To enable the reader to better understand the specific embodiments and their advantages, it is recommended to refer to the following examples. The specification and examples are intended to be exemplary.

[0168] Although specific terms, apparatus, and methods have been used to describe various aspects and embodiments of the invention, this description is for illustrative purposes only. The terms used are descriptive and not limiting. It should be understood that those skilled in the art can make various changes and modifications without departing from the spirit or scope of the invention as set forth in the following claims. Furthermore, it should be understood that the various embodiments may be interchanged in whole or in part, or may be combined and / or used in any way. Therefore, the spirit and scope of the appended claims should not be limited to the preferred form of the description contained herein.

[0169] Example 1

[0170] Oxygen Permeability Measurement

[0171] The apparent oxygen permeability of the lens and the oxygen transmittance of the lens material can be determined using 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, edited by HD Cavanagh, Raven Press: New York 1988, pp. 273-280), the entire contents of which are incorporated herein by reference. The oxygen flux (J) is measured at 34°C in a wetting chamber (i.e., with the airflow maintained at approximately 100% relative humidity) using a Dk1000 instrument (available from Applied Design and Development, Norcross, GA) or a similar analytical instrument. An airflow with a known oxygen percentage (e.g., 21%) is passed through one side of the lens at a rate of approximately 10 cm³ / min to 20 cm³ / min, while a nitrogen airflow is passed through the opposite side of the lens at a rate of approximately 10 cm³ / min to 20 cm³ / min. Before measurement, equilibrate the sample in the test medium (i.e., saline or distilled water) at the specified test temperature for at least 30 minutes but no more than 45 minutes. Before measurement, equilibrate any test medium used as the cover layer at the specified test temperature for at least 30 minutes but no more than 45 minutes. Set the stirring motor speed to 1200 ± 50 rpm, corresponding to the specified setting of the stepper motor controller 400 ± 15. Measure the atmospheric pressure P around the system. Determine the thickness (t) of the area of ​​the lens exposed for testing by measuring approximately 10 locations using a Mitotoya VL-50 micrometer or a similar instrument and averaging these measurements. Measure the oxygen concentration in the nitrogen flow (i.e., the oxygen diffused through the lens) using a DK1000 instrument. The apparent oxygen permeability Dkapp of lens material is determined according to the following formula: Dkapp = Jt / (P_oxygen) Where J = oxygen flux [µL O2 / cm2-min] P_oxygen = (P_measured value - P_water vapor) = (O2 in the airflow) [mm Hg] = partial pressure of oxygen in the airflow P_measured value = atmospheric pressure (mm Hg) P_water vapor = 0 mm Hg, at 34°C (in a dry chamber) (mm Hg) P_water vapor = 40 mm Hg, at 34°C (in a wet chamber) (mm Hg) t = average thickness of the exposed test area of ​​the lens (mm) Dkapp is expressed in barrers.

[0172] The apparent oxygen permeability (Dk / t) of the material is calculated by dividing the apparent oxygen permeability (Dkapp) by the average thickness (t) of the lens.

[0173] The above measurements did not correct for the so-called boundary layer effect, which can be attributed to the water or saline bath used on top of the contact lens during oxygen flux measurements. The boundary layer effect causes the reported apparent Dk value of the polysilicon-oxygen hydrogel material to be lower than the actual intrinsic Dk value. Furthermore, the relative impact of the boundary layer effect is greater for thinner lenses than for thicker lenses. The net effect is that the reported Dk appears to vary with lens thickness (when it should remain constant).

[0174] The inherent Dk value of the lens can be estimated based on the Dk value corrected for the oxygen flux surface resistance caused by the following boundary layer effects.

[0175] Measure the apparent oxygen permeability (single point) of a reference lotrafilcon A (Focus® N&D®, from CIBA VISION) or lotrafilcon B (AirOptix™, from CIBA VISION) lens using the same equipment. The reference lens and the test lens have similar optical power and are measured simultaneously.

[0176] Using the same equipment, measure the oxygen flux through the thickness series of lotrafilcon A or lotrafilcon B (reference) lenses according to the above apparent Dk measurement procedure to obtain the intrinsic Dk value (Dki) of the reference lens. The thickness series should cover a thickness range of approximately 100 µm or greater. Preferably, the range of reference lens thicknesses will encompass the thickness of the test lens. The Dkapp of these reference lenses must be measured on the same equipment as the test lens and ideally should be measured simultaneously with the test lens. Throughout the experiment, the equipment settings and measurement parameters should remain constant. If necessary, individual samples may be measured multiple times.

[0177] In the calculation, Equation 1 is used to determine the residual oxygen resistance value Rr based on the results of the reference lens. (1) Where t is the thickness of the test lens (i.e., the reference lens), and n is the number of reference lenses measured. The residual oxygen resistance value Rr is plotted against the t data and fitted with a curve of the form Y=a+bX, where for the j-th lens, Yj=(ΔP / J)j and X=tj. The residual oxygen resistance Rr is equal to a.

[0178] Based on Equation 2, the corrected oxygen permeability Dkc (estimated intrinsic Dk) of the test lens is calculated using the residual oxygen resistance value measured above. Dkc=t / [(t / Dka)-Rr] (2)

[0179] Based on Equation 3, the apparent Dk (Dka_std) of a standard thickness lens under the same test environment can be calculated using the estimated intrinsic Dk of the test lens. The standard thickness (tstd) of lotrafilcon A is 85 µm. The standard thickness of lotrafilcon B is 60 µm. Dka_std = tstd / [(tstd / Dkc) + Rr_std] (3)

[0180] Measurement of ion permeability.

[0181] The ion permeability of the lens was measured according to the procedure set forth in U.S. Patent No. 5,760,100 (the entire contents of which are incorporated herein by reference). The ion permeability values ​​reported in the following examples are relative ion flux diffusion coefficients (D / Dref) (with Alsacon lens material as a reference). The ionoflux diffusion coefficient of Alsacon is 0.314 x 10⁻³ mm² / min.

[0182] Lubricity Assessment

[0183] The lubricity rating is a qualitative rating scheme, where 0 indicates a control lens coated with polyacrylic acid, 1 indicates a commercial Oasys™ / TruEye™ lens, and 4 indicates a commercial Air Optix™ lens. The sample is rinsed at least three times with excess DI water and then transferred to PBS for evaluation. Before evaluation, hands are washed with soapy water, thoroughly rinsed with DI water, and then dried with a KimWipe® towel. The sample is handled between the fingers, and a numerical value for each sample relative to the aforementioned standard lens is assigned. For example, if a lens is measured to be only slightly better than an Air Optix™ lens, it is assigned a value of 3. To ensure consistency, all ratings are performed independently by the same two operators to avoid bias, and the data demonstrate good qualitative synergy and consistency in the evaluation.

[0184] Surface Wettability Test. The water contact angle of a contact lens is a general measure of the surface wettability of a contact lens. Specifically, a low water contact angle corresponds to a wetter surface. The average contact angle (fixed droplet) of the contact lens was measured using a VCA 2500 XE contact angle measuring device purchased from AST Corporation, Boston, Massachusetts. This device can measure the advancing or receding contact angle or the fixed (static) contact angle. Measurements were performed on a fully hydrated contact lens immediately after the imprint dried, as described below. The contact lens was removed from the vial and washed three times in approximately 200 ml of fresh DI water to remove loosely bonded packaging additives from the lens surface. The lens was then placed on a lint-free cleaning cloth (Alpha Wipe TX1009) and thoroughly wiped to remove surface water. It was then mounted on the contact angle measuring base, dried with a stream of dry air, and finally the fixed droplet contact angle was automatically measured using the manufacturer's software. The DI water used for measuring the contact angle has a resistivity >18 MΩcm and the droplet volume used is 2 μl. Typically, uncoated polysiloxane hydrogel lenses (after autoclaving) have a fixation droplet contact angle of approximately 120 degrees. The tweezers and base are thoroughly washed with isopropyl alcohol and rinsed with DI water before contact with the contact lens.

[0185] Water Breakup Time (WBUT) Test. The surface hydrophilicity of a lens is evaluated by measuring the time required for the water film on the lens surface to begin to break up (after autoclaving). In short, the lens is removed from the vial and washed three times in approximately 200 ml of fresh DI water to remove loosely bound packaging additives from the lens surface. The lens is removed from the solution and held close to a bright light source using tweezers. The time required for the water film to break up (dehumidify) and expose the underlying lens material is observed visually. Uncoated lenses typically break up immediately upon removal from DI water, and the designated WBUT is 0 seconds. Lenses exhibiting a WBUT ≥ 5 seconds are considered to have good hydrophilicity and are expected to provide sufficient tear film maintenance for the eye.

[0186] Coating Integrity Test. The integrity of the coating on the surface of a contact lens can be tested according to the Sudan Black staining test as described below. Immerse the contact lens with a coating (LbL coating, plasma coating, or any other coating) in a Sudan Black dye solution (Sudan Black in vitamin E oil) and then rinse thoroughly with water. Sudan Black dye is hydrophobic and tends to be absorbed by hydrophobic materials or onto hydrophobic spots on the surface of the hydrophobic lens or on partially coated surfaces of hydrophobic lenses (e.g., polysiloxane hydrogel contact lenses). If the coating on the hydrophobic lens is intact, no staining spots should be observed on or within the lens. All lenses tested were fully hydrated.

[0187] Coating durability test. Wipe the lens 30 times with a finger using Solo-care® multi-purpose lens care solution and then rinse with saline solution. Repeat the above procedure a given number of times, for example, 1 to 30 times (i.e., the number of consecutive finger wiping tests simulating cleaning and soaking cycles). Then perform the Sudan Black test (i.e., the coating integrity test described above) on the lens to verify that the coating remains intact. To withstand the finger rubbing test, there should be no significant increase in staining spots (e.g., staining spots covering no more than about 5% of the total lens surface). Measure the water contact angle to determine coating durability.

[0188] Determination of Azo-Heterocyclic Butyron Content. The azo-cyclic butyron content in PAE can be determined by one of the following analyses.

[0189] PPVS Analysis. The charge density of PAE (i.e., the content of aziridine) can be determined by PPVS analysis, which is a colorimetric titration analysis in which potassium ethylene sulfate (PPVS) is used as the titrant and toluidine blue is used as the indicator. See SK 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 to positively charged substances, such as toluidine blue and the aziridine group of PAE. An increase in the absorbance intensity of toluidine blue indicates a proportional increase in the charge density of PAE (aziridine content).

[0190] PES-Na Analysis. PES-Na analysis is another colorimetric titration used to determine the charge density of PAE (azacyclobutane content). In this analysis, the titrant is sodium polyvinyl sulfonate (PES-Na) instead of PPVS. This analysis is identical to the PPVS analysis described above.

[0191] PCD Analysis. PCD analysis is a potential titration analysis used to determine the charge density (aziridine content) of PAE. The titrant is sodium polyvinyl sulfonate (PES-Na), PPVS, or other titrants. For example, the PAE charge is detected by electrodes using a Mütek PCD-04 particle charge detector from BTG. The measurement principle of this detector can be found on the BTG website: http: / / www.btg.com / products.asp?langage=1&appli=5&numProd=357&cat=prod).

[0192] NMR method. The active positively charged portion of the PAE is the azacyclobutane 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.

[0193] Debris Adhesion Test. Contact lenses with highly charged surfaces may be prone to increased debris adhesion during patient handling. Wipe a gloved hand with a tissue and then wipe both sides of the lens with your fingers to transfer any debris to the lens surface. Briefly rinse the lens and then observe it under a microscope. Evaluate each lens using a qualitative rating scale from 0 (no debris adhesion) to 4 (debris adhesion equal to a control lens coated with PAA). Lenses rated "0" or "1" are considered acceptable.

[0194] Example 2

[0195] Preparation of CE-PDMS macromonomer

[0196] In the first step, α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn=2000, Shin-Etsu, KF-6001a) was end-capped by reacting 49.85 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane with 11.1 g of isophorone diisocyanate (IPDI) in 150 g of anhydrous 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 h to form IPDI-PDMS-IPDI. In the second step, a mixture of 164.8 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn=3000, Shin-Etsu, KF-6002) and 50 g of anhydrous MEK was added dropwise to an IPDI-PDMS-IPDI solution, which already contained an additional 0.063 g of DBTDL. The reactor was maintained at approximately 40°C for 4.5 h to form HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. MEK was then removed under reduced pressure. In the third step, the terminal hydroxyl groups were capped with methacryloyloxyethyl by adding 7.77 g of ethyl isocyanate methacrylate (IEM) and an additional 0.063 g of DBTDL to form IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM (i.e., CE-PDMS capped with methacrylate groups).

[0197] Preparation of CE-PDMS macromonomers with terminal methacrylate groups

[0198] 240.43 g of KF-6001 was added to a 1-L reactor equipped with a stirrer, thermometer, cryostat, dropping funnel, and nitrogen / vacuum inlet adapter, and then dried by applying a high vacuum (2 × 10⁻² mbar). Then, under a dry nitrogen atmosphere, 320 g of distilled MEK was added to the reactor and the mixture was thoroughly stirred. 0.235 g of DBTDL was added to the reactor. After heating the reactor to 45°C, 45.86 g of IPDI was added to the reactor over 10 minutes with moderate stirring using a feeding funnel. The reaction was maintained at 60°C for 2 hours. Then, 630 g of KF-6002 dissolved in 452 g of distilled MEK was added and stirred until a homogeneous solution was formed. 0.235 g of DBTDL was added, and the reactor was maintained overnight at approximately 55°C under a dry nitrogen atmosphere. The next day, MEK was removed by rapid distillation. The reactor was cooled, and then 22.7 g of IEM was loaded into the reactor, followed by approximately 0.235 g of DBTDL. After approximately 3 hours, an additional 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 obtain the CE-PDMS macromonomer with terminal methacrylate groups.

[0199] Example 3

[0200] Preparation of lens fitting materials

[0201] A lens formulation was prepared by dissolving the components in 1-propanol to have the following composition: 33% by weight of the CE-PDMS macromonomer prepared in Example 2, 17% by weight of N-[tris(trimethylsiloxy)-methoxypropyl]acrylamide (TRIS-Am), 24% by weight of N,N-dimethylacrylamide (DMA), 0.5% by weight of N-(carbonyl-methoxy polyethylene glycol-2000)-1,2-distearate-sn-glycerol-3-phosphate ethanolamine (sodium salt) (L-PEG), 1.0% by weight of Darocur 1173 (DC1173), 0.1% by weight of visitint (a 5% copper phthalocyanine blue pigment dispersion in tris(trimethylsiloxy)-methoxypropyl methacrylate (TRIS)), and 24.5% by weight of 1-propanol.

[0202] Lens Manufacturing

[0203] Lenses are manufactured by casting the lens formulation obtained above in a reusable mold, which is similar to the molds shown in Figures 1-6 of U.S. Patents 7,384,590 and 7,387,759. The mold includes a concave mold half made of CaF2 and a convex mold half made of PMMA. The UV irradiation source is a Hamamatsu lamp with an intensity of about 4 mW / cm2 and a WG335+TM297 cutoff filter. The lens formulation in the mold is irradiated with UV irradiation for about 25 seconds. The cast-molded lens is extracted using isopropanol (or methyl ethyl ketone MEK), rinsed in water, coated with polyacrylic acid (PAA) by immersing the lens in a propanol solution of PAA (0.1% by weight, acidified with formic acid to about pH 2.5), and hydrated in water. The resulting lens with the reactive PAA-LbL base coating was measured to have the following properties: ion permeability of about 8.0 to about 9.0 relative to Alsacon lens material; apparent Dk (single point) of about 90 to 100; water content of about 30% to about 33%; and bulk modulus of elasticity of about 0.60 MPa to about 0.65 MPa.

[0204] Example 4

[0205] The in-package coating (IPC) brine was prepared by adding 0.2% polyaminoamine-epoxychloropropane (PAE) (Kymene, from Ashland, in aqueous solution and used as received, with a nitrogen heterocyclic butyronium content of 0.46 as analyzed by NMR) to 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 then adjusting the pH to 7.2-7.4.

[0206] The lens from Example 3 was placed in a polypropylene lens packaging shell containing 0.6 mL of IPC saline (half of the IPC saline was added before inserting the lens). The blister pack was then sealed with foil and autoclaved at 121°C for about 30 minutes to form a cross-linked coating (PAA-x-PAE coating) on ​​the lens.

[0207] Then the lens's debris adhesion, surface cracking, lubricity, contact angle, and water breakup time (WBUT) were evaluated. The test lens (packaged / autoclaved in IPC saline, i.e., a lens with a PAA-x-PAE coating) showed no debris adhesion after wiping with a paper towel, while the control lens (packaged / autoclaved in PBS, i.e., a lens with a PAA-LbL base coating) showed severe debris adhesion. The test lens had a lower water contact angle (WCA) (approximately 20 degrees), but a WBUT of less than 2 seconds. Severe cracking lines were observed under a dark-field microscope after handling the lens (inverting the lens and wiping it between fingers). The test lens had significantly less lubricity than the control lens, as determined by a qualitative finger-wiping test.

[0208] Example 5

[0209] Purchase poly(acrylamide-co-acrylic acid) (or PAAm-PAA or poly(AAm-co-AA) or p(AAm-co-AA)) sodium metasodium salt (approximately 80% solids content, poly(AAm-co-AA)(80 / 20), Mw. 520,000, Mn 150,000) from Aldrich and use it in the received condition.

[0210] IPC brine was prepared by dissolving 0.02% poly(AAm-co-AA) (80 / 20) and 0.2% PAE (Kymene, from Ashland, in aqueous solution and used in the receiving state, with a nitrogen-containing heterocyclic butylene content of 0.46 as analyzed by NMR) in PBS. The pH was adjusted to 7.2 to 7.4. PBS was prepared by dissolving 0.76% NaCl, 0.044% NaH2PO4·H2O, and 0.388% Na2HPO4·2H2O in water.

[0211] The lens with the PAA-LbL base coating prepared in Example 3 was placed in a polypropylene lens packaging shell containing 0.6 mL of IPC saline (half of the saline was added before inserting the lens). The blister pack 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 autoclaving.

[0212] The test lens (packaged / autoclaved in IPC saline, i.e., a lens with a PAA-x-PAE-x-poly(AAm-co-AA) crosslinked coating) did not leave any debris after wiping with a tissue. The test lens had a WBUT of more than 10 seconds. When observed under a dark-field microscope, a tear line was visible after wiping the test lens. The lubricity of the test lens was much greater than that of the test lens from Example 4, but still not as lubricant as the control lens packaged in PBS.

[0213] Example 6

[0214] IPC brine was prepared by dissolving 0.02% poly(AAm-co-AA) (80 / 20) and 0.2% PAE (Kymene, from Ashland, in aqueous solution and used in the receiving state, with a nitrogen-hexacyclobutane content of 0.46 as analyzed by NMR) in PBS and adjusting the pH to 7.2 to 7.4. The brine was then treated by heating to approximately 70°C and maintaining that temperature for 4 hours (thermal pretreatment). During this thermal pretreatment, the poly(AAm-co-AA) and PAE partially crosslinked with each other (i.e., without consuming all the nitrogen-hexacyclobutane groups of PAE) to form a water-soluble and thermally crosslinkable hydrophilic polymer containing nitrogen-hexacyclobutane groups within the branched polymer network of the IPC brine. After thermal pretreatment, the final IPC brine was filtered using a 0.22-micron polyether ether (PES) membrane filter and cooled to room temperature.

[0215] The lens with the PAA-LbL base coating prepared in Example 3 was placed in a polypropylene lens packaging shell containing 0.6 mL of IPC saline (half of the saline was added before inserting the lens). The blister pack 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) on the lens.

[0216] The test lens (packaged in heat-pretreated IPC saline, i.e., a lens with a PAA-x-hydrophilic polymer coating) showed no debris adhesion after wiping with a paper towel, while the control lens (packaged in PBS, i.e., a lens with a non-covalently bonded layer of PAA) showed severe debris adhesion. The test lens had a WBUT of more than 10 seconds. No tear lines were observed after wiping the test lens under a dark-field microscope. The test lens was extremely smooth in the finger-wiping test, comparable to the control lens.

[0217] A series of experiments were conducted to investigate the effect of the heat pretreatment conditions (duration and / or temperature) of IPC brine on the surface properties of lenses coated with IPC brine. Heat treatment times of approximately 6 hours or longer at approximately 70°C produced lenses with similar debris adhesion to the control lens. It is believed that the longer preheating treatment consumes most of the nitrogen-heterobutylene groups, and therefore the amount of remaining nitrogen-heterobutylene groups in the branched polymer network of the resulting water-soluble polymer is insufficient to attach the polymer to the PAA coating. Heat treatment of only 4 hours at 50°C produced lenses that showed similar surface crack lines under a dark-field microscope after rubbing between fingers, as the test lens in Example 5 (which did not undergo heat pretreatment with IPC brine). It is believed that a shorter preheating treatment can consume a small amount of nitrogen-heterobutylene groups, and thus the resulting water-soluble polymeric material has a higher number of remaining nitrogen-heterobutylene groups in the branched polymer network, resulting in an excessively high crosslinking density in the crosslinked coating (PAA-x-hydrophilic polymeric material) on the lens.

[0218] Example 7

[0219] Purchase poly(acrylamide-co-acrylic acid) sodium salt (approximately 90% solids content, poly(AAm-co-AA)(90 / 10), Mw 200,000) from Polysciences and use it in the received condition.

[0220] An IPC brine was prepared by dissolving 0.07% PAAm-PAA (90 / 10) and 0.2% PAE (Kymene, from Ashland, in aqueous solution and used in the receiving state, with a nitrogen-hexacyclobutane content of 0.46 as analyzed by NMR) in PBS and adjusting the pH to 7.2 to 7.4. The brine was then heat-pretreated at approximately 70°C for approximately 4 hours (heat pretreatment). During this heat pretreatment, the poly(AAm-co-AA) and PAE partially crosslinked with each other (i.e., without consuming all the nitrogen-hexacyclobutane groups of PAE) to form a water-soluble and thermally crosslinkable hydrophilic polymer containing nitrogen-hexacyclobutane groups within the branched polymer network of the IPC brine. After heat pretreatment, the IPC brine was filtered using a 0.22-micron polyether ether (PES) membrane filter and cooled to room temperature.

[0221] The lens with the PAA-LbL base coating manufactured in Example 3 and the uncoated Lotrafilcon B lens (from CIBA VISION CORPORATION) immersed in a PAA acidic propanol solution (approximately 0.1%, pH approximately 2.5) were placed in a polypropylene lens packaging shell containing 0.6 mL of heat-pretreated IPC saline (half of the IPC saline was added before inserting the lens). The blister pack was then sealed with foil and autoclaved at 121°C for approximately 30 minutes to form a cross-linked coating (PAA-x-hydrophilic polymer) on the lens.

[0222] The test lenses (Lotrafilcon B and Example 3 lens with PAA-x-hydrophilic polymer) did not leave any debris after wiping with a tissue. The test lenses had a WBUT of more than 10 seconds. When observed under a dark-field microscope, no break lines were visible after wiping the lenses between fingers. The lenses were extremely smooth in the qualitative finger-wiping test.

[0223] Example 8

[0224] In the Design of Experiment (DOE), an IPC brine containing approximately 0.05% to 0.09% PAAm-PAA and approximately 0.075% to 0.19% PAE (Kymene, from Ashland, in aqueous solution and used as received, with a nitrogen-containing heterocyclic butylene content of 0.46 as analyzed by NMR) was prepared. The IPC brine was heat-treated at 60°C for 8 hours, and the lenses from Example 3 were packaged in the heat-pretreated IPC brine. No difference was observed in the final lens surface properties, and all lenses exhibited excellent lubricity, debris adhesion resistance, excellent wettability, and no evidence of surface cracking.

[0225] Example 9

[0226] In the Design of Experiments (DOE), an IPC brine containing approximately 0.07% PAAm-PAA and sufficient PAE (approximately 0.15% PAE) to provide an initial nitrogen-containing cyclobutane content of approximately 8.8 mmol / L was generated. In the central composite design, the thermal pretreatment conditions varied between 50°C and 70°C, and the pre-reaction time varied between approximately 4 hours and approximately 12 hours. A 24-hour pretreatment time at 60°C was also tested. 10 ppm hydrogen peroxide was then added to the brine to prevent bioburden growth, and the IPC brine was filtered using a 0.22-micron polyether ether (PES) membrane filter.

[0227] Lenses from Example 3 were packaged in heat-pretreated IPC saline solution and then autoclaved at 121°C for 45 minutes. All lenses exhibited excellent lubricity, wettability, and surface breakage resistance. Some lenses showed adhesion of tissue paper debris as shown in Table 1. Table 1 Debris Adhesion Assessment Temperature (°C) Time (hr) 50 55 60 65 70 4 qualified 6 qualified qualified 8 qualified qualified Unqualified 10 qualified Unqualified 12 qualified twenty four Unqualified

[0228] Example 10

[0229] Evaluation of copolymers of methacryloxyethyl phosphocholine (MPC) with a carboxyl-containing vinyl monomer (CH2=CH(CH3)C(O)OC2H4OC(O)C2H4COOH (MS), methacrylic acid (MA)) in the absence or presence of butyl methacrylate (BMA) in packaging inner coating systems combined with PAE.

[0230] Prepare PBS containing NaCl (0.75 wt%), NaH2PO4·H2O (0.0536 wt%), Na2HPO4·2H2O (0.3576 wt%), and DI water (97.59 wt%), and add 0.2% PAE (polycup 3160). Adjust the pH to approximately 7.3.

[0231] Then 0.25% of one of the MPC copolymers is added to form an IPC brine, and the IPC brine is pretreated at 70°C for 4 hours (heat pretreatment). During this heat pretreatment, the MPC and PAE partially crosslink with each other (i.e., without consuming all the nitrogen-containing butyronitrile groups of the PAE) to form a water-soluble and thermally crosslinkable hydrophilic polymer containing nitrogen-containing butyronitrile groups within the branched polymer network of the IPC brine. After 4 hours, the heat-pretreated IPC brine is filtered through a 0.2-micron polyether ether (PES) membrane filter (Fisher Scientific catalog number 09-741-04, Thermo Scientific nalgene number 568-0020 (250 ml)).

[0232] Lenses with the PAA-LbL substrate coating obtained in Example 3 were packaged in heat-pretreated IPC brine and autoclaved at 121°C for approximately 30 minutes. Table 2 shows that all lenses exhibited excellent surface properties. Table 2 MPC copolymer* DA fracture lubricity Wettability WBUT (sec.) Polymer (MPC / MA) 90 / 10 qualified qualified Excellent Excellent Polymer (MPC / BMA / MA) 40 / 40 / 20 qualified qualified Excellent Excellent Polymer (MPC / BMA / MA) 70 / 20 / 10 qualified qualified Excellent Excellent Polymer (MPC / BMA / MS) 70 / 20 / 10 qualified qualified Excellent Excellent *Numbers represent the mole percentage of monomer units in the copolymer. DA = Debris adhesion WBUT longer than 10 seconds.

[0233] Example 11

[0234] PAA-coated lens. A lens was cast from the lens formulation prepared in Example 3 according to the molding process described in Example 3 and coated by immersion in the following series of baths: 3 MEK baths (22 seconds, 78 seconds and 224 seconds); DI water bath (56 seconds); 2 PAA coating solution baths (prepared by dissolving 3.6 g PAA (MW: 450 kDa, from Lubrizol) in 975 ml 1-propanol and 25 ml formic acid) (held for 44 seconds and 56 seconds respectively); and 3 DI water baths (held for 56 seconds each).

[0235] Lens coated with PAE / PAA. The lens with the PAA base coating prepared above was continuously immersed in the following baths: two PAE coating solution baths (prepared by dissolving 0.25 wt% PAE (Polycup 172, from Hercules) in DI water, adjusting the pH to approximately 5.0 with sodium hydroxide, and finally filtering the solution through a 5 μm filter) (held for 44 seconds and 56 seconds respectively); and three DI water baths (held for 56 seconds each). After this treatment, the lens has one PAA layer and one PAE layer.

[0236] Lens with a PAA-x-PAE-x-CMC coating. A batch of lenses with one PAA layer and one PAE layer were packaged in 0.2% sodium carboxymethyl cellulose (CMC, product number 7H 3SF PH, Ashland Aqualon) in phosphate-buffered saline (PBS), and the pH was adjusted to 7.2-7.4. The blister packs were then sealed and autoclaved at 121°C for approximately 30 minutes to form a cross-linked coating (PAA-x-PAE-x-CMC) on the lenses.

[0237] Lens with a PAA-x-PAE-x-HA coating. Another batch of lenses with a PAA layer and a PAE layer 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 blister packs 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.

[0238] Lenses with a PAA-x-PAE-x-CMC coating or a PAA-x-PAE-x-HA coating showed no Sudan Black staining, no debris adhesion, and no cracks under microscopic examination. Lenses with a PAA-x-PAE-x-CMC coating had an average contact angle of 30 ± 3 degrees, while lenses with a PAA-x-PAE-x-HA coating had an average contact angle of 20 ± 3 degrees.

[0239] Example 12

[0240] IPC Solution Preparation. A reaction mixture was prepared by dissolving 2.86 wt% mPEG-SH 2000 (methoxy-poly(ethylene glycol)-thiol, average Mw 2000, product number MPEG-SH-2000, Laysan Bio) and 2 wt% PAE (Kymene, from Ashland, in aqueous solution and used in the receiving state, with a nitrogen-heterobutylium content of 0.46 as analyzed by NMR) in PBS, and adjusting the final pH to 7.5. The solution was pretreated at 45°C for approximately 4 hours (heat pretreatment). During this heat pretreatment, mPEG-SH 2000 and PAE react with each other to form a water-soluble and thermally crosslinkable hydrophilic polymer containing nitrogen-heterobutylium groups and chemically grafted polyethylene glycol polymer chains. Following heat treatment, the solution was diluted 10-fold with PBS containing 0.25% sodium citrate, the pH was adjusted to 7.2-7.4, and then filtered using a 0.22-micron polyether ether (PES) membrane filter. The final IPC brine contained 0.286 wt% hydrophilic polymeric material (composed of approximately 59 wt% MPEG-SH-2000 chains and approximately 41 wt% PAE chains) and 0.25 wt% sodium citrate dihydrate. PBS was prepared by dissolving 0.74% NaCl, 0.053% NaH₂PO₄·H₂O, and 0.353% Na₂HPO₄·2H₂O in water.

[0241] Lenses with a cross-linked coating. PAA-coated lenses from Example 11 were packaged in the aforementioned IPC saline solution within a polypropylene lens packaging shell and then autoclaved at approximately 121°C for approximately 30 minutes, thereby forming a cross-linked coating on these lenses. The final lenses showed no debris adhesion and no tear lines after wiping. Compared to the PAA-coated control lenses, the lenses were extremely smooth during the finger-wiping test.

[0242] A series of experiments were conducted to investigate the effects of conditions (reaction time and mPEG-SH2000 solution concentration (with a constant PAE concentration of 2%)) on the surface properties of lenses coated with IPC brine. The results are shown in Table 3. Table 3 [mPEG-SH2000] 1 (wt%) Reaction time (hr) at 45°C DA fracture lubricity WCA Test 1 Test 2 2.86 0 0,2 0,2; 2,NA 3 3 17 2.86 0.5 0,0 0,2; 0,2 2-3 2 twenty one 2.86 2 0,0 0,0; ​​0,0 2 2 20 2.86 4 0,0 0,0; ​​0,0 1-2 1 37 0.5 4 0 0,2; NA 4 3-4 15 1.5 4 0 0,0; ​​NA 3 3 20 6 4 0 0,0; ​​NA 0-1 0 51 DA = Debris adhesion; WCA = Water contact angle. 1. PAE concentration: 2% by weight.

[0243] As the solution concentration of mPEGSH2000 increases, the lubricity of the lens increases accordingly. It is believed that the increase in surface contact angle may be due to the increase in the density of terminal methyl groups on the surface with increasing grafting density. At high grafting density, corresponding to a solution concentration of 0.6%, the contact angle is close to the measurement value obtained on a polyethylene glycol (PEG) monolayer grafted planar substrate (Reference: Langmuir 2008, 24, 10646-10653).

[0244] Example 13

[0245] A series of experiments were conducted to investigate the effect of the molecular weight of mPEG-SH. IPC brine was prepared using a procedure similar to that described in Example 12. However, the following mPEG-SHs were used to prepare the brine: mPEG-SH 1000, mPEG-SH 2000, mPEG-SH 5000, and mPEG-SH 20000. All brines were heat-treated at 45°C for 4 hours and diluted 10-fold. The results and reaction conditions are shown below: mPEG-SH DA fracture lubricity WCA MW (Dalton) concentration(%)* Test 1 Test 2 1000 1.5 none none 2 1 twenty one 1000 2.86 none none 1 1 27 2000 1.5 none none 2 2 28 2000 2.86 none none 0-1 0 twenty one 5000 1.5 none none 2 2 18 5000 2.86 none none 0-1 0-1 26 20000 1.5 none none 3 2 twenty one 20000 2.86 none none 2 1 twenty one DA = Debris adhesion; WCA = Water contact angle. *Initial concentration of MPEG-SH in IPC brine with 2% PAE before heat pretreatment and 10x dilution.

[0246] Example 14

[0247] A reaction mixture was prepared by dissolving 2.5% mPEG-SH 2000, 10% PAE (Kymene, from Ashland, in aqueous solution and used in the receiving state, with a nitrogen-containing butyronium content of 0.46 as analyzed by NMR) in PBS and 0.25% sodium citrate dihydrate. The pH of this solution was then adjusted to 7.5, and degassed by bubbling nitrogen through the container for 2 hours. The solution was then heat-treated at 45°C for approximately 6 hours to form a thermally crosslinkable hydrophilic polymer containing mPEG-SH-2000 groups chemically grafted onto the polymer through a reaction with the nitrogen-containing butyronium groups in PAE. After heat treatment, the solution was diluted 50-fold with PBS containing 0.25% sodium citrate, the pH was adjusted to 7.2 to 7.4, and then filtered using a 0.22-micron polyether ether (PES) membrane filter. The final IPC brine contains approximately 0.30 wt% of polymeric material (composed of approximately 17 wt.% mPEG-SH-2000 and approximately 83 wt.% PAE) and 0.25% sodium citrate dihydrate.

[0248] The PAA-coated lenses from Example 11 were packaged in the aforementioned IPC saline solution within a polypropylene lens packaging shell and then autoclaved at approximately 121°C for approximately 30 minutes, thereby forming a cross-linked coating on the lenses. The final lenses showed no debris adhesion and no tear lines after wiping. Compared to the PAA-coated control lenses, the test lenses were extremely smooth during the finger-wiping test.

[0249] Example 15

[0250] A reaction mixture was prepared by dissolving 3.62% mPEG-NH2 550 (methoxy-poly(ethylene glycol)-amine, MW approximately 550, product number MPEG-NH2-550, Laysan Bio) and 2% PAE (Kymene, from Ashland, in aqueous solution and used in the receiving state, with a nitrogen-hexacyclobutane content of 0.46 as analyzed by NMR) in PBS, and the final pH was adjusted to 10. The solution was heat-treated at 45°C for approximately 4 hours to form a thermally crosslinkable hydrophilic polymer containing MPEG-NH2-550 groups chemically grafted onto the polymer through a reaction with the nitrogen-hexacyclobutane groups in PAE. Following heat treatment, the solution was diluted 10-fold with PBS containing 0.25% sodium citrate, the pH was adjusted to 7.2-7.4, and then filtered using a 0.22-micron polyether ether (PES) membrane filter. The final IPC brine contained approximately 0.562 wt.% of polymeric material (composed of 64 wt.% MPEG-SH-2000 and approximately 36 wt.% PAE) and 0.25% sodium citrate dihydrate. PBS was prepared by dissolving 0.74% NaCl, 0.053% NaH₂PO₄·H₂O, and 0.353% Na₂HPO₄·2H₂O in water.

[0251] The PAA-coated lenses from Example 11 were packaged in the above-mentioned IPC brine 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 lenses.

[0252] The final lens showed no debris adhering to it, and no crack lines were observed after wiping the lens with a finger.

[0253] Example 16

[0254] Use Poloxamer 108 (sample) and Nelfilcon A (CIBA VISION) in the receiving state. Nelfilcon A is a polymerizable polyvinyl alcohol obtained by modifying polyvinyl alcohol with N-(2,2-dimethoxyethyl)acrylamide (e.g., Gohsenol KL-03 from Nippon Gohsei or similar) under cyclic acetal formation 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 are modified with N-(2,2-dimethoxyethyl)acrylamide.

[0255] An IPC brine was prepared by dissolving 0.004% poloxamer 108, 0.8% nelfilcon A, 0.2% PAE (Kymene, Polycup 3160), 0.45% NaCl, and 1.1% Na2HPO4·2H2O in DI water. The brine was heat-pretreated by stirring at approximately 65°C–70°C for 2 hours. After heat pretreatment, the brine was cooled to room temperature and then filtered using a 0.2 µm PES filter.

[0256] The lenses prepared in Example 3 were placed in polypropylene lens packaging shells containing 0.6 mL of IPC saline (half the saline was added before inserting the lens). The blister packs were then sealed with foil and autoclaved at 121°C for approximately 30 minutes. Test lenses showed no debris adhering after wiping with a paper towel. The lenses had a WBUT of more than 10 seconds. No tear lines were observed after wiping the lenses between fingers under a dark-field microscope. The lenses were significantly more lubricating than those from Example 4, but still less lubricating than the PAA-coated control lenses packaged in PBS.

[0257] Example 17

[0258] A. Synthesis of 80% olefin-functionalized extended-chain polysiloxanes

[0259] 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 individually dried at approximately 60°C for 12 hours (or overnight) under high vacuum in a single-necked flask. The OH molar equivalent weights of KF-6001A and KF-6002A were determined by titration of hydroxyl groups, and the millimoles equivalent (mM) to be used in the synthesis were calculated using these OH molar equivalent weights.

[0260] The 1-liter reactor vessel was evacuated overnight to remove moisture, and the vacuum was broken using dry nitrogen. 75.00 g (75 meq) of dried KF6001A was packed into the reactor, and then 16.68 g (150 meq) of freshly distilled IPDI was added to the reactor. The reactor was purged with nitrogen and heated to 45°C with stirring, and then 0.30 g of DBTDL was added. The reactor was sealed, and nitrogen was kept flowing in a positive direction. The exothermic reaction was initiated, and then the reaction mixture was cooled and stirred at 55°C for 2 hours. After the exothermic reaction was achieved, 248.00 g (150 meq) of dried KF6002A was added to the reactor at 55°C, and then 100 μL of DBTDL was added. The reactor was stirred for 4 hours. Heating was stopped and the reactor was cooled overnight. Nitrogen bubbling was stopped and the reactor was opened to the atmosphere for 30 minutes while stirring appropriately. Forming a chain-extended polysiloxane HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH (or HO-CE-PDMS-OH) with hydroxyl-terminated segments of 3 polysiloxane segments.

[0261] For 80% olefin-functionalized polysiloxane, 18.64 g (120 meq) IEM and 100 μL DBTDL were added to the reactor. The reactor was stirred for 24 hours, and then the product (80% IEM-terminated CE-PDMS) was decanted and stored under refrigeration.

[0262] B: Synthesis of non-UV-absorbing amphiphilic branched polysiloxane prepolymers

[0263] Equip a 1-L jacketed reactor with a 500-mL feed funnel, a top-mounted stirrer, a reflux condenser with a nitrogen / vacuum inlet adapter, a thermometer, and a sampling adapter. Charge 45.6 g of the 80% IEM-terminated CE-PDMS prepared above into the reactor and seal it. Charge the feed funnel with a solution of 0.65 g of hydroxyethyl methacrylate (HEMA), 25.80 g of DMA, and 27.80 g of tris(trimethylsilyl)-methoxypropyl methacrylate (TRIS) in 279 g of ethyl acetate. Degas the reactor for 30 minutes using a high-vacuum pump at <1 mbar and room temperature. Degas the monomer solution for 10 minutes at 100 mbar and room temperature, repeating this process three times, breaking the vacuum with nitrogen between degassing cycles. Then charge the monomer solution into the reactor, and then stir the reaction mixture and heat it to 67°C. While heating, a solution of 1.50 g mercaptoethanol (chain transfer agent, CTA) and 0.26 g azoisobutyronitrile dissolved in 39 g ethyl acetate was added to a feeding funnel, and the mixture was deoxidized three times over 10 minutes at 100 mbar and room temperature. When the reactor temperature reached 67°C, the initiator / CTA solution was added to the PDMS / monomer solution in the reactor. The reaction was carried out for 8 hours, and then heating was stopped, allowing the reactor temperature to reach room temperature within 15 minutes.

[0264] The resulting reaction mixture was then siphoned into a dry single-necked flask with an airtight lid, and 4.452 g of IEM and 0.21 g of DBTDL were added. The mixture was stirred at room temperature for 24 h to form a non-UV-absorbing amphiphilic branched polysiloxane prepolymer. 100 μL of a hydroxy-tetramethylene piperine oxyhydroxide solution (2 g / 20 mL) in ethyl acetate was added to this mixture. The solution was then concentrated to 200 g (approximately 50%) using a rotary evaporator at 30 °C and filtered through 1 μm filter paper. After solvent exchange with 1-propanol, the solution was further concentrated to the desired concentration.

[0265] C. Synthesis of UV-absorbing amphiphilic branched polysiloxane prepolymers

[0266] Equip a 1-L jacketed reactor with a 500-mL feed funnel, a top-mounted stirrer, a reflux condenser with a nitrogen / vacuum inlet adapter, a thermometer, and a sampling adapter. Then, charge the reactor with 45.98 g of the 80% IEM-terminated CE-PDMS prepared above and seal the reactor. Charge the feed funnel with 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. Degas the reactor for 30 minutes using a high-vacuum pump at <1 mbar and room temperature. Degas the monomer solution for 10 minutes at 100 mbar and room temperature and perform three cycles, breaking the vacuum with nitrogen between degassing cycles. Then, charge the reactor with the monomer solution, and then stir the reaction mixture and heat to 67°C. While heating, a solution of 1.480 g mercaptoethanol (chain transfer agent, CTA) and 0.260 g azoisobutyronitrile dissolved in 38 g ethyl acetate was added to a feeding funnel, and the mixture was deoxidized three times over 10 minutes at 100 mbar and room temperature. When the reactor temperature reached 67°C, the initiator / CTA solution was added to the PDMS / monomer solution in the reactor. The reaction was carried out for 8 hours, and then heating was stopped, allowing the reactor temperature to reach room temperature within 15 minutes.

[0267] The resulting reaction mixture was then siphoned into a dry single-necked flask with an airtight lid, and 3.841 g of isocyanate ethyl acrylate and 0.15 g of DBTDL were added. The mixture was stirred at room temperature for 24 h to form a UV-absorbing amphiphilic branched polysiloxane prepolymer. 100 μL of a hydroxy-tetramethylene piperine oxyhydroxide solution (2 g / 20 mL) in ethyl acetate was added to this mixture. The solution was then concentrated to 200 g (approximately 50%) using a rotary evaporator at 30 °C and filtered through 1 μm filter paper.

[0268] D-1: Lens formulation containing non-UV-absorbing polysiloxane prepolymer

[0269] In a 100 mL amber flask, add 4.31 g of the synthetic macromonomer solution (82.39%, in 1-propanol) prepared above. In a 20 mL vial, dissolve 0.081 g of TPO and 0.045 g of 1,2-dimyristyl-sn-glycerol-3-phosphocholine (DMPC) in 10 g of 1-propanol and then transfer the solution to the macromonomer solution. Concentrate the mixture to 5.64 g using a rotary evaporator at 30 °C, add 0.36 g of DMA, and homogenize the formulation at room temperature. Approximately 6 g of clear lens formulation D-1 is obtained.

[0270] D-2: Lens formulation with UV-absorbing polysiloxane prepolymer (4% DMA)

[0271] In a 100 mL amber flask, add 24.250 g of the macromonomer solution (43.92%, stored in ethyl acetate) prepared above. In a 50 mL vial, dissolve 0.15 g of TPO and 0.75 g of DMPC in 20 g of 1-propanol and then transfer the solution to the macromonomer solution. Remove 20 g of solvent using a rotary evaporator at 30 °C, then add 20 g of 1-propanol. After two cycles, concentrate the mixture to 14.40 g. Add 0.6 g of DMA to this mixture and homogenize the formulation at room temperature. Approximately 15 g of clear lens formulation D-2 is obtained.

[0272] D-3: Lens formulation with UV-absorbing polysiloxane prepolymer (2% DMA / 2% HEA)

[0273] In a 100 mL amber flask, add 24.250 g of the macromonomer solution (43.92%, stored in ethyl acetate) prepared above. In a 50 mL vial, dissolve 0.15 g of TPO and 0.75 g of DMPC in 20 g of 1-propanol and then transfer the solution to the macromonomer solution. Remove 20 g of solvent using a rotary evaporator at 30 °C, then add 20 g of 1-propanol. After two cycles, concentrate the mixture to 14.40 g. Add 0.3 g of DMA and 0.3 g of HEA to this mixture and homogenize the formulation at room temperature. Approximately 15 g of clear lens formulation D-3 is obtained.

[0274] Example 18

[0275] Example E: Covalent attachment of modified PAE-coated polymer

[0276] Purchase N-(3-aminopropyl)methacrylamide hydrochloride (APMAA-HCl) or N-(2-aminoethyl)methacrylamide hydrochloride (AEMAA-HCl) containing an amino group from Polysciences and use them in the receiving state. Receive poly(acrylamide-co-acrylic acid) (PAE) in aqueous solution form from Ashland and use it in the receiving state. Use 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 methacryloxyethyl phosphocholine (MPC) and aminoethyl methacrylate (AeMA)) from NOF in the receiving state.

[0277] The 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 concentration of 1 wt%.

[0278] A reactive packaged brine was prepared by dissolving the components listed in Table 4 and a suitable buffer salt in DI water. The brine was heat-pretreated by stirring at approximately 60°C for 8 hours. After heat pretreatment, the brine was cooled to room temperature and then filtered using a 0.2 µm PES filter. Table 4 Packaged saline samples 1 2 3 4 5 pH 7.4 7.4 7.4 8 8 PAE 0.2% 0.2% 0.2% 0.2% 0.2% (AAm-Total-AA) (90 / 10) 0.07% 0.2% -- -- -- mPEG-SH, Mw=2000 -- -- 0.3% -- -- mPEG-SH, Mw=10000 -- -- -- 0.2% -- (MPC-Co-AeMA) (90 / 10) -- -- -- -- 0.2%

[0279] Lens formulation D-1 prepared in Example 17 was improved by adding APMMA-HCl monomer (a stock solution of APMMA-HCl in a 1:1 methanol:propanol mixture) and cured at 16 mW / cm² using a 330 nm filter. Lens formulations D-2 and D-3 prepared in Example 17 were improved by adding APMMA-HCl monomer and cured at 4.6 mW / cm² using a 380 nm filter.

[0280] DSM Lens. Approximately 75 microliters of the lens formulation prepared above are filled into the concave portion of a polypropylene lens mold, and then the mold is closed using the convex portion of a polypropylene lens mold (base bending mold). The closed mold is cured for approximately 5 minutes using a UV irradiation source (a Hamamatsu lamp with an intensity of approximately 16 mW / cm² and a 330 nm cutoff filter) to obtain a contact lens.

[0281] LS Lens. LS lenses are manufactured by casting a lens preparation obtained above into a reusable mold, which is similar to the molds shown in Figures 1-6 of U.S. Patents 7,384,590 and 7,387,759. The mold includes a concave mold half made of CaF2 and a convex mold half made of PMMA. The UV irradiation source is a Hamamatsu lamp with an intensity of approximately 4.6 mW / cm² and a 380 nm cutoff filter. The lens preparation in the mold is irradiated with UV light for approximately 30 seconds.

[0282] Lens formulation D-1 modified with APMAA-HCl was cured according to the above-mentioned DSM and LS methods, and lens formulation D-2 or D-3 was cured according to the above-mentioned LS method.

[0283] Molded lenses were extracted in methyl ethyl ketone, hydrated, and packaged in one of the saline solutions listed in Table 4. The lenses were placed in a polypropylene lens package containing 0.6 mL of IPC saline (half the saline was added before inserting the lens). The blister packs were then sealed with foil and autoclaved at 121°C for 30 min.

[0284] Evaluation of the lens surface showed that no debris adhered to any of the tested lenses after wiping with a tissue. When observed under a dark-field microscope, no crack lines were visible after wiping the lenses between fingers.

[0285] The surface wettability (WBUT), lubricity, and contact angle of the lens were measured, and the results are summarized in Table 5. Unless otherwise specified, the lenses were manufactured according to the DSM method. Lubricity was rated using a qualitative scale from 0 to 5, with lower values ​​indicating greater lubricity. Generally, all properties were improved after the application of the inner coating. Table 5 Lens mixing materials used in the manufacture of lenses brine 1 WBUT (seconds) lubricity Contact angle [°] D1, as a control (Excluding APMAA) 1 0 4-5 114 3 0 4 119 D1 w / 1% APMAA 1 10 0-1 104 3 2 0-1 99 D2, as a control (Excluding APMAA) 1 0 4-5 115 3 0 3 107 4 0 2 3-4 2 116 2 D2 w / 1% APMAA 1 5 2-3 90 3 6 1 95 4 5-10 2 3 2 106 2 D3 w / 1% APMAA 2 9 3-4 103 3 14 2-3 91 4 15 3 54 5 13 2 69 1. The serial number in the packaged saline solution shown in Table 4. 2. LS lens.

[0286] Example 19

[0287] Preparation of lens formulation. A lens formulation was prepared by dissolving each component in 1-propanol to have the following composition: about 32% by weight of the CE-PDMS macromonomer prepared in Example 2, about 21% by weight of TRIS-Am, about 23% by weight of DMA, about 0.6% by weight of L-PEG, about 1% by weight of DC1173, about 0.1% by weight of visitint (a 5% copper phthalocyanine blue pigment dispersion in TRIS), about 0.8% by weight of DMPC, about 200 ppm of H-tempo, and about 22% by weight of 1-propanol.

[0288] Lens manufacturing. Lenses are manufactured by casting the lens preparation obtained above into a reusable mold (a quartz concave mold half and a glass convex mold half), the reusable mold being similar to the molds shown in Figures 1-6 of U.S. Patents 7,384,590 and 7,387,759. The lens preparation in the mold is irradiated with UV light (13.0 mW / cm²) for approximately 24 seconds.

[0289] PAA Coating Solution. A PAA coating solution was prepared by dissolving a certain amount of PAA (MW: 450 kDa, from Lubrizol) in a given volume of 1-propanol to a concentration of about 0.36% by weight, and adjusting the pH to about 2.0 using formic acid.

[0290] PAA-coated lenses. The above-cast contact lenses were extracted and coated by immersion in the following series of baths: DI water bath (approximately 56 seconds); 6 MEK baths (held for approximately 44, 56, 56, 56, and 56 seconds respectively); DI water bath (approximately 56 seconds); one PAA coating solution bath in 100% 1-propanol (approximately 0.36% by weight, acidified with formic acid to approximately pH 2.0) (approximately 44 seconds); one water / 1-propanol 50% / 50% mixture bath (approximately 56 seconds); 4 DI water baths (each held for approximately 56 seconds); one PBS bath (held for approximately 56 seconds); and one DI water bath (held for approximately 56 seconds).

[0291] IPC brine. Poly(AAm-co-AA)(90 / 10) sodium metasodium salt (approximately 90% solids content, Mw 200,000) was purchased from Polysciences and used as received. PAE (Kymene, NMR analysis showed a nitrogen-containing butyronium content of 0.46%) in aqueous solution was purchased from Ashland and used as received. IPC brine was prepared by dissolving approximately 0.07% w / w poly(AAm-co-AA) (90 / 10) and approximately 0.15% PAE (approximately 8.8 mmol initial aziridine millimole equivalents) in PBS (approximately 0.044 w / w% NaH2PO4·H2O, approximately 0.388 w / w% Na2HPO4·2H2O, and approximately 0.79 w / w% NaCl) and adjusting the pH to 7.2 to 7.4. The IPC brine was then heat-pretreated at approximately 70°C for approximately 4 hours (heat pretreatment). During this heat pretreatment, the poly(AAm-co-AA) and PAE partially crosslinked with each other (i.e., without consuming all the aziridine groups of PAE) to form a water-soluble and thermally crosslinkable hydrophilic polymer containing aziridine groups within the branched polymer network of the IPC brine. After heat pretreatment, the IPC brine was filtered using a 0.22-micron PES membrane filter and cooled back to room temperature. Then, 10 ppm hydrogen peroxide was added to the final IPC brine to prevent bioburden growth, and the IPC brine was filtered using a 0.22-micron PES membrane filter.

[0292] Application of cross-linked coating. The lens with the PAA-LbL base coating prepared above is placed in a polypropylene lens packaging shell (each shell containing one lens) containing 0.6 mL of IPC saline (half of the saline is added before inserting the lens). The blister is then sealed with foil and autoclaved at about 121°C for about 30 minutes to form a SiHy contact lens with a cross-linked coating (PAA-x-hydrophilic polymer).

[0293] Characteristics of SiHy lenses. SiHy contact lenses with a cross-linked coating (PAA-x-hydrophilic polymer) showed no debris adhesion after wiping with a tissue, while control lenses (packaged in PBS, i.e., lenses with a non-covalent PAA layer) showed severe debris adhesion. These lenses had an oxygen permeability (Dkc or estimated intrinsic Dk) of 146 barrer, a bulk modulus of elasticity of 0.76 MPa, a water content of approximately 32% by weight, a relative ion permeability of approximately 6 (compared to Alsacon lenses), a contact angle of approximately 34 to 47 degrees, and a WBUT of more than 10 seconds. No crack lines were observed after wiping the test lenses under a dark-field microscope. The lenses were extremely smooth and comparable to the control lenses in the finger-wiping test.

[0294] Example 20 The following biocompatibility studies were conducted on SiHy lenses and IPC saline prepared in Examples 6, 14 and 19 in autoclaved lens packaging.

[0295] In vitro cytotoxicity assessment. SiHy lenses were evaluated using USP direct contact material analysis. Lens extracts were evaluated using USP MEM elution and ISO CEN cell growth inhibition analysis, and IPC saline in autoclaved packaging was evaluated using a modified elution test. All lenses and lens extracts evaluated fully met the acceptance criteria for each test, and no unacceptable cytotoxicity was observed.

[0296] In vivo testing. ISO systemic toxicity studies in mice showed no evidence of systemic toxicity of the lens extract in mice. ISO eye irritation studies in rabbits showed that the lens extract should not be considered an irritant to rabbit eye tissues. ISO eye irritation studies in rabbits showed that the IPC saline solution in the autoclaved package should not be considered an irritant to rabbit eye tissues. Lenses worn continuously for 22 days in a daily disposable mode were not irritating to rabbit models, and eyes treated with the test lens were similar to those treated with the control lens. ISO sensitization studies (maximum sensitization of the packaged solution in guinea pigs) showed that the autoclaved IPC saline solution did not cause any delayed dermal contact sensitization in guinea pigs. ISO sensitization studies (maximum sensitization of the lens extract in guinea pigs) showed that the sodium chloride and sesame oil extracts in the lens did not cause delayed dermal contact sensitization in guinea pigs.

[0297] Genotoxicity Tests. In bacterial reverse mutation analysis (Ames test), IPC saline and SiHy lens extract from the lens packaging were found to be non-mutagenic against test strains of *Salmonella typhimurium* TA98, TA100, TA1535, and TA1537 and *Escherichia coli* WPuvrA lineage. In mammalian erythrocyte micronucleus analysis, the SiHy lens extract showed no cleavage-inducing activity and was negative in mouse bone marrow micronucleus testing. In testing IPC saline from the lens packaging according to chromosomal abnormality assays in Chinese hamster ovaries, the IPC saline was negative for both structural and quantitative chromosomal abnormality analyses induced in CHO cells in both inactive and S9 activated assay systems. In cellular gene mutation assays (mouse lymphoma mutagenesis analysis), the lens extract was negative in mouse lymphoma mutagenesis analysis.

[0298] Example 21

[0299] The surface composition of vacuum-dried contact lenses was determined by characterizing them using X-ray photoelectron spectrometry (XPS) to determine the surface composition of pre-formed SiHy contact lenses (i.e., SiHy contact lenses without any coating and before the application of a PAA base coating), SiHy contact lenses with a PAA coating (i.e., those lenses before sealing and autoclaving in a lens package containing IPC saline), and SiHy contact lenses with a crosslinked coating (all prepared according to the procedure described in Example 19). XPS is a method for measuring the surface composition of lenses using a sampling depth of approximately 10 nm. The surface compositions of the three types of lenses are reported in Table 6. Table 6 Surface atomic composition (%) SiHy lenses C N O F* Si Pre-formed (uncoated) 58.0 6.2 23.0 0.8 12.1 With PAA coating 48.9 1.6 42.1 2.9 4.5 With cross-linked coating 59.1 10.8 25.4 3.2 1.4 *: Fluorine was detected, most likely from surface contamination during the vacuum drying and XPS analysis process.

[0300] Table 6 shows that when a PAA coating is applied to a SiHy lens (an uncoated pre-formed lens), the silicon atomic composition is substantially reduced (from 12.1% to 4.5%) and the nitrogen atomic composition is also reduced (from 6.2% to 1.6%). When a crosslinked coating is further applied to the PAA coating, the surface composition is mainly carbon, nitrogen, and oxygen, which is a triatomic composition (excluding hydrogen, as XPS does not count hydrogen in the surface composition). These results suggest that the outermost layer of a SiHy contact lens with a crosslinked coating is likely composed primarily of a hydrophilic polymer, which is a reaction product of poly(AAm-co-AA)(90 / 10)(60% C, 22% O, and 18% N) and PAE.

[0301] XPS analysis was also performed on the following commercial SiHy lenses after vacuum drying. The surface composition of these commercial SiHy contact lenses is reported in Table 7. Table 7 Surface atomic composition (%) C N O F* Si N&D® Aqua TM 68.4 9.1 18.6 1.5 2.4 Air Optix® Aqua TM 67.7 9.9 18.2 1.9 2.4 PureVision® 58.2 6.9 26.0 1.1 7.9 Premio TM 61.1 6.9 23.6 1.8 6.6 Acuvue® Advance® 61.1 4.9 24.9 0.7 8.4 Acuvue® Oasys® 61.5 5.0 24.4 0.6 8.5 TruEye TM 63.2 4.9 24.2 0.8 7.0 Biofinity® 46.5 1.4 28.9 5.3 17.9 Avaira TM 52.4 2.5 27.8 4.2 13.1 *: Fluorine was also detected in Advance, Oasys, and TruEye lenses, most likely originating from surface contamination during the vacuum drying process and XPS analysis.

[0302] It was found that the SiHy contact lens of the present invention has a nominal silicon content of approximately 1.4% in the surface layer, which is far lower than that of other commercial SiHy lenses (Acuvue® Advance®, Acuvue® Oasys®, TruEye™, Biofinity®, Avaira™) without plasma coating, as well as PureVision® (subjected to plasma oxidation) and Premio™ (subjected to unknown plasma treatment), and even lower than SiHy lenses (N&D® Aqua™ and Air Optix® Aqua™) with a plasma deposition coating of approximately 25 nm thickness. This extremely low Si% value is comparable to the silicon atomic percentage of control samples polyethylene (LDPE, d=0.015 mm; LS356526 SDS; ET31111512; 3004622910) from Goodfellow. These results indicate that the extremely low values ​​in the XPS analysis of the vacuum-dried SiHy contact lenses of this invention are likely due to contaminants introduced during the preparation process (including the vacuum drying process) and the XPS analysis, similar to the fluorine content observed in fluorine-free lenses. In the SiHy contact lenses of this invention, polysiloxane has been successfully shielded from XPS analysis.

[0303] XPS analysis was also performed on the SiHy contact lenses of the present invention (prepared according to the procedure described in Example 19), commercial SiHy contact lenses (CLARITI™ 1 Day, ACUVUE® TruEye™ (narafilcon A and narafilcon B)), polyethylene sheets from Goodfellow (LDPE, d=0.015 mm; LS356526 SDS; ET31111512; 3004622910), DAILIES® (polyvinyl alcohol hydrogel lenses, i.e., non-silicone hydrogel lenses), and ACUVUE® Moist (polyhydroxyethyl methacrylate hydrogel lenses, i.e., non-silicone hydrogel lenses). All lenses were vacuum dried. Polyethylene sheets, DAILIES®, and ACUVUE® Moist were used as controls because they are silicone-free. The silicon atom composition in the surface layer of the test samples is as follows: 1.3±0.2 (polysiloxane film); 1.7±0.9 (DAILIES®); 2.8±0.9 (ACUVUE® Moist); 3.7±1.2 (three SiHy lenses prepared according to the procedure described in Example 19); 5.8±1.5 (CLARITI™ 1 Day); 7.8±0.1 (ACUVUE® TruEye™ (narafilcon A)); and 6.5±0.1 (ACUVUE® TruEye™ (narafilcon B)). The results of the SiHy contact lenses of the present invention are closer to those of conventional hydrogels than polysiloxane hydrogels.

[0304] Example 22

[0305] Para-F (PAA-F) with fluorescein labeling.

[0306] PAA-F was synthesized in vitro by covalently attaching 5-aminoluciferin to PAA (Mw 450k). The luciferin labeling level is a few percentages, for example, about 2 moles (or n / (m+n)=2% in the formula shown below) of luciferin-labeled PAA (PAA-F). X: luciferin fraction

[0307] The manufacture of lenses.

[0308] A lens was manufactured by casting the lens preparation obtained in Example 19 above into a reusable mold (a quartz concave mold half and a glass convex mold half), the reusable mold being similar to the molds shown in Figures 1-6 of U.S. Patents 7,384,590 and 7,387,759. The lens preparation in the mold was irradiated with UV irradiation (13.0 mW / cm2) for approximately 24 seconds.

[0309] PAA-F coating solution.

[0310] A PAA-F coating solution was prepared by dissolving a certain amount of PAA-F prepared above in a given volume of a 1-PrOH / water (95 / 5) solvent mixture to a concentration of about 0.36% by weight, and the pH was adjusted to about 2.0 using formic acid. About 5% water was used to dissolve PAA-F.

[0311] Lens coated with PAA.

[0312] The cast contact lens was extracted and coated by immersion in the following series of baths: DI water bath (approximately 56 seconds); 6 MEK baths (held for approximately 44, 56, 56, 56, and 56 seconds respectively); DI water bath (approximately 56 seconds); one PAA-F coating solution bath in a 1-PrOH / water (95 / 5) solvent mixture (approximately 0.36% by weight, acidified with formic acid to approximately pH 2.0) (approximately 44 seconds); one water / 1-propanol 50% / 50% mixture bath (approximately 56 seconds); 4 DI water baths (each held for approximately 56 seconds); one PBS bath (held for approximately 56 seconds); and one DI water bath (held for approximately 56 seconds).

[0313] Application of cross-linked coating.

[0314] The lens with the PAA-LbL base coating prepared above was placed in a polypropylene lens packaging shell (each shell containing one lens) containing 0.6 mL of IPC saline (prepared according to the procedure described in Example 19, with half of the saline added before inserting the lens). The blister was then sealed with foil and autoclaved at approximately 121°C for approximately 30 minutes to form a SiHy contact lens with a cross-linked coating (PAA-x-hydrophilic polymer).

[0315] Confocal laser fluorescence microscope.

[0316] A cross-section of a hydrated SiHy lens (prepared above) with a cross-linked coating was cut and placed between two glass coverslips, and images were collected on a confocal laser fluorescence microscope (model: Zeiss LSM 510 Vis). Scanning was performed from the front curved side of the lens to the bottom curved side, or vice versa. The presence of PAA-F was revealed by green fluorescence, and confocal laser fluorescence microscopy images were obtained. Examination of the confocal laser fluorescence microscopy images showed that a PAA-F-rich layer was present on both lens surfaces (front and back surfaces) and at the surrounding edges, while PAA-F was not observed in the bulk material of the hydrated lens.

[0317] Fluorescence intensity curves were examined by traversing the lens cross-section along a line passing through the rear and front surfaces and perpendicular to the rear surface. Figure 3 shows two representative fluorescence intensity curves along two lines traversing the lens cross-section, one at a lens thickness of approximately 100 µm (Image A) and the other at a lens thickness of approximately 200 µm (Image B). The initial point in Figure 3 is the center point along these lines between the front and rear surfaces. It can be noted in Figure 3 that a PAA-F-rich layer is present near the outermost surface of the SiHy lens with the cross-linked coating, while no PAA-F is present in the lens body, and the coating thickness is similar across both cross-sections, regardless of the cross-sectional thickness.

[0318] The thickness of the PAA-F-rich layer (i.e., the sum of the injection depth into the outer hydrogel layer and the penetration depth of PAA-F in the bulk material (i.e., the inner layer)) or the transition layer (schematically illustrated in Figure 2, transition layer 115) can be estimated from the fluorescence intensity curves shown in Figure 3. The possible thickness of the transition layer (PAA-F-rich layer) is estimated by the distance from zero intensity across the peak intensity and back to zero intensity. Considering the possible contribution of unknown factors (e.g., scattering) to the fluorescence intensity, the minimum layer thickness is the thickness that retains at least 10% of the fluorescence intensity of the maximum peak intensity. Based on this estimate, the minimum PAA-F-rich layer thickness can be at least about 5 micrometers. It should be noted that, considering that the PAA concentration used is 10 times that used in the experiments described herein, the thickness of the SiHy lens with PAA coating in the previous example may be higher. Lenses with thicker coatings can also be produced by using an immersion time greater than 44 seconds, which is the immersion time for PAA-F used in this experiment. Lenses with thicker coatings can also be produced by using PAA with different molecular weights.

[0319] Example 23

[0320] This example illustrates how to determine the water content of the cross-linked coating (two outer hydrogel layers) on the SiHy of the present invention. To attempt to determine the potential water content of the cross-linked coating on the SiHy lens in Example 19, a polymer sample consisting of the coating components was prepared for evaluation. The resulting gel water was then combined and tested to determine the water content.

[0321] A solution was prepared using the two polymeric components of the crosslinked coating formed in Example 19: poly(AAm-co-AA)(90 / 10) and PAE, to have the following composition: 12.55% w / w PAE, 6.45% w / w poly(AAm-co-AA)(90 / 10), and 81% w / w water. The PAE / poly(AAm-co-AA) ratio was the same as that of the IPC brine in Example 19, but the concentrations of each component were higher to ensure gel formation during autoclaving.

[0322] The solution was then autoclaved at 121°C for approximately 45 minutes, after which the sample gelled. Gel samples were then prepared for determining the water content by testing the hydrated samples (n=3). Hydrated samples were prepared by immersing the gel samples in SoftWear saline for at least approximately 6 hours (i.e., overnight hydration).

[0323] The hydrated sample was dried and the mass of the hydrated state was calculated by mass balance. After recording the mass of the hydrated state, all samples were placed in a vacuum oven set at about 50°C and dried overnight under a vacuum of <1 inch Hg.

[0324] After overnight drying, the dried sample was removed from the vacuum oven and then measured to record the drying mass. The water content was calculated using the following relationship: Water content = (wet mass - dry mass) / wet mass × 100%. The water content of the sample was determined to be 84.6 ± 0.4 w / w.

[0325] It is believed that this water content of the PAE / poly(AAm-co-AA) hydrogel represents the outer hydrogel layer (crosslinked coating) of the SiHy contact lens in Example 19 for the following reasons. First, it is reasonable to assume that the hydrophobic bulk lens polymer (polysilicon-oxygen hydrogel) is not present in the outer surface layer. This seems to be an excellent assumption based on XPS data. According to XPS data in Example 21, there is no or very low silicon content on the surface of the SiHy lens with the crosslinked coating, indicating that the outer surface layer is almost entirely composed of the coating polymer (PAE and PAAm-PAA). Second, the polyacrylic acid (PAA) base coating (transition layer) may have a negligible effect on the water content of the surface layer. This assumption may be invalid. However, if any charged PAA is present in the outer surface layer, it further increases the water content to over 84.6%. Third, compared to the IPC brine used in Example 19, extremely high concentrations of PAE and PAAm-PAA are required to generate the PAE / poly(AAm-co-AA) hydrogel. This results in a higher crosslinking density of the PAE / poly(AAm-co-AA) hydrogel, which artificially yields a low water content. It is believed that the presence of PAA and a lower crosslinking density in the outer hydrogel layer (attributed to a lower concentration of polymeric material during crosslinking) (in Example 19) can result in a water content in the surface layer (outer hydrogel layer) that is even higher than that measured in the tests in this example. It can be assumed that the outer coating layer of the SiHy contact lens in Example 19 contains at least 80% water, and even more when fully hydrated.

[0326] Example 24

[0327] The refractive index of contact lenses is typically measured using an Abbe refractometer. The difference in refractive index between the test lens and the instrument prism produces a unique total internal reflection angle, which generates a dark, visible shadow line. The angle at which this shadow line appears is directly related to the refractive index of the test lens. Most contact lenses (including the uncoated SiHy contact lens prepared in Example 19) produce a significant shadow line in the Abbe refractometer, but the SiHy in Example 19, which has a cross-linked coating (i.e., an outer hydrogel layer), does not produce a significant shadow line. This phenomenon is believed to be due to the fact that the refractive index is lower at the surface of the lens compared to the bulk and that the transition from the bulk to the surface is not abrupt. In addition, it is believed that the water content begins to increase near the lens surface, causing a local decrease in the refractive index of the lens. This will actually produce shadow lines at multiple angles simultaneously, resulting in a blurred image of the shadow line.

[0328] Abbe data shows that the outer surface layer is characterized by an increase in water content near the lens surface, which is consistent with the results described in Example 23.

[0329] Example 25

[0330] The SiHy contact lens with a cross-linked coating (i.e., an outer hydrogel layer) prepared in Example 19 was desalinated in ultrapure water and placed individually in a 50 mL disposable beaker containing 50 mL of ultrapure water. The beaker was then frozen by placing it in a bath containing dry ice and isopropanol. The beaker was wrapped in aluminum foil and placed on a VirTis Freezemobile 35EL with a vacuum pressure of 30 μbar and a condenser temperature of -70 °C. After 24 hours, the aluminum foil was removed to increase heat transfer, and the flask was left to stand for another 24–48 hours to remove residual moisture. The flask was capped to prevent the introduction of moisture from the air until the time of analysis. The lens sample was cut in half, and two strips were cut from the middle of each half and mounted from their edges for cross-sectional imaging. The sample was then sputter-coated with Au / Pd for about 1 min and sampled using a Bruker Quantax Microanalysis System via SEM (JEOL JSM-800LV SEM). Based on the analyst's advice, the sample stage is tilted approximately 0-60° to obtain the desired sample orientation.

[0331] It is believed that the hydrated surface structure of the lens can be preserved or maintained to a certain extent during the freeze-drying of SiHy contact lenses. Image A of Figure 4 shows a top view of the surface SEM image of the freeze-dried SiHy contact lens prepared in Example 19. As can be seen from Figure 4, the freeze-dried SiHy contact lens has a sponge-like surface structure, which is expected of a high-water-content hydrogel. This result further confirms that the SiHy contact lens of the present invention comprises two outer hydrogel layers of a high-water-content hydrogel. Images B and C of Figure 4 show side views of the cross-section of the freeze-dried SiHy contact lens shown in Image A from two different angles. Images B and C show a thick inner layer with a smooth surface, a transition layer (PAA layer) with a brighter color located on top of the inner layer, and an outer hydrogel layer with a sponge-like structure located on top of the transition layer. Based on the data shown in Images B and C, the thickness of the freeze-dried outer hydrogel layer is estimated to be between approximately 2 µm and 2.5 µm.

[0332] Example 26

[0333] Fluorescently labeled poly(AAm-co-AA)(90 / 10) (referred to as PAAm-PAA-F).

[0334] PAAm-PAA-F was synthesized in vitro by covalently attaching 5-aminoluciferin to PAAm-PAA (90 / 10) using a procedure similar to that used in the preparation of PAA-F. Sodium poly(AAm-co-AA) (90 / 10) salt (approximately 90% solids content, poly(AAm-co-AA) 90 / 10, Mw 200,000) was purchased from Polysciences and used in the receiving state. The luciferin was labeled to approximately 0.04 mol%.

[0335] Use PAAm-PAA-F modified IPC saline.

[0336] This brine was prepared by the same IPC preparation procedure as described in Example 19, except that PAAm-PAA-F was used instead of PAAm-PAA.

[0337] Lens coated with PAA.

[0338] A lens was manufactured by casting the lens preparation obtained in Example 19 above into a reusable mold (a quartz concave mold half and a glass convex mold half), the reusable mold being similar to the molds shown in Figures 1-6 of U.S. Patents 7,384,590 and 7,387,759. The lens preparation in the mold was irradiated with UV irradiation (13.0 mW / cm2) for approximately 24 seconds. The cast contact lens was extracted and coated by immersion in the following series of baths: DI water bath (approximately 56 seconds); 6 MEK baths (approximately 44, 56, 56, 56, and 56 seconds respectively); DI water bath (approximately 56 seconds); one PAA coating solution bath in 1-PrOH solvent (approximately 0.36% by weight, acidified with formic acid to approximately pH 2.0) (approximately 44 seconds); one water / 1-propanol 50% / 50% mixture bath (approximately 56 seconds); 4 DI water baths (each approximately 56 seconds); one PBS bath (approximately 56 seconds); and one DI water bath (approximately 56 seconds).

[0339] Application of cross-linked coating.

[0340] The lens with the PAA base coating prepared above is placed in a polypropylene lens packaging shell (each shell containing one lens) containing 0.6 mL of the modified IPC saline prepared above using PAAm-PAA-F (half of the saline is added before inserting the lens). The blister is then sealed with foil and autoclaved at approximately 121°C for approximately 30 minutes to form a SiHy contact lens with a cross-linked coating (PAA-x-hydrophilic polymer material).

[0341] Confocal laser fluorescence microscope.

[0342] A hydrated SiHy lens (prepared above) with a cross-linked coating was placed between two glass coverslips, and images were collected using a confocal laser fluorescence microscope (model: Zeiss LSM 510 Vis). Scanning was performed from the front curved side of the lens to the bottom curved side, or vice versa. The presence of PAAm-PAA-F was revealed by green fluorescence, and confocal laser fluorescence microscopy images were obtained. Examination of the confocal laser fluorescence images showed that the PAAm-PAA-F-rich layer (i.e., the outer hydrogel layer) was present on both lens surfaces (front and back surfaces) and at the surrounding edges, while PAAm-PAA-F was not observed in the bulk material of the lens.

[0343] The fluorescence intensity curve is examined by traversing the lens cross-section along a line passing through the rear and front surfaces and perpendicular to the rear surface. The thickness of the PAAm-PAA-F rich layer can be estimated from the fluorescence intensity curve traversing the lens. The possible thickness of the outer hydrogel layer (PAAm-PAA-F rich layer) is estimated by the distance from zero intensity across the peak intensity and back to zero intensity. Considering the possible contribution of unknown factors (such as scattering) to the fluorescence intensity, the minimum layer thickness is the thickness that retains at least 10% of the fluorescence intensity at the maximum peak intensity. Based on this estimate, the minimum thickness of the PAAm-PAA-F rich layer (hydrated outer hydrogel layer) can be at least about 5 micrometers.

[0344] Example 27

[0345] Lens formulation D-2 (Example 17) with an added concentration of 1% APMAA monomer was used to manufacture the lens. LS lenses were manufactured by casting the lens formulation obtained above in a reusable mold similar to the molds shown in Figures 1-6 (Figures 1-6) of U.S. Patents 7,384,590 and 7,387,759. The mold included a concave mold half made of glass and a convex mold half made of quartz. The UV irradiation source was a Hamamatsu lamp with an intensity of approximately 4.6 mW / cm² and a 380 nm cutoff filter. The lens formulation in the mold was irradiated with UV irradiation for approximately 30 seconds.

[0346] The molded lens was extracted using methyl ethyl ketone (MEK), rinsed in water, coated with polyacrylic acid (PAA) by immersing the lens in a propanol solution of PAA (0.0044% by weight, acidified with formic acid to about pH 2.5), and hydrated in water.

[0347] IPC saline was prepared using pre-reaction conditions of approximately 60°C for 8 hours according to the composition described in Example 9. The lens was placed in a polypropylene lens packaging shell containing 0.6 mL of IPC saline (half the saline was added before inserting the lens). The blister pack was then sealed with foil and autoclaved at 121°C for 30 min.

[0348] Evaluation of the lens surface showed that none of the tested lenses had any debris adhering to them. 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 rating was "1", and the contact angle was approximately 20°.

[0349] Example 28

[0350] Cast-molded contact lenses (without any coating) prepared from Example 19 were used. All lenses were extracted overnight in MEK to ensure removal of all residual monomers. The first set of lenses (lenses with a hydrated crosslinked coating) was immersed overnight in a PAA coating solution (0.36% by weight PAA in 1-propanol, pH adjusted to 1.7-2.3 using formic acid), while the second set of lenses (control) was immersed in 1-propanol for the same duration. Both sets of lenses were packaged in IPC saline prepared in Example 19 and autoclaved. The autoclaved lenses (in groups of 5) were tested using gravimetric analysis to determine the weight of the dry and wet contact lenses (N=14 for the first set of lenses; N=18 for the second set of lenses). The results are shown in Table 8. Table 8 Wet weight (for 5 lenses) Dry weight (for 5 lenses) Water content % average value Standard deviation average value Standard deviation average value Standard deviation Group 1 0.144 0.001 0.0950 0.001 34.2 0.4 Group 2 0.137 0.001 0.0947 0.002 30.8 0.4

[0351] There was a statistically significant difference (7 mg) in wet weight between the first and second groups of contact lenses. This was due to the presence of a hydrated cross-linked coating in the first group of contact lenses compared to the control lens (uncoated). However, the difference in dry weight between the first and second groups of contact lenses was approximately 0.3 mg and was not statistically significant. Based on the following calculations, the water content of the coated lens was estimated to be approximately 96%. It should be understood that the estimated water content of the cross-linked coating on the contact lenses may not be accurate because the difference in dry or wet weight between the first and second groups of contact lenses is too small and may even be less than the standard deviation.

[0352] Example 29

[0353] This example illustrates how the lubricity of SiHy contact lenses can be quantified using the tilt plate method (“Derby friction test”). The tilt plate method is a simple test setup as shown in Figure 5. The setup for the tilt plate method consists of a plastic reservoir or canister 501 filled with phosphate-buffered saline (PBS, pH approximately 7.3) 502, a borosilicate glass plate 503, and a height-adjustable pad 506 with a height ranging from 5 mm to 20 mm. Both the borosilicate glass plate 503 and the pad 506 are immersed in the phosphate-buffered saline 502 in the plastic reservoir or canister 501. In the test, the contact lens 504 is placed on the borosilicate glass plate and then a stainless steel collar 505 is placed on top (to provide physiologically relevant pressure). The critical coefficient of friction is equal to tan θ, where θ is the critical angle, FN is the normal force, and Ft is the tangential force. The highest angle at which a lens continues to slide after being pushed but stops before reaching the end, or takes more than 10 seconds to reach the end, is defined as the "critical angle θ". The critical coefficient of friction (CCOF) is the tangent of the critical angle θ. A lens that does not move has a CCOF lower than that, while a lens that does not stop during the movement distance has a CCOF higher than that. Angles below or above CCOF are removed by self-analysis. The Derby friction test provides a direct way to measure the kinematic coefficient of friction.

[0354] In the test according to the tilt plate method, all lenses were stored in PBS solution for at least overnight (>6 hours) before the test to remove any residual packaging solution. The glass plates (6'' × 4'' borosilicate glass) were scrubbed and wiped with soap solution (1% Micro-90) and AlphaWipe TX1009. Each plate was thoroughly rinsed in DI water for approximately 2 minutes. The rubbed areas of the test plate were wiped with fingers to ensure all soap solution was removed. Water was wiped off with a paper towel (KimTech Kimwipe No.: 34705) and inspected under light to ensure no foreign particles remained on the glass. The glass plates were placed on pads at different heights in a plastic reservoir or container, and the height of this plane was measured and recorded using a micrometer. The reservoir was filled with phosphate-buffered saline (PBS) to ensure the lenses were completely submerged (28 mm depth).

[0355] Place each lens on the “starting line” and drop a 0.79 g ring (1 / 4” stainless steel for providing physiologically relevant pressure) onto the lens surface. Slide the lens down the plate and record the time taken for the lens to move 96 mm.

[0356] Move the lens to the starting position while removing the weight before retesting. This "preload" effect should be minimized for optimal repeatability. The lens can be tested from multiple angles to obtain the ideal CCOF.

[0357] The CCOF of 16 commercial contact lenses and the polysiloxane hydrogel contact lenses prepared in Example 19 were tested, and the results are reported in Table 9. The results show that the SiHy contact lens of the present invention (prepared in Example 19, having a cross-linked coating) has the lowest CCOF among all commercially available and tested polysiloxane hydrogel lenses, thereby exhibiting the highest lubricity. Table 9 contact lenses SiHy CH (mm) CA (degrees) CCOF Example 19 Y 5.7 2.2 0.038 DAILIES AquaComfortPlus N 6.0 2.3 0.040 1Day Acuvue N 6.5 2.5 0.043 Dailies Aqua N 6.8 2.6 0.045 1-Day Acuvue TruEye (narafilcon B) Y 7.2 2.8 0.048 SofLens Daily Disposable N 7.6 2.9 0.051 1-Day Acuvue Moist N 7.7 3.0 0.052 Proclear 1-Day N 8.3 3.2 0.056 1-Day Acuvue TruEye (narafilcon A) Y 8.8 3.4 0.059 Clariti 1-Day Y 9.2 3.5 0.062 Acuvue Moist Y 7.7 2.9 0.051 Air Optix Aqua Y 8.1 3.1 0.054 Biofinity Y 8.1 3.1 0.054 PureVision Y 9.4 3.6 0.063 Acuvue Advance Y 9.7 3.7 0.065 Acuvue Oasys Y 9.9 3.6 0.066 Clariti Y 12.5 4.8 0.084 CH: Critical Height; CA: Critical Angle

[0358] Example 30

[0359] This example illustrates how to characterize the negatively charged surface of a SiHy contact lens based on a positively charged particle adhesion test.

[0360] The surface charge of a lens can be detected indirectly through its interaction with charged particles or beads. Negatively charged surfaces attract positively charged particles. Surfaces without negative charge or substantially without negative charge will not attract positively charged particles or will attract very few positively charged particles.

[0361] The following tests were conducted on uncoated SiHy contact lenses (i.e., cast and molded as described in Example 19 and extracted using MEK), PAA-coated SiHy contact lenses (as prepared in Example 19), and SiHy contact lenses with a crosslinked coating (as prepared in Examples 14 and 19). The PAA coating of the PAA-coated contact lens had a surface concentration of approximately 62.5% by weight of carboxylic acid groups (where MCOOH is the mass of carboxylic acid groups and MAA is the mass of acrylic acid). The crosslinked coating of the contact lens in Example 14 theoretically contained no carboxylic acid groups, while the crosslinked coating of the contact lens in Example 19 may contain a low surface concentration of carboxylic acid groups (which must be less than [amount] by weight). The lens was immersed in a dispersion containing positively charged particles, and after appropriate rinsing, the number of particles adhering to the lens was visually assessed and estimated or counted.

[0362] Purchase DOWEXTM 1×4 20-50 mesh resin from Sigma-Aldrich and use it as received. DOWEXTM 1×4 20-50 mesh resin is a spherical, type I strong base anion exchange resin containing N+(CH3)3Cl- functional groups and 4% divinylbenzene, a styrene / divinylbenzene copolymer. Disperse 5% of the 1×4 20-50 mesh resin in PBS and mix thoroughly by stirring or vortexing at approximately 1000 rpm for 10 seconds. Immerse the lens in this dispersion and vortex at 1000-1100 rpm for 1 min, then rinse with DI water and vortex for 1 min. Then, place the lens in water in a glass culture dish and acquire an image of the lens using bottom illumination with a Nikon optical microscope. As shown in Figure 6, almost the entire surface of the PAA-coated lens is covered with adhered positively charged particles (Figure 6a), while a total of approximately 50 positively charged particles adhere to the lens with the cross-linked coating prepared in Example 19 (Figure 6B), and no positively charged particles adhere to the lens with the cross-linked coating prepared in Example 14 (Figure 6C). Some loosely adhered particles may detach from the lens surface and may also be found in the water surrounding the lens.

[0363] It should be understood that the number of particles adhering to the lens can be reduced when using positively charged particles with larger sizes (i.e., DOWEXTM monosphere ion exchange resin, cross-linked polystyrene beads, chloride form, approximately 590 micrometers in size, from Sigma-Aldrich) in the test. Approximately 30% of these DOWEX monosphere resins were dispersed in PBS. The lenses were immersed in this dispersion for approximately 1 min, followed by rinsing with DI water. The lenses were then placed in water in glass culture dishes, and images of the lenses were acquired using a Nikon optical microscope with bottom illumination. Many particles (approximately 200 particles) were found to adhere to PAA-coated lenses, and no particles adhered to lenses with cross-linked coatings. Several commercially available contact lenses were also tested. No particles were observed on the following lenses: Acuvue® TruEye™, Acuvue® Advance®, Acuvue® Oasys®, Avaira™, Biofinity®, Air Optix®, and Focus® Night & Day®. Particles were observed on the following four types of lenses (in order of increasing particle count): PureVision®, 1 Day Acuvue® Moist®, Proclear 1 day, and Acuvue® (Etafilcon A) lenses. The almost entire surface of the Acuvue® (Etafilcon A) lens was covered with adhered positively charged particles.

[0364] Negatively charged resin (Amberlite CG50) was purchased from Sigma and used as received. 5% of these Amberlite CG50 beads were dispersed in PBS and vortexed at approximately 1000 rpm for 10 seconds. PAA-coated lenses were immersed in this dispersion and vortexed at 1000-1100 rpm for 1 min, followed by rinsing with DI water and vortexing for 1 min. The lenses were then placed in water in a glass culture dish, and images of the lenses were acquired using a Nikon optical microscope with bottom illumination. No Amberlite particles (negatively charged) were found on the PAA-coated lenses.

[0365] Negatively charged beads (Amberlite CG50) coated with polyethyleneimine (PEI, a positively charged electrolyte) were used in this experiment. The PEI coating procedure was performed as follows. The PEI (Lupasol SK, 24%, in water, Mw approximately 2,000,000) was purchased from BASF and used as received. An aqueous dispersion of 1% Amberlite particles and 5% PEI was prepared. The pH was adjusted to 7 and the solution was thoroughly mixed (e.g., by stirring for 30 min). The dispersion was then suspended in a large volume of water 2 to 3 times and filtered 2 to 3 times, and the particles (PEI-coated Amberlite) were collected. 5% of these PEI-coated Amberlite CG50 beads were dispersed in PBS and vortexed at approximately 1000 rpm for 10 seconds. Lenses were immersed in this dispersion and vortexed at 1000-1100 rpm for 1 min, followed by rinsing with DI water and vortexing for 1 min. The lens was then placed in water in a glass culture dish, and an image of the lens was acquired using bottom illumination with a Nikon optical microscope. It was observed that a large number of PEI-coated Amberlite particles (positively charged particles due to the presence of PEI) adhered to the PAA-coated lens (Example 19). However, no PEI-coated Amberlite particles actually adhered to the uncoated SiHy contact lens (Example 19), the SiHy contact lens with a cross-linked coating (Example 19), or the PAExPAA-coated lens (Example 4).

[0366] Example 31

[0367] Sample preparation:

[0368] AFM studies were performed on SiHy contact lenses (prepared in Example 19) in both hydrated and dry states. The lenses were removed from blister packs (sealed and autoclaved) and cut in cross-section (e.g., using a razor). The cross-sectional slice of the lens was vertically mounted in metal clamps, as shown in Figure 7. The smaller slice of the lens was positioned above the holder to allow the AFM tip (above the lens cross-section in Figure 7) to scan it.

[0369] AFM Experiment:

[0370] Two separate AFM instruments were used to characterize the lens cross-section. In both cases (except for dry samples), AFM scans were performed in phosphate buffer solution (PBS with or without NaCl but with substantially the same permeability as physiological saline) to maintain the hydrogel samples in a fully hydrated state.

[0371] The first AFM instrument is the Veeco BioScope AFM with a Nanoscope IV controller. Data is collected using a triangular silicon cantilever with a spring constant of 0.58 N / m and a nominal tip curvature radius of 20-60 nm. Scans are performed in constant contact (force-volume) mode using a probe rate of 30 μm / s and a force-volume scan rate of 0.19 Hz. Topological and force-volume data are collected simultaneously. Each force curve consists of approximately 30 data points. During AFM scanning, the lens is completely immersed in PBS. A maximum scan size of 20 μm is typically used to achieve sufficiently high resolution for force-volume imaging. For each image, a 128x128 pixel force curve is collected over approximately 3 hours.

[0372] An AFM image of a cross-section of a fully hydrated SiHy contact lens (Example 19) with a cross-linked coating, obtained by a force-volume method, is shown in Figure 8. In this image, the darker colored area 420 represents the coating and the lighter colored area 410 represents the bulk material of the lens. The average thickness of the cross-linked coating (i.e., the front outer layer and the back outer layer) of the SiHy contact lens (Example 19) was measured to be approximately 5.9 µm (standard deviation of 0.8 µm), as obtained from seven images of four lenses.

[0373] AFM technology enables the determination of the surface modulus (surface softness) at a specific location on the cross-section of a lens. Figure 9 shows the cross-sectional surface modulus curve of a fully hydrated SiHy contact lens with a cross-linked coating (prepared in Example 19). Since the surface modulus of a material is proportional to the cantilever deflection, the cross-sectional surface modulus curve of a contact lens can be approximated by plotting the cantilever deflection value (as a measure of the surface modulus of the material at a specific location on the lens cross-section) as a function of the distance from the side surface of the cross-section (front or back surface) along two lines across the cross-section as shown in Figure 8. As shown in Figure 9, the cross-linked coating (the front and back outer layers of the contact lens in Example 19) is softer than the bulk polysilicon-oxygen hydrogel lens material (inner layer). As the lens moves along the two lines, the surface modulus initially remains almost constant in the region between 0 and approximately 5.9 micrometers, with an average cantilever deflection of approximately 52 nm (i.e., the average surface modulus). It then gradually increases further into the lens until reaching a maximum, and then remains substantially constant (a plateau) in a region greater than approximately 7 micrometers, with an average cantilever deflection of approximately 91 (i.e., the average surface modulus). The gradual transition from the softer, cross-linked coating to the harder bulk SiHy material over a span of several micrometers suggests a possible gradient in morphology or composition (water content) between the coating surface and the lens body. The surface modulus in the region between 5.9 micrometers and approximately 7 micrometers (i.e., the region around the boundary between the outer hydrogel layer and the inner layer of the polysiloxane hydrogel material) is not used to calculate the average surface modulus. It can be calculated that the front and back outer hydrogel layers (with cross-linked coating) of the SiHy contact lens (Example 19) have a reduced surface modulus of approximately 43% (wherein is the average surface modulus of the back or front hydrogel layer and the average surface modulus of the inner layer).

[0374] The SiHy contact lens (prepared in Example 19) was studied using a second AFM instrument. Scans were performed using a Bruker Icon AFM in Quantitative Nanomechanical Measurements (PeakForce QNM) mode with the lens in either fully hydrated (PBS, NaCl-free but with glycerol for similar permeability) or dry state. The lens cross-section was mounted in the aforementioned metal clamp. Test conditions included: a spring constant of 1.3 N / m, a tip radius of 33.3 nm, a sensitivity of 31 nm / V, a scan rate of 0.4 Hz, and a scan resolution of 512 × 512.

[0375] AFM images of the cross-sections of the fully hydrated and dry SiHy contact lenses (Example 19) were obtained using the PeakForce QNM method. Analysis of the obtained images showed that the thickness of the cross-linked coating in the fully hydrated state was approximately 4.4 micrometers, while the thickness of the cross-linked coating in the dry state was approximately 1.2 micrometers (for the vacuum-dried sample) and approximately 1.6 micrometers (for the oven-dried sample). The water expansion rate of the cross-linked coating of the SiHy contact lens (prepared in Example 19), where L represents the average thickness of the outer hydrogel layer of the fully hydrated SiHy contact lens and L represents the average thickness of the outer hydrogel layer of the dry SiHy contact lens, was calculated to be approximately 277% (oven-dried sample) or approximately 369% (vacuum-dried sample).

[0376] Example 32

[0377] Preparation of lens fitting materials

[0378] Formulation I was prepared by dissolving each component in 1-propanol to have the following composition: 33% by weight of the CE-PDMS macromonomer prepared in Example 2, 17% by weight of N-[tris(trimethylsiloxy)-methoxypropyl]acrylamide (TRIS-Am), 24% by weight of N,N-dimethylacrylamide (DMA), 0.5% by weight of N-(carbonyl-methoxy polyethylene glycol-2000)-1,2-distearate-sn-glycerol-3-phosphate ethanolamine (sodium salt) (L-PEG), 1.0% by weight of Darocur 1173 (DC1173), 0.1% by weight of visitint (a 5% copper phthalocyanine blue pigment dispersion in tris(trimethylsiloxy)methoxypropyl methacrylate (TRIS)), and 24.5% by weight of 1-propanol.

[0379] Formulation II was prepared by dissolving each component in 1-propanol to have the following composition: about 32% by weight of the CE-PDMS macromonomer prepared in Example 2, about 21% by weight of TRIS-Am, about 23% by weight of DMA, about 0.6% by weight of L-PEG, about 1% by weight of DC1173, about 0.1% by weight of visitint (5% copper phthalocyanine blue pigment dispersion in TRIS), about 0.8% by weight of DMPC, about 200 ppm of H-tempo, and about 22% by weight of 1-propanol.

[0380] Lens Manufacturing

[0381] A lens is manufactured by casting the lens preparation obtained above in a reusable mold (a quartz concave mold half and a glass convex mold half), the reusable mold being similar to the molds shown in Figures 1-6 of U.S. Patents 7,384,590 and 7,387,759. The UV irradiation source is a Hamamatsu lamp with an intensity of approximately 4 mW / cm² and a WG335+TM297 cutoff filter. The lens preparation in the mold is irradiated with UV irradiation for approximately 25 seconds. The cast-molded lens is extracted using methyl ethyl ketone (MEK) (or propanol or isopropanol).

[0382] Applying a PAA undercoat to the SiHy contact lens

[0383] A polyacrylic acid coating solution (PAA-1) was prepared by dissolving a certain amount of PAA (MW: 450 kDa, from Lubrizol) in a given volume of 1-propanol to a concentration of about 0.36% by weight, and the pH was adjusted to about 2.0 using formic acid.

[0384] 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 / H2O) to a concentration of about 0.39% by weight, and the pH was adjusted to about 2.0 using formic acid.

[0385] The SiHy contact lens obtained above is subjected to one of the immersion processes shown in Tables 10 and 11. Table 10 bath time Soaking process 20-0 20-1 20-2 20-3 20-4 20-5 1 56s H2O H2O H2O H2O H2O H2O 2 44s MEK MEK MEK MEK MEK MEK 3 56s MEK MEK MEK MEK MEK MEK 4 56s MEK MEK MEK MEK MEK MEK 5 56s MEK MEK MEK MEK MEK MEK 6 56s MEK MEK MEK MEK MEK MEK 7 56s MEK MEK MEK MEK MEK MEK 8 56s H2O H2O H2O H2O H2O H2O 9 44s PAA-1 PAA-1 PAA-1 PAA-2 PAA-2 PAA-1 10 56s PAA-1 PAA-1 PAA-1 PAA-2 PAA-2 PAA-1 11 56s H2O PrOH H2O H2O H2O H2O 12 44s H2O PrOH PrOH PrOH 50 / 50 50 / 50 13 56s H2O H2O H2O H2O H2O H2O 14 56s H2O H2O H2O H2O H2O H2O 15 56s PBS PBS PBS PBS PBS PBS 16 56s H2O H2O H2O H2O H2O H2O PrOH represents 100% 1-propanol; PBS represents phosphate-buffered saline solution; MEK represents methyl ethyl ketone; 50 / 50 represents a 50 / 50 solvent mixture of 1-PrOH / H2O. Table 11 bath time Soaking process 80-0 80-1 80-2 80-3 80-4 80-5 80-6 1 56s H2O H2O H2O H2O H2O H2O H2O 2 44s MEK MEK MEK MEK MEK MEK MEK 3 56s MEK MEK MEK MEK MEK MEK MEK 4 56s MEK MEK MEK MEK MEK MEK MEK 5 56s MEK MEK MEK MEK MEK MEK MEK 6 56s MEK MEK MEK MEK MEK MEK MEK 7 56s MEK MEK MEK MEK MEK MEK MEK 8 56s H2O H2O H2O H2O H2O H2O H2O 9 44s PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 10 56s PAA-1 50 / 50 PrOH 50 / 50 PrOH PrOH H2O 11 56s H2O H2O H2O 50 / 50 PrOH 50 / 50 50 / 50 12 44s H2O H2O H2O H2O H2O H2O H2O 13 56s H2O H2O H2O H2O H2O H2O H2O 14 56s H2O H2O H2O H2O H2O H2O H2O 15 56s PBS PBS PBS PBS PBS PBS PBS 16 56s H2O H2O H2O H2O H2O H2O H2O PrOH represents 100% 1-propanol; PBS represents phosphate-buffered saline; MEK represents methyl ethyl ketone; 50 / 50 represents a 50 / 50 solvent mixture of 1-PrOH / H2O.

[0386] Application of cross-linked hydrophilic coating

[0387] Purchased sodium poly(acrylamide-co-acrylic acid) and poly(AAm-co-AA)(90 / 10) (approximately 90% solids content, Mw 200,000) from Polysciences and used as received. Purchased PAE (Kymene, with NMR analysis showing a nitrogen-containing butyronium content of 0.46) in aqueous solution from Ashland and used as received. An in-package crosslinking (IPC) brine was prepared by dissolving approximately 0.07% w / w poly(AAm-co-AA) (90 / 10) and approximately 0.15% PAE (approximately 8.8 mmol initial aziridine millimole equivalents) in phosphate-buffered saline (PBS) (approximately 0.044 w / w% NaH2PO4·H2O, approximately 0.388 w / w% Na2HPO4·2H2O, and approximately 0.79 w / w% NaCl) and adjusting the pH to 7.2 to 7.4. The IPC brine was then heat-pretreated at approximately 70°C for approximately 4 hours (heat pretreatment). During this heat pretreatment, the poly(AAm-co-AA) and PAE partially crosslinked with each other (i.e., without consuming all the aziridine groups of the PAE) to form a water-soluble and thermally crosslinkable hydrophilic polymer containing aziridine groups within the branched polymer network of the IPC brine. After heat pretreatment, the IPC brine was filtered using a 0.22-micron polyether slag (PES) membrane filter and cooled to room temperature. Then, 10 ppm hydrogen peroxide was added to the final IPC brine to prevent bioburden growth, and the IPC brine was filtered again using a 0.22-micron PES membrane filter.

[0388] The lens with the PAA undercoat prepared above is placed in a polypropylene lens packaging shell (each shell contains one lens) containing 0.6 mL of IPC saline (half of the saline is added before inserting the lens). The blister is then sealed with foil and autoclaved at about 121°C for about 30 minutes to form a SiHy contact lens with a cross-linked hydrophilic coating.

[0389] Characteristics of SiHy lenses.

[0390] The SiHy contact lens having a cross-linked hydrophilic coating and a center thickness of about 0.95 micrometers has the following characteristics: oxygen permeability (Dkc or estimated intrinsic Dk) of about 142 barrer to about 150 barrer, bulk modulus of elasticity of about 0.72 MPa to about 0.79 MPa, water content of about 30% to about 33% by weight, relative ion permeability of about 6 (relative to Alsacon lenses), and contact angle of about 34 degrees to about 47 degrees.

[0391] Characterization of Nanotextile Surfaces of Contact Lenses

[0392] Transmission Differential Interference Contrast (TDIC) Method. A contact lens is placed on a glass slide and flattened by pressing the lens between the slide and a coverslip. The contact lens surface is positioned and examined by focusing through the lens using a Nikon ME600 microscope equipped with transmission differential interference contrast optics at 40x objective. The obtained TDIC image is then evaluated to determine the presence of wrinkled surface patterns (e.g., random and / or ordered worm-like patterns, or the like).

[0393] Reflective Differential Interference Contrast (RDIC) Method. The lens is placed on a glass slide and flattened by making four radial cuts approximately every 90 degrees. Excess saline solution is blown off the surface using compressed air. The lens surface is then examined using 10x, 20x, and 50x objectives with a Nikon Optiphot-2 equipped with reflective differential interference contrast optics to determine the presence of a wrinkled surface pattern on the contact lens surface. Representative images of each side are obtained using the 50x objective. The contact lens is then inverted, excess saline solution is removed, and the other side of the contact lens is examined in the same manner. The obtained RDIC images are then evaluated to determine the presence of a wrinkled surface pattern (e.g., random and / or ordered worm-like patterns, or the like).

[0394] Dark-field microscopy (DFLM). DFLM is typically based on dark-field illumination, a method to enhance the contrast ratio of observed specimens. This technique consists of a light source located outside or blocking the observer's field of view, illuminating the specimen at an angle relative to the perpendicular transmitted light. Because the unscattered light from the light source is not focused by the objective lens, it is not part of the image, and the image background appears darker. Since the light source is illuminating the specimen at an angle, the light observed in the specimen image is the light scattered from the specimen toward the observer, and a contrast ratio is then created between this scattered light from the specimen and the dark background of the image. This contrast ratio mechanism makes dark illumination particularly useful for observing scattering phenomena such as turbidity.

[0395] The haze of contact lenses was evaluated using DFLM as described below. It is believed that dark-field data can provide a worst-case estimate of haze because dark-field setups involve scattered light. In an 8-bit grayscale digital image, a grayscale intensity (GSI) value ranging from 0 to 255 was assigned to each image pixel. Zero represents a pixel that is completely black, and 255 represents a pixel that is completely white. Increasing the amount of scattered light captured in the image will produce 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 dark-field image. Haze is represented by calculating the average GSI value of all pixels in the target area (AOI) (e.g., the entire lens or the lens area or optical area of ​​the lens). The experimental setup consisted of a microscope or equivalent optical components, an attached digital camera, and a dark-field support with a ring light and variable intensity light source. The optical components were designed / arranged to fill the field of view (typically approximately 15 mm × 20 mm) with the entire contact lens to be observed. The illumination is set to a value suitable for observing the desired changes in the relevant samples. The light intensity of each set of samples is adjusted / calibrated to the same value using density / light scattering standards known to those skilled in this technique. For example, the standard consists of two overlapping plastic coverslips (identical and lightly or moderately frosted). The standard comprises three regions with different average GSIs, including two regions with intermediate gray levels and saturated white (edges). The black region represents the empty dark field. The black and saturated white regions can be used to verify the camera's gain and offset (contrast ratio and brightness) settings. The intermediate gray levels provide three points to verify the camera's linear response. The light intensity is adjusted so that the average GSI of the empty dark field is close to 0, and the average GSI of the defined AOI in the digital image of the standard is the same each time, within ±5 GSI units. After calibrating the light intensity, the contact lens is immersed in 0.2 µm filtered phosphate-buffered saline in a quartz petri dish or a dish with similar clarity, which is placed on a DFLM support. Then, an 8-bit grayscale digital image of the lens was obtained when viewed under calibrated illumination, and the average GSI of the AOI (Area of ​​Interest) defined within the image containing the lens was measured. This process was repeated for the contact lens sample group. The light intensity calibration was periodically reassessed during the testing process to ensure consistency. The haze value under the DFLM test refers to the DFLM haze.

[0396] The PAA undercoat of the SiHy contact lens, obtained according to either immersion process 20-0 or 80-0, was measured to have an average DFLM haze of approximately 73%, and exhibited a wrinkled surface pattern (random worm-like pattern) that could be visually observed by examining the hydration state of the contact lens using either the aforementioned RDIC or TDIC method. However, the wrinkled surface pattern did not actually have an adverse effect on the light transmittance of the contact lens.

[0397] The SiHy contact lens, the PAA undercoat obtained according to any one of the soaking processes 20-1 to 20-4, was measured to have a lower average DFLM haze of about 26% (possibly due to the presence of visitint pigment particles), and showed that no wrinkled surface pattern (random worm-like pattern) was observed when tested under any of the above RDIC or TDIC.

[0398] High-percentage SiHy contact lenses, with PAA undercoat obtained according to any immersion process 20-5, were measured to have a moderate average DFLM haze of approximately 45%, and showed a slightly observable wrinkled surface pattern when tested under any of the aforementioned RDIC or TDIC conditions. However, the wrinkled surface pattern actually has no adverse effect on the light transmittance of the contact lens.

[0399] The PAA undercoat of SiHy contact lenses obtained according to any one of the soaking processes 80-1, 80-2, 80-3, 80-5, and 80-6 does not show an observable wrinkled surface pattern when tested under any of the aforementioned RDIC or TDIC conditions. However, the PAA undercoat of SiHy contact lenses obtained according to any one of the soaking processes 80-0 and 80-4 shows an observable wrinkled surface pattern when tested under any of the aforementioned RDIC or TDIC conditions. However, the wrinkled surface pattern does not actually have an adverse effect on the light transmittance of the contact lens.

[0400] Example 33

[0401] Synthesis of UV-absorbing amphiphilic branched copolymers

[0402] The 1-L jacketed reactor was equipped with a 500-mL feed funnel, a top stirrer, a reflux condenser with a nitrogen / vacuum inlet adapter, a thermometer, and a sampling adapter. 89.95 g of 80% partially olefinically functionalized polysiloxane (A) prepared in Example 17 was charged into the reactor and then degassed at a vacuum of less than 1 mbar and room temperature 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 into the 500-mL feed funnel, then degassed at a vacuum of 100 mbar and room temperature for 10 minutes and then refilled with nitrogen. The monomer solution was degassed again under the same conditions for two cycles. The monomer solution was then charged into the reactor. The reaction mixture was heated to 67°C with appropriate stirring. While heating, a solution consisting of 2.96 g mercaptoethanol (chain transfer agent, CTA), 0.72 g dimethyl 2,2'-azobis(2-methylpropionic acid) ester (V-601-initiator), and 76.90 g ethyl acetate was loaded into a feeding funnel, followed by the same degassing process 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 copolymerization was complete, the reactor temperature was cooled to room temperature.

[0403] Synthesis of UV-absorbing amphiphilic branched prepolymers

[0404] An amphiphilic branched prepolymer was formed by olefinic functionalization of the copolymer solution prepared above by adding 8.44 g of IEM (or a desired molar equivalent of ethyl 2-isocyanate methacrylate) in the presence of 0.50 g DBTDL. The mixture was stirred at room temperature and under sealed conditions for 24 hours. The prepared prepolymer was then stabilized with 100 ppm hydroxy-tetramethylene piperine oxyhydroxide, and the solution was concentrated to 200 g (approximately 50%) and filtered through 1 μm filter paper. After the reaction solvent was replaced with 1-propanol by repeated cycles of evaporation and dilution, the solution was prepared for formulation. The solids content was measured by removing the solvent in a vacuum oven at 80 °C.

[0405] Preparation of lens fitting materials

[0406] Preparation of a lens formulation having the following composition: 71 wt% of the prepolymer prepared above; 4 wt% of DMA; 1 wt% of TPO; 1 wt% of DMPC; 1 wt% of Brij 52 (from Sigma-Aldrich); and 22 wt% of 1-PrOH.

[0407] Lens Manufacturing

[0408] A lens is manufactured by casting a reusable mold from the lens preparation obtained above under the spatial constraints of UV irradiation. This reusable mold is similar to the molds shown in Figures 1-6 of U.S. Patents 7,384,590 and 7,387,759. The mold includes a concave mold half made of glass and a convex mold half made of quartz. The UV irradiation source is a Hamamatsu lamp with an intensity of approximately 4.6 mW / cm² and a 380 nm cutoff filter. The lens preparation in the mold is irradiated with UV light for approximately 30 seconds.

[0409] The molded lens was extracted using methyl ethyl ketone (MEK), rinsed in water, coated with polyacrylic acid (PAA) by immersing the lens in a propanol solution of PAA (0.004% by weight, acidified with formic acid to approximately pH 2.0), and hydrated in water.

[0410] IPC brine was prepared from a composition containing approximately 0.07% PAAm-PAA and PAE (approximately 0.15% PAE) sufficient to provide an initial nitrogen-containing heterocyclic butylene content of approximately 8.8 mmol / L under pre-reaction conditions of approximately 60°C for 6 hours. 5 ppm hydrogen peroxide was then added to the IPC brine to prevent bioburden growth, and the IPC brine was filtered using a 0.22 μm polyether ether (PES) membrane filter. Lenses were placed in polypropylene lens packaging shells containing 0.6 mL of IPC brine (half the brine was added before lens insertion). The blister packs were then sealed with foil and autoclaved at 121°C for 30 min.

[0411] Lens Characterization

[0412] The obtained lens has the following properties: E' is approximately 0.82 MPa; DKc is approximately 159.4 (using Lotrafilcon B as a reference lens, with an average center thickness of 80 µm and an intrinsic Dk of 110); IP is approximately 2.3; water% is approximately 26.9%; and UVA / UVB%T is approximately 4.6 / 0.1. No crack lines were observed after wiping the test lens under a dark-field microscope. The lens was extremely smooth during finger-wiping tests, comparable to the control lens. [Simplified Explanation of the Diagram]

[0011] Figure 1 schematically illustrates a cross-sectional view of the structural configuration of a SiHy contact lens in a preferred embodiment of the present invention. Figure 2 schematically illustrates a cross-sectional view of the structural configuration of a SiHy contact lens in another preferred embodiment of the present invention. Figure 3 shows the fluorescence intensity curve across a cross section of a SiHy contact lens during confocal laser fluorescence microscopy. Figure 4 shows a SEM (scanning electron microscope) image of a freeze-dried SiHy contact lens of the present invention. Figure 5 schematically illustrates the setup of a tilting plate method in a preferred embodiment. Figure 6 shows an optical microscopic image of a contact lens with different coatings after immersion in a dispersion of positively charged particles (DOWEXTM 1x4 20-50 mesh resin). Figure 7 schematically illustrates how a cross-sectional slice of the SiHy contact lens of the present invention for AFM testing is vertically mounted in a metal clamp. Figure 8 shows an AFM (atomic force microscope) image of a cross-sectional portion of a fully hydrated SiHy contact lens (in phosphate buffered saline, pH approximately 7.3) according to a preferred embodiment of the present invention. Figure 9 shows the cross-sectional surface modulus curve of the SiHy contact lens of the present invention in a fully hydrated state (in phosphate buffered saline, pH of about 7.3) according to a preferred embodiment of the present invention. It is obtained by the two shortest lines between the front and rear surfaces of the cross-sectional surface of the SiHy contact lens, which is approximately represented by a curve of cantilever deflection as a function of distance.

Claims

1. A hydrated polysiloxane hydrogel contact lens, comprising: a front surface and an opposing rear surface; a layered structural configuration from the front surface to the rear surface, wherein the layered structural configuration includes a front outer hydrogel layer having a first water content, an inner layer having a second water content, and a rear outer hydrogel layer having a third water content; a water content gradient from the inner layer to the front outer hydrogel layer or the rear outer hydrogel layer in the structural configuration, wherein the first and third water contents are higher than the second water content; a surface wettability characterized by an average water contact angle of 80 degrees or less; and a water content of 10% to 70% by weight; an elastic modulus of 0.3 MPa to 1.8 MPa; wherein the hydrated polysiloxane contact lens, after being immersed in a Sudan Black dye solution and then thoroughly rinsed in water, has no staining spots on it. The inner layer is the bulk material of the hydrated polysiloxane contact lens and is composed of polysiloxane hydrogel material, which is obtained by polymerizing a polysiloxane hydrogel lens formulation containing reactive vinyl monomers having carboxyl, primary amine and / or secondary amine groups; each of the front outer hydrogel layer and the rear outer hydrogel layer is composed of a cross-linked polymer material, which contains polymer chains derived from a copolymer, the copolymer being a polymer product comprising: (i) at least 60% by weight or less of a reactive vinyl monomer having carboxyl, primary amine and / or secondary amine groups, and (ii) at least one vinyl monomer containing phosphocholine.

2. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the hydrated polysiloxane hydrogel contact lens has a water breakup time of at least 10 seconds.

3. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the at least one reactive vinyl monomer is selected from the group consisting of: (meth)acrylate amino-C1-C6 alkyl ester, (meth)acrylate C1-C6 alkylamino-C1-C6 alkyl ester, allylamine, vinylamine, amino-C1-C6 alkyl(meth)acrylamide, C1-C6 alkylamino-C1-C6 alkyl(meth)acrylamide, acrylic acid, C1-C4 alkyl acrylic acid, N,N-2-acrylamide glycolic acid, β-methacrylic acid, α-phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenylbutadiene-1,3, itaconic acid, citraconic acid, mesocarboxylic acid, pentenediaic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof.

4. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the at least one reactive vinyl monomer is selected from the group consisting of: (meth)acrylic acid, C2-C4 alkylacrylic acid, vinylamine, allylamine, (meth)acrylic acid amino-C2-C4 alkyl ester, and combinations thereof.

5. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the at least one ethylene monomer containing phosphocholine comprises (meth)acryloxyethyl phosphocholine.

6. The hydrated polysiloxane hydrogel contact lens of claim 2, wherein the at least one ethylene monomer containing phosphocholine comprises (meth)acryloxyethyl phosphocholine.

7. The hydrated polysiloxane hydrogel contact lens of claim 5, wherein the hydrated polysiloxane contact lens has an oxygen permeability of at least 60 barrer / mm.

8. The hydrated polysiloxane hydrogel contact lens of claim 5, wherein the hydrated polysiloxane contact lens has an oxygen permeability of at least 80 barrer / mm.

9. The hydrated polysiloxane hydrogel contact lens of claim 5, wherein the hydrated polysiloxane contact lens has an oxygen permeability of at least 100 barrer / mm.

10. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the cross-linked polymer material of each of the front outer hydrogel layer and the rear outer hydrogel layer further comprises polymer chains of polyamine or polyamide derived from epichlorohydrin-functionalized polyamine or polyamide.

11. A hydrated polysiloxane hydrogel contact lens as claimed in any of claims 1 to 10, wherein the polysiloxane hydrogel material comprises repeating units derived from polysiloxane-containing monomers from the group consisting of: N-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide, N-[tris(dimethylpropylsiloxy)silylpropyl](meth)acrylamide, N-[tris(dimethylphenyl ... [2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propoxy)propyl]-2-methylpropenylamine, N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propoxy)propyl)propyl)propenylamine, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propoxy)propyl]-2-methylpropenylamine, N,N-bis[2 -hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propoxy)propyl]acrylamide, N-(2-hydroxy-3-(3-(tri(trimethylsilyloxy)silyl)propoxy)propyl)-2-methylacrylamide, N-(2-hydroxy-3-(3-(tri(trimethylsilyloxy)silyl)propoxy)propyl)acrylamide, N,N-bis[2-hydroxy-3-(3-(tri(trimethylsilyloxy)silyl)propoxy)propyl]-2-methyl Acrylamide, N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propoxy)propyl]acrylamide, N-[2-hydroxy-3-(3-(tert-butyldimethylsilyl)propoxy)propyl]-2-methylacrylamide, N-[2-hydroxy-3-(3-(tert-butyldimethylsilyl)propoxy)propyl]acrylamide, N,N-bis[2-hydroxy-3-(3-(tert-butyldimethylsilyl)propoxy)propyl]-2-methylacrylamide;N,N-bis[2-hydroxy-3-(3-(tert-butyldimethylsilyl)propoxy)propyl]acrylamide, 3-methacryloxypropylpentamethyldisiloxane, tris(trimethylsilyloxy)methacrylate (TRIS), (3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxane), (3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxane), 3-methacryloxy-2-(2-hydroxyethoxy)propoxy)propylbis(trimethylsiloxane), N-2-methacryloxyethyl-O-(methyl) bis-trimethylsilyloxy-3-propyl)methoxyalkylaminocarbamate, 3-(trimethylsilyl)propyl vinyl carbonate, 3-(vinyloxycarbonylthio)propyl-tris(trimethylsilyloxy)silane, 3-[tris(trimethylsilyloxy)silyl]propyl vinyl aminocarbamate, 3-[tris(trimethylsilyloxy)silyl]propyl allyl aminocarbamate, 3-[tris(trimethylsilyloxy)silyl]propyl vinyl carbonate, tributyldimethyl-silyloxyethyl vinyl carbonate, trimethylsilyl ethyl vinyl carbonate, and trimethylsilyl methyl vinyl carbonate, and combinations thereof.

12. The hydrated polysiloxane hydrogel contact lens of claim 11, wherein the polysiloxane hydrogel material further comprises repeating units derived from polysiloxane ethylene type monomers.

13. The hydrated polysiloxane hydrogel contact lens of claim 12, wherein the polysiloxane hydrogel material comprises repeating units derived from hydrophilic vinyl monomers of the group consisting of: N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, 2-acrylaminoglycolic acid, 3-acrylamino-1-propanol, N-hydroxyethylacrylamide, N-[tri(hydroxymethyl)methyl]acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, trimethylammonium methacrylate 2-hydroxypropyl methacrylate hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate, glyceryl methacrylate, allyl alcohol, C1-C4-alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 1500, methacrylic acid, N-methyl-3-aminopropyl methacrylate, etc. Methyl-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, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3 -Methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, N-vinyl-2-pyrrolidone, vinylpyridine, N-vinylmethoxyamine, N-vinylacetamide, N-vinylisopropylamine, N-vinyl-N-methylacetamide, N-vinylcaprolactam and mixtures thereof.

14. The hydrated polysiloxane hydrogel contact lens of claim 11, wherein the polysiloxane hydrogel material comprises repeating units derived from hydrophilic vinyl monomers of the group consisting of: N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, 2-acrylaminoglycolic acid, 3-acrylamino-1-propanol, N-hydroxyethylacrylamide, N-[tri(hydroxymethyl)methyl]acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, trimethylammonium methacrylate 2-hydroxypropyl methacrylate hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate, glyceryl methacrylate, allyl alcohol, C1-C4-alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 1500, methacrylic acid, N-methyl-3-aminopropyl methacrylate, etc. Methyl-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, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3 -Methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, N-vinyl-2-pyrrolidone, vinylpyridine, N-vinylmethoxyamine, N-vinylacetamide, N-vinylisopropylamine, N-vinyl-N-methylacetamide, N-vinylcaprolactam and mixtures thereof.

15. The hydrated polysiloxane hydrogel contact lens of claim 11, wherein the polysiloxane hydrogel material further comprises repeating units derived from a crosslinking agent belonging to the group consisting of: tetraethylene glycol diacrylate, triethylene glycol diacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, tetraethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylpropane trimethacrylate, isopentetrate tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethacrylate, ethylenediamine dimethacrylate, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1,3 -bis(methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane, N,N'-methylenebisacrylamide, N,N'-methylenebisacrylamide, N,N'-ethylbisacrylamide, N,N'-ethylbisacrylamide, 1,3-bis(N-methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane Disiloxane, 1,3-bis(methacrylaminobutyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(acrylaminopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(methacryloxyethylureopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane and combinations thereof.

16. The hydrated polysiloxane hydrogel contact lens of claim 12, wherein the polysiloxane hydrogel material further comprises repeating units derived from a crosslinking agent belonging to the group consisting of: tetraethylene glycol diacrylate, triethylene glycol diacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, tetraethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylpropane trimethacrylate, isopentetrate tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethacrylate, ethylenediamine dimethacrylate, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1,3 -bis(methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane, N,N'-methylenebisacrylamide, N,N'-methylenebisacrylamide, N,N'-ethylbisacrylamide, N,N'-ethylbisacrylamide, 1,3-bis(N-methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane Disiloxane, 1,3-bis(methacrylaminobutyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(acrylaminopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(methacryloxyethylureopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane and combinations thereof.

17. The hydrated polysiloxane hydrogel contact lens of claim 13, wherein the polysiloxane hydrogel material further comprises repeating units derived from a crosslinking agent belonging to the group consisting of: tetraethylene glycol diacrylate, triethylene glycol diacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, tetraethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylpropane trimethacrylate, isopentetrate tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethacrylate, ethylenediamine dimethacrylate, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1,3 -bis(methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane, N,N'-methylenebisacrylamide, N,N'-methylenebisacrylamide, N,N'-ethylbisacrylamide, N,N'-ethylbisacrylamide, 1,3-bis(N-methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane Disiloxane, 1,3-bis(methacrylaminobutyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(acrylaminopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(methacryloxyethylureopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane and combinations thereof.

18. The hydrated polysiloxane hydrogel contact lens of claim 14, wherein the polysiloxane hydrogel material further comprises repeating units derived from a crosslinking agent belonging to the group consisting of: tetraethylene glycol diacrylate, triethylene glycol diacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, tetraethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylpropane trimethacrylate, isopentetrate tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethacrylate, ethylenediamine dimethacrylate, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1,3 -bis(methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane, N,N'-methylenebisacrylamide, N,N'-methylenebisacrylamide, N,N'-ethylbisacrylamide, N,N'-ethylbisacrylamide, 1,3-bis(N-methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane Disiloxane, 1,3-bis(methacrylaminobutyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(acrylaminopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(methacryloxyethylureopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane and combinations thereof.

19. A hydrated polysiloxane hydrogel contact lens as claimed in any of claims 1 to 10, wherein the polysiloxane hydrogel material further comprises repeating units derived from polysiloxane ethylene type monomers.

20. The hydrated polysiloxane hydrogel contact lens of claim 19, wherein the polysiloxane hydrogel material comprises repeating units derived from hydrophilic vinyl monomers of the group consisting of: N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, 2-acrylaminoglycolic acid, 3-acrylamino-1-propanol, N-hydroxyethylacrylamide, N-[tri(hydroxymethyl)methyl]acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, trimethylammonium methacrylate 2-hydroxypropyl methacrylate hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate, glyceryl methacrylate, allyl alcohol, C1-C4-alkoxy polyethylene glycol (meth)acrylate with a weight average molecular weight of up to 1500, methacrylic acid, N-methyl-3-methylpropanediol, etc. Methyl-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, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3 -Methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, N-vinyl-2-pyrrolidone, vinylpyridine, N-vinylmethoxyamine, N-vinylacetamide, N-vinylisopropylamine, N-vinyl-N-methylacetamide, N-vinylcaprolactam and mixtures thereof.

21. The hydrated polysiloxane hydrogel contact lens of claim 20, wherein the polysiloxane hydrogel material further comprises repeating units derived from a crosslinking agent belonging to the group consisting of: tetraethylene glycol diacrylate, triethylene glycol diacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, tetraethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylpropane trimethacrylate, isopentetrate tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethacrylate, ethylenediamine dimethacrylate, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1,3 -bis(methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane, N,N'-methylenebisacrylamide, N,N'-methylenebisacrylamide, N,N'-ethylbisacrylamide, N,N'-ethylbisacrylamide, 1,3-bis(N-methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane Disiloxane, 1,3-bis(methacrylaminobutyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(acrylaminopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(methacryloxyethylureopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane and combinations thereof.

22. The hydrated polysiloxane hydrogel contact lens of claim 19, wherein the polysiloxane hydrogel material further comprises repeating units derived from a crosslinking agent belonging to the group consisting of: tetraethylene glycol diacrylate, triethylene glycol diacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, tetraethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylpropane trimethacrylate, isopentetrate tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethacrylate, ethylenediamine dimethacrylate, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1,3 -bis(methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane, N,N'-methylenebisacrylamide, N,N'-methylenebisacrylamide, N,N'-ethylbisacrylamide, N,N'-ethylbisacrylamide, 1,3-bis(N-methacrylaminopropyl)-1,1,3,3-tetra(trimethylsiloxy)diasiloxane Disiloxane, 1,3-bis(methacrylaminobutyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(acrylaminopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane, 1,3-bis(methacryloxyethylureopropyl)-1,1,3,3-tetra(trimethylsilyloxy)-disiloxane and combinations thereof.

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