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] The present invention generally relates to ophthalmic devices, particularly silicone hydrogel contact lenses, which have a lens structural configuration that produces a water content gradient and include: a silicone hydrogel bulk material having a water content (expressed as WC SiHy) 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 silicone hydrogel bulk material and composed of a hydrogel material that is completely or substantially free of silicone and has a higher water content, the higher water content being characterized by a water expansion ratio of at least about 100% if WC SiHy≤45% or a water expansion ratio of at least about 100% if WC SiHy>45%. , as measured by AFM using a cross-section of a silicone hydrogel contact lens in a fully hydrated state. Prior Art

[0002] Silicone hydrogel (SiHy) contact lenses are widely used to correct many different types of visual defects. They are composed of a hydrated, cross-linked polymeric material containing silicone and a certain amount of water in equilibrium within the lens polymer matrix. According to the FDA's contact lens classification, hydrogel contact lenses are generally divided into two 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 silicone into the cross-linked polymeric material rather than by increasing the water content, which is desirable for contact lenses with minimal adverse effects on corneal health. Thus, unlike conventional hydrogel contact lenses, SiHy contact lenses can have a low water content while still having a relatively high oxygen permeability (Dk), e.g., Focus® Night & Day® from CIBA Vision (about 23.5% H 2 O and a Dk of about 140 Barrers); Air Optix® from CIBA Vision (about 33% H 2 O and a Dk of about 110 Barrers); PureVision® from Bausch & Lomb (about 36% H 2 O and a Dk of about 100 Barrers); Acuvue® Oasys® from Johnson & Johnson (about 38% H 2 O, a Dk of about 105 Barrers); Acuvue® Advance® from Johnson & Johnson (about 47% H 2 O, a Dk of about 65 Barrers); Acuvue® TruEye™ from Johnson & Johnson (about 46% H 2 O, a Dk of about 100 Barrers). from CooperVision (about 48% H 2O, Dk of about 128 Barrer); Avaira ™ from CooperVision (about 46% H 2O, Dk of about 100 Barrer); and PremiO ™ from Menicon (about 40% H 2O, Dk of about 129 Barrer).

[0003] Water in SiHy contact lenses can provide the desired softness that enables SiHy lenses to be worn for a sufficient period of time and provide benefits to patients including: appropriate initial comfort (i.e., immediately after lens insertion), relatively short adaptation time required for patients to get used to the lenses, and / or comfortable wear. It is desirable that the water content is higher to provide SiHy contact lenses with biocompatibility and comfort. However, as with conventional hydrogel contact lenses, there is a limit to the amount of water (believed to be 80%) that SiHy contact lenses can contain while still having sufficient mechanical strength and rigidity required for contact lenses. In addition, high water content can also have undesirable consequences. For example, increasing the water content can be detrimental to the oxygen permeability of SiHy contact lenses. In addition, high water content in SiHy lenses can cause greater intraocular dehydration and thereby dehydration-induced wearing discomfort, because SiHy contact lenses with high water content can deplete the limited supply of tears (water) in the eye. It is believed that intraocular dehydration can result from evaporation (i.e., water loss) at the anterior surface of the contact lens and that this water loss is primarily controlled by water diffusion through the lens from the posterior surface to the anterior surface, with the rate of diffusion being approximately proportional to the water content of the lens bulk material at equilibrium (L. Jones et al., Contact Lens & Anterior Eye 25 (2002) 147-156, incorporated herein by reference in its entirety).

[0004] Incorporating silicone into contact lens materials also has an undesirable effect on the biocompatibility of the contact lenses, since silicone is hydrophobic and has a greater tendency to migrate to the lens surface exposed to air. Therefore, SiHy contact lenses typically require surface modification processes to eliminate or minimize silicone exposure of the contact lenses and maintain a hydrophilic surface, including, for example, various plasma treatments (e.g., Focus® Night & Day® and Air Optix® from CIBA Vision, Inc.; PureVision® from Bausch & Lomb; and PremiO™ from Menicon); internal wetting agents that are physically and / or chemically embedded in the SiHy polymer matrix (e.g., Acuvue® Oasys®, Acuvue® Advance®, and Acuvue® TruEye™ from Johnson & Johnson; Biofinity® and Avaira™ from CooperVision). Although the surface modification techniques used in commercial SiHy lens production can provide fresh (unused) SiHy lenses with suitably hydrophilic surfaces, SiHy lenses worn in the eye may have dry spots and / or hydrophobic surface areas resulting from air exposure, eyelid shear forces, silicone migration, and / or partial failure to prevent silicone exposure. These dry spots and / or hydrophobic surface areas are non-wettable and easily absorb lipids or proteins from the ocular environment and may adhere to the eye, causing discomfort to the patient.

[0005] Therefore, there is still a need in the industry for SiHy contact lenses with hydrophilic surfaces that have durable hydrophilicity, wettability, and lubricity that can be maintained in the eye throughout the day. Summary of the invention

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

[0007] In one aspect, the present invention provides a hydrated silicone hydrogel contact lens comprising: an anterior (convex) surface and an opposing posterior (concave) surface; and a layered structural configuration from the anterior surface to the posterior surface, wherein the layered structural configuration comprises an anterior outer hydrogel layer, an inner layer of silicone hydrogel material, and a posterior outer hydrogel layer, wherein the silicone hydrogel material has an oxygen permeability (Dk) of at least about 50 barrers, preferably at least about 60 barrers, more preferably at least about 70 barrers, even more preferably at least about 90 barrers, most preferably at least about 110 barrers, and has a first water content (expressed as WC) of about 10% to about 70%, preferably about 10% to about 65%, more preferably about 10% to about 60%, even more preferably about 15% to about 55%, most preferably about 15% to about 50% by weight. SiHy), wherein the front outer hydrogel layer and the back outer hydrogel layer are substantially uniform in thickness and merge at the peripheral edge of the contact lens to completely surround the inner layer of the polysilicone hydrogel material, wherein the front outer hydrogel layer and the back outer hydrogel layer independently have a second water content higher than WC SiHy, characterized in that if WC SiHy≤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%, most preferably at least about 300%), or if WC SiHy>45%, the water swelling rate is at least about (Preferably , better , or even better ), wherein the thickness of each of the front outer hydrogel layer and the rear outer hydrogel layer is from about 0.1 µm to about 20 µm, preferably from about 0.25 µm to about 15 µm, more preferably from about 0.5 µm to about 12.5 µm, even more preferably from about 1 µm to about 10 µm (as measured using atomic force microscopy across a cross-section from the rear surface to the front surface of the silicone hydrogel contact lens in a fully hydrated state).

[0008] In another aspect, the present invention provides a hydrated silicone hydrogel contact lens. The hydrated silicone hydrogel contact lens of the present invention comprises: a silicone hydrogel material as a bulk material, a front surface and an opposite back surface; wherein the oxygen permeability 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 surface and the back surface on the cross-sectional surface of the contact lens includes an anterior outer region (including and close to the anterior surface), an inner region (including and surrounding the center of the shortest line), and a back outer region (including and close to the back surface), wherein the anterior outer region has an average anterior surface modulus (expressed as ) and the rear outer region has an average rear surface modulus (expressed as ), where the interior region has an average internal surface modulus (expressed as ),in and At least one of the above 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 aspect, the present invention provides hydrated silicone hydrogel contact lenses. The hydrated silicone hydrogel contact lens of the present invention comprises: a silicone hydrogel material as a bulk material, an anterior surface and an opposing posterior 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, even more preferably at least about 110 barrer / mm, and (2) has a surface lubricity characterized by a critical coefficient of friction (expressed as CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less, wherein the anterior and posterior surfaces have a low surface concentration of negatively charged groups (including carboxylic acid groups), characterized by attracting at most about 200, preferably at most about 160, more preferably at most about 120, even more preferably at most about 90, and most preferably at most about 60 positively charged particles in a positively charged particle attachment test.

[0010] These and other aspects of the present invention, including any combination of the preferred embodiments, will become apparent from the following description of the presently preferred embodiments. The detailed description merely illustrates the present invention and does not limit the scope of the present 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 may be made to the present invention without departing from the spirit and scope of the novel concepts of the present disclosure. Simple diagram description

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

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

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

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

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

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

[0017] As used in this application, the term "silicone hydrogel" refers to a hydrogel containing silicone. Silicone hydrogel is usually obtained by copolymerizing a polymerizable composition, which includes at least one silicone-containing vinyl monomer or at least one silicone-containing vinyl macromonomer or at least one silicone-containing prepolymer having an ethylenically unsaturated group.

[0018] As used in this application, the term "vinyl monomer" refers to a compound that has one unique ethylenically unsaturated group and can be polymerized actinically or thermally.

[0019] As used in this application, the term "ethylenically unsaturated group" or "ethylenically unsaturated group" is used herein in a broad sense and is intended to encompass any group containing at least one >C=C< group. Exemplary ethylenically unsaturated groups include Containing but not limited to (meth)acryloyl ( and / or ), Allyl, vinyl ( ), styryl, or other C=C containing 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 vinylic monomer" refers to a vinylic monomer that, typically in homopolymer form, yields a polymer that is water soluble or can absorb at least 10% by weight of water.

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

[0024] As used in this application, the term "macromer" or "prepolymer" refers to medium and high molecular weight compounds or polymers containing two or more ethylenically unsaturated groups. Medium molecular weight and high molecular weight generally refer to average molecular weights greater than 700 Daltons.

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

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

[0027] As used in this application, the term "molecular weight" of a polymeric material (including monomeric or macromeric material) refers to the weight average molecular weight, unless specifically stated otherwise or unless testing conditions dictate otherwise.

[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 or branched chain alkyl group.

[0029] As used in this application, the term "epichlorohydrin-functionalized polyamine" or "epichlorohydrin-functionalized polyamidoamine" refers to a polymer obtained by reacting a polyamine or polyamidoamine with epichlorohydrin to convert all or a substantial proportion of the amine groups in the polyamine or polyamidoamine into azetidinium groups.

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

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

[0032] As used in this application, the term "phosphocholine" refers to a zwitterionic group , wherein n is an integer from 1 to 5, and R 1, R 2 and R 3 are independently C 1-C 8 alkyl or C 1-C 8 hydroxyalkyl.

[0033] As used in this application, the term "reactive vinyl monomer" refers to a vinyl monomer having a carboxyl group or an amine group (ie, a primary or secondary amine 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 amine groups (ie, primary or secondary amine groups). Non-reactive vinyl monomers may contain tertiary or quaternary amine groups.

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

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

[0037] As used in this application, the term "integrity" with respect to a coating on a SiHy contact lens is intended to describe the extent to which the contact lens can be stained by Sudan Black in the Sudan Black staining test described in Example 1. Good integrity of the coating on a SiHy contact lens means that there is virtually no Sudan Black staining of the contact lens.

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

[0039] As used in this application, the term "withstands the finger wipe test" or "withstands the durability test" with respect to a coating on a contact lens means that after the lens is finger wiped according to the procedure described in Example 1, the water contact angle on the finger wiped 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 intrinsic "oxygen permeability" Dk of a material is the rate at which oxygen passes through the material. As used in this application, the term "oxygen permeability (Dk)" with respect to a hydrogel (silicone or non-silicone) or a contact lens means the measured oxygen permeability (Dk) corrected for the surface resistance to oxygen flux caused by boundary layer effects according to the procedure shown in the Examples below. Oxygen permeability is usually expressed in units of barrers, where "barrer" is defined as [(cm 3 oxygen)(mm) / (cm 2)(sec)(mm Hg)]×10-10.

[0041] The "oxygen permeability" Dk / t of a lens or material is the rate at which oxygen passes through a particular lens or material having an average thickness of t [in mm] over the measured area. Oxygen permeability is usually expressed in barrer / mm, where "barrer / mm" is defined as [(cm 3 oxygen) / (cm 2) (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 [mm 2 / min]) is determined by applying Fick's law as follows: D = -n' / (A × dc / dx) Where n' = ion transport rate [mol / min]; A = exposed lens area [mm2]; dc = concentration difference [mol / L]; dx = lens thickness [mm]. []

[0043] As used in this application, the term "ophthalmically compatible" refers to materials or material surfaces that can be in close contact with the ocular environment for extended periods of time without significant harm to the ocular environment and without significant user discomfort.

[0044] As used in this application, the term "ophthalmologically safe" with respect to packaging solutions for sterilizing and storing contact lenses means that contact lenses stored in the solution are safe when placed directly on the eye without rinsing after autoclaving, and that the solution is safe and sufficiently comfortable for daily contact with the eye through the contact lens. According to international ISO standards and U.S. FDA regulations, an ophthalmologically safe packaging solution has a tonicity and pH compatible with the eye after autoclaving and is substantially free of irritating or ocular cytotoxic materials.

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

[0046] The terms "surface modulus", "surface softness", "surface elastic modulus", "surface Young's modulus", or surface compression modulus are used interchangeably in this application to refer to nanomechanical properties (elastic properties) measured by atomic force microscopy (AFM) on the surface of the 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 mode, nanoindentation method, Peakforce QNM method, or tuned force method known to those skilled in the art. Jan Domke and Manfred Radmacher reported that 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 in González-Méijome JM, Almeida JB, and Parafita MA in 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), which is incorporated herein by reference in its entirety. It should be noted that nanoindentation is used to analyze the surface cross-section of the contact lens using AFM 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). Nanoindentation methods, Peakforce QNM methods, and tuned force methods are described in Kim Sweers et al., Nanoscale Research Letters 2011, 6:270, entitled “Nanomechanical properties of a-synuclein amyloid fibrils: a comparative study by nanoindentation, harmonic force microscopy, and Peakforce QNM” (incorporated herein by reference in its entirety).It should also be understood that when measuring the surface elastic modulus using AFM across a cross section from the anterior surface to the bulk or from the bulk to the posterior surface (or vice versa) in a fully hydrated SiHy contact lens, a surface modulus curve across the cross section of the contact lens can be established along the shortest line between the anterior surface and the posterior surface on the cross-sectional surface of the contact lens. It should further be understood that, as a good approximation, any experimentally and directly measured quantity can be used to represent the surface modulus, as long as the quantity measured is proportional to the surface modulus.

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

[0048] As used in this application, the term "posterior outer hydrogel layer" with respect to the SiHy contact lens of the present invention means a hydrogel layer comprising the posterior surface of the contact lens, having a substantially uniform thickness (i.e., a thickness variation of no more than about 10% compared to the average thickness of the layer), and having an average thickness of at least about 0.1 μm. In this application, the "average thickness" of the posterior outer hydrogel layer is referred to simply as the "thickness of the posterior outer hydrogel layer".

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

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

[0051] As used in this application, the term "water swelling ratio" with respect to the front outer hydrogel layer or the back outer hydrogel layer of the hydrogel material of the SiHy contact lens of the present invention means the water swelling ratio measured using AFM according to the The value determined by , wherein WSR is the water swelling rate of one of the front outer hydrogel layer and the rear outer hydrogel layer, Lwet 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, pH of about 7.3 ± 0.2), and Ldry 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 (dried without retaining the porosity of the hydrogel material, e.g., vacuum dried) and in a substantially dry atmosphere. It is believed that the water swelling rate of each outer hydrogel layer (with respect to the SiHy contact lenses of the present invention) is proportional to the water content of each outer hydrogel layer, and is at least about 100% or more. The water swelling ratio (no matter how large, WC SiHy is the water content of the bulk (or inner layer) polysilicone hydrogel material of the SiHy contact lens of the present invention) can be used as a good indicator of the properties of the outer hydrogel layer of the SiHy contact lens of the present invention that has a higher water content than the bulk (or inner layer) polysilicone hydrogel material.

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

[0053] "Critical coefficient of friction" is the tangent of the critical angle, which is the highest tilt angle of the inclined plate at which the lens begins to slide on the inclined 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) of hydrated SiHy contact lenses. The Positively Charged Particle Adhesion Test was performed as described below. An aqueous dispersion of DOWEX TM1×4 20-50 mesh resin (which is a spherical Type I strong base resin (styrene / divinylbenzene copolymer containing N+(CH3)3Cl- functional groups and 4% divinylbenzene)) was prepared by dispersing a given amount of DOWEX TM1×4 20-50 mesh resin in phosphate buffered saline (pH of about 7.3) to have a resin concentration of 5 wt %, and then thoroughly mixed by shaking or stirring or vortexing at about 1000 rpm for 10 seconds. The hydrated silicone hydrogel contact lens was immersed in the aqueous dispersion of DOWEX TM1×4 20-50 mesh resin prepared above and vortexed at about 1000-1100 rpm for about 1 minute, followed by rinsing with DI water and vortexing in DI water for about 1 minute. The lens was then placed in water in a glass Petri dish and an image of the lens was acquired using a Nikon optical microscope using bottom illumination. The number of positively charged particles attached to the surface of each lens can be counted. The number of positively charged particles attached to the lens surface is proportional to the surface concentration of negatively charged groups of the contact lens.

[0055] As used in this application, the term "carboxylic acid content" with respect to the crosslinked coating or outer hydrogel layer of the SiHy contact lens of the present invention means the weight percentage of carboxylic acid groups (COOH) based on the weight of the crosslinked coating or outer hydrogel layer of the SiHy contact lens. The carboxylic acid content of the crosslinked coating or outer hydrogel layer can be estimated theoretically based on the composition of the starting materials used to make the crosslinked coating or outer hydrogel layer and the carboxylic acid content of each starting material.

[0056] The present invention relates to a SiHy contact lens having a layered structural configuration and a unique water gradient from the inside to the outside of the SiHy contact lens: a silicone hydrogel core (or bulk material) with a lower water content is completely covered by an outer (surface) hydrogel layer, the outer (surface) hydrogel layer has a higher water content and a suitable thickness (at least about 0.1 μm) and is substantially free of silicone (preferably completely free of silicone); 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. FIG1 schematically illustrates a SiHy contact lens having a layered structural configuration of a preferred embodiment. According to this preferred embodiment of the present invention, the SiHy contact lens 100 has a front surface (or front curve or convex surface) 101 and an opposite rear surface (or bottom curve or concave surface) 102 that is placed on the cornea of ​​the eye when worn by the user. The SiHy contact lens 100 includes an inner (or middle) layer 110 and two outer layers 120. The inner layer 110 is the bulk material of the SiHy contact lens 100 and has a 3-dimensional shape that is extremely close to the SiHy contact lens 100. The inner layer 110 is preferably composed of a relatively low water content silicone hydrogel. The two outer layers 120 (substantially the same as each other) are substantially uniform in thickness and are composed of a hydrogel material that is substantially free of silicone (preferably completely free of silicone) and has 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 structural configuration of the present invention can provide several advantages over contact lenses in the prior art. First, such a SiHy contact lens can still have high oxygen permeability, which is required to maintain the health of the cornea of ​​the eye. Secondly, because the inner layer (bulk material) provides the body mechanical strength and rigidity required for the contact lens, the outer hydrogel layer can have no restrictions on water content and can contain as much water as possible. Therefore, the outer hydrogel layer can provide an overly water-rich cortex to the contact lens or provide a water content gradient in the lens structural configuration (with the highest water content in the area close to and including the lens surface and the lowest water content in the lens core). Third, the SiHy contact lens with a layered structural configuration of the present invention can have lower intraocular dehydration, can cause less dryness in the eye, and therefore can have enhanced daytime wearing comfort. It is believed that the inner layer with a low water content (that is, the bulk material of the lens) will control (limit) the rate at which water diffuses through the lens from the back surface to the front surface, and then control the evaporation (water loss) of water at the front surface of the lens. In addition, it is believed that the layered structural configuration of the present invention can produce an inward water concentration gradient (i.e., the water content gradually decreases as one approaches inward from the front surface toward the lens core), which, based on Fick's laws of diffusion, does not favor the diffusion of water through the lens from the back surface to the front surface. 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% H 2 O) in the outer hydrogel layer is located at and close to the front and back surfaces, which are in direct contact with the eye and where biocompatibility is considered to be optimal. Fifth, the high water content in the outer hydrogel layer with an 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 lubricious surface. It is believed that an outer hydrogel layer with a very high water content and an appropriate thickness will provide a "water-loving" surface that can attract tears to spread on the lens surface. It is believed that the outer hydrogel layer, which is much softer than the bulk lens material (inner layer), can be very easy to deform under pressure (i.e., shear force of the eyelid) and can provide hydroelastic lubrication when such a SiHy contact lens is worn in the eye. Seventh, the layered structural configuration in the SiHy contact lens of the present invention can prevent silicone exposure. It is believed that the three-dimensional mesh network (i.e., polymer matrix) of the outer hydrogel layer with an appropriate thickness can encapsulate silicone and prevent silicone from migrating 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 of the protein in tears is positively charged).

[0058] In one aspect, the present invention provides a hydrated silicone hydrogel contact lens comprising: an anterior (convex) surface and an opposite posterior (back) surface; and a layered structure configuration from the anterior surface to the back surface, wherein the layered structure configuration comprises an anterior outer hydrogel layer, an inner layer of silicone hydrogel material, and a posterior outer hydrogel layer, wherein the silicone hydrogel material has an oxygen permeability (Dk) of at least about 50 barrers, preferably at least about 60 barrers, more preferably at least about 70 barrers, even more preferably at least about 90 barrers, most preferably at least about 110 barrers, and has a first water content (expressed as WC) of 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 %, most preferably about 15 wt % to about 50 wt %. SiHy), wherein the front outer hydrogel layer and the back outer hydrogel layer are substantially uniform in thickness and merge at the peripheral edge of the contact lens to completely surround the inner layer of the polysilicone hydrogel material, and wherein the front outer hydrogel layer and the back outer hydrogel layer independently have a second water content higher than WC SiHy, characterized in that if WC SiHy≤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 WC SiHy>45%, the water swelling rate is at least about (Preferably , better , or even better ), wherein each outer hydrogel layer has a thickness of 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 atomic force microscopy across a cross section from the rear surface to the front surface of the silicone hydrogel contact lens in a fully hydrated state). Preferably, the front and rear surfaces have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups), characterized by attracting at most about 200, preferably at most about 160, more preferably at most about 120, even more preferably at most about 90, and most preferably at most about 60 positively charged particles in a positively charged particle attachment test. Also preferably, the hydrated silicone hydrogel contact lenses have a surface lubricity characterized by a critical coefficient of friction (expressed as CCOF) of about 0.046 or less, 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 preformed SiHy contact lens in a surface modification process, in which the two outer hydrogel layers are applied and attached directly and / or indirectly to the preformed SiHy contact lens. The preformed SiHy contact lens can be any commercial SiHy lens, for example, any of those described above. Alternatively, the preformed SiHy can be made according to any method known to those skilled in the art. For example, preformed contact lenses can be produced in conventional "spincast molds" (e.g., as described in U.S. Pat. No. 3,408,429), or by a static form of an all-cast molding process (as described in U.S. Pat. Nos. 4,347,198, 5,508,317, 5,583,463, 5,789,464, and 5,849,810), or by lathe cutting silicone hydrogel buttons (as used in making custom contact lenses). In cast molding, the lens formulation is typically dispensed into a mold and cured (i.e., polymerized and / or cross-linked) in the mold used to make the contact lens. To produce preformed SiHy contact lenses, SiHy lens formulations for cast molding or spincast molding or for making SiHy rods (for lathe cutting contact lenses) typically include at least one component selected from the group consisting of polysiloxane-containing monomers, polysiloxane-containing macromers, polysiloxane-containing prepolymers, hydrophilic vinyl monomers, hydrophobic vinyl monomers, crosslinkers (compounds having a molecular weight of about 700 Daltons or less and containing at least two ethylenically unsaturated groups), free radical initiators (photoinitiators or thermal initiators), hydrophilic vinyl macromers / prepolymers, and combinations thereof, as are well known to those skilled in the art. The SiHy contact lens formulation may also include other necessary 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 may then be extracted using an extraction solvent to remove unpolymerized components from the resulting lens and perform a hydration process, as known to those skilled in the art. In addition, the preformed SiHy contact lens may be a colored contact lens (i.e., the SiHy contact lens has at least one colored pattern printed thereon, as is well known to those skilled in the art).

[0060] Any suitable polysiloxane-containing monomer can be used in the present invention. Preferred examples of polysiloxane-containing monomers include, but are not limited to, N-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide, N-[tris(dimethylpropylsiloxy)-silylpropyl](meth)acrylamide, N-[tris(dimethylphenylsiloxy)-silylpropyl](meth)acrylamide, N-[tris(dimethylethylsiloxy)silylpropyl](meth)acrylamide, N-(2-hydroxy-3-(3-(bis(2-hydroxy-3-(2-hydroxy-3-(2-hydroxy-3-(2-hydroxy-3-(2-hydroxy-3-(2-hydroxy-3-(2-hydroxy-3-(2-hydroxy-3-(2-hydroxy-3- (Trimethylsilyloxy)methylsilyl)propoxy)propyl)-2-methylacrylamide, N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propoxy)propyl)acrylamide, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propoxy)propyl]-2-methylacrylamide, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propoxy)propyl]-2-methylacrylamide Silyl) propoxy) propyl] acrylamide, N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl) propoxy) propyl)-2-methyl acrylamide, N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl) propoxy) propyl) acrylamide, N,N-bis[2-hydroxy-3-(3-(tris(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-methacryloyloxypropyl pentamethyldisiloxane, tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS), (3-methacryloyloxy-2-hydroxypropyloxy)propylbis(trimethylsilyloxy)methylsilane), (3-methacryloyloxy-2-hydroxypropyloxy)propyltris(trimethylsilyloxy)silane, 3-methacryloyloxy-2-(2-hydroxyethoxy)-propoxy)propylbis(trimethylsilyloxy)methylsilane, N-2-methacryloyloxyethyl-O-( methyl-bis-trimethylsilyloxy-3-propyl)silylcarbamate, 3-(trimethylsilyl)propylvinyl carbonate, 3-(vinyloxycarbonylthio)propyl-tri(trimethyl-silyloxy)silane, 3-[tri(trimethylsilyloxy)silyl]propylvinyl carbamate, 3-[tri(trimethylsilyloxy)silyl]propylallylcarbamate, 3-[tri(trimethylsilyloxy)silyl]propylvinyl carbonate, tert-butyldimethyl-siloxyethylvinyl carbonate, trimethylsilylethylvinyl carbonate, and trimethylsilylmethylvinyl carbonate). The best siloxane (meth)acrylamide monomer of formula (1) is N-[tri(trimethylsilyloxy)silylpropyl]acrylamide, TRIS, N-[2-hydroxy-3-(3-(tert-butyldimethylsilyl)propoxy)propyl]acrylamide, or a combination thereof. ;

[0061] Preferred types of polysiloxane vinyl monomers or macromers are polysiloxane vinyl monomers or macromers. Examples of such polysiloxane vinyl monomers or macromers are monomethacrylated or monoacrylated polydimethylsiloxanes of various molecular weights (e.g., mono-3-methacryloxypropyl-terminated, mono-butyl-terminated polydimethylsiloxane or mono-(3-methacryloxy-2-hydroxypropyloxy)propyl-terminated, mono-butyl-terminated polydimethylsiloxane); dimethacrylated or diacrylated polydimethylsiloxanes of various molecular weights; polydimethylsiloxanes terminated with vinyl carbonate; polydimethylsiloxanes terminated with vinyl carbamate; alkane; vinyl terminated polydimethylsiloxane of different molecular weight; methacrylamide terminated polydimethylsiloxane; acrylamide terminated polydimethylsiloxane; acrylate terminated polydimethylsiloxane; methacrylate terminated polydimethylsiloxane; bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane; N,N,N',N'-tetrakis(3-methacryloxy-2-hydroxypropyl)-α,ω-bis-3-aminopropyl-polydimethylsiloxane; polysiloxyalkyl alkyl (meth) acrylic acid monomer; selected from US 5,760,100 (the entire contents of which are incorporated herein by reference); a siloxane-containing macromer consisting of the group consisting of macromer A, macromer B, macromer C, and macromer D described in U.S. Pat. No. 5,760,100 (the entire contents of which are incorporated herein by reference); a reaction product of glycidyl methacrylate and an amino-functional polydimethylsiloxane; a hydroxy-functional siloxane-containing vinyl monomer or macromer; a polysiloxane-containing macromer disclosed in: U.S. Pat. No. 4,136,250, No. 4,153,641, No. 4,182,822, No. 4,189,546, No. 4,343,927, No. 4,254,248, No. 4,355,147, No. 4,276,402, No. 4,327,203, No. 4,341,889, No. 4,486,577, No. 4,543,398, No. 4, No. 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. 5,010,141, No. 5,034,461, No. 5,070,170, No. 5,079,319, No. 5,03 No. 9,761, 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. 5,962,548, No. 5,981,675, No. 6,039,913, and No. 6,762,264 (the entire contents of which are incorporated herein by reference);Polysiloxane-containing macromers disclosed in U.S. Pat. Nos. 4,259,467, 4,260,725, and 4,261,875 (the entire contents of which are incorporated herein by reference). Diblock and triblock macromers composed of polydimethylsiloxane and polyalkylene oxide 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 silicone-containing vinyl monomers / macromers and suitable multifunctional hydroxyl-functionalized silicone-containing vinyl monomers / macromers are available from Gelest Corporation, Morrisville, PA.;

[0062] Another preferred class of silicone-containing macromers includes silicone-containing prepolymers having a hydrophilic segment and a hydrophobic segment. Any suitable silicone-containing prepolymer having a hydrophilic segment and a hydrophobic segment can be used in the present invention. Examples of such silicone-containing prepolymers include those described in commonly owned U.S. Pat. Nos. 6,039,913, 7,091,283, 7,268,189 and 7,238,750, 7,521,519; commonly owned U.S. Patent Application Publication Nos. US 2008-0015315 A1, US 2008-0143958 A1, US 2008-0143003 A1, US 2008-0234457 A1, US 2008-0231798 A1, and commonly owned U.S. Patent Application Nos. 61 / 180,449 and 61 / 180,453; all of which are incorporated herein by reference in their entirety.

[0063] Examples of preferred hydrophilic vinyl monomers are N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA), 2-acrylamidoglycolic acid, 3-acrylamido-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 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 ester hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate (DMAEMA), glycerol methacrylate (GMA), N-vinyl-2-pyrrolidone (NVP), allyl alcohol, vinyl pyridine, C with a weight average molecular weight of up to 1500 1-C4-alkoxy polyethylene glycol (meth)acrylate, methacrylic acid, N-vinylformamide, N-vinylacetamide, N-vinylisopropamide, 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, vinyl toluene, vinyl ethyl ether, perfluorohexylethyl-thio-carbonyl-aminoethyl methacrylate, isoborneol methacrylate, trifluoroethyl methacrylate, hexafluoroisopropyl methacrylate, 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, trimethylolpropane trimethacrylate, pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethacrylamide, ethylenediamine diacrylamide, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1,3-bis(methacrylamidopropyl)-1,1,3,3-tetra(tri( ... 1,3-Bis(N-methylacrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane, 1,3-bis(methyl) ... The crosslinking agent is preferably selected from the group consisting of tetra(ethylene glycol) diacrylate, tri(ethylene glycol) diacrylate, ethylene glycol diacrylate, di(ethylene glycol) diacrylate, methylenebisacrylamide, triallyl isocyanurate, or triallyl cyanurate. The amount of the crosslinking agent used is expressed as a weight content relative to the total polymer, and is 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 are benzoin methyl ether, diethoxyacetophenone, benzylphosphine oxide, 1-hydroxycyclohexylphenyl ketone and Darocur and Irgacur types, preferably Darocur 1173® and Darocur 2959®. Examples of benzylphosphine oxide initiators include 2,4,6-trimethylbenzyldiphenylphosphine oxide, bis-(2,6-dichlorobenzyl)-4-N-propylphenylphosphine oxide, and bis-(2,6-dichlorobenzyl)-4-N-butylphenylphosphine oxide. Reactive photoinitiators which can be incorporated, for example, into macromonomers or can be 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. The polymerization can then be triggered by actinic radiation, for example light of a suitable wavelength, in particular UV light. Therefore, the spectral requirements can be controlled by adding suitable photosensitizers, if appropriate.

[0068] Any suitable polymerizable UV absorber can be used in the present invention. Preferably, the polymerizable UV absorber includes a benzotriazole moiety or a benzophenone moiety. Examples of preferred polymerizable UV absorbers include, but are not limited to, 2-(2-hydroxy-5-vinylphenyl)-2H-benzotriazole, 2-(2-hydroxy-5-acryloxyphenyl)-2H-benzotriazole, 2-(2-hydroxy-3-methacrylamidomethyl-5-tert-octylphenyl)benzotriazole, 2-(2'-hydroxy-5'-methacrylamidophenyl)-5-chlorobenzotriazole, 2-(2'-hydroxy-5'-methacrylamidophenyl)-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-acryloxyalkoxybenzophenone, 2-hydroxy-4-methacryloxyalkoxybenzophenone, allyl-2-hydroxybenzophenone, 2-hydroxy-4-methacryloxybenzophenone.

[0069] A bioactive agent is any compound that can prevent eye discomfort or reduce symptoms of 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 a pharmaceutically acceptable salt or ester thereof. Other examples of bioactive agents include 2-pyrrolidone-5-carboxylic acid (PCA), alpha hydroxy acids (e.g., glycolic acid, lactic acid, malic acid, tartaric acid, mandelic acid, and citric acid and salts thereof, etc.), linoleic acid and gamma 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., without ethylenically unsaturated groups). Any hydrophilic polymer or copolymer that does not contain any ethylenically 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), polyamides, polyimides, polylactones, homopolymers of vinyl lactams, copolymers of at least one vinyl lactam in the presence or absence of one or more hydrophilic vinylic comonomers, homopolymers of acrylamide or methacrylamide, copolymers of acrylamide or methacrylamide and one or more hydrophilic vinylic monomers, polyethylene oxide (i.e., polyethylene glycol (PEG)), polyoxyethylene derivatives, poly-NN-dimethylacrylamide, polyacrylic acid, poly-2-ethyloxazoline, heparin polysaccharides, polysaccharides, and mixtures thereof. The weight average molecular weight Mw of the non-crosslinkable hydrophilic polymer is preferably 5,000 to 1,00,000.

[0071] Examples of leachable tear stabilizers include, but are not limited to, phospholipids, monoglycerides, diglycerides, triglycerides, glycolipids, glyceroglycolipids, sphingolipids, sphingolipids, fatty alcohols, fatty acids, mineral oils, and mixtures thereof. Preferably, the tear stabilizer is a phospholipid, a monoglyceride, a diglyceride, a triglyceride, a glycolipid, a glyceroglycolipid, a sphingolipid, a sphingolipid, a fatty acid having 8 to 36 carbon atoms, a fatty alcohol having 8 to 36 carbon atoms, or a mixture 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] SiHy lens formulations can be prepared by dissolving all desired components in any suitable solvent, such as water, a mixture of water and one or more water-miscible organic solvents, an organic solvent, or a mixture of one or more organic solvents, as 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, amyl acetate, lactone, 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 phenyl ether, dipropylene glycol dimethyl ether, polyethylene glycol, polypropylene glycol, ethyl acetate, butyl acetate, amyl acetate, lactone, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, methyl lactate, ethyl lactate, isopropyl lactate, dichloromethane, 2-butanol, 1-propanol, 2-propanol, menthol, cyclohexanol, cyclopentanol and exo-norborneol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, tert-butanol, tert-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-Methyl-2-octanol, 2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol, 3- Hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol, 2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol and 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl-2-propanol, tert-pentanol, isopropanol, 1-methyl-2-pyrrolidone, N,N-dimethylpropionamide, dimethylformamide, dimethylacetamide, dimethylpropionamide, N-methylpyrrolidone, and mixtures thereof.

[0075] Many SiHy lens formulations have been described in many patents and patent applications published as of the filing date of the present application. All of these SiHy lens formulations can be used to obtain preformed SiHy lenses that subsequently become the inner layer of the SiHy contact lenses of the present invention, as long as they produce SiHy materials with the Dk and water content specified above. SiHy lens formulations used to make 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 make preformed SiHy contact lenses (inner layer of the SiHy contact lenses of the present invention).

[0076] Lens molds for manufacturing contact lenses are well known to those skilled in the art and are used, for example, for cast molding or spin casting. For example, a mold (for cast molding) typically includes 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 to form a lens-forming cavity between the first molding surface and the second molding surface. The molding surface of the mold half is the cavity-forming surface of the mold and is in direct contact with the lens-forming material.

[0077] Those skilled in the art are generally familiar with methods of making mold sections for cast molded contact lenses. The present method is not limited to any particular method of forming the mold. In fact, any method of forming the 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. Examples of suitable methods of forming the mold halves are disclosed in the patent application U.S. Patent No. 4,444,711 issued to [Schad] [Boehm] No. 4,460,534 of [et al.], issued to No. 5,843,346 of [Morrill], and [Boneberger] No. 5,894,002 to [et al.], which is also incorporated herein by reference.

[0078] Virtually all materials known in the art for making molds can be used to make molds for making 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 the like can be used. Other materials that allow UV light to pass through can be used, such as quartz glass and sapphire.

[0079] In a preferred embodiment, a reusable mold is used and the silicone hydrogel lens forming composition is cured actinically under spatial confinement of actinic radiation to form a SiHy contact lens. Examples of preferred reusable molds are those disclosed in U.S. Patent Application Nos. 08 / 274,942, filed on July 14, 1994, 10 / 732,566, filed on December 10, 2003, 10 / 721,913, filed on 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 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 silicone hydrogel (bulk material) of the inner layer is at least about 50 barrers, preferably at least about 60 barrers, more preferably at least about 70 barrers, even more preferably at least about 90 barrers, and most preferably at least about 110 barrers. The silicone hydrogel material may also have the following (first) water content WC SiHy: 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 silicone hydrogel material may further have the following bulk elastic modulus or bulk Young's modulus (hereinafter, if the term is not modified by the word "surface", the terms "softness", "elastic modulus", and "Young's modulus" are used interchangeably in this application to refer to the bulk elastic modulus): about 0.3 MPa to about 1.8 MPa, preferably 0.4 MPa to about 1.5 MPa, more preferably about 0.5 MPa to about 1.2 MPa. The oxygen permeability, elastic modulus, and water content of the inner layer of the silicone hydrogel material in the SiHy contact lens of the present invention can be measured by measuring the oxygen permeability, elastic modulus, and water content of the preformed SiHy lens from which the inner layer is derived. It should be understood that, as a reasonable approximation, the elastic modulus of the SiHy contact lens of the present invention can be regarded as the elastic modulus of the silicone hydrogel material of the inner layer, because the outer hydrogel layer is very thin. Those skilled in the art are familiar with how to determine the elastic modulus and water content of silicone hydrogel materials or SiHy contact lenses. For example, all commercial SiHy contact lenses have reported values ​​for elastic modulus and water content.

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

[0082] The layered structural configuration of the SiHy contact lens of the present invention can be established by analyzing a cross section of the SiHy contact lens in a fully hydrated state (i.e., directly in water or buffered saline) using an atomic force microscope (AFM), as described above and shown in the Examples. The surface modulus of the cross section can be characterized (imaged) using AFM (e.g., force-volume mode) to visually detect any change in the surface modulus across the cross section from the back surface side to the front surface side. A significant change in the surface modulus observed (e.g., about 20% or more, preferably about 30% or more) (by examining the AFM image) across a cross section of the SiHy contact lens in a fully hydrated state along the shortest line between the front and back surfaces in 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 indicates a transition from one layer to a different layer. The average thickness of each outer hydrogel layer can be measured from the AFM image, which is well known to those skilled in the art.

[0083] The two outer hydrogel layers of the SiHy contact lens of the present invention are substantially uniform in thickness. They merge at the peripheral edge of the contact lens to completely surround the inner layer of silicone hydrogel material. The thickness of each outer hydrogel layer is from about 0.1 μm to about 20 μm, preferably from about 0.25 μm to about 15 μm, even more preferably from about 0.5 μm to about 12.5 μm, and most preferably from 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 a cross section of the SiHy contact lens in a fully hydrated state. In another preferred embodiment, the thickness of each outer hydrogel layer is preferably at most about 30% (i.e., 30% or less), preferably at most about 20% (20% or less), and more preferably at most about 10% (10% or less) of the center thickness of the SiHy contact lens in a fully hydrated state.

[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 analyzing the cross-section of the freeze-dried SiHy contact lens shown in the Examples by scanning electron microscopy (SEM). SEM can show different compositions and / or structures of each layer in the cross-section of the freeze-dried SiHy contact lens. Across the cross-section of the freeze-dried SiHy contact lens in 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, the observed significant composition changes (e.g., about 20% or more, preferably about 30% or more) and / or significant (visible) structural changes (by examining the SEM images) indicate the transition from one layer to a different layer. However, the thickness values ​​based on the SEM analysis of the cross-section of the freeze-dried SiHy lens are generally lower than the actual values, because the outer hydrogel layer, the transition layer (if applicable), and the inner layer collapse after freeze-drying.

[0085] According to this aspect of the invention, the two outer hydrogel layers (the front outer hydrogel layer and the rear outer hydrogel layer) of the SiHy contact lens of the invention include a (second) water content that must be higher than the (first) water content (WC SiHy) of the inner layer of the silicone hydrogel material, and more specifically must be at least about 1.2 times (i.e., 120%) the (first) water content (WC SiHy) of the inner layer of the silicone hydrogel material. It is believed that the water swelling rate of each outer hydrogel layer is related to its water content and can appropriately represent the water content of the outer hydrogel layer as a good approximation. In alternative preferred embodiments, if the water content (WC SiHy) of the inner layer of the silicone 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 (WC SiHy) of the inner layer of the silicone 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 (WC SiHy) of the inner layer of the silicone hydrogel material is about 65% or less, the water swelling rate of each outer hydrogel layer is at least about 250%; if the water content (WC SiHy) of the inner layer of the silicone 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 outer hydrogel layer and the rear outer hydrogel layer (cross-linked coating) can be more accurately measured according to the procedure described in Example 23. Alternatively, the water content of the two outer hydrogel layers (cross-linked coating) can be measured using an article comprising a water-impermeable thin substrate and a cross-linked coating thereon, wherein the cross-linked coating is applied to the water-impermeable thin substrate according to the same coating process as used for SiHy contact lenses under substantially the same conditions. 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 article with the cross-linked coating.

[0087] According to the present invention, each of the two outer hydrogel layers is substantially free of polysilicone, preferably completely free of polysilicone. However, it is well known that when using X-ray photoelectron spectroscopy (XPS) to determine the presence or absence of silicon in the outer hydrogel layer (typically, the detection depth is 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 theoretically does not contain any silicon atoms, such as polyethylene sheets, DAILIES® AquaComfortPlus™ contact lenses from CIBA VISION, or ACUVUE® Moist from Johnson & Johnson (see Example 21 below). Thus, the term "substantially silicon-free" is used in this application to mean that the surface silicon atomic percentage 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%, even more preferably less than about 125% of the silicon atomic percentage of a control sample known to be inherently (theoretically) silicon-free (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, as characterized by a silicon atomic percentage of about 5% or less, preferably about 4% or less, 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 silicone may be incorporated into the polymer network of the outer hydrogel layer as desired (but not preferred) as long as it does not significantly disrupt the surface properties (hydrophilicity, wettability, and / or lubricity) of the SiHy contact lens.

[0088] In a preferred embodiment, the crosslinking density (crosslinking density or crosslink density) of the front outer hydrogel layer and the rear outer hydrogel layer (crosslinked coating) is low enough to provide a crosslinked coating or outer hydrogel layer (i.e., SiHy contact lens) with high finger wiping resistance, as characterized by the absence of visible surface crack lines under dark field after wiping the SiHy contact lens between fingers. It is believed that surface cracking caused by finger wiping can reduce surface lubricity and / or may not prevent silicone from migrating to the surface (exposure). Surface cracking can also indicate that there is too much crosslinking density in the surface layer, which can affect the surface elastic modulus. Preferably, the non-silicone hydrogel material in the outer hydrogel layer (crosslinked coating) includes crosslinks derived from azetidinium groups in a thermally induced coupling reaction.

[0089] In another preferred embodiment, the front and back surfaces have a low surface concentration of negatively charged groups (including carboxylic acid groups), as characterized by attracting at most about 200, preferably at most about 160, more preferably at most about 120, even more preferably at most about 90, and most preferably at most about 60 positively charged particles in a positively charged particle attachment test. It is desirable to have a minimal surface concentration of negatively charged groups (e.g., carboxylic acid groups) on the SiHy contact lenses of the present invention because contact lenses with a high surface concentration of negatively charged groups (e.g., carboxylic acid groups) tend to produce high debris adhesion (during patient handling), high protein adhesion (during wear) (it is believed that most of the protein in tears is positively charged), 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 outer hydrogel layer and the back outer hydrogel layer should have a relatively low carboxylic acid content. Preferably, the carboxylic acid content of the front outer hydrogel layer and the rear outer hydrogel layer is about 20 wt % or less, preferably about 15 wt % or less, even more preferably about 10 wt % or less, most preferably about 5 wt % 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 (expressed as CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less. Alternatively, the SiHy contact lens of the present invention preferably has better lubricity than 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 comprises two transition layers of polymeric material in its layered structural configuration, as schematically shown in FIG. 2 . 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 silicone hydrogel material. The presence and thickness of the transition layer can preferably be determined by AFM analysis of a cross section of the SiHy contact lens in a fully hydrated state, as described above for the outer hydrogel layer and the inner layer.

[0092] The two transition layers of the SiHy contact lens of the present invention are essentially base (or bottom) coatings that are applied to a preformed SiHy contact lens having a desired Dk, water content, and bulk modulus, and then a crosslinked coating (outer hydrogel layer) is applied thereon. The transition layer (base coating) serves to anchor / attach the outer hydrogel layer. Preferably, the transition layer comprises a carboxyl (COOH)-containing polymer, preferably a homopolymer or copolymer of acrylic acid or methacrylic acid or C2-C12 alkyl acrylic acid. It is understood that the carboxyl-containing polymer can penetrate into the bulk material and extend into the outer hydrogel layer. When such penetration occurs in the inner layer of the silicone hydrogel material, each transition layer will include a carboxyl-containing polymer and a silicone hydrogel entangled together. It is also believed that the presence of the transition layer, especially when comprising 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, because the carboxyl group has a high water binding property. In addition, even though the transition layer may contain a high concentration of carboxylic acid groups, it has minimal adverse effect on the surface concentration of carboxylic acid groups of the SiHy contact lens, since 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 can prevent deposition of positively charged proteins from the tears of patients wearing the lens.

[0093] In another preferred embodiment, the front outer hydrogel layer and the rear outer hydrogel layer independently 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 outer hydrogel layer and the rear outer hydrogel layer are preferably composed of the same or substantially the same material (preferably completely free of silicone) and can be formed by applying a water-soluble and cross-linkable hydrophilic polymeric material to 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 cross-linking it, wherein the pre-formed SiHy contact lens becomes the inner layer after cross-linking.

[0095] According to the present invention, a 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 preformed SiHy hydrogel contact lens inherently includes amine and / or carboxyl groups on and / or near its surface, it is obtained by polymerizing a silicone hydrogel lens formulation including a reactive vinylic monomer.

[0097] Examples of preferred reactive vinyl monomers include, but are not limited to, (meth)acrylic acid amino-C 2-C 6 alkyl esters, (meth)acrylic acid C 1-C 6 alkylamino-C 2-C 6 alkyl esters, allylamine, vinylamine, amino-C 2-C 6 alkyl (meth) acrylamide, C 1-C 6 alkylamino-C 2-C 6 alkyl (meth) acrylamide, acrylic acid, C 1-C 1,2-alkyl acrylic acid (e.g., methacrylic acid, ethyl acrylic acid, propyl acrylic acid, butyl acrylic acid, pentyl acrylic acid, etc.), N,N-2-acrylamidoglycolic acid, β-methyl-acrylic acid (crotonic acid), α-phenyl acrylic acid, β-acryloyloxypropionic acid, sorbic acid, angelica acid, cinnamic acid, 1-carboxy-4-phenylbutadiene-1,3, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof. Preferably, the SiHy contact lenses are made from a lens formulation comprising at least one reactive vinyl monomer selected from the group consisting of amido-C2-C6 alkyl (meth)acrylates, C1-C6 alkylamido-C2-C6 alkyl (meth)acrylates, allylamine, vinylamine, amido-C1-C6 alkyl (meth)acrylamide, C1-C6 alkylamido-C2-C6 alkyl (meth)acrylamide, acrylic acid, C1-C12 alkyl acrylic acid, N,N-2-acrylamidoglycolic acid, and combinations thereof.

[0098] The lens formulation preferably includes from about 0.1 wt % to about 10 wt %, more preferably from about 0.25 wt % to about 7 wt %, even more preferably from about 0.5 wt % to about 5 wt %, most preferably from about 0.75 wt % to about 3 wt % of the above reactive vinylic monomer.

[0099] The preformed SiHy contact lens can also be subjected to 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 by energy (e.g., plasma, static charge, irradiation, or other energy sources), chemical treatment, chemical vapor deposition, grafting of hydrophilic vinyl monomers or macromers onto the surface of an object, layer-by-layer coating ("LbL coating") (obtained according to the methods described in the following documents: U.S. Pat. Nos. 6,451,871, 6,719,929, 6,793,973, 6,811,805, and 6,896,926 and U.S. Patent Application Publication Nos. 2007 / 0229758A1, 2008 / 0152800A1, and 2008 / 0226922A1, 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 a contact lens and is obtained by depositing charged or chargeable (by protonation or deprotonation) and / or uncharged materials on the lens layer by layer ("LbL"). 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 silicone hydrogel contact lens includes a reactive LbL base coating (i.e., two transition layers) containing at least one layer of a reactive polymer (i.e., a polymer having pendant amine and / or carboxyl groups), wherein the reactive LbL base coating is obtained by contacting the contact lens with a solution of the reactive polymer. The contacting of the contact lens with the coating solution of the reactive polymer can be carried out by soaking it in the coating solution or by spraying it with the coating solution. One contacting process involves merely soaking the contact lens in a bath of the coating solution for a period of time, or alternatively soaking the contact lens in a series of baths of the coating solution, each bath lasting a short fixed period of time. Another contacting process involves merely spraying the coating solution. However, many alternatives involve various combinations of spray-and-soak steps that can be designed by those skilled in the art. The contact time of the contact lens with the coating solution of the reactive polymer can last up to about 10 minutes, preferably from about 5 seconds to about 360 seconds, more preferably from about 5 seconds to about 250 seconds, even more preferably from about 5 seconds to about 200 seconds.

[0101] According to this reactive LbL base coating embodiment, the reactive polymer may be a linear or branched polymer having pendant amine and / or carboxyl groups. Any polymer having pendant amine and / or carboxyl groups may be used as a reactive polymer for forming a base coating on a silicone hydrogel contact lens. Examples of such reactive polymers include, but are not limited to, homopolymers of reactive vinyl monomers, copolymers of two or more reactive vinyl monomers, copolymers of reactive vinyl monomers and one or more non-reactive hydrophilic vinyl monomers (i.e., hydrophilic vinyl monomers that do not contain any carboxyl or (primary or secondary) amine groups), polyethyleneimine (PEI), polyvinyl alcohol having pendant amine groups, cellulose containing carboxyl groups (e.g., carboxymethyl cellulose, carboxyethyl cellulose, carboxypropyl cellulose), hyaluronate, chondroitin sulfate, poly(glutamic acid), poly(aspartic acid), and combinations thereof.

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

[0103] Preferred examples of non-reactive hydrophilic vinyl monomers without carboxyl or amine 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-acrylamido-1-propanol, N-hydroxyethyl acrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, C with a weight average molecular weight of up to 1500 Daltons 1-C4-alkoxypolyethylene glycol (meth)acrylate, N-vinylformamide, N-vinylacetamide, N-vinylisopropamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in the copolymer), vinyl monomers containing phosphorylcholine (including (meth)acryloyloxyethylphosphorylcholine and those described in U.S. Pat. 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 base coating is polyacrylic acid, polymethacrylic acid, poly(C 2 -C 12 alkyl acrylic acid), poly[acrylic acid-co-methacrylic acid], poly[C 2 -C 12 alkyl acrylic acid-co-(meth)acrylic acid], poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylic acid-co-vinyl pyrrolidone], poly[C 2 -C 12 alkyl acrylic acid-co-acrylamide], poly[C 2 -C 12 alkyl acrylic acid-co-vinyl pyrrolidone], hydrolyzed poly[(meth)acrylic acid-co-vinyl acetate], hydrolyzed poly[C 2 -C 12 alkyl acrylic acid-co-vinyl acetate], polyethyleneimine (PEI), polyallylamine hydrochloride (PAH) homopolymer or copolymer, 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, more preferably about 100,000 Daltons to 5,000,000 Daltons.

[0106] The solution of reactive polymers used to form the reactive LbL base coating on the contact lens can be prepared by dissolving one or more reactive polymers in water, a mixture of water and one or more water-miscible organic solvents, an organic solvent, or a mixture of one or more organic solvents. Preferably, the reactive polymer is dissolved in a mixture of water and one or more organic solvents, an organic solvent, or a mixture of one or more organic solvents. It is believed that the solvent system containing at least one organic solvent can cause the preformed SiHy contact lens to swell, so that a portion of the reactive polymer can penetrate into the preformed SiHy contact lens and increase the durability of the reactive base coating. Any of the above organic solvents can be used to prepare the solution of the reactive polymer as long as it can dissolve the reactive polymer.

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

[0108] In another preferred embodiment (reactive plasma primer coating), a preformed SiHy contact lens is subjected to a plasma treatment to form a covalently attached reactive plasma primer coating on the contact lens, i.e., one or more reactive vinyl monomers (any of those described above) are polymerized under the influence of a plasma generated by an electric discharge (so-called plasma-induced polymerization). The term "plasma" means an ionized gas generated, for example, by a 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 usually called "low temperature plasma". For a review of plasma polymerization and its uses, 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), pages 377-399; and N. Dilsiz and G. Akovali, "Plasma Polymerization of Selected Organic Compounds", Polymer, Vol. 37 (1996), pages 333-341.Preferably, the plasma-induced polymerization is "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 surface thus activated is exposed to a vinyl monomer having an amine or carboxyl group (any of the reactive vinyl monomers described above), while the plasma power supply is turned off. The activation results in the formation of free radicals on the surface in a plasma-induced manner, which in a subsequent step initiate the polymerization of the vinyl monomer thereon.

[0109] According to the present invention, the water-soluble and cross-linkable hydrophilic polymeric material used to form the outer hydrogel layer (or the cross-linked coating) includes a cross-linkable group, preferably a thermally cross-linkable group, and more preferably an azetidinium group. Preferably, the water-soluble and cross-linkable hydrophilic polymeric material used to form the outer hydrogel layer (or the cross-linked coating) is a partially cross-linked polymeric material, which includes a three-dimensional network and a cross-linkable (preferably thermally cross-linkable) group, more preferably an azetidinium group, located in the network. The term "partially cross-linked" with respect to the polymeric material means that the cross-linkable groups of the starting material used to prepare the polymeric material in the cross-linking reaction are not completely consumed. Examples of cross-linkable groups include, but are not limited to, azetidinium groups, epoxy groups, isocyanate groups, aziridine groups, azlactone groups, and combinations thereof.

[0110] In a preferred embodiment, the water-soluble and cross-linkable hydrophilic polymeric material used to form the outer hydrogel layer (or cross-linked coating) comprises: (i) about 20% to about 95% by weight of first polymer chains derived from epichlorohydrin functionalized polyamines or polyamidoamines; (ii) about 5% to about 80% by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity enhancing agent having at least one selected from the group consisting of amine groups, carboxyl groups, thiol groups, and combinations thereof. The invention relates to a hydrophilicity enhancing agent comprising: (i) an azetidinium group which is a part of the first polymer chains or is covalently attached to the second polymer chains via one or more covalent linkages, each covalent linkage being formed between an azetidinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and an amine, carboxyl or thiol group of the hydrophilicity enhancing agent; and (ii) an azetidinium group which is part of the first polymer chains or is covalently attached to a side chain or terminal group of the first polymer chains.

[0111] Using this water-soluble and cross-linkable hydrophilic polymeric material, the outer hydrogel layer (or cross-linked coating) can be formed simply 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 to a temperature of about 40° C. to about 140° C. in the presence of the hydrophilic polymeric material, and maintaining 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 linkages, each covalent linkage being formed between one azetidinium 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 cross-linked hydrophilic coating on the contact lens. It should be understood that any water-soluble and cross-linkable hydrophilic polymeric material containing cross-linkable groups (e.g., those described above) can be used in the present invention to form the front outer hydrogel layer and the back outer hydrogel layer of the SiHy contact lens.

[0112] The water-soluble and heat-crosslinkable hydrophilic polymeric material containing azetidinium groups comprises (i.e., has a composition comprising) 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 polyamidoamine; and about 5% to about 80% by weight, preferably about 10% to about 65% by weight, even more preferably about 15% to about 50% by weight of a hydrophilic moiety or second polymer chain derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of an amine group, a carboxyl group, a thiol group, and combinations thereof. The composition of the hydrophilic polymeric material is determined by the composition of the reactant mixture used to prepare the heat-crosslinkable hydrophilic polymeric material according to the crosslinking reaction shown in Reaction Scheme 1 above (based on the total weight of the reactants). For example, if the reactant mixture includes about 75 weight percent of the epichlorohydrin functionalized polyamine or polyamidoamine and about 25 weight percent of at least one hydrophilicity enhancing agent (based on the total weight of the reactants), the resulting hydrophilic polymeric material includes about 75 weight percent of first polymer chains derived from the epichlorohydrin functionalized polyamine or polyamidoamine and about 25 weight percent of hydrophilic moieties or second polymer chains derived from the at least one hydrophilicity enhancing agent. The azetidinium groups of the thermally crosslinkable hydrophilic polymeric material are those azetidinium groups (groups of the epichlorohydrin functionalized polyamine or polyamidoamine) that do not participate in the crosslinking reaction used to prepare the thermally crosslinkable hydrophilic polymeric material.

[0113] Epichlorohydrin functionalized polyamines or polyamidoamines can be obtained by reacting epichlorohydrin with a polyamine polymer or a polymer containing primary or secondary amine groups. For example, a poly(alkylene imine) or poly(amidoamine) derived from a polycondensate of a polyamine and a dicarboxylic acid (e.g., adipic acid-diethylenetriamine copolymer) can be reacted with epichlorohydrin to form an epichlorohydrin functionalized polymer. Similarly, a homopolymer or copolymer of aminoalkyl (meth)acrylate, monoalkylaminoalkyl (meth)acrylate, aminoalkyl (meth)acrylamide, or monoalkylaminoalkyl (meth)acrylamide can also be reacted with epichlorohydrin to form an epichlorohydrin functionalized polyamine. Reaction conditions for epichlorohydrin functionalization of polyamine or polyamidoamine polymers are taught in EP1465931 (the entire contents of which are incorporated herein by reference). Preferred epichlorohydrin functionalized polymers are polyaminoamide-epichlorohydrin (PAE) (or polyamide-polyamine-epichlorohydrin or polyamide-epichlorohydrin), for example, Kymene® or Polycup® resins (epichlorohydrin functionalized adipic acid-diethylenetriamine copolymer) from Hercules or Polycup® or Servamine® resins from Servo / Delden.

[0114] Any suitable hydrophilicity-enhancing agent may be used in the present 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 hydrophilic enhancers include, but are not limited to, monosaccharides containing amino groups, carboxyl groups or thiol groups (e.g., 3-amino-1,2-propanediol, 1-thioglycerol, 5-keto-D-gluconic acid, galactosamine, glucosamine, galacturonic acid, gluconic acid, aminogluconic acid, mannosamine, sucrose 1,4-lactone, sugar acid, 2-keto-3-deoxynonulosonic acid (Ketodeoxynonulosonic acid) acid), N-methyl-D-glucosamine, 1-amino-1-deoxy-β-D-galactose, 1-amino-1-deoxysorbitol, 1-methylamino-1-deoxysorbitol, N-aminoethylglucosylamine); disaccharides containing an amino group, a carboxyl group or a thiol group (for example, chondroitin disaccharide sodium salt, di(β-D-xylopyranosyl)amine, lactobionic acid, heparin disaccharide, hyaluronic acid disaccharide, lactobionic acid); and oligosaccharides containing an amino group, a carboxyl group or a thiol group (for example, carboxymethyl-β-cyclodextrin sodium salt, 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, the content of monomer units having an amine group (-NHR', wherein R' is as defined above), a carboxyl group (-COOH) and / or a thiol (-SH) group in the hydrophilic polymer as the hydrophilicity enhancer is less than about 40% by weight, 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, based on the total weight of the hydrophilic polymer.

[0117] A preferred type of hydrophilic polymer as a hydrophilicity enhancer is a polysaccharide containing an amino group or a carboxyl group, for example, carboxymethyl cellulose (carboxyl content of about 40% or less, which is estimated based on the composition of the repeating unit -[C 6H 10-mO 5(CH 2CO 2H) m]-, wherein m is 1 to 3), carboxyethyl cellulose (carboxyl content of about 36% or less, which is estimated based on the composition of the repeating unit -[C 6H 10-mO 5(C 2H 4CO 2H) m]-, wherein m is 1 to 3), carboxypropyl cellulose (carboxyl content of about 32% or less, which is estimated based on the composition of the repeating unit -[C 6H 10-mO 5(C 3H 6CO 2H) m]-, wherein m is 1 to 3), hyaluronic acid (carboxyl content of about 11%, which is estimated based on the composition of the repeating unit -(C 13H 20O 9NCO 2H)-), chondroitin sulfate (the carboxyl content is about 9.8%, which is estimated based on the composition of the repeating unit -(C 12H 18O 13NS CO 2H)-), or a combination thereof.

[0118] Another preferred class of hydrophilic polymers as hydrophilicity enhancers include, but are not limited to: poly(ethylene glycol) (PEG) having a mono-amine, carboxyl or thiol group (e.g., PEG-NH2, PEG-SH, PEG-COOH); H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; ...COOH; HOOC-PEG-SH; H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; HOOC-PEG-SH; HOOC-PEG-SH; HOOC-PEG-SH; HOOC-PEG-SH; HOOC-PEG-SH; HOOC-PEG-SH; HOOC-PEG-SH; HOOC 2N-PEG-SH; multi-arm PEG with one or more amine, carboxyl or thiol groups; PEG dendrimer with one or more amine, carboxyl or thiol groups; diamine- or dicarboxyl-terminated homopolymers or copolymers of non-reactive hydrophilic vinyl monomers; monoamine- or monocarboxyl-terminated homopolymers or copolymers of non-reactive hydrophilic vinyl monomers; copolymers that are the polymerization product of a composition comprising: (1) about 60 wt % or less, preferably about 0.1 wt % to about 30 wt %, more preferably about 0.5 wt % to about 20 wt %, even more preferably about 1 wt % to about 15 wt % 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 phosphorylcholine; and combinations thereof. The reactive vinyl monomers and the non-reactive hydrophilic vinyl monomers are those described above.

[0119] More preferably, the hydrophilic polymer used as the hydrophilicity enhancer is PEG-NH 2; PEG-SH; PEG-COOH; H 2N-PEG-NH 2; HOOC-PEG-COOH; HS-PEG-SH; H 2N-PEG-COOH; HOOC-PEG-SH; H 2N-PEG-SH; a multi-arm PEG having one or more amine, carboxyl or thiol groups; a PEG dendrimer having one or more amine, carboxyl or thiol groups; a monoamine-, monocarboxyl-, diamine- or dicarboxyl-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer selected from the group consisting of acrylamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, a C 1-C 2-hydroxy-1-hydroxy- ... 4-alkoxy polyethylene glycol (meth)acrylate, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, N,N-dimethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylamide, (meth)acryloxyethyl phosphorylcholine, and combinations thereof; copolymers as polymerization products of a composition comprising: (1) 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, C 2-C 12 alkylacrylic acid, vinylamine, allylamine and / or (meth)acrylamide-C 2-C and (2) (meth)acryloxyethyl phosphorylcholine and / or at least one non-reactive hydrophilic vinyl monomer selected from the group consisting of acrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of up to 400 Daltons, vinyl alcohol, and combinations thereof.

[0120] Most preferably, the hydrophilicity enhancer is PEG-NH2; PEG-SH; PEG-COOH; monoamine-, monocarboxyl-, diamine- or dicarboxyl-terminated polyvinylpyrrolidone; monoamine-, monocarboxyl-, diamine- or dicarboxyl-terminated polyacrylamide; monoamine-, monocarboxyl-, diamine- or dicarboxyl-terminated poly(DMA); monoamine- or monocarboxyl-, diamine- or dicarboxyl-terminated poly(DMA-co-NVP); monoamine-, monocarboxyl-, diamine- or dicarboxyl terminated poly(NVP-co-(meth)acrylate N,N-dimethylaminoethyl); monoamine-, monocarboxyl-, diamine-, or dicarboxyl terminated poly(vinyl alcohol); monoamine-, monocarboxyl-, diamine-, or dicarboxyl terminated poly[(meth)acryloyloxyethyl phosphorylcholine] homopolymer or copolymer; monoamine-, monocarboxyl-, diamine-, or dicarboxyl terminated poly(NVP-co-vinyl alcohol); monoamine-, monocarboxyl % 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; a copolymer which is the polymerization product of a composition comprising: (1) (meth)acryloxyethylphosphorylcholine 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 a carboxylic acid-containing vinyl monomer and / or an amine-containing vinyl monomer; and combinations thereof.

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

[0122] Monoamine-, monocarboxyl-, diamine-, or dicarboxyl-terminated homopolymers or copolymers of one or more non-reactive hydrophilic vinyl monomers or vinyl monomers containing phosphorylcholine can be prepared according to the procedures described in U.S. Pat. No. 6,218,508 (the entire contents of which are incorporated herein by reference). For example, to prepare diamine- or dicarboxyl-terminated homopolymers or copolymers of non-reactive hydrophilic vinyl monomers, non-reactive vinyl monomers, chain transfer agents having amine or carboxyl groups (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, thioacetic acid, thiolactic acid, or other hydroxythiols, aminothiols, or carboxyl-containing thiols), and optionally other vinyl monomers are copolymerized (thermally or photochemically) with reactive vinyl monomers (having amine or carboxyl groups) in the presence of a free radical initiator. Typically, the molar ratio of the chain transfer agent to all vinyl monomers except the reactive vinyl monomer is about 1:5 to about 1:100, and the molar ratio of the chain transfer agent to the reactive vinyl monomer is 1:1. In the preparation, the chain transfer agent having an amine group or a carboxyl group is used to control the molecular weight of the resulting hydrophilic polymer and to form the terminal of the resulting hydrophilic polymer to provide one terminal amine group or carboxyl group to the resulting hydrophilic polymer, while the reactive vinyl monomer provides other terminal carboxyl groups or amine groups to the resulting hydrophilic polymer. Similarly, to prepare a monoamine- or monocarboxyl-terminated homopolymer or copolymer of a non-reactive hydrophilic vinylic monomer, the non-reactive vinylic monomer, a chain transfer agent having an amine or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, thioacetic acid, thiolactic acid, or other hydroxythiols, aminothiols, or carboxyl-containing thiols), and optionally other vinylic monomers are copolymerized (thermally or actinically) in the absence of any reactive vinylic monomer.

[0123] As used in this application, copolymers of non-reactive hydrophilic vinyl monomers refer to the polymerization product of non-reactive hydrophilic vinyl monomers and one or more additional vinyl monomers. Copolymers comprising non-reactive hydrophilic vinyl monomers and reactive vinyl monomers (e.g., vinyl monomers containing carboxyl groups) can be prepared according to any conventional free radical polymerization method or obtained from commercial suppliers. Copolymers containing methacryloyloxyethyl phosphorylcholine and carboxyl-containing vinyl monomers can be obtained from NOP Corporation (e.g., LIPIDURE®-A and LIPIDURE®-AF).

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

[0125] According to the present invention, the reaction between the hydrophilicity-enhancing agent and the epichlorohydrin-functionalized polyamine or polyamidoamine is carried out at a temperature of about 40° C. to about 100° C. for a time sufficient to form a water-soluble and thermally cross-linkable hydrophilic polymeric material containing azetidinium groups (about 0.3 hours to about 24 hours, preferably about 1 hour to about 12 hours, and even more preferably about 2 hours to about 8 hours).

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

[0127] According to the present invention, heating is preferably performed by autoclaving a preformed 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 immersed in a packaging solution (i.e., a buffered aqueous solution) containing a water-soluble heat-crosslinkable 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 a buffered aqueous solution that is safe for the eye after autoclaving. Alternatively, heating is preferably performed by autoclaving a preformed SiHy contact lens comprising a base coating and a layer of a water-soluble heat-crosslinkable hydrophilic polymeric material on top of the base coating, and immersed in a packaging solution (i.e., a buffered 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 autoclave sterilization and storage of soft contact lenses in lens packages (or containers). Any lens package can be used in the present invention. Preferably, the lens package is a blister package comprising a base and a cover, wherein the cover is detachably sealed to the base, wherein the base comprises a cavity for containing a sterile packaging solution and a contact lens.

[0129] The lenses are packaged in individual packages, sealed, and sterilized (e.g., by autoclaving at about 120° C. or higher for at least 30 minutes) before being distributed to users. One skilled in the art should fully understand how to seal and sterilize lens packages.

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

[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 may be used. Buffers suitable as components of the contact lens care compositions of the present invention are known to those skilled in the art. Examples are boric acid, borates (e.g., sodium borate), citric acid, citrates (e.g., potassium citrate), bicarbonates (e.g., sodium bicarbonate), TRIS (2-amino-2-hydroxymethyl-1,3-propanediol), Bis-Tris (bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane), bis-amino polyols, triethanolamine, ACES (N-(2-hydroxyethyl)-2-aminoethanesulfonic acid), BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), HEPES (4-(2-hydroxyethyl)-1-hexahydropyrazineethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), MOPS (3-[N-morpholino]-propanesulfonic acid), PIPES (hexahydropyrazine-N,N'-bis(2-ethanesulfonic acid), TES (N-[tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid), salts thereof, phosphate buffers (e.g., Na 2HPO 4, NaH 2PO 4, and KH 2PO 4) 4) or a mixture thereof. The preferred bis-amino polyol is 1,3-bis(tris(hydroxymethyl)-methylamino)propane (bis-TRIS-propane). The amount of each buffer in the packaging solution is preferably 0.001 wt % to 2 wt %, preferably 0.01 wt % to 1 wt %; and most preferably about 0.05 wt % to about 0.30 wt %.

[0132] The tonicity of the packaging solution is about 200 milliosmolecular (mOsm) to about 450 milliosmolecular, preferably about 250 mOsm to about 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 pressure 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, preferably about 1.2 centipoise to about 10 centipoise, and more preferably about 1.5 centipoise to about 5 centipoise.

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

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

[0136] Preferred viscosity-increasing polymers include, but are not limited to, water-soluble cellulose ethers (e.g., methylcellulose (MC), ethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), or mixtures thereof), water-soluble polyvinyl alcohol (PVA), high molecular weight poly(ethylene oxide) having a molecular weight greater than about 2000 (up to 10,000,000 Daltons), polyvinylpyrrolidone having a molecular weight of about 30,000 Daltons to about 1,000,000 Daltons, copolymers of N-vinylpyrrolidone and at least one dialkylaminoalkyl (meth)acrylate having 7-20 carbon atoms, and combinations thereof. Water-soluble cellulose ethers and copolymers of vinylpyrrolidone and dimethylaminoethyl methacrylate are the most preferred viscosity-increasing polymers. N-vinylpyrrolidone and dimethylaminoethyl methacrylate are commercially available, for example, Copolymer 845 and Copolymer 937 from ISP.

[0137] The viscosity-enhancing polymer is present in the packaging solution in an amount of about 0.01 wt % to about 5 wt %, preferably about 0.05 wt % to about 3 wt %, even more preferably about 0.1 wt % to about 1 wt %, based on the total amount of the packaging solution.

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

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

[0140] Exemplary α-hydroxy-polyacids or biocompatible salts thereof include, but are not limited to, citric acid, 2-oxoglutaric acid, or malic acid or biocompatible (preferably ophthalmologically compatible) salts thereof. More preferably, the α-hydroxy-polyacid is citric acid or malic acid or a biocompatible (preferably ophthalmologically compatible) salt thereof (e.g., sodium salt, potassium salt, 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 above-mentioned exemplary mucin-like material, the above-mentioned exemplary ophthalmologically beneficial material, and the above-mentioned 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 break-up time (WBUT). WBUT is the time required for the water film to break (dewet) and expose the underlying lens material under naked eye observation. SiHy contact lenses with longer WBUT can maintain a water (tear) film on their surface for a relatively long period of time when worn on the eye. Dry spots are less likely to occur during eyelid blinking and enhanced wearing comfort can be provided. WBUT can be measured according to the procedures described in the Examples below. Preferably, the SiHy contact lens of the present invention has a surface hydrophilicity characterized by having a water break-up time of at least about 10 seconds.

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

[0144] In a preferred embodiment, the SiHy contact lens 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, 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 described above separately in this aspect of the present invention, these embodiments may be combined and / or used together in any desired form to achieve different embodiments of the silicone hydrogel contact lens of the present invention.

[0146] In another aspect, the present invention provides a hydrated silicone hydrogel contact lens. The hydrated silicone hydrogel contact lens of the present invention comprises: a silicone hydrogel material as a bulk material, a front surface and an opposite back surface; wherein the oxygen permeability 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 surface and the back surface on the cross-sectional surface of the contact lens includes an anterior outer region (including and close to the anterior surface), an inner region (including and surrounding the center of the shortest line), and a back outer region (including and close to the back surface), wherein the anterior outer region has an average anterior surface modulus (expressed as ) and the rear outer region has an average rear surface modulus (expressed as ), where the interior region has an average internal surface modulus (expressed as ),in and Preferably, the front outer region and the rear outer region cover a span 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.

[0147] In a preferred embodiment, the hydrated silicone 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%, and most preferably about 25% to about 55% by weight; a 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, and most preferably about 50 degrees or less; a surface hydrophilicity characterized by having a WBUT of at least about 10 seconds; or a combination thereof.

[0148] In another preferred embodiment, the front and back surfaces have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups), characterized by attracting at most about 200, preferably at most about 160, more preferably at most about 120, even more preferably at most about 90, and most preferably at most about 60 positively charged particles in a positively charged particle attachment test. To have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups), the front outer hydrogel layer and the back outer hydrogel layer should have a relatively low carboxylic acid content. Preferably, the carboxylic acid content of the front outer hydrogel layer and the back outer hydrogel layer is about 20 wt % or less, preferably about 15 wt % or less, even more preferably about 10 wt % or less, and most preferably about 5 wt % 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 (expressed as CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less. Alternatively, the SiHy contact lens of the present invention preferably has better lubricity than 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 wiping, as characterized by the absence of visible surface crack lines under dark field after wiping the SiHy contact lens between fingers. It is believed that surface cracks caused by finger wiping can reduce surface lubricity and / or may not prevent silicone from migrating to the surface (exposure).

[0151] In another preferred embodiment, the hydrated SiHy contact lens of the present invention comprises an inner layer of a silicone hydrogel material, a front outer hydrogel layer, and a rear outer hydrogel layer, wherein the front outer hydrogel layer and the rear outer hydrogel layer are substantially uniform in thickness and merge at the peripheral edge of the contact lens to completely surround the inner layer of the silicone 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, and the inner region corresponds to the inner layer of the silicone hydrogel material. All of the above-mentioned embodiments of the outer hydrogel layer (cross-linked coating) used in other aspects of the present invention can be used alone or in any combination in this aspect of the present invention as the outer hydrogel layer. All of the above-mentioned embodiments of the inner layer of the silicone hydrogel material used in other aspects of the present invention can be used alone or in any combination in this aspect of the present invention as the inner layer of the silicone hydrogel material.

[0152] According to this aspect 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 a cross section of the SiHy contact lens in a fully hydrated state as described above. In another preferred embodiment, the thickness of each outer hydrogel layer is at most about 30% (i.e., 30% or less), preferably at most about 20% (20% or less), and more preferably at most about 10% (10% or less) of the center thickness of the SiHy contact lens in a fully hydrated state. In addition, each of the two outer hydrogel layers is substantially free of polysilicone (as characterized by a silicon atomic percentage of about 5% or less, preferably about 4% or less, 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), preferably completely free of polysilicone. It should be understood that a small percentage of polysilicone can be incorporated into the polymer network of the outer hydrogel layer as desired (but not preferred) as long as it does not significantly destroy 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 include a water content that is higher than the water content of the hydrated silicone hydrogel contact lens (expressed as WC lens), and more specifically must be at least about 1.2 times (i.e., 120%) of the WC lens. It is believed that the water swelling 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 swelling 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 swelling rate of each outer hydrogel layer is at least about , preferably about , better , or even better In alternative preferred embodiments, 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%; 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 comprises a transition layer between the silicone hydrogel material and the outer hydrogel layer. All the various embodiments of the transition layer described in the previous aspects of the present invention can be used in this aspect of the present invention alone or in any combination.

[0155] The hydrated SiHy contact lens of the present invention can be made according to the above method. All the various embodiments of the above inner layer (i.e., the silicone hydrogel material) can be used alone or in any combination in this aspect of the present invention as the silicone hydrogel core. All the various embodiments described for the previous aspects of the present invention can be used alone or in any combination in this aspect of the present invention.

[0156] It should be understood that although various embodiments including preferred embodiments of the present invention may be described above separately in this aspect of the present invention, these embodiments may be combined and / or used together in any desired form to achieve different embodiments of the silicone hydrogel contact lens of the present invention. All various embodiments described for the previous aspects of the present invention may be used in this aspect of the present invention alone or in combination in any desired form.

[0157] In another aspect, the present invention provides hydrated silicone hydrogel contact lenses. The hydrated silicone hydrogel contact lens of the present invention comprises: a silicone hydrogel material as a bulk material, an anterior surface and an opposing posterior 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, even more preferably at least about 110 barrer / mm, and (2) has a surface lubricity characterized by a critical coefficient of friction (expressed as CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less, wherein the anterior and posterior surfaces have a low surface concentration of negatively charged groups (including carboxylic acid groups), characterized by attracting at most about 200, preferably at most about 160, more preferably at most about 120, even more preferably at most about 90, and most preferably at most about 60 positively charged particles in a positively charged particle attachment test.

[0158] In a preferred embodiment, the hydrated silicone 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%, and most preferably about 25% to about 55% by weight; a 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, and most preferably about 50 degrees or less; a 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 wiping, as characterized by the absence of visible surface crack lines under dark field after wiping the SiHy contact lens between fingers. It is believed that surface cracks caused by finger wiping can reduce surface lubricity and / or may not prevent silicone from migrating to the surface (exposure).

[0160] In another preferred embodiment, the hydrated SiHy contact lens of the present invention comprises an inner layer of a silicone hydrogel material, a front outer hydrogel layer, and a rear outer hydrogel layer, wherein the front outer hydrogel layer and the rear outer hydrogel layer are substantially uniform in thickness and merge at the peripheral edge of the contact lens to completely surround the inner layer of the silicone 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, and the inner region corresponds to the inner layer of the silicone hydrogel material. All of the above-mentioned embodiments of the outer hydrogel layer (cross-linked coating) used in other aspects of the present invention can be used alone or in any combination in this aspect of the present invention as the outer hydrogel layer. All of the above-mentioned embodiments of the inner layer of the silicone hydrogel material used in other aspects of the present invention can be used alone or in any combination in this aspect of the present invention as the inner layer of the silicone hydrogel material.

[0161] According to this aspect 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 a cross section of the SiHy contact lens in a fully hydrated state as described above. In another preferred embodiment, the thickness of each outer hydrogel layer is preferably at most about 30% (i.e., 30% or less), preferably at most about 20% (20% or less), and more preferably at most about 10% (10% or less) of the center thickness of the SiHy contact lens in a fully hydrated state. In addition, each of the two outer hydrogel layers is substantially free of polysilicones (as characterized by a silicon atomic percentage of about 5% or less of the total elemental percentage, preferably about 4% or less, even more preferably about 3% or less, as measured by XPS analysis of the contact lens in a dry state), preferably completely free of polysilicones. It should be understood that a smaller percentage of polysilicones can be incorporated into the polymer network of the outer hydrogel layer as desired (but not preferred) as long as it does not significantly destroy the surface properties (hydrophilicity, wettability, and / or lubricity) of the SiHy contact lens. In order to have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups), the front outer hydrogel layer and the rear outer hydrogel layer should have a relatively low carboxylic acid content. Preferably, the carboxylic acid content of the front outer hydrogel layer and the rear outer hydrogel layer 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 include a water content that is higher than the water content of the hydrated silicone hydrogel contact lens (expressed as WC lens), and more specifically must be at least about 1.2 times (i.e., 120%) the water content of the hydrated silicone hydrogel contact lens (expressed as WC lens). It is believed that the water swelling 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 swelling 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 swelling rate of each outer hydrogel layer is at least about , preferably about , better , or even better In alternative preferred embodiments, 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%; 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 independently 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.

[0164] Preferably, the SiHy contact lens further comprises a transition layer between the silicone hydrogel material and the outer hydrogel layer. All the various embodiments of the transition layer described in the previous aspects of the present invention can be used in this aspect of the present invention alone or in any combination.

[0165] The hydrated SiHy contact lens of the present invention can be made according to the above method. All the various embodiments of the above inner layer (i.e., the silicone hydrogel material) can be used alone or in any combination in this aspect of the present invention as the silicone hydrogel core. All the various embodiments described for the previous aspects of the present invention can be used alone or in any combination in this aspect of the present invention.

[0166] It should be understood that although various embodiments including preferred embodiments of the present invention may be described above separately in this aspect of the present invention, these embodiments may be combined and / or used together in any desired form to achieve different embodiments of the silicone hydrogel contact lens of the present invention. All various embodiments described for the previous aspects of the present invention may be used in this aspect of the present invention alone or in combination in any desired form.

[0167] The foregoing disclosure will enable one skilled in the art to practice the present invention. Various modifications, variations, and combinations may be made to the various embodiments described herein. In order for the reader to better understand the specific embodiments and their advantages, reference is made to the following examples. It is intended that the description and examples be considered illustrative.

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

[0169] [Example] [1]

[0170] [Oxygen permeability measurement] []

[0171] The apparent oxygen permeability of a lens and the oxygen transmission rate of a lens material may be determined according to techniques similar to those described in U.S. Pat. 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), both of which are incorporated herein by reference in their entirety. Oxygen flux (J) is measured in a wet cell (i.e., the airflow is maintained at about 100% relative humidity) at 34° C. using a Dk1000 instrument (available from Applied Design and Development, Norcross, GA) or similar analytical instrument. A gas flow of a known percentage of oxygen (e.g., 21%) is passed through one side of the lens at a rate of about 10 cm 3 / min. to 20 cm 3 / min., while a nitrogen flow is passed through the opposite side of the lens at a rate of about 10 cm 3 / min. to 20 cm 3 / min. Before measurement, allow the specimen to equilibrate in the test medium (i.e., saline or distilled water) at the specified test temperature for at least 30 minutes but not more than 45 minutes. Before measurement, allow any test medium used as a cover layer to equilibrate at the specified test temperature for at least 30 minutes but not more than 45 minutes. Set the stirring motor speed to 1200±50 rpm, which corresponds to the specified setting of 400±15 for the stepper motor controller. Measure the atmospheric pressure P measured value surrounding the system. Determine the thickness (t) of the area of ​​the lens exposed for testing by measuring approximately 10 locations with a Mitotoya micrometer VL-50 or similar instrument and taking the average of these measurements. Measure the oxygen concentration in the nitrogen gas stream (i.e., the oxygen diffused through the lens) using a DK1000 instrument. Determine the apparent oxygen permeability Dk app of the lens material according to the following formula: Dk app=Jt / (P oxygen) [] Where J = oxygen flux [μL O 2 / cm 2-minute] P oxygen = (P measured value - P water vapor) = (O 2% in the air flow) [mm Hg] = partial pressure of oxygen in the air flow P measured value = atmospheric pressure (mm Hg) P Water vapor = 0 mm Hg, at 34°C (in a drying bath) (mm Hg) P water vapor = 40 mm Hg at 34°C (in a wet cell) (mm Hg) t = average thickness of the exposed test area of ​​the lens (mm) Dk app is expressed in barrer.

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

[0173] The above measurements are not corrected 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 the oxygen flux measurement. The boundary layer effect causes the reported value of the apparent Dk of the silicone hydrogel material to be lower than the actual intrinsic Dk value. In addition, 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] Based on the following The intrinsic Dk value of the lens is estimated by correcting the Dk value for the surface resistance to oxygen flux caused by the [boundary] layer effect.

[0175] The apparent oxygen permeability values ​​(single point) of reference lotrafilcon A (Focus® N&D®, from CIBA VISION) or lotrafilcon B (AirOptix™, from CIBA VISION) lenses were measured using the same equipment. The reference lenses had similar optical power to the test lenses and were measured simultaneously with the test lenses.

[0176] According to the above appearance [Dk] Measurement Procedure The oxygen flux through a series of lotrafilcon A or lotrafilcon B (reference) lens thicknesses is measured using the same equipment to obtain the intrinsic Dk value (Dk i) of the reference lens. The thickness series should cover a thickness range of about 100 µm or greater. Preferably, the range of reference lens thicknesses will encompass the thickness of the test lenses. The Dk app of these reference lenses must be measured on the same equipment as the test lenses and ideally should be measured at the same time as the test lenses. The equipment settings and measurement parameters should be kept constant throughout the experiment. Individual samples can be measured multiple times if necessary.

[0177] When calculating, use [Equation] 1 Determine the residual oxygen resistance value R r based on the reference lens results. (1) Where t is the thickness of the test lens (i.e., also the reference lens), and n is the number of reference lenses measured. The residual oxygen resistance value R r and t data are plotted and fitted with a curve of the form Y = a + bX, where for the jth lens, Y j = (ΔP / J) j and X = tj. The residual oxygen resistance R r is equal to a.

[0178] Based on Equation 2, the corrected oxygen permeability Dk c (estimated intrinsic Dk) of the test lens was calculated using the residual oxygen resistance values ​​measured above. Dk c = t / [(t / Dk a)-R r] (2)

[0179] Based on Equation 3, the estimated intrinsic Dk of the test lens can be used to calculate [Same] Apparent Dk of standard thickness lenses in the test environment (Dk a_std). Standard thickness of lotrafilcon A (t std) = 85 µm. Standard thickness of lotrafilcon B = 60 µm. Dk a_std=t std / [(t std / Dk c)+R r_std] (3)

[0180] [Ion permeability measurement.] []

[0181] The ion permeability of the lens was measured according to the procedure described in U.S. Pat. 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 / D ref ) (with reference to the lens material Alsacon as the reference material). The ionoflux diffusion coefficient of Alsacon is 0.314×10 -3 mm 2 / min.

[0182] [Lubricity evaluation] []

[0183] The lubricity rating is a qualitative rating scheme where 0 indicates a polyacrylic acid coated control lens, 1 indicates an Oasys TM / TruEye TM commercial lens and 4 indicates a commercial Air Optix TM lens. The specimens were rinsed at least three times with excess DI water and then transferred to PBS prior to evaluation. Prior to evaluation, hands were rinsed with a soap solution, rinsed thoroughly with DI water and then dried with a KimWipe® towel. The specimens were handled between the fingers and each specimen was assigned a numerical number relative to the above standard lens. For example, if a lens was measured to be only slightly better than an Air Optix TM lens, it would be assigned a value of 3. For consistency, all ratings were performed independently by the same two operators to avoid bias, and the data revealed good qualitative synergy and consistency in the evaluations.

[0184] [Surface Wettability Test.] The water contact angle of a contact lens is a general measure of the wettability of the contact lens surface. Specifically, a low water contact angle corresponds to a wetter surface. The average contact angle (sessile droplet) of the contact lens was measured using a VCA 2500 XE contact angle measuring device purchased from AST, Inc., Boston, Massachusetts. This device is capable of measuring advancing or receding contact angles or sessile (static) contact angles. The measurements were performed as described below on fully hydrated contact lenses and immediately after the blots dried. The contact lenses were removed from the vials and washed three times in approximately 200 ml of fresh DI water to remove loosely bound packaging additives from the lens surface. The lenses were then placed on top of a lint-free cleaning cloth (Alpha Wipe TX1009), wiped thoroughly to remove surface water, mounted on a contact angle measurement base, blown dry with a stream of dry air, and finally the sessile droplet contact angle was automatically measured using the software provided by the manufacturer. The DI water used to measure the contact angle has a resistivity of >18 MΩcm and the drop volume used is 2 μl. Typically, uncoated silicone hydrogel lenses (after autoclaving) have a sessile drop contact angle of approximately 120 degrees. The tweezers and base were thoroughly washed with isopropyl alcohol and rinsed with DI water before contacting the contact lens.

[0185] [Water Break Time] [(WBUT)] [Test.] The surface hydrophilicity of the lens was evaluated (after autoclaving) by determining the time required for the water film on the lens surface to begin to break. Briefly, the lens was removed from the vial and washed 3 times in approximately 200 ml of fresh DI water to remove loosely bound packaging additives from the lens surface. The lens was removed from the solution and held against a bright light source using tweezers. Note the time required for the water film to break (dewet) to expose the underlying lens material by visual observation. Uncoated lenses typically break immediately upon removal from DI water and are assigned a WBUT of 0 seconds. Lenses that exhibit a WBUT ≥ 5 seconds are considered to have good hydrophilicity and are expected to exhibit adequate ability to maintain a tear film to the eye.

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

[0187] [Testing of coating durability.] The lens is finger-rubbed 30 times with Solo-care® multi-purpose lens care solution and then rinsed with saline. The above procedure is repeated a given number of times, for example, 1 to 30 times (i.e., the number of consecutive finger-rub tests simulating a cleaning and soaking cycle). The lens is then subjected to a Sudan Black test (i.e., the above-mentioned coating integrity test) to verify whether the coating is still intact. To withstand the finger rubbing test, there must not be a significant increase in staining spots (e.g., staining spots covering no more than about 5% of the total lens surface). The water contact angle is measured to determine the coating durability.

[0188] [Determination of Azetidinium Content.] The azetidinium content in PAE can be determined according to one of the following analyses.

[0189] [PPVS] [Analysis.] The PAE charge density (i.e., azetidinium content) can be determined according to the PPVS analysis, which is a colorimetric titration assay in which the titrant is potassium vinyl sulfate (PPVS) and toluidine blue is the indicator. See SK Kam and J. Gregory, "Charge determination of synthetic cationic polyelectrolytes by colloid titration," Colloid & Surface A: Physicochem. Eng. Aspect, 159: 165-179 (1999). PPVS binds a positively charged species, such as toluidine blue, and the azetidinium group of PAE. An increase in the absorbance intensity of toluidine blue indicates a proportional PAE charge density (azetidinium content).

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

[0191] [PCD] [Analysis.] PCD analysis is a potentiometric titration analysis for determining the charge density (azetidinium content) of PAE. The titrant is sodium polyvinyl sulfonate (PES-Na), PPVS or other titrants. For example, the Mütek PCD-04 particle charge detector from BTG is used to detect the PAE charge via electrodes. 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] [Methods.] The active positively charged moiety in PAE is the azetidinium group (AZR). The NMR ratio method is the ratio of the number of AZR group-specific protons to the number of non-AZR related protons. This ratio is an indication 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. Use a paper towel to wipe gloved hands and then use fingers to wipe both sides of the lens to transfer any debris to the lens surface. Rinse the lens briefly and then observe under a microscope. Use a qualitative rating scale of 0 (no debris adhesion) to 4 (debris adhesion equal to the PAA-coated control lens) to rate each lens. Lenses rated "0" or "1" are considered acceptable.

[0194] [Example] [2] []

[0195] [CE-PDMS] [Preparation of macromonomers] []

[0196] In the first step, α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn=2000, Shin-Etsu, KF-6001a) was capped with IPDI 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 the IPDI-PDMS-IPDI solution to which an additional 0.063 g of DBTDL had been added. The reactor was kept at about 40° C. for 4.5 h to form HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. The MEK was then removed under reduced pressure. In the third step, the terminal hydroxyl groups were capped with methacryloyloxyethyl groups by adding 7.77 g of isocyanatoethyl methacrylate (IEM) and an additional 0.063 g of DBTDL in the third step to form IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM (i.e., CE-PDMS capped with methacrylate groups).

[0197] [having terminal methacrylate groups] [CE-PDMS] [Alternative preparation of macromonomers] []

[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 high vacuum (2×10 -2 mbar). Then, under dry nitrogen atmosphere, 320 g of distilled MEK was then added to the reactor and the mixture was stirred thoroughly. 0.235 g of DBTDL was added to the reactor. After the reactor was warmed to 45° C., 45.86 g of IPDI was added to the reactor with moderate stirring via an addition funnel within 10 minutes. 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 at about 55° C. under dry nitrogen atmosphere overnight. The next day, MEK was removed by flash distillation. The reactor was cooled, and then 22.7 g of IEM was loaded into the reactor, followed by about 0.235 g of DBTDL. After about 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 about 18° C. to obtain a CE-PDMS macromonomer with terminal methacrylate groups.

[0199] [Example] [3]

[0200] [Preparation of lens formulations] []

[0201] The components were prepared by dissolving them in 1-propanol to have the following composition: [Preparation] Lens formulation: 33 wt% of CE-PDMS macromer prepared in Example 2, 17 wt% of N-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24 wt% of N,N-dimethylacrylamide (DMA), 0.5 wt% of N-(Carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt) (L-PEG), 1.0 wt% of Darocur 1173 (DC1173), 0.1 wt% of visitint (5% copper phthalocyanine blue pigment dispersion in tris(trimethylsiloxy)silylpropyl methacrylate TRIS), and 24.5 wt% of 1-propanol.

[0202] [Manufacture of lenses] []

[0203] By making the lens obtained above in a reusable mold [Formulation] is cast molded to make lenses, the reusable mold is similar to the mold shown in Figures 1-6 (Figures 1-6) of U.S. Patent Nos. 7,384,590 and 7,387,759. The mold includes a female mold half composed of CaF2 and a male mold half composed 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 lenses are extracted with isopropyl alcohol (or methyl ethyl ketone MEK), rinsed in water, coated with polyacrylic acid (PAA) by immersing the lenses in a propanol solution of PAA (0.1 wt%, acidified to about pH 2.5 with formic acid), and hydrated in water. The resulting lenses having the reactive PAA-LbL base coating thereon were determined 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 inner package coating (IPC) saline was prepared by adding 0.2% polyamidoamine-epichlorohydrin (PAE) (Kymene, from Ashland, in the form of an aqueous solution and used as received, azetidinium content of 0.46 using NMR analysis) in phosphate buffered saline (hereinafter PBS) (about 0.044 w / w% NaH2PO4·H2O, about 0.388 w / w / % Na2HPO4·2H2O, about 0.79 w / w% NaCl), and then adjusting the pH to 7.2-7.4.

[0206] The lenses from Example 3 were placed in a polypropylene lens packaging case with 0.6 mL of IPC saline (half of the IPC saline was added before inserting the lenses). The blisters were 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 lenses.

[0207] The lenses were then evaluated for debris adhesion, surface cracking, lubricity, contact angle, and water breakup time (WBUT). The test lenses (packaged / autoclaved in IPC saline, i.e., lenses with PAA-x-PAE coating thereon) showed no debris adhesion after wiping with a paper towel, while the control lenses (packaged / autoclaved in PBS, i.e., lenses with PAA-LbL base coating thereon) showed severe debris adhesion. The water contact angle (WCA) of the test lenses was low (approximately 20 degrees), but the WBUT was less than 2 seconds. When viewed under a dark field microscope, severe crack lines were seen after handling the lenses (inverting the lenses and wiping between fingers). The lubricity of the test lenses was much less than that of the control lenses, as judged by a qualitative finger rub test.

[0208] [Example] [5]

[0209] Poly(acrylamide-co-acrylic acid) (or PAAm-PAA or poly(AAm-co-AA) or p(AAm-co-AA)) partial sodium salt (about 80% solid content, poly(AAm-co-AA) (80 / 20), Mw. 520,000, Mn 150,000) was purchased from Aldrich and used as received.

[0210] IPC saline was prepared by dissolving 0.02% poly(AAm-co-AA) (80 / 20) and 0.2% PAE (Kymene from Ashland, in aqueous solution and used as received, azetidinium content of 0.46 by NMR analysis) in PBS. The pH was adjusted to 7.2-7.4. PBS was prepared by dissolving 0.76% NaCl, 0.044% NaH2PO4.H2O, and 0.388% Na2HPO4.2H2O in water.

[0211] The lenses prepared in Example 3 with the PAA-LbL base coating thereon were placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline was added before inserting the lenses). The blisters were then sealed with foil and autoclaved at about 121° C. for about 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 lenses during autoclaving.

[0212] Test lenses (packaged / autoclaved in IPC saline [Sterilization], i.e., lenses with PAA-x-PAE-x-poly(AAm-co-AA) crosslinked coating thereon) had no debris adhered after wiping with a paper towel. The test lenses had a WBUT longer than 10 seconds. When observed under a dark field microscope, crack lines were visible after wiping the test lenses. The lubricity of the test lenses was much greater than the test lenses from Example 4, but still not as lubricious as the control lenses packaged in PBS.

[0213] [Example] [6]

[0214] The IPC saline was prepared by dissolving 0.02% poly(AAm-co-AA) (80 / 20) and 0.2% PAE (Kymene, from Ashland, in aqueous solution and used as received, azetidinium content of 0.46 using NMR analysis) in PBS and adjusting the pH to 7.2-7.4. The saline was then treated by heating to about 70°C and maintaining at that temperature for 4 hours (heat pretreatment). During this heat pretreatment, poly(AAm-co-AA) and PAE partially cross-linked with each other (i.e., not all azetidinium groups of PAE were consumed) to form a water-soluble and heat-cross-linkable hydrophilic polymeric material containing azetidinium groups within the branched polymer network in the IPC saline. After the heat pretreatment, the final IPC saline was filtered using a 0.22 micron polyethersulfone (PES) membrane filter and cooled back to room temperature.

[0215] Will be in The lens having the PAA-LbL base coating thereon prepared in [Example] 3 was placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline was added before inserting the lens). The blister was then sealed with foil and autoclaved at about 121° C. for about 30 minutes to form a cross-linked coating (PAA-x-hydrophilic polymeric material) on the lens.

[0216] test [Lenses] (packaged in heat pre-treated IPC saline, i.e., lenses with a PAA-x-hydrophilic polymer coating thereon) showed no debris adhesion after wiping with a paper towel, while control lenses (packaged in PBS, i.e., lenses with a non-covalently attached layer of PAA thereon) showed severe debris adhesion. The test lenses had a WBUT longer than 10 seconds. When observed under a dark field microscope, no crack lines were seen after wiping the test lenses. The test lenses were extremely lubricious in the finger rub test and comparable to the control lenses.

[0217] Implementation [A series of] experiments to investigate the effect of the heat pre-treatment conditions (duration and / or temperature) of the IPC saline on the surface properties of the resulting lenses coated with the IPC saline. Heat treatment times of about 6 hours or longer at about 70°C produce lenses that tend to have similar debris adhesion as the control lenses. It is believed that longer pre-heat treatments may consume a large portion of the azetidinium groups and thus the number of remaining azetidinium groups in the branched polymer network of the resulting water-soluble polymeric material is insufficient to attach the polymeric material to the PAA coating. Heat treatment of only 4 hours at 50°C produces lenses that exhibit similar surface crack lines under dark field microscopy after rubbing between fingers as the test lenses in Example 5 (where the IPC saline was not heat pre-treated). It is believed that a shorter pre-heat treatment may consume a small amount of azetidinium groups and thus the number of remaining azetidinium groups in the branched polymer network of the resulting water-soluble polymeric material is higher, so that the resulting cross-linked coating (PAA-x-hydrophilic polymeric material) on the lens may have too high a cross-linking density.

[0218] [Example] [7]

[0219] since Poly(acrylamide-co-acrylic acid) partial sodium salt (about 90% solids content, poly(AAm-co-AA) (90 / 10), Mw 200,000) was purchased from [Polysciences] and used as received.

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

[0221] The lens with the PAA-LbL base coating thereon produced in Example 3 and the uncoated Lotrafilcon B lens (from CIBA VISION CORPORATION) soaked in the PAA acidic propanol solution (about 0.1%, pH about 2.5) were placed in a polypropylene lens packaging case with 0.6 mL of hot pre-treated IPC saline (half of the IPC saline was added before inserting the lens). The blister was then sealed with foil and autoclaved at 121° C. for about 30 minutes to form a cross-linked coating (PAA-x-hydrophilic polymeric material) on the lens.

[0222] test [Lenses] (both Lotrafilcon B and Example 3 lenses with PAA-x-hydrophilic polymer thereon) had no debris adhered after wiping with a paper towel. The test lenses had a WBUT longer than 10 seconds. When viewed under a dark field microscope, no crack lines were visible after wiping the lenses between fingers. The lenses were extremely lubricious in the qualitative finger wipe test.

[0223] [Example] [8]

[0224] In a design of experiment (DOE), an IPC saline containing about 0.05% to about 0.09% PAAm-PAA and about 0.075% to about 0.19% PAE (Kymene from Ashland, in aqueous solution and used as received, azetidinium content of 0.46 using NMR analysis) in PBS was generated. The IPC saline was heat treated at 60°C for 8 hours and the lenses from Example 3 were packaged in the heat pre-treated IPC saline. No differences in the final lens surface properties were observed, and all lenses showed excellent lubricity, resistance to debris adhesion, excellent wettability, and no evidence of surface cracking.

[0225] [Example] [9]

[0226] exist [Design] of Experiments (DOEs) were performed to generate IPC saline containing about 0.07% PAAm-PAA and sufficient PAE (about 0.15% PAE) to provide an initial azetidinium content of about 8.8 mmol equivalents / L. In a central composite design, thermal pretreatment conditions were varied between 50°C and 70°C and pre-reaction times were varied between about 4 hours and about 12 hours. A 24 hour pretreatment time at 60°C was also tested. 10 ppm hydrogen peroxide was then added to the saline to prevent bioburden growth, and the IPC saline was filtered using a 0.22 micron polyethersulfone [PES] membrane filter.

[0227] The lenses from Example 3 were packaged in heat pre-conditioned IPC saline and the blisters were then autoclaved at 121°C for 45 minutes. All lenses had excellent lubricity, wettability, and resistance to surface cracking. Some lenses showed debris sticking from the paper towel as shown in Table 1. Table 1 [] Debris Adhesion Assessment Temperature(℃) Time (hr) 50 55 60 65 70 4 qualified 6 qualified qualified 8 qualified qualified Failure 10 qualified Failure 12 qualified twenty four Failure

[0228] [Example]

[10] []

[0229] In with Copolymers of methacryloyloxyethyl phosphorylcholine (MPC) and a carboxy vinyl monomer (CH2=CH(CH3)C(O)OC2H4OC(O)C2H4COOH (MS), methacrylic acid (MA)) in the absence or presence of butyl methacrylate (BMA) were evaluated in a [PAE] combined packaging inner coating system.

[0230] Prepare PBS containing NaCl (0.75 wt%), NaH 2PO 4·H 2O (0.0536 wt%), Na 2HPO 4·2H 2O (0.3576 wt%) and DI water (97.59 wt%) and add 0.2% PAE (polycup 3160). Adjust pH to about 7.3.

[0231] 0.25% of one of several MPC copolymers was then added to form an IPC saline, and the IPC saline was heat pretreated at 70°C for 4 hours (heat pretreatment). During this heat pretreatment, MPC and PAE partially crosslinked with each other (i.e., without consuming all of the azetidinium groups of PAE) to form a water-soluble and heat-crosslinkable hydrophilic polymeric material containing azetidinium groups within the branched polymer network in the IPC saline. After 4 hours, the heat pretreated IPC saline was filtered through a 0.2 micron polyethersulfone [PES] membrane filter (Fisher Scientific catalog number 09-741-04, Thermo Scientific nalgene number 568-0020 (250 ml)).

[0232] The lenses prepared in Example 3 having the PAA-LbL base coating thereon were packaged in heat pre-conditioned IPC saline and autoclaved at 121° C. for about 30 minutes. Table 2 shows that all lenses had excellent surface properties. Table 2 [] [MPC] [Copolymer] [*] [DA] [fracture] [Lubricity] [Wettability] [ , , ] [WBUT (sec.)] Poly (MPC / MA) 90 / 10 qualified qualified Excellent Excellent Poly(MPC / BMA / MA) 40 / 40 / 20 qualified qualified Excellent Excellent Poly(MPC / BMA / MA) 70 / 20 / 10 qualified qualified Excellent Excellent Poly(MPC / BMA / MS) 70 / 20 / 10 qualified qualified Excellent Excellent * Values ​​are the molar percentages of monomer units in the copolymer. DA = Debris Adhesion WBUT is longer than 10 seconds.

[0233] [Example]

[11]

[0234] [through] [PAA] [Coated lenses.] Lenses cast molded from the lens formulation prepared in Example 3 according to the molding process described in Example 3 were extracted and coated by immersion in the following series of baths: 3 MEK baths (22 seconds, 78 seconds, and 224 seconds); a 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] [through] [PAE / PAA] [Coated lenses.] The lenses prepared above with the PAA base coating thereon were immersed in the following baths successively: 2 baths of PAE coating solution (prepared by dissolving 0.25 wt% PAE (Polycup 172, from Hercules) in DI water and adjusting the pH to about 5.0 using sodium hydroxide, and finally filtering the resulting solution using a 5 um filter) (held for 44 seconds and 56 seconds respectively); and 3 DI water baths (held for 56 seconds each). After this treatment, the lens had one PAA layer and one PAE layer.

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

[0237] [Above] [PAA-x-PAE-x-HA] [Coated lenses.] Another batch of lenses with one PAA layer and one PAE layer thereon were packaged in 0.2% hyaluronic acid (HA, product number 6915004, Novozymes) in phosphate buffered saline (PBS), and the pH was then adjusted to 7.2-7.4. The blisters were then sealed and autoclaved at 121° C. for about 30 minutes to form a cross-linked coating (PAA-x-PAE-x-HA) on the lenses.

[0238] The resulting lenses having a PAA-x-PAE-x-CMC coating thereon or having a PAA-x-PAE-x-HA coating thereon showed no Sudan Black staining, no debris adhesion, and no cracking under microscopic examination. The lenses having a PAA-x-PAE-x-CMC coating thereon had an average contact angle of 30±3 degrees, while the lenses having a PAA-x-PAE-x-HA coating thereon 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 % of mPEG-SH 2000 (methoxy-poly(ethylene glycol)-thiol, average Mw 2000, product number MPEG-SH-2000, Laysan Bio) and 2 wt % of PAE (Kymene, from Ashland, in aqueous solution and used as received, azetidinium content of 0.46 by NMR analysis) in PBS, and the final pH was adjusted to 7.5. The solution was heat-pretreated at 45° C. for about 4 hours (heat pretreatment). During this heat pretreatment, mPEG-SH 2000 and PAE reacted with each other to form a water-soluble and heat-crosslinkable hydrophilic polymeric material containing azetidinium groups and chemically grafted polyethylene glycol polymer chains. After heat treatment, the solution was diluted 10 times 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 polyethersulfone (PES) membrane filter. The final IPC saline contained 0.286 wt % of hydrophilic polymeric material (composed of about 59 wt % of MPEG-SH-2000 chains and about 41 wt % of PAE chains) and 0.25 wt % of sodium citrate dihydrate. PBS was prepared by dissolving 0.74% NaCl, 0.053% NaH 2PO 4.H 2O, and 0.353% Na 2HPO 4.2H 2O in water.

[0241] [Lenses with cross-linked coating thereon.] The PAA-coated lenses from Example 11 were packaged in the above-described IPC saline in a polypropylene lens packaging shell and then autoclaved at about 121° C. for about 30 minutes to form a cross-linked coating on the lenses. The final lenses showed no debris sticking, no crack lines after wiping the lenses. The lenses were extremely lubricious in the finger rub test compared to the PAA-coated control lenses.

[0242] Implementation [A series of] experiments to study the effect of conditions (reaction time and solution concentration of mPEG-SH2000 (with constant PAE concentration 2%)) on the surface properties of the resulting lenses coated with IPC saline. The results are shown in Table 3. Table 3 [] [[mPEG-SH2000] , 1 , ] [(wt%)] [exist]

[45] [℃] [Reaction time below] [(hr)] [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 wt%. []

[0243] As the concentration of mPEGSH2000 solution increases, the lens lubricity 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 as the grafting density increases. At high grafting density, corresponding to a solution concentration of 0.6%, the contact angle is close to the measurement obtained on a polyethylene glycol (PEG) monolayer grafted flat substrate (reference: Langmuir 2008, 24, 10646-10653).

[0244] [Example]

[13]

[0245] A series of experiments were performed to study the effect of the molecular weight of mPEG-SH. IPC saline was prepared with a procedure similar to that described in Example 12. However, the following mPEG-SHs were used to prepare the saline: mPEG-SH 1000, mPEG-SH 2000, mPEG-SH 5000, and mPEG-SH 20000. All salines were heat treated at 45°C for 4 hours and diluted 10 times. The results and reaction conditions are as follows: [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 saline with 2% PAE before heat pretreatment and 10-fold dilution. []

[0246] [Example]

[14]

[0247] The reaction mixture was prepared [by] dissolving 2.5% mPEG-SH 2000, 10% PAE (Kymene, from Ashland, in aqueous solution and used as received, azetidinium content of 0.46 using NMR analysis) in PBS and 0.25% sodium citrate dihydrate. The pH of this solution was then adjusted to 7.5, and also degassed by bubbling nitrogen through the container for 2 hours. This solution was then heat treated at 45°C for about 6 hours to form a thermally cross-linkable hydrophilic polymeric material containing mPEG-SH-2000 groups chemically grafted onto the polymer by reaction with the azetidinium groups in PAE. After the heat treatment, the solution was diluted 50 times 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 polyethersulfone (PES) membrane filter. The final IPC saline contained about 0.30 wt.% polymeric material (consisting of about 17 wt.% mPEG-SH-2000 and about 83 wt.% PAE) and 0.25% sodium citrate dihydrate.

[0248] The PAA-coated lenses from Example 11 were packaged in the above-described IPC saline in a polypropylene lens packaging case and then autoclaved at about 121° C. for about 30 minutes to form a cross-linked coating on the lenses. The final lenses showed no debris sticking and no crack lines after wiping the lenses. The test lenses were extremely lubricious in the finger rub test compared to the PAA coated control lenses.

[0249] [Example]

[15]

[0250] A reaction mixture was prepared by dissolving 3.62% mPEG-NH 2550 (methoxy-poly(ethylene glycol)-amine, MW about 550, product number MPEG-NH 2-550, Laysan Bio) and 2% PAE (Kymene, from Ashland, in aqueous solution and used as received, azetidinium content of 0.46 by NMR analysis) in PBS and the final pH was adjusted to 10. The solution was heat treated at 45° C. for about 4 hours to form a thermally cross-linkable hydrophilic polymeric material containing MPEG-NH 2-550 groups chemically grafted onto the polymer by reacting with the azetidinium groups in PAE. After heat treatment, the solution was diluted 10-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 polyethersulfone (PES) membrane filter. The final IPC saline contained about 0.562 wt.% polymeric material (composed of 64 wt.% MPEG-SH-2000 and about 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-described IPC saline in a polypropylene lens packaging case and then autoclaved at about 121° C. for about 30 minutes to form a cross-linked coating on the lenses.

[0252] The final lenses showed no debris adherence and no crack lines were observed after digitally (finger) wiping the lenses.

[0253] [Example]

[16]

[0254] Poloxamer 108 (sample) and nelfilcon A (CIBA VISION) were used as received. Nelfilcon A is a polymerizable polyvinyl alcohol obtained by modifying polyvinyl alcohol (e.g., Gohsenol KL-03 from Nippon Gohsei or the like) with N-(2,2-dimethoxyethyl)acrylamide under cyclic acetal-forming reaction conditions (Bühler et al., CHIMIA, 53 (1999), 269-274, the entire contents of which are incorporated herein by reference). About 2.5% of the vinyl alcohol units in nelfilcon A were modified with N-(2,2-dimethoxyethyl)acrylamide.

[0255] IPC saline was prepared by dissolving 0.004% poloxamer 108, 0.8% nelfilcon A, 0.2% PAE (Kymene, Polycup 3160), 0.45% NaCl, and 1.1% Na 2HPO 4.2H 2O in DI water. The saline was heat pretreated by stirring at about 65° C.- 70° C. for 2 hr. After heat pretreatment, the saline 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 with 0.6 mL of IPC saline (half of the saline was added before inserting the lenses). The blisters were then sealed with foil and autoclaved at 121°C for approximately 30 minutes. The test lenses showed no debris sticking after wiping with a paper towel. The lenses had a WBUT of greater than 10 seconds. When viewed under a dark field microscope, no crack lines were visible after wiping the lenses between fingers. The lubricity of the lenses was much greater than the lenses from Example 4, but still not as lubricious as the PAA coated control lenses packaged in PBS.

[0257] [Example]

[17] []

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

[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 dried separately at about 60°C for 12 hours (or overnight) in a single-necked flask under high vacuum. The OH molar equivalent weights of KF-6001A and KF-6002A were determined by titration of the hydroxyl groups and used to calculate the millimolar equivalents to be used in the synthesis.

[0260] The one liter reaction vessel was evacuated overnight to remove moisture, and the vacuum was broken using dry nitrogen. 75.00 g (75 meq) of dry KF6001A was charged to 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 a positive flow of nitrogen was maintained. An exotherm began to occur, and the reaction mixture was then cooled and stirred at 55°C for 2 hours. After the exotherm was reached, 248.00 g (150 meq) of dry KF6002A was added to the reactor at 55°C, and then 100 μL of DBTDL was added. The reactor was stirred for 4 hours. The heating was stopped and the reactor was cooled overnight. The nitrogen bubbling was stopped and the reactor was opened to the atmosphere for 30 minutes with moderate stirring. A hydroxyl terminated chain-extended polysiloxane HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH (or HO-CE-PDMS-OH) having 3 polysiloxane segments was formed.

[0261] For 80% olefinically 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-capped CE-PDMS) was decanted and stored under refrigeration.

[0262] [B] [:] [No] [UV] [Synthesis of absorbent amphiphilic branched polysiloxane prepolymer] []

[0263] A 1-L jacketed reactor was equipped with a 500-mL addition funnel, overhead stirring, a reflux condenser with a nitrogen / vacuum inlet adapter, a thermometer, and a sampling adapter. The reactor was charged with 45.6 g of the 80% IEM-terminated CE-PDMS prepared above and sealed. The addition funnel was charged with a solution of 0.65 g hydroxyethyl methacrylate (HEMA), 25.80 g DMA, 27.80 g (tris(trimethylsilyl))-siloxypropyl) methacrylate (TRIS) in 279 g ethyl acetate. The reactor was degassed using a high vacuum pump at <1 mbar and room temperature for 30 minutes. The monomer solution was degassed at 100 mbar and room temperature for 10 minutes and three cycles, breaking the vacuum with nitrogen between degassing cycles. The reactor was then charged with the monomer solution, and the reaction mixture was then stirred and heated to 67°C. While heating, a solution of 1.50 g of mercaptoethanol (chain transfer agent, CTA) and 0.26 g of azoisobutyronitrile dissolved in 39 g of ethyl acetate was charged to the addition funnel and deoxidized three times at 100 mbar and room temperature for 10 minutes. When the reactor temperature reached 67°C, the initiator / CTA solution was added to the PDMS / monomer solution in the reactor. The reaction was carried out for 8 hours, and then the heating was stopped and the reactor temperature was allowed 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. To this mixture solution was added 100 uL of a hydroxy-tetramethylene piperonyloxy solution (2 g / 20 mL) in ethyl acetate. The solution was then concentrated to 200 g (about 50%) at 30 °C using a rotary evaporator and filtered through a 1 um pore size filter paper. After solvent exchange to 1-propanol, the solution was further concentrated to the desired concentration.

[0265] [C. UV] [Synthesis of absorbent amphiphilic branched polysiloxane prepolymer] []

[0266] A 1-L jacketed reactor was equipped with a 500-mL addition funnel, overhead stirring, a reflux condenser with a nitrogen / vacuum inlet adapter, a thermometer, and a sampling adapter. The reactor was then charged with 45.98 g of the 80% IEM-terminated CE-PDMS prepared above and sealed. The addition funnel was charged with a solution of 0.512 g HEMA, 25.354 g DMA, 1.38 g Norbloc methacrylate, 26.034 g TRIS in 263 g ethyl acetate. The reactor was degassed using a high vacuum pump at <1 mbar and room temperature for 30 minutes. The monomer solution was degassed at 100 mbar and room temperature for 10 minutes and three cycles, breaking the vacuum with nitrogen between degassing cycles. The reactor was then charged with the monomer solution, and the reaction mixture was then stirred and heated to 67°C. While heating, a solution of 1.480 g of mercaptoethanol (chain transfer agent, CTA) and 0.260 g of azoisobutyronitrile dissolved in 38 g of ethyl acetate was charged to the addition funnel and deoxidized three times at 100 mbar and room temperature for 10 minutes. When the reactor temperature reached 67°C, the initiator / CTA solution was added to the PDMS / monomer solution in the reactor. The reaction was carried out for 8 hours, and then the heating was stopped and the reactor temperature was allowed 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 isocyanatoethyl 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. To this mixture solution was added 100 uL of a hydroxy-tetramethylene piperonyloxy solution (2 g / 20 mL) in ethyl acetate. The solution was then concentrated to 200 g (about 50%) at 30°C using a rotary evaporator and filtered through a 1 um pore size filter paper.

[0268] [D-1] [:] [with non] [UV] [Absorbent polysiloxane prepolymer lens formulation] []

[0269] In a 100 mL amber flask, 4.31 g of the synthetic macromer solution (82.39% in 1-propanol) prepared above was added. In a 20 mL vial, 0.081 g of TPO and 0.045 g of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) were dissolved in 10 g of 1-propanol and then transferred to the macromer solution. After the mixture was concentrated to 5.64 g using a rotary evaporator at 30 °C, 0.36 g of DMA was added and the formulation was homogenized at room temperature. Approximately 6 g of clear lens formulation D-1 was obtained.

[0270] [D-2] [:] [have] [UV] [Absorbent polysiloxane prepolymer lens formulation] [(4% DMA)]

[0271] In a 100 mL amber flask, 24.250 g of the macromer solution prepared above (43.92% in ethyl acetate) was added. In a 50 mL vial, 0.15 g of TPO and 0.75 g of DMPC were dissolved in 20 g of 1-propanol and then transferred to the macromer solution. 20 g of solvent was stripped off using a rotary evaporator at 30°C, followed by the addition of 20 g of 1-propanol. After two cycles, the mixture was concentrated to 14.40 g. To this mixture was added 0.6 g of DMA and the formulation was homogenized at room temperature. Approximately 15 g of clear lens formulation D-2 was obtained.

[0272] [D-3] [:have] [UV] [Absorbent polysiloxane prepolymer lens formulation] [(2% DMA / 2% HEA)] []

[0273] In a 100 mL amber flask, 24.250 g of the macromer solution prepared above (43.92% in ethyl acetate) was added. In a 50 mL vial, 0.15 g of TPO and 0.75 g of DMPC were dissolved in 20 g of 1-propanol and then transferred to the macromer solution. 20 g of solvent was stripped off using a rotary evaporator at 30°C, followed by the addition of 20 g of 1-propanol. After two cycles, the mixture was concentrated to 14.40 g. To this mixture was added 0.3 g of DMA and 0.3 g of HEA and the formulation was homogenized at room temperature. Approximately 15 g of clear lens formulation D-3 was obtained.

[0274] [Example]

[18]

[0275] [Example] [E] [:] [Improved] [PAE] [Covalent attachment of coating polymer] []

[0276] Amine-containing monomers N-(3-aminopropyl)methacrylamide hydrochloride (APMAA-HCl) or N-(2-aminoethyl)methacrylamide hydrochloride (AEMAA-HCl) were purchased from Polysciences and used as received. Poly(amidoamine epichlorohydrin) (PAE) was received from Ashland in aqueous solution and used as received. Poly(acrylamide-co-acrylic acid) (poly(AAm-co-AA)) (90 / 10) from Polysciences, mPEG-SH from Laysan Bio, and poly(MPC-co-AeMA) (i.e., a copolymer of methacryloyloxyethylphosphorylcholine (MPC) and aminoethyl methacrylate (AeMA)) from NOF were used as received.

[0277] APMAA-HCl monomer was dissolved in methanol and added to lens formulations D-1, D-2, and D-3 (prepared in Example 17) to achieve a 1 wt% concentration.

[0278] Reactive packaging saline was prepared by dissolving the components listed in Table 4 and the appropriate buffer salt in DI water. The saline was heat pretreated by stirring at about 60° C. for 8 hr. After heat pretreatment, the saline was cooled to room temperature and then filtered using a 0.2 μm PES filter. Table 4 [] [Packaging salt water sample] [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% Poly(AAm-co-AA) (90 / 10) 0.07% 0.2% -- -- -- mPEG-SH, Mw=2000 -- -- 0.3% -- -- mPEG-SH, Mw=10000 -- -- -- 0.2% -- Poly(MPC-co-AeMA) (90 / 10) -- -- -- -- 0.2%

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

[0280] [DSM] [Lens.] The concave part of the polypropylene lens mold was filled with about 75 microliters of the lens formulation prepared as above, and then the mold was closed with the convex part of the polypropylene lens mold (base curved mold). The contact lens was obtained by curing the closed mold for about 5 minutes using a UV irradiation source (Hamamatsu lamp with an intensity of about 16 mW / cm2 and a 330 nm cutoff filter).

[0281] [LS] [Lens.] LS lenses are made by cast molding the lens formulation prepared above in a reusable mold similar to the mold shown in Figs. 1-6 (Figs. 1-6) of U.S. Pat. Nos. 7,384,590 and 7,387,759. The mold includes a female mold half composed of CaF2 and a male mold half composed of PMMA. The UV irradiation source is a Hamamatsu lamp with an intensity of about 4.6 mW / cm2 and a 380 nm cutoff filter. The lens formulation in the mold is irradiated with UV irradiation for about 30 seconds.

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

[0283] The molded lenses were extracted in methyl ethyl ketone, hydrated, and packaged in one of the salines described in Table 4. The lenses were placed in polypropylene lens packaging shells with 0.6 mL of IPC saline (half of the saline was added before inserting the lenses). The blisters were then sealed with foil and autoclaved at 121°C for 30 min.

[0284] Evaluation of the lens surface showed that all tested lenses had no debris adherence after wiping with a paper towel. When observed under a dark field microscope, no crack lines were visible after wiping the lens between fingers.

[0285] The lens surface wettability (WBUT), lubricity, and contact angle 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 on a qualitative scale of 0 to 5, with lower values ​​indicating greater lubricity. In general, all properties showed improvement after application of the inner packaging coating. Table 5 [] [Lens formulations used to manufacture lenses] [brine] [ , 1 , ] [WBUT(] [Second] [)] [Lubricity] [Contact angle] [[°]] [D1] [, as a control] [ , , ( ] [Not included] [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] [ , , ( ] [Not included] [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 number of the packaged brine number shown in Table 4. 2.LS lenses

[0286] [Example]

[19] []

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

[0288] [Manufacturing of lenses.] Lenses were manufactured by cast molding the lens formulation prepared above in a reusable mold (a quartz concave mold half and a glass convex mold half) similar to the mold shown in FIGS. 1-6 (FIGs. 1-6) of U.S. Pat. Nos. 7,384,590 and 7,387,759. The lens formulation in the mold was irradiated with UV radiation (13.0 mW / cm2) for about 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 have a concentration of about 0.36 wt %, and the pH was adjusted to about 2.0 using formic acid.

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

[0291] [IPC] [Salt water.] Poly(AAm-co-AA) (90 / 10) partial sodium salt (about 90% solids content, poly(AAm-co-AA) (90 / 10), Mw 200,000) was purchased from Polysciences and used as received. PAE (Kymene, azetidinium content of 0.46 by NMR analysis) was purchased from Ashland in aqueous solution and used as received. IPC saline was prepared by dissolving about 0.07% w / w poly(AAm-co-AA) (90 / 10) and about 0.15% PAE (about 8.8 mmol initial azetidinium millimolar equivalent) in PBS (about 0.044 w / w% NaH 2PO 4·H 2O, about 0.388 w / w / % Na 2HPO 4·2H 2O, about 0.79 w / w% NaCl) and adjusting the pH to 7.2-7.4. The IPC saline was then heat pretreated at about 70° C. for about 4 hours (heat pretreatment). During this heat pretreatment, poly(AAm-co-AA) and PAE partially cross-linked with each other (i.e., not all azetidinium groups of PAE were consumed) to form a water-soluble and heat-crosslinkable hydrophilic polymeric material containing azetidinium groups within the branched polymer network in the IPC saline. After heat pretreatment, the IPC saline was filtered using a 0.22 micron PES membrane filter and cooled back to room temperature. 10 ppm hydrogen peroxide was then added to the final IPC saline to prevent bioburden growth, and the IPC saline was filtered using a 0.22 micron PES membrane filter.

[0292] [Application of cross-linked coating.] The lenses having the PAA-LbL base coating thereon prepared above were placed in polypropylene lens packaging shells (each shell containing one lens) with 0.6 mL of IPC saline (half of the saline was added before inserting the lens). The blisters were then sealed with foil and autoclaved at about 121° C. for about 30 minutes, thereby forming SiHy contact lenses having the cross-linked coating thereon (PAA-x-hydrophilic polymeric material).

[0293] [SiHy] [Characterization of Lenses.] The resulting SiHy contact lenses having a crosslinked coating (PAA-x-hydrophilic polymeric material) thereon showed no debris adhesion after wiping with a paper towel, while the control lenses (packaged in PBS, i.e., lenses having a non-covalently attached layer of PAA thereon) showed severe debris adhesion. The lenses had an oxygen permeability (Dk c or estimated intrinsic Dk) of 146 barrers, a bulk elastic modulus of 0.76 MPa, a water content of about 32 wt%, a relative ion permeability of about 6 (relative to Alsacon lenses), a contact angle of about 34 to 47 degrees, and a WBUT longer than 10 seconds. When observed under a dark field microscope, no crack lines were seen after wiping the test lenses. The lenses were extremely lubricious in the finger rub test and comparable to the control lenses.

[0294] [Example]

[20] [] The following biocompatibility studies were performed on the SiHy lenses prepared in Examples 6, 14, and 19 and IPC saline in post-autoclave lens packaging.

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

[0296] [ , Living , ] [Tested internally.] ISO systemic toxicity in mice showed no evidence of systemic toxicity for lens extracts in mice. ISO ocular irritation studies in rabbits showed that lens extracts should not be considered an irritant to rabbit ocular tissues. ISO ocular irritation studies in rabbits showed that IPC saline in the autoclaved packaging should not be considered an irritant to rabbit ocular tissues. Lenses worn continuously for 22 days in a daily disposable wear pattern were non-irritating to the rabbit model, and eyes treated with the test lenses were similar to eyes treated with the control lenses. ISO sensitization studies (Guinea Pig Maximization of packaging solution) showed that IPC saline in the autoclaved packaging did not cause any delayed dermal contact sensitization in guinea pigs. ISO sensitization studies (Guinea Pig Maximization of lens extracts) showed that sodium chloride and sesame oil extracts of the lenses did not cause delayed dermal contact sensitization in guinea pigs.

[0297] [Genotoxicity Test.] When IPC saline and SiHy lens extracts from lens packaging were tested in a bacterial reverse mutation assay (Ames test), the lens extracts and IPC saline were found to be non-mutagenic to Salmonella typhimurium test strains TA98, TA100, TA1535 and TA1537 and Escherichia coli WPuvrA. When SiHy lens extracts were tested in a mammalian erythrocyte micronucleus assay, they had no clastogenic activity and were negative in a mouse bone marrow micronucleus test. When IPC saline from lens packaging was tested according to a chromosome abnormality test in Chinese hamster ovary, IPC saline was negative for inducing structural and quantitative chromosome abnormality assays using CHO cells in both the non-activated and S9 activated test systems. When SiHy lens extracts were tested according to a cellular gene mutation assay (mouse lymphoma mutagenesis assay), the lens extracts were negative in a mouse lymphoma mutagenesis assay.

[0298] [Example] [twenty one] []

[0299] The surface composition of preformed SiHy contact lenses (i.e., SiHy contact lenses without any coating and before application of the PAA base coating), SiHy contact lenses with PAA coatings (i.e., those lenses before sealing in lens packaging with IPC saline and autoclaving), and SiHy contact lenses with crosslinked coatings thereon (all of which were made according to the procedure described in Example 19) was determined by characterizing vacuum dried contact lenses using X-ray photoelectron spectroscopy (XPS). XPS is a method for measuring the surface composition of lenses using a sampling depth of approximately 10 nm. The surface composition of the three types of lenses is reported in Table 6. Table 6 [] [] [Surface atomic composition] [(%)] [SiHy] [lens] C N O F* Si [Preformation] [(] [Uncoated] [)] 58.0 6.2 23.0 0.8 12.1 [have] [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 vacuum drying and XPS analysis []

[0300] Table 6 shows that when the PAA coating was applied to the SiHy lens (preformed lens without coating), the silicon atomic composition was substantially reduced (from 12.1% to 4.5%) and the nitrogen atomic composition was also reduced (from 6.2% to 1.6%). When the crosslinked coating was further applied to the PAA coating, the surface composition was primarily carbon, nitrogen, and oxygen, which is a triatomic composition (hydrogen is not included because XPS does not count hydrogen in the surface composition). These results indicate that the outermost layer of the SiHy contact lens with the crosslinked coating is likely to be composed essentially of a hydrophilic polymeric material that is the reaction product of poly(AAm-co-AA) (90 / 10) (60% C, 22% O, and 18% N) and PAE.

[0301] XPS analysis was also performed on the following commercial SiHy lenses that were vacuum dried. The surface compositions of those commercial SiHy contact lenses are 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 from surface contamination during vacuum drying and XPS analysis []

[0302] The SiHy contact lenses of the present invention were found to have a nominal silicon content of about 1.4% in the surface layer, which is much lower than those commercial SiHy lenses without plasma coating (Acuvue® Advance®, Acuvue® Oasys®, TruEye™, Biofinity®, Avaira™) and PureVision® (subjected to plasma oxidation) and Premio™ (subjected to unknown plasma treatment), and even lower than SiHy lenses with plasma deposited coatings of about 25 nm thick (N&D® Aqua™ and Air Optix® Aqua™). This extremely low value of Si% is comparable to the silicon atomic percentage of a control sample polyethylene from Goodfellow (LDPE, d=0.015 mm; LS356526 SDS; ET31111512; 3004622910). These results indicate that the extremely low values ​​in the XPS analysis of the vacuum dried SiHy contact lenses of the present invention may be due to contaminants introduced during the manufacturing process (including the vacuum drying process) and the XPS analysis, which is similar to the fluorine content observed in lenses without fluorine. In the SiHy contact lenses of the present invention, polysilicone has been successfully shielded from the XPS analysis.

[0303] XPS analysis was also performed on 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), 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 do not contain silicon. The silicon atomic composition in the surface layer of the test samples was as follows: 1.3±0.2 (polysilicone flakes); 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 those of silicone hydrogels.

[0304] [Example] [twenty two] []

[0305] [fluorescein labeled] [PAA (PAA-F)] [.] []

[0306] PAA-F was synthesized in-house by covalently attaching 5-aminofluorescein to PAA (Mw 450k). The degree of labeling with fluorescein was a few percent, for example, about 2 mol% (or n / (m+n)=2% in the formula shown below). Fluorescently labeled PAA (PAA-F) X: Fluorescent moiety

[0307] [Manufacture of lenses.] []

[0308] Lenses were made by cast molding in a reusable mold (a quartz female mold half and a glass male mold half) from the lens formulation prepared above in Example 19, similar to the molds shown in FIGS. 1-6 (FIGS. 1-6) of U.S. Pat. Nos. 7,384,590 and 7,387,759. The lens formulation in the mold was irradiated with UV radiation (13.0 mW / cm2) for approximately 24 seconds.

[0309] [PAA-F] [Coating solution.] []

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

[0311] [through] [PAA] [Coated lenses.] []

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

[0313] [Application of cross-linked coating.] []

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

[0315] [Confocal laser fluorescence microscopy.] []

[0316] A cross section of a hydrated SiHy lens (prepared above) with a cross-linked coating was cut and placed between two glass cover slips, and images were collected on a confocal laser fluorescence microscope (model: Zeiss LSM 510 Vis). Scans were performed from the front curved side of the lens to the bottom curved side of the lens, or vice versa. The presence of PAA-F was revealed by green fluorescence and confocal laser fluorescence microscopy images were obtained. Inspection of the confocal laser fluorescence microscopy images showed that a PAA-F-rich layer was present on both lens surfaces (front and back) and at the surrounding edges, while no PAA-F was observed in the bulk material of the hydrated lens.

[0317] Fluorescence intensity curves were examined across a cross section of the lens along a line passing through the back and front surfaces and perpendicular to the back surface. FIG3 shows two representative fluorescence intensity curves along two lines across a cross section of the lens, one line where the lens thickness is approximately 100 μm (Panel A) and the other line where the lens thickness is approximately 200 μm (Panel B). The initial point in FIG3 is the center point along the lines between the front and back surfaces. It can be noted in FIG3 that there is a PAA-F-rich layer near the outermost surface of the SiHy lens with the cross-linked coating, no PAA-F is present in the bulk of the lens, and the coating thickness is similar in the two cross sections regardless of the thickness of the cross section.

[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 the PAA-F in the bulk material (i.e., the inner layer)), or the transition layer (see FIG. 2 for a schematic illustration, transition layer 115) can be estimated from the fluorescence intensity curve shown in FIG. 3. The possible thickness of the transition layer (PAA-F-rich layer) is estimated by the distance from zero intensity to zero intensity again after crossing the peak intensity. Taking into account the possible contribution of unknown factors (e.g., scattering) to the fluorescence intensity, the minimum layer thickness is the thickness that retains the fluorescence intensity of at least 10% of the maximum peak intensity. Based on this estimate, the minimum PAA-F-rich layer thickness may be at least about 5 microns. It should be noted that the thickness of the SiHy lens with PAA coating in the previous example may be higher considering that the PAA concentration used is 10 times the PAA-F concentration used in the experiments herein. Lenses with thicker coatings can also be made by using a dip coating time greater than 44 seconds, which is the dip coating time for PAA-F used in this experiment. Lenses with thicker coatings can also be made by using PAA of different molecular weights.

[0319] [Example] [twenty three]

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

[0321] A solution was prepared using the two polymeric components of the cross-linked 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 ratio of PAE / poly(AAm-co-AA) was the same as the IPC saline of Example 19, but the concentration of each component was higher to ensure gel formation during autoclaving.

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

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

[0324] After overnight drying, the dried samples were taken out of the vacuum oven and then measured to record the dry 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 this PAE / poly(AAm-co-AA) hydrogel represents the outer hydrogel layer (cross-linked 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 (polysilicone hydrogel) is not present in the outer surface layer. This appears to be an excellent assumption based on the XPS data. According to the XPS data in Example 21, there is no or very low silicon content on the surface of the SiHy lens with the cross-linked 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 very small effect on the water content of the surface layer. This assumption may not be valid. However, if any charged PAA is present in the outer surface layer, it further increases the water content to more than 84.6%. Third, a very high concentration of PAE and PAAm-PAA is required to produce the PAE / poly(AAm-co-AA) hydrogel compared to that used in the IPC saline of Example 19. This can result in a higher crosslink density for the PAE / poly(AAm-co-AA) hydrogel, which can artificially give low water content results. It is believed that the presence of PAA and the lower crosslink density (due to the lower concentration of polymerized material during crosslinking) in the outer hydrogel layer (in Example 19) can result in a water content of the surface layer (outer hydrogel layer) that is even higher than that measured in the testing in this example. It can be assumed that the outer coating layer of the SiHy contact lens in Example 19 includes at least 80% water and can be even higher when fully hydrated.

[0326] [Example] [twenty four] []

[0327] The refractive index of contact lenses is usually measured using an Abbe refractometer. The difference in refractive index between the test lens and the instrument prism will produce a unique total internal reflection angle, which will produce 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 lenses made in Example 19) produce significant shadow lines in the Abbe refractometer, but the SiHy with a cross-linked coating (i.e., an outer hydrogel layer) in Example 19 does not produce significant shadow lines. It is believed that this phenomenon is due to the fact that the refractive index of the lens is reduced at the surface compared to the bulk and the transition from the bulk to the surface is not abrupt. In addition, it is believed that near the surface of the lens, the water content begins to increase, which causes the refractive index of the lens to be locally reduced. This will actually produce shadow lines at multiple angles simultaneously, resulting in a blurred image of the shadow line.

[0328] The Abbe data showed that the outer surface layer was 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 lenses with crosslinked coatings (i.e., outer hydrogel layers) prepared in Example 19 were desalted in ultrapure water, placed individually in 50 mL disposable beakers with 50 mL ultrapure water and frozen by placing the beaker in a bath with dry ice and isopropanol. The beakers were wrapped in aluminum foil and placed on a VirTis Freezemobile 35EL at vacuum pressure = 30 microbars and condenser temperature = -70°C. After 24 hours, the aluminum foil was removed to increase heat transfer and the flasks were placed for another 24-48 hours to remove residual moisture. The flasks were covered to prevent the introduction of moisture from the air until the time of analysis. The lens samples were cut in half, and then two strips were cut from the middle of each half and mounted from their edges for cross-sectional imaging. The samples were then sputter coated with Au / Pd for about 1 min and spot examined by SEM (JEOL JSM-800LV SEM) using a Bruker Quantax Microanalysis System. Depending on the analyst's preference, the sample stage was tilted approximately 0-60° to obtain the desired sample orientation.

[0331] It is believed that when the SiHy contact lens is freeze-dried, the hydrated surface structure of the lens can be retained or maintained to a certain extent. Figure 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 for a high water content hydrogel. This result further confirms that the SiHy contact lens of the present invention includes two outer hydrogel layers of a high water content hydrogel. Figures B and C of Figure 4 show side views of two different angles of the cross-section of the freeze-dried SiHy contact lens shown in Figure A. Figures 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 Figures B and C, the thickness of the freeze-dried outer hydrogel layer is estimated to be between about 2 μm and 2.5 μm.

[0332] [Example]

[26]

[0333] [Fluorescein-labeled polymerase] [(AAm-] [common] [-AA)(90 / 10)(] [called] [PAAm-PAA-F)] [.] []

[0334] 5-Aminofluorescein was covalently attached to PAAm-PAA (90 / 10) by a procedure similar to that used to prepare PAA-F. PAAm-PAA-F was synthesized in house. Poly(AAm-co-AA) (90 / 10) partial sodium salt (about 90% solids content, poly(AAm-co-AA) 90 / 10, Mw 200,000) was purchased from Polysciences and used as received. The labeling level of luciferin was about 0.04 mol%.

[0335] [use] [PAAm-PAA-F] [Improvements] [IPC] [Salt water.] []

[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] [through] [PAA] [Coated lenses.] []

[0338] Lenses were made by cast molding in a reusable mold (a quartz female mold half and a glass male mold half) from the lens formulation prepared above in Example 19, similar to the molds shown in FIGS. 1-6 (FIGS. 1-6) of U.S. Pat. Nos. 7,384,590 and 7,387,759. The lens formulation in the mold was irradiated with UV radiation (13.0 mW / cm2) for approximately 24 seconds. The cast molded contact lenses were extracted and coated by immersion in the following series of baths: a DI water bath (about 56 seconds); 6 MEK baths (held for about 44, 56, 56, 56, 56, and 56 seconds, respectively); a DI water bath (about 56 seconds); a PAA coating solution bath in 1-PrOH solvent (about 0.36 wt %, acidified to about pH 2.0 using formic acid) (about 44 seconds); a water / 1-propanol 50% / 50% mixture bath (about 56 seconds); 4 DI water baths (each held for about 56 seconds); a PBS bath (held for about 56 seconds); and a DI water bath (held for about 56 seconds).

[0339] [Application of cross-linked coating.] []

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

[0341] [Confocal laser fluorescence microscopy.] []

[0342] A piece of hydrated SiHy lens (prepared above) with a cross-linked coating was placed between two glass cover slips 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 of the lens, 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 microscopy images showed that a PAAm-PAA-F-rich layer (i.e., an outer hydrogel layer) was present on both lens surfaces (front and back surfaces) and at the surrounding edges, while no PAAm-PAA-F was observed in the bulk material of the lens.

[0343] The fluorescence intensity curve is examined across the cross section of the lens along a line passing through the back and front surfaces and perpendicular to the back surface. The thickness of the PAAm-PAA-F rich layer can be estimated from the fluorescence intensity curve across the lens. The possible thickness of the outer hydrogel layer (PAAm-PAA-F rich layer) is estimated by the distance from zero intensity to zero intensity again after crossing the peak intensity. Taking into account 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 of the maximum peak intensity. Based on this estimate, the minimum PAAm-PAA-F rich layer (hydrated outer hydrogel layer) thickness can be at least about 5 microns.

[0344] [Example]

[27]

[0345] Lenses were made using lens formulation D-2 (Example 17) with an added concentration of 1% APMAA monomer. LS lenses were made by cast molding the lens formulation prepared above in a reusable mold similar to the mold 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 composed of glass and a convex mold half composed of quartz. The UV irradiation source was a Hamamatsu lamp with an intensity of about 4.6 mW / cm2 and a 380 nm cutoff filter. The lens formulation in the mold was irradiated with UV irradiation for about 30 seconds.

[0346] The cast molded lenses were extracted with methyl ethyl ketone (MEK), rinsed in water, coated with polyacrylic acid (PAA) by soaking the lenses in a propanol solution of PAA (0.0044 wt %, acidified to about pH 2.5 with formic acid), and hydrated in water.

[0347] IPC saline was prepared according to the composition described in Example 9 using pre-reaction conditions of about 8 hr at 60°C. The lenses were placed in polypropylene lens packaging cases with 0.6 mL of IPC saline (half of the saline was added before inserting the lenses). The blisters were then sealed with foil and autoclaved at 121°C for 30 min.

[0348] Evaluation of the lens surface showed that all tested lenses had no debris adherence. 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 about 20°.

[0349] [Example]

[28]

[0350] The cast molded contact lenses made from Example 19 (without any coating) were used. All lenses were extracted in MEK overnight to ensure that all residual monomers were removed. The first set of lenses (lenses with hydrated cross-linked coatings thereon) were soaked in a PAA coating solution (0.36 wt % PAA in 1-propanol, pH adjusted to 1.7-2.3 using formic acid) overnight, while the second set of lenses (control) were soaked in 1-propanol for the same duration. Both sets of lenses were packaged in IPC saline made in Example 19 and autoclaved. The autoclaved lenses (groups of 5) were tested using gravimetric techniques to determine the weight of dry and wet contact lenses (N=14 for the first set of contact lenses; N=18 for the second set of contact 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 in wet weight (7 mg) between the first set of contact lenses and the second set of contact lenses due to the presence of the hydrated cross-linked coating in the first set of contact lenses compared to the control lenses (no coating). However, the difference in dry weight between the first set of contact lenses and the second set of contact lenses was approximately 0.3 mg and was not statistically significant. Based on the following calculation ( ), the lens water content of the coated lens can be estimated to be about 96%. It should be understood that the water content of the cross-linked coating on the contact lens estimated here may not be accurate because the difference in dry or wet weight between the first group of contact lenses and the second group of contact lenses is too small and even smaller than the standard deviation.

[0352] [Example]

[29]

[0353] This example illustrates how to quantify the lubricity of SiHy contact lenses according to the tilted plate method ("Derby Friction Test"). The tilted plate method is a simple test that is set up as shown in FIG. 5 . The setup for the tilted plate method consists of a plastic reservoir or tank 501 filled with phosphate buffered saline (PBS, pH about 7.3) 502, a borosilicate glass plate 503, and a spacer 506 with an adjustable height of 5 mm to 20 mm in height. Both the borosilicate glass plate 503 and the spacer 506 are immersed in the phosphate buffered saline 502 in the plastic reservoir or tank 501. In the test, a contact lens 504 is placed on the borosilicate glass plate and then a stainless steel ferrule 505 is placed (to provide physiologically relevant pressure). Critical coefficient of friction = =tan θ, where θ is the critical angle, FN is the normal force, and Ft is the tangential force. The highest angle at which the 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 is below the CCOF, while a lens that does not stop during the moving distance is above the CCOF. Angles below or above the CCOF are removed from the analysis. The Derby friction test provides a direct way to measure the kinematic coefficient of friction.

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

[0355] Each lens was placed on the "starting line" and a 0.79 g ferrule (1 / 4" stainless steel to provide physiologically relevant pressure) was dropped onto the lens surface. The lens was slid down the plate and the time it took for the lens to move 96 mm was recorded.

[0356] Allow the lens to move to the starting position while the weight is removed before retesting. For best repeatability, this "preload" effect should be minimized. The lens can be tested at multiple angles to obtain the ideal CCOF.

[0357] The CCOF of 16 commercial contact lenses and the silicone hydrogel contact lenses prepared in Example 19 were tested and the results are reported in Table 9. The results show that the SiHy contact lenses of the present invention (prepared in Example 19, with a crosslinked coating thereon) have the lowest CCOF, and thus the highest lubricity, of any type of silicone hydrogel lenses commercially available and tested. Table 9 [] [Contact lenses] [SiHy] [CH (mm)] [CA (] [Spend] [)] [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) AND 8.8 3.4 0.059 Clariti 1-Day AND 9.2 3.5 0.062 Acuvue Moist AND 7.7 2.9 0.051 Air Optix Aqua AND 8.1 3.1 0.054 Biofinity AND 8.1 3.1 0.054 PureVision AND 9.4 3.6 0.063 Acuvue Advance AND 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 the Positively Charged Particle Adhesion Test.

[0360] The surface charge of the lens surface can be detected indirectly through its interaction with charged particles or beads. Negatively charged surfaces attract positively charged particles. Surfaces that contain no negative charge or substantially no negative charge will attract no positively charged particles or will attract very few positively charged particles.

[0361] Uncoated SiHy contact lenses (i.e., cast molded as described in Example 19 and extracted with MEK), PAA coated SiHy contact lenses (prepared as in Example 19), and SiHy contact lenses having a crosslinked coating thereon (prepared as in Examples 14 and 19) were tested as follows. The PAA coating of the PAA coated contact lenses had a surface concentration of carboxylic acid groups of approximately 62.5 wt % ( , where M COOH is the mass of carboxylic acid groups and M AA is the mass of acrylic acid). The crosslinked coating of the contact lens in Example 14 theoretically contains 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 (must be less than 10% by weight). ). The lens is immersed in a dispersion of positively charged particles. After appropriate rinsing, the number of particles adhering to the lens is visually inspected and estimated or counted.

[0362] DOWEX TM1×4 20-50 mesh resin was purchased from Sigma-Aldrich and used as received. DOWEX TM1×4 20-50 mesh resin is a spherical, type I strong base anionic resin and is a styrene / divinylbenzene copolymer containing N+(CH3)3Cl- functional groups and 4% divinylbenzene. 5% of 1×4 20-50 mesh resin was dispersed in PBS and mixed thoroughly by stirring or vortexing at about 1000 rpm for 10 seconds. The 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 petri dish and images of the lenses were acquired using a Nikon optical microscope using bottom illumination. As shown in Figure 6, almost the entire surface of the PAA coated lens was covered with adhered positively charged particles (Figure 6a), while a total of about 50 positively charged particles adhered to the lens with a cross-linked coating prepared in Example 19 (Figure 6B), and no positively charged particles adhered to the lens with a cross-linked coating prepared in Example 14 (Figure 6C). Some loosely adhered particles may fall off the lens surface and may also be found in the water around the lens.

[0363] It is understood that the number of particles adhering to the lens may be reduced when positively charged particles of larger size (i.e., DOWEX™ monosphere ion exchange resin, cross-linked polystyrene beads, chloride form, approximately 590 microns in size, from Sigma-Aldrich) are used 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 and then rinsed with DI water. The lenses were then placed in water in a glass petri dish and images of the lenses were acquired using a Nikon optical microscope using bottom illumination. Many particles (approximately 200 particles) were found to adhere to the PAA coated lenses and no particles adhered to the lenses with the cross-linked coating. Some 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 4 types of lenses (in order of increasing number of particles): PureVision®, 1 Day Acuvue® Moist®, Proclear 1 day, Acuvue® (Etafilcon A) lenses. Almost the 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 this Amberlite CG50 beads were dispersed in PBS and vortexed at about 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 petri dish and images of the lenses were acquired using a Nikon optical microscope using 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 described below. PEI (Lupasol SK, 24% in water, Mw of about 2000000) 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 ensured to be well mixed (e.g., by stirring for 30 min). The dispersion was then suspended in a large amount of water 2 to 3 times and filtered 2 to 3 times before collecting the particles (PEI-coated Amberlite). 5% of this PEI-coated Amberlite CG50 beads were dispersed in PBS and vortexed at about 1000 rpm for 10 seconds. The lenses were immersed in this dispersion and vortexed at 1000-1100 rpm for 1 min, then rinsed with DI water and vortexed for 1 min. The lenses were then placed in water in a glass petri dish and images of the lenses were acquired using a Nikon optical microscope using bottom illumination. 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 lenses (Example 19). However, virtually no PEI-coated Amberlite particles adhered to the uncoated SiHy contact lenses (Example 19), the SiHy contact lenses with crosslinked coatings (Example 19), or the PAExPAA-coated lenses (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 the blister pack (sealed and autoclaved) and cross sections were cut (e.g., by using a razor). The cross-sectional slices of the lenses were mounted vertically in a metal clamp, as shown in FIG7 . The smaller slices of the lenses were allowed to extend out of the top of the holder to allow the AFM tip (above the lens cross section in FIG7 ) to scan them.

[0369] [AFM] [experiment] [:] []

[0370] Two separate AFM instruments were used to characterize the lens cross-sections. In both cases (except for the dried samples), AFM scans were performed under phosphate buffered saline (PBS with or without NaCl but with substantially the same osmotic pressure as saline) to maintain the fully hydrated state of the hydrogel samples.

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

[0372] AFM images of cross sections of fully hydrated state SiHy contact lenses (Example 19) with cross-linked coatings were obtained via the force-volume method and are shown in Figure 8. In the image, the darker colored areas 420 represent the coatings and the lighter colored areas 410 represent the bulk material of the lens. The average thickness of the cross-linked coatings (i.e., the front and back outer layers) of the SiHy contact lenses (Example 19) was determined to be approximately 5.9 μm (with a standard deviation of 0.8 μm), as obtained from 7 images of 4 lenses.

[0373] AFM technology enables the determination of the surface modulus (surface softness) at a specific location on a cross-section of the lens. FIG. 9 shows a cross-sectional surface modulus curve of a fully hydrated SiHy contact lens (prepared in Example 19) with a cross-linked coating. 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 of the cross-section (front surface or back surface) along the two lines across the cross-section shown in FIG. 8 . As shown in FIG. 9 , the cross-linked coating (the front outer layer and the back outer layer of the contact lens in Example 19) are softer than the bulk silicone hydrogel lens material (the inner layer). When moving along the two lines, the surface modulus first remains almost constant in the region between 0 and about 5.9 microns with an average cantilever deflection of about 52 nm (i.e., average surface modulus), and then gradually increases until reaching a maximum value at a position further into the lens and then remains approximately constant (plateau) in the region greater than about 7 microns with an average cantilever deflection of about 91 (i.e., average surface modulus). The gradual transition from the softer cross-linked coating to the harder bulk SiHy material over a span of several microns indicates that there may be a gradient in morphology or composition (water content) between the coating surface and the lens bulk. The surface modulus in the region between 5.9 microns and about 7 microns (i.e., the region around the boundary between the outer hydrogel layer and the inner layer of silicone hydrogel material) is not used to calculate the average surface modulus. It can be calculated that the front outer hydrogel layer and the rear outer hydrogel layer (cross-linked coating) of the SiHy contact lens (Example 19) have a reduced surface modulus ( ,in is the average surface modulus of the rear hydrogel layer or the front hydrogel layer, and is the average surface modulus of the inner layer).

[0374] A second AFM instrument was used to study the SiHy contact lenses (prepared in Example 19). Scans were performed using a Bruker Icon AFM in Quantitative Nanomechanical Measurements (PeakForce QNM) mode using lenses in either fully hydrated (PBS without NaCl but with glycerol to achieve similar permeability) or dry states. The lens cross-sections were mounted in the metal clamps described above. Test conditions included: spring constant of 1.3 N / m, tip radius of 33.3 nm, sensitivity of 31 nm / V, scan rate of 0.4 Hz, and scan resolution of 512×512.

[0375] AFM images of cross sections of SiHy contact lenses (Example 19) in fully hydrated and dry states were obtained according to the PeakForce QNM method. By analyzing the images obtained, the thickness of the crosslinked coating in the fully hydrated state was determined to be about 4.4 microns, while the thickness of the crosslinked coating in the dry state was determined to be about 1.2 microns for vacuum dried samples and about 1.6 microns for oven dried samples. Water swelling ratio ( , where Lwet is the average thickness of the outer hydrogel layer of the SiHy contact lenses in a fully hydrated state, and Ldry is the average thickness of the outer hydrogel layer of the SiHy contact lenses in a dry state) was calculated to be about 277% (oven dried samples) or about 369% (vacuum dried samples).

[0376] [Example]

[32]

[0377] [Preparation of lens formulations] []

[0378] Formulation I was prepared by dissolving the components in 1-propanol to have the following composition: 33 wt % of the CE-PDMS macromer prepared in Example 2, 17 wt % of N-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24 wt % of N,N-dimethylacrylamide (DMA), 0.5 wt % of N-(Carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt) (L-PEG), 1.0 wt % of Darocur 1173 (DC1173), 0.1 wt % of visitint (5% copper phthalocyanine blue pigment dispersion in tris(trimethylsiloxy)silylpropyl methacrylate TRIS), and 24.5 wt % of 1-propanol.

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

[0380] [Manufacture of lenses] []

[0381] The lenses are made by cast molding from the lens formulation prepared above in a reusable mold (a quartz female mold half and a glass male mold half) similar to the mold shown in FIGS. 1-6 (FIGS. 1-6) of U.S. Pat. Nos. 7,384,590 and 7,387,759. 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 lenses are extracted using methyl ethyl ketone (MEK) (or propanol or isopropanol).

[0382] [exist] [SiHy] [Apply to contact lenses] [PAA] [Base coating] []

[0383] The 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 have a concentration of about 0.36 wt %, 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 / H 2 O) to have a concentration of about 0.39 wt %, and the pH was adjusted to about 2.0 using formic acid.

[0385] The SiHy contact lenses obtained above were 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; MEK represents methyl ethyl ketone; and 50 / 50 represents a 50 / 50 1-PrOH / H 2 O solvent mixture. 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 1-PrOH / H 2 O solvent mixture.

[0386] [Application of cross-linked hydrophilic coating] []

[0387] Poly(acrylamide-co-acrylic acid) partial sodium salt, poly(AAm-co-AA) (90 / 10) (about 90% solids, poly(AAm-co-AA) (90 / 10), Mw 200,000) was purchased from Polysciences and used as received. PAE (Kymene, azetidinium content 0.46 by NMR analysis) was purchased from Ashland in aqueous solution and used as received. In-package crosslinking (IPC) saline was prepared by dissolving about 0.07% w / w poly(AAm-co-AA) (90 / 10) and about 0.15% PAE (about 8.8 mmol initial azetidinium millimolar equivalent) in phosphate buffered saline (PBS) (about 0.044 w / w% NaH 2PO 4·H 2O, about 0.388 w / w / % Na 2HPO 4·2H 2O, about 0.79 w / w% NaCl) and adjusting the pH to 7.2 to 7.4. The IPC saline was then heat pretreated at about 70° C. for about 4 hours (heat pretreatment). During this heat pretreatment, poly(AAm-co-AA) and PAE partially cross-linked with each other (i.e., without consuming all of the azetidinium groups of PAE) to form a water-soluble and heat-cross-linkable hydrophilic polymeric material containing azetidinium groups within a branched polymer network in the IPC saline. After the heat pretreatment, the IPC saline was filtered using a 0.22 micron polyethersulfone [PES] membrane filter and cooled back to room temperature. 10 ppm hydrogen peroxide was then added to the final IPC saline to prevent bioburden growth, and the IPC saline was filtered using a 0.22 micron polyethersulfone [PES] membrane filter.

[0388] The lenses prepared above with PAA primer coatings thereon were placed in polypropylene lens packaging shells (each shell containing one lens) with 0.6 mL of IPC saline (half of the saline was added before inserting the lenses). The blisters were then sealed with foil and autoclaved at about 121° C. for about 30 minutes to form SiHy contact lenses with cross-linked hydrophilic coatings thereon.

[0389] [SiHy] [Characterization of the lens.] []

[0390] The resulting SiHy contact lenses having a cross-linked hydrophilic coating thereon and having a center thickness of about 0.95 microns have the following characteristics: an oxygen permeability (Dk c or estimated intrinsic Dk) of about 142 barrers to about 150 barrers, a bulk elastic modulus of about 0.72 MPa to about 0.79 MPa, a water content of about 30 wt % to about 33 wt %, a relative ion permeability of about 6 (relative to Alsacon lenses), and a contact angle of about 34 degrees to about 47 degrees.

[0391] [Characterization of nanotextured 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 glass slide and a glass cover slip. The contact lens surface is positioned and examined by focusing through the lens using a Nikon ME600 microscope with transmissive differential interference contrast optics using a 40x objective. The resulting TDIC image is then evaluated to determine the presence of a wrinkled surface pattern (e.g., random and / or ordered worm-like patterns, or the like).

[0393] [Reflection Differential Interference Contrast] [(RDIC)] [Methods.] The lens was placed on a glass slide and flattened by making 4 radial cuts every approximately 90 degrees. Excess saline was blown off the surface using compressed air. The lens surface was then examined using a Nikon Optiphot-2 with reflective differential interference contrast optics using 10x, 20x, and 50x objectives to determine the presence of a wrinkled surface pattern on the contact lens surface. A representative image of each side was obtained using a 50x objective. The contact lens was then turned over, excess saline removed, and the other side of the contact lens was examined in the same manner. The obtained RDIC images were then evaluated to determine the presence of a wrinkled surface pattern (e.g., a random and / or ordered worm-like pattern, or the like).

[0394] [Dark-field light microscopy] [(DFLM)] [.]DFLM is usually [Based on] darkfield illumination, which is a method of enhancing contrast ratios in observed specimens. This technique consists of a light source outside or blocking the observer's field of view to illuminate the specimen at an angle relative to vertical transmitted light. Because the unscattered light from the light source is not collected by the objective lens, it is not part of the image and the image background appears darker. Because the light source is illuminating the specimen at an angle, the light observed in the specimen image is 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 darkfield illumination particularly useful for observing scattering phenomena such as turbidity.

[0395] The haze of contact lenses is evaluated using DFLM as described below. It is believed that because the darkfield setting involves scattered light, the darkfield data can provide a worst-case estimate of haze. In an 8-bit grayscale digital image, each image pixel is assigned a grayscale intensity (GSI) value ranging from 0-255. Zero represents a completely black pixel and 255 represents a completely white pixel. Increasing the 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 darkfield image. Haze is represented by calculating the average of the GSI values ​​of all pixels in the target area (AOI) (e.g., the entire lens or the lens area or optical zone of the lens). The experimental setup consists of a microscope or equivalent optical components, an attached digital camera, and a darkfield stand with a ring light and a variable intensity light source. The optical components are designed / arranged so that the entire contact lens to be observed fills the field of view (the field of view is typically about 15 mm×20 mm). The illumination is set to a value suitable for observing the expected changes in the relevant sample. The light intensity of each set of samples is adjusted / calibrated to the same value using a density / light scattering standard known to those skilled in the art. For example, the standard consists of two overlapping plastic cover slips (identical and lightly or moderately frosted). The standard consists of regions with three 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 gain and offset (contrast ratio and brightness) settings of the camera. The intermediate gray levels provide three points to verify the linear response of the camera. 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 lenses are immersed in 0.2 µm filtered phosphate buffered saline in a quartz petri dish or a dish of similar clarity, which is placed on a DFLM holder. An 8-bit grayscale digital image of the lens is then acquired when viewed using the calibrated illumination, and the average GSI of the AOI defined within the imaged portion of the lens is determined. This process is repeated for the sample set of contact lenses. The light intensity calibration is re-evaluated periodically during the test to ensure consistency. Haze values ​​under the DFLM test refer to the DFLM haze values. .

[0396] SiHy contact lenses, PAA primer coatings obtained according to any of the immersion processes 20-0 and 80-0 were measured to have an average DFLM haze of about 73%, and showed a wrinkled surface pattern (random worm-like pattern) that can be visually observed by inspecting the contact lens in a hydrated state according to any of the above RDIC or TDIC methods. However, the wrinkled surface pattern actually has no adverse effect on the light transmittance of the contact lens.

[0397] SiHy contact lenses, PAA base coatings obtained according to any of the immersion processes 20-1 to 20-4 were determined to have a lower average DFLM haze of about 26% (possibly due to the presence of visitint pigment particles), and showed no wrinkled surface pattern (random worm-like pattern) observed when examined under any of the above RDIC or TDIC.

[0398] High percentage SiHy contact lenses, PAA base coatings obtained according to any of the immersion processes 20-5 were determined to have a moderate average DFLM haze of about 45% and showed a slightly observable wrinkled surface pattern when examined under any of the above RDIC or TDIC. However, the wrinkled surface pattern had virtually no adverse effect on the light transmittance of the contact lenses.

[0399] SiHy contact lenses, PAA primers obtained according to any of the immersion processes 80-1, 80-2, 80-3, 80-5 and 80-6, do not show observable wrinkled surface patterns when examined under any of the above RDIC or TDIC. However, SiHy contact lenses, PAA primers obtained according to any of the immersion processes 80-0 and 80-4, show observable wrinkled surface patterns when examined under any of the above RDIC or TDIC. However, the wrinkled surface patterns do not actually have adverse effects on the light transmittance of the contact lenses.

[0400] [Example]

[33] []

[0401] [UV] [Synthesis of absorbent amphiphilic branched copolymers] []

[0402] A 1-L jacketed reactor was equipped with a 500-mL addition funnel, overhead stirring, 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 to the reactor and then degassed at less than 1 mbar vacuum and room temperature for about 30 minutes. A monomer solution prepared by mixing 1.03 g HEMA, 50.73 g DMA, 2.76 g Norbloc methacrylate, 52.07 g TRIS, and 526.05 g ethyl acetate was charged to a 500-mL addition funnel, then degassed at 100 mbar vacuum and room temperature for 10 minutes and then refilled with nitrogen. The monomer solution was degassed for two more cycles using the same conditions. The monomer solution was then charged to the reactor. The reaction mixture was heated to 67° C. with appropriate stirring. While heating, a solution of 2.96 g of mercaptoethanol (chain transfer agent, CTA) and 0.72 g of 2,2'-azobis(2-methylpropionic acid) dimethyl ester (V-601-initiator) and 76.90 g of ethyl acetate was charged into the addition 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 the copolymerization was completed, the reactor temperature was cooled to room temperature.

[0403] [UV] [Synthesis of absorbent amphiphilic branched prepolymer] []

[0404] The copolymer solution prepared above was olefinically functionalized by adding 8.44 g of IEM (or the desired molar equivalent of 2-isocyanatoethyl methacrylate) in the presence of 0.50 g of DBTDL to form an amphiphilic branched prepolymer. The mixture was stirred for 24 hours at room temperature under sealed conditions. The prepared prepolymer was then stabilized using 100 ppm of hydroxy-tetramethylene piperonyloxy, after which the solution was concentrated to 200 g (about 50%) and filtered through a 1 um pore size filter paper. After exchanging the reaction solvent to 1-propanol through repeated cycles of evaporation and dilution, the solution was ready for formulation. The solid content was measured by removing the solvent in a vacuum oven at 80°C.

[0405] [Preparation of lens formulations] []

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

[0407] [Lens manufacturing] []

[0408] The lenses are manufactured by cast molding from the lens formulations prepared above using a reusable mold similar to the molds shown in Figs. 1-6 (Figs. 1-6) of U.S. Pat. Nos. 7,384,590 and 7,387,759 under the spatial confinement of UV irradiation. The molds include a female mold half composed of glass and a male mold half composed of quartz. The UV irradiation source is a Hamamatsu lamp with an intensity of about 4.6 mW / cm2 and a 380 nm cutoff filter. The lens formulation in the mold is irradiated with UV irradiation for about 30 seconds.

[0409] The cast molded lenses were extracted with methyl ethyl ketone (MEK), rinsed in water, coated with polyacrylic acid (PAA) by soaking the lenses in a propanol solution of PAA (0.004 wt %, acidified to about pH 2.0 with formic acid), and hydrated in water.

[0410] IPC saline was prepared from a composition containing about 0.07% PAAm-PAA and PAE (about 0.15% PAE) sufficient to provide an initial azetidinium content of about 8.8 mmol equivalents / liter under pre-reaction conditions at about 60°C for 6 hr. 5 ppm hydrogen peroxide was then added to the IPC saline to prevent bioburden growth and the IPC saline was filtered using a 0.22 micron polyethersulfone [PES] membrane filter. The lenses were placed in a polypropylene lens packaging case with 0.6 mL of IPC saline (half of the saline was added before inserting the lenses). The blisters were then sealed with foil and autoclaved at 121°C for 30 min.

[0411] [Lens Characterization] []

[0412] The resulting lenses had the following properties: E' of about 0.82 MPa; DK c of about 159.4 (using lotrafilcon B as a reference lens with an average center thickness of 80 µm and an intrinsic Dk of 110); IP of about 2.3; water % of about 26.9%; and UVA / UVB %T of about 4.6 / 0.1. When observed under a dark field microscope, no crack lines were seen after wiping the test lenses. The lenses were extremely lubricious in the finger rub test and comparable to the control lenses.

[0413] 100:SiHy contact lenses 101: front surface 102: Relative rear surface 103: surrounding edge 110: Inner layer 115: Transition layer 120: External layer 410: Brighter colored area 420: Darker colored area 501: Plastic liquid container or tank 502: Phosphate buffered saline 503:Borosilicate glass plate 504: Contact lenses 505: Stainless steel ferrule 506: Gasket

Claims

1. A hydrated polysiloxane hydrogel contact lens, comprising: a front surface and an opposite 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; an oxygen transmittance of at least 40 barrer / mm; an elastic modulus (or Young's modulus) of 0.3 MPa to 1.8 MPa; and an average water contact angle of 80 degrees or less and / or a water breakup time of at least 10 seconds; The inner layer is the bulk material of the hydrated contact lens and is composed of polysiloxane hydrogel comprising: (i) repeating units derived from polysiloxane-type monomers, polysiloxane-type macromonomers, polysiloxane prepolymers, or combinations thereof, and (ii) repeating units derived from hydrophilic vinyl monomers; wherein each of the front outer hydrogel layer and the rear outer hydrogel layer is composed of a cross-linked polymer material containing polyethylene glycol (PEG) chains, and wherein the hydrated polysiloxane hydrogel contact lens has no visible surface cracks in a dark field after being rubbed between fingers.

2. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the hydrated contact lens has an oxygen permeability of at least 60 barrer / mm.

3. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the hydrated contact lens has an oxygen permeability of at least 80 barrer / mm.

4. The hydrated polysilicon-oxygen hydrogel contact lens of claim 1, wherein the hydrated contact lens has an oxygen permeability of at least 100 barrer / mm.

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

6. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the hydrated contact lens has an average water contact angle of 70 degrees or less.

7. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the hydrated contact lens has an average water contact angle of 60 degrees or less.

8. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the hydrated contact lens has an average water contact angle of 50 degrees or less.

9. The hydrated polysiloxane hydrogel contact lens of claim 2, wherein the hydrated contact lens has an average water contact angle of 60 degrees or less.

10. The hydrated polysiloxane hydrogel contact lens of claim 2, wherein the hydrated contact lens has an average water contact angle of 50 degrees or less.

11. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the PEG chain is derived from at least one member selected from the group consisting of: PEG-SH; HS-PEG-SH; HOOC-PEG-SH; H2N-PEG-SH; multi-arm PEG having one or more thiol groups; PEG dendritic polymer having one or more thiol groups; and combinations thereof.

12. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the PEG chain is derived from at least one member selected from the group consisting of: PEG-NH2; H2N-PEG-NH2; H2N-PEG-COOH; multi-arm PEG having one or more amino groups; PEG dendritic polymer having one or more amino groups; and combinations thereof.

13. The hydrated polysiloxane hydrogel contact lens of claim 1, wherein the PEG chain is derived from at least one member selected from the group consisting of: PEG-COOH; HOOC-PEG-COOH; multi-arm PEG having one or more carboxyl groups; PEG dendritic polymer having one or more carboxyl groups; and combinations thereof.

14. A hydrated polysiloxane hydrogel contact lens as claimed in any one of claims 2 to 13, wherein the PEG chain is derived from at least one member selected from the group consisting of: PEG-SH; HS-PEG-SH; HOOC-PEG-SH; H2N-PEG-SH; multi-arm PEG having one or more thiol groups; PEG dendritic polymer having one or more thiol groups; PEG-NH2; H2N-PEG-NH2; H2N-PEG-COOH; multi-arm PEG having one or more amino groups; PEG dendritic polymer having one or more amino groups; PEG-COOH; HOOC-PEG-COOH; multi-arm PEG having one or more carboxyl groups; PEG dendritic polymer having one or more carboxyl groups; and combinations thereof.

15. A hydrated polysiloxane hydrogel contact lens as claimed in any of claims 1 to 13, wherein the polysiloxane hydrogel material comprises repeating units derived from polysiloxane vinyl monomers, polysiloxane vinyl macromonomers, or combinations thereof.

16. The hydrated polysiloxane hydrogel contact lens of claim 15, wherein the polysiloxane vinyl monomer or macromolecular monopolymer is monomethacrylated or monoacrylated polydimethylsiloxane, vinyl carbonate-terminated polydimethylsiloxane, aminocarbamate-terminated polydimethylsiloxane, vinyl-terminated polydimethylsiloxane, methacrylamide-terminated polydimethylsiloxane, acrylamide-terminated polydimethylsiloxane, acrylate-terminated... The reaction products of polydimethylsiloxane, methacrylate-terminated polydimethylsiloxane, bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane, N,N,N',N'-tetra(3-methacryloxy-2-hydroxypropyl)-α,ω-bis-3-aminopropyl-polydimethylsiloxane, polysiloxane alkyl (meth)acrylic acid monomers or glycidyl methacrylates with amino-functionalized polydimethylsiloxane.

17. The hydrated polysiloxane hydrogel contact lens of claim 16, 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.

18. The hydrated polysiloxane hydrogel contact lens of claim 17, 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. The hydrated polysiloxane hydrogel contact lens of claim 17, wherein the polysiloxane hydrogel bulk material further comprises a UV absorber, a visible colorant, an antimicrobial agent, a bioactive agent, an leaching lubricant, an leaching tear stabilizer, or a mixture thereof.

20. A hydrated polysiloxane hydrogel contact lens as claimed in any of claims 1 to 13, wherein the polysiloxane hydrogel material comprises repeating units derived from hydrophilic vinyl monomers from 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-Methylene-2-pyrrolidone, 1-Ethyl-3-methylene-2-pyrrolidone, 1-Methyl-5-methylene-2-pyrrolidone, 1-Ethyl-5-methylene-2-pyrrolidone, 5-Methyl-3-methylene-2-pyrrolidone, 5-Ethyl-3-methylene-2-pyrrolidone, 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. A hydrated polysiloxane hydrogel contact lens as claimed in any of claims 1 to 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'-methylenebismethacrylamide, N,N'-ethylbisacrylamide, N,N'-ethylbismethacrylamide, 1,3-bis(N-methacrylaminopropyl)-1,1,3,3-tetra-(trimethylsilane) 1,3-bis(methacrylaminobutyl)-1,1,3,3-tetra(trimethylsilyloxy)-diasiloxane, 1,3-bis(acrylaminopropyl)-1,1,3,3-tetra(trimethylsilyloxy)diasiloxane, 1,3-bis(methacryloxyethylureopropyl)-1,1,3,3-tetra(trimethylsilyloxy)diasiloxane, and combinations thereof.

22. A hydrated polysiloxane hydrogel contact lens as claimed in any of claims 1 to 13, wherein the polysiloxane hydrogel bulk 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-(2-hydroxy-3-(3-(bis(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]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 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) 3-[trimethylsilyloxy-3-propyl]methoxycarbamate, 3-(trimethylsilyl)propyl vinyl carbonate, 3-(vinyloxycarbonylthio)propyl-tris(trimethyl-silyloxy)silane, 3-[tris(trimethylsilyloxy)silyl]propyl vinyl carbamate, 3-[tris(trimethylsilyloxy)silyl]propyl allyl carbamate, 3-[tris(trimethylsilyloxy)silyl]propyl vinyl carbonate, tributyldimethyl-silyloxyethyl vinyl carbonate, trimethylsilyl ethyl vinyl carbonate, trimethylsilyl methyl vinyl carbonate, and combinations thereof.

23. The hydrated polysiloxane hydrogel contact lens of claim 22, 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.

24. The hydrated polysiloxane hydrogel contact lens of claim 23, 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.

25. The hydrated polysiloxane hydrogel contact lens of claim 23, wherein the polysiloxane hydrogel bulk material further comprises a UV absorber, a visible colorant, an antimicrobial agent, a bioactive agent, an leaching lubricant, an leaching tear stabilizer, or a mixture thereof.

26. A hydrated polysiloxane hydrogel contact lens as claimed in any one of claims 1 to 13, wherein the polysiloxane hydrogel bulk material further comprises a UV absorber, a visible colorant, an antimicrobial agent, a bioactive agent, an leaching lubricant, an leaching tear stabilizer, or a mixture thereof.

27. A hydrated polysiloxane hydrogel contact lens as claimed in any of claims 1 to 13, wherein the front outer hydrogel layer and the rear outer hydrogel layer have a thickness of at least 1 µm, independently of each other.

Images