Silicone hydrogel lenses with a surface that has a high moisture content

Abstract

To provide SiHy contact lenses with hydrophilic surfaces which exhibit persistent hydrophilicity, wettability, and lubricity that can be maintained in the eye throughout the entire day.SOLUTION: The present invention relates to a hydrated silicone hydrogel contact lens having a layered structural configuration, and a low-water-content silicone hydrogel core (or bulk material) completely covered with a layer of a water-rich (e.g., a water content greater than 80%) hydrogel totally or substantially free of silicone. The hydrated silicone hydrogel contact lens of the present invention has a high oxygen permeability to maintain corneal health, and a soft, water-rich, lubricious surface for wearing comfort.SELECTED DRAWING: Figure 4C

Description

[Technical Field]

[0001] The present invention generally relates to ophthalmic devices, particularly those having a lens structure shape that generates a water content gradient, and a water content of approximately 10% to approximately 70% (by weight) (WC). SiHy A silicone hydrogel bulk material having (represented as) and a hydrogel material having a thickness of about 0.1 to about 20 μm, completely covering the silicone hydrogel bulk material, and being completely or substantially silicone-free, and when the cross-section of a fully hydrated silicone hydrogel contact lens is measured by AFM, WC SiHy If ≤45%, it is characterized by a water expansion coefficient of at least approximately 100%, or WC SiHy If it is >45%, then at least about [120·WC] SiHy / (1-WC SiHy The present invention relates to a silicone hydrogel contact lens comprising an outer surface layer having a higher water content and characterized by a water expansion coefficient of %)%.

[0002] background Silicone hydrogel (SiHy) contact lenses are widely used to correct various types of vision abnormalities. These consist of a hydrated cross-linked polymer 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 classified into two main categories: low water content contact lenses (containing less than 50% water) and high water content contact lenses (containing more than 50% water). In the case of SiHy contact lenses, the high oxygen permeability necessary to minimize the harmful effects of contact lenses on corneal health is achieved not by increasing the water content, but by incorporating silicone into the cross-linked polymer material. As a result, unlike conventional hydrogel contact lenses, SiHy contact lenses can have a low water content while still having a relatively high oxygen permeability (Dk). For example, CIBA Vision Corporation's Focus® Night&Day® (approximately 23.5% H2O and Dk ~ 140 Barrel; CIBA Vision Corporation's Air Optix (registered trademark) (approx. 33% H2O and Dk ~ 110 Barrer); PureVision (registered trademark) from Bausch & Lomb (approx. 36% H2O and Dk ~ 100 Barrer); Acuvue (registered trademark) Oasys (registered trademark) from Johnson & Johnson (approx. 38% H2O and Dk ~ 105 Barrer); Acuvue (registered trademark) Advance (registered trademark) from Johnson & Johnson (approx. 47% H2O and Dk ~ 65 Barrer) rer); Johnson & Johnson's Acuvue (registered trademark), TruEye (trademark) (approx. 46% H2O, Dk ~ 100 Barrel); CooperVision's Biofinity (registered trademark) (approx. 48% H2O, Dk ~ 128 Barrel); CooperVision's Avaira (trademark) (approx. 46% H2O, Dk ~ 100 Barrel); and Menicon's PremiO (trademark) (approx. 40% H2O, Dk ~ 129 Barrel).

[0003] The water content in SiHy contact lenses allows for sufficiently long-term wear and provides the desired flexibility, offering patients benefits such as moderate initial comfort (i.e., immediately after lens insertion), a relatively short adaptation time, and / or proper fit. Higher water content would be desirable to provide SiHy contact lenses with biocompatibility and comfort. However, there are limitations to the amount of water that SiHy contact lenses can contain (considered to be around 80%) while still possessing sufficient mechanical strength and rigidity required for contact lenses, like conventional hydrogel contact lenses. Furthermore, high water content can also have undesirable effects. For example, the oxygen permeability of SiHy contact lenses may decrease with higher water content. In addition, high water content in SiHy contact lenses can lead to increased intraocular dehydration, potentially causing discomfort due to dehydration, as SiHy contact lenses may lose the limited supply of tears (water) in the eye. Intraocular dehydration can result from evaporation (i.e., loss of water) at the anterior surface of the contact lens, and such water loss is thought to be primarily controlled by the diffusion of water from the posterior surface to the anterior surface of the lens, with the rate of diffusion being closely proportional to the water content of the lens bulk material at equilibrium (L. Jones et al., Contact Lens & Anterior Eye 25 (2002) 147-156, the whole of which is incorporated herein by reference).

[0004] Incorporating silicone into contact lens materials also has undesirable effects on the biocompatibility of contact lenses because silicone is hydrophobic and tends to migrate to the lens surface exposed to air. As a result, SiHy contact lenses generally require surface modification processes, such as various plasma treatments (e.g., CIBA Vision Corporation's Focus® Night&Day® and Air Optix®; Bausch & Lomb's PureVision®; and Menicon's PremiO®); or internal wetting agents physically and / or chemically embedded in the SiHy polymer matrix (e.g., Johnson & Johnson's Acuvue® Oasys®, Acuvue® Advance®, and Acuvue® TruEye®; CooperVision's Biofinity® and Avaira®). Surface modification techniques used in the manufacture of commercially available SiHy lenses can provide new (unused) SiHy lenses with a moderately hydrophilic surface. However, SiHy lenses implanted in the eye may have dry spots and / or hydrophobic surface areas resulting from partial inadequate protection due to exposure to air, eyelid shearing force, silicone migration, and / or silicone exposure. These dry spots and / or hydrophobic surface areas are non-wetting, readily adsorb lipids or proteins from the intraocular environment, and can adhere to the eye, potentially causing discomfort to the patient.

[0005] Therefore, there is a need for SiHy contact lenses with a hydrophilic surface that possess sustained hydrophilicity, wetting, and lubricity that can be maintained within the eye throughout the day.

[0006] Summary of the Invention The present invention can meet the need of SiHy contact lenses having a hydrophilic surface with sustained surface hydrophilicity, surface wettability and surface lubricity throughout the day in the eye.

[0007] In one aspect, the present invention is a hydrated silicone hydrogel contact lens including a front (convex) surface and an opposite rear (concave) surface; and a layer structure shape from the front surface to the rear surface, the layer structure shape including an outer front hydrogel layer, an inner layer of silicone hydrogel material and an outer rear hydrogel layer, the silicone hydrogel material having an oxygen permeability (Dk) of at least about 50, preferably at least about 60, more preferably at least about 70, even more preferably at least about 90 barrer, most preferably at least about 110 barrer, and a first water content (WC SiHy as represented) 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), the outer front and rear hydrogel layers having a substantially uniform thickness and being fused at the peripheral edge of the contact lens so as to completely enclose the inner layer of the silicone hydrogel material, the outer front and rear hydrogel layers being, independently of each other, when WC SiHy ≦45%, having a water swelling ratio (represented as WSR) of 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 when WC>45%, having a water swelling ratio of at least about [120·WC SiHy / (1-WC SiHy )]% (preferably [130·WC SiHy / (1-WC SiHy )]%, more preferably [140·WC SiHy / (1-WC SiHy )]%, even more preferably [150·WC SiHy / (1-WC SiHy )]%), characterized in that WC SiHyThe present invention provides a hydrated silicone hydrogel contact lens having a higher secondary water content, with each of the front and rear outer hydrogel layers having a thickness of approximately 0.1 μm to approximately 20 μm, preferably approximately 0.25 μm to approximately 15 μm, more preferably approximately 0.5 μm to approximately 12.5 μm, and even more preferably approximately 1 μm to approximately 10 μm (measured by atomic force microscopy across the cross-section from the rear to the front of a fully hydrated silicone hydrogel contact lens).

[0008] In another embodiment, 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 rear surface; the contact lens has an oxygen transfer coefficient of at least about 40, preferably at least about 60, more preferably at least about 80, and even more preferably at least about 110 barser / mm, and a surface modulus profile (including the front surface and its vicinity along the shortest line between the front and rear surfaces of the cross-sectional surface of the contact lens; including the center of the shortest line and its periphery; and including the rear surface and its vicinity, the rear surface outer region, the front outer region being the average front modulus

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[0009] In a further embodiment, 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 rear surface; the contact lens has surface lubricity characterized by (1) an oxygen transfer rate of at least about 40, preferably at least about 60, more preferably at least about 80, and even more preferably at least about 110 bars / mm, and (2) a critical coefficient of friction (represented as CCOF) of about 0.046 or less, preferably about 0.043 or less, and more preferably about 0.040 or less; the front and rear surfaces have negatively charged groups, such as carboxylic acid groups, at a low surface concentration, characterized by attracting a maximum of about 200, preferably about 160, more preferably about 120, even more preferably about 90, and most preferably about 60 positively charged particles in a positively charged particle adhesion test.

[0010] These and other aspects of the Invention, including various preferred embodiments in any combination, will become apparent from the following description of preferred embodiments of the Invention. The detailed description is for illustrative purposes only and does not limit the scope of the Invention as defined by the appended claims and equivalents. As will be apparent to those skilled in the art, many variations and modifications of the Invention can be carried out without departing from the spirit and scope of the novel concepts of this disclosure. [Brief explanation of the drawing]

[0011] [Figure 1] Figure 1 schematically shows a cross-sectional view of the structural shape of a SiHy contact lens according to a preferred embodiment of the present invention. [Figure 2]Figure 2 schematically shows a cross-sectional view of the structural shape of a SiHy contact lens according to another preferred embodiment of the present invention. [Figure 3A] Figure 3A shows the fluorescence intensity profile across a cross-section of a SiHy contact lens using confocal laser fluorescence microscopy. [Figure 3B] Figure 3B shows the fluorescence intensity profile across a cross-section of a SiHy contact lens using confocal laser fluorescence microscopy. [Figure 4A] Figure 4A shows a scanning electron microscope (SEM) image of the SiHy contact lens of the present invention in a freeze-dried state. [Figure 4B] Figure 4B shows a scanning electron microscope (SEM) image of the SiHy contact lens of the present invention in a freeze-dried state. [Figure 4C] Figure 4C shows a scanning electron microscope (SEM) image of the SiHy contact lens of the present invention in a freeze-dried state. [Figure 5] Figure 5 schematically illustrates the setup of the inclined plate method according to a preferred embodiment. [Figure 6A] Figure 6A shows optical microscope images of contact lenses with various coatings applied after being immersed in a dispersion of positively charged particles (DOWEX® 1×4 20-50 mesh resin). [Figure 6B] Figure 6B shows optical microscope images of contact lenses with various coatings applied after being immersed in a dispersion of positively charged particles (DOWEX® 1×4 20-50 mesh resin). [Figure 6C] Figure 6C shows optical microscope images of contact lenses with various coatings applied after being immersed in a dispersion of positively charged particles (DOWEX® 1×4 20-50 mesh resin). [Figure 7] Figure 7 schematically illustrates a method for vertically mounting a cross-sectional piece of the SiHy contact lens of the present invention in a metal clamp for AFM testing. [Figure 8]Figure 8 shows an AFM (atomic force microscopy) image of a portion of the cross-section of a SiHy contact lens in a fully hydrated state (in phosphate-buffered saline, pH ~7.3) according to a preferred embodiment of the present invention. [Figure 9] Figure 9 shows the cross-sectional surface coefficient profile of the SiHy contact lens of the present invention in a fully hydrated state (in phosphate-buffered saline, pH ~7.3), approximately represented by plotting the deflection of the cantilever as a function of distance, along two shortest lines between the front and back surfaces of the cross-sectional surface of the SiHy contact lens according to a preferred embodiment of the present invention.

[0012] Detailed description of embodiments of the invention Hereinafter, embodiments of the present invention will be described in detail. Those skilled in the art will see that various modifications, variations, and combinations can be carried out in the present invention without departing from the scope or spirit of the invention. For example, further embodiments can be obtained by using features exemplified or described as part of one embodiment in another embodiment. Therefore, it is intended that the present invention encompasses such modifications, variations, and combinations, so as to remain within the scope of the appended claims and their equivalents. Other objects, features, and aspects of the present invention are disclosed or evident in the detailed description below. Those skilled in the art will understand that the considerations of the present invention merely describe exemplary embodiments and do not limit the broader aspects of the present invention.

[0013] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which the present invention pertains. Generally, the nomenclature and laboratory procedures used herein are well known and commonly used in the art. These procedures, as given in the art and in various general references, employ conventional methods. Where a term is given in the singular form, the inventors also assume the plural form of that term. The nomenclature and laboratory procedures used herein 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 containing a silicone hydrogel material.

[0015] As used in this application, the terms “hydrogel” or “hydrogel material” refer to a crosslinked polymer material that is water-insoluble and, when fully hydrated, can contain at least 10% (by weight) of water in its polymer matrix.

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

[0017] As used in this application, the term “silicone hydrogel” refers to a hydrogel containing silicone. Silicone hydrogels are typically obtained by copolymerization of a polymerizable composition comprising at least one silicone-containing vinyl monomer or at least one silicone-containing vinyl macromer or at least one silicone-containing prepolymer having an ethylenically unsaturated group.

[0018] As used in this application, the term "vinyl monomer" refers to a compound having one single ethylenically unsaturated group and that can be polymerized by chemical radiation or heat.

[0019] As used in this application, the terms “olefinic unsaturated group” or “ethylenically unsaturated group” are used herein in a broad sense and are intended to encompass any group containing at least one >C=C< group. Typical ethylenically unsaturated groups include: [ka] This includes, but is not limited to, styrenyl 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 vinyl monomer” refers to a vinyl monomer that, as a homopolymer, typically produces a polymer that is water-soluble or capable of absorbing at least 10% (by weight) of water.

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

[0024] As used in this application, the terms “macromer” or “prepolymer” refer to a medium-to-high molecular weight compound or polymer containing two or more ethylenically unsaturated groups. Medium-to-high molecular weight typically means an average molecular weight greater than 700 daltons.

[0025] As used in this application, the term "crosslinking agent" refers to a compound having at least two 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, macromers, or prepolymers.

[0027] As used in this application, the term "molecular weight" for polymer materials (including monomer or macromer materials) refers to the weight-average molecular weight unless otherwise specifically indicated or the test conditions are otherwise specified.

[0028] As used in this application, the term "amino group" means, unless otherwise specifically indicated, the formula -NHR' (wherein R' is hydrogen or C1-C 20 This refers to a primary or secondary amino group (which is unsubstituted or substituted, linear or branched alkyl group).

[0029] As used in this application, the terms “epichlorohydrin-functionalized polyamine” or “epichlorohydrin-functionalized polyamidoamine” refer to polymers obtained by reacting a polyamine or polyamidoamine with epichlorohydrin to convert all or a significant proportion of the amine groups of the polyamine or polyamidoamine into azetidinium groups.

[0030] As used in this application, the term "azetidinium group" is, [ka] This refers to a positively charged group represented by [this symbol].

[0031] As used in this application, the term "thermally crosslinkable" means that, with respect to a polymer material or functional group, the crosslinking (or coupling) reaction between the polymer material or functional group and another material or functional group can be carried out at relatively high temperatures (about 40°C to about 140°C), while the same crosslinking (or coupling) reaction between the polymer material or functional group and another material or functional group cannot be carried out at room temperature (i.e., about 22°C to about 28°C, preferably about 24°C to about 26°C, particularly about 25°C) (until it takes about 1 hour to reach a detectable level (i.e., more than about 5%)).

[0032] As used in this application, the term "phosphorylcholine" is, [ka] (In the formula, n is an integer between 1 and 5, and R1, R2, and R3 are independently C1-C8 alkyl or C1-C8 hydroxyalkyl.) This refers to the zwitterionic group represented by [this symbol].

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

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

[0035] As used in this application, the term “water-soluble” means that, with respect to a polymer, the polymer can be dissolved in water to such an extent that it is sufficient to produce an aqueous solution of the polymer having a maximum concentration of about 30% (by weight) at room temperature (as defined above).

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

[0037] As used in this application, the term “undamaged” is intended to describe, with respect to the coating on the SiHy contact lens, the extent to which the contact lens can be stained by Sudan Black in the Sudan Black staining test described in Example 1. Good undamaged status of the coating on the SiHy contact lens means that the contact lens is substantially not stained by Sudan Black.

[0038] As used in this application, the term “durability” is intended to mean, with respect to coatings on SiHy contact lenses, that the coatings on SiHy contact lenses can withstand a digital friction test.

[0039] As used in this application, the terms “to withstand digital friction test” or “to withstand durability test” mean, with respect to a coating on a contact lens, that the water contact angle of the finger-rubbed lens after rubbing the lens with a finger according to the procedure described in Example 1 is still about 100 degrees or less, preferably about 90 degrees or less, more preferably about 80 degrees or less, and most preferably about 70 degrees or less.

[0040] The inherent "oxygen permeability" Dk of a material is the rate at which oxygen permeates the material. As used in this application, the term "oxygen permeability (Dk)" means the measured oxygen permeability (Dk) corrected for surface resistance to the oxygen flux resulting from the boundary layer effect, in relation to hydrogels (silicone or non-silicone) or contact lenses, according to the procedures shown in the examples below. Oxygen permeability has conventionally been expressed in units of bars, where "barrer" is [(oxygen cm) 3 )(mm) / (cm 2 )(sec)(mmHg)]×10 -10 It is defined as follows.

[0041] The "oxygen transfer coefficient" Dk / t of a lens or material is the rate at which oxygen passes through a particular lens or material having an average thickness t [in mm] over the measured area. Traditionally, oxygen transfer coefficients have been expressed in units of bars / mm, where "barrel / mm" is [(oxygen cm 3 ) / (cm 2 )(sec)(mmHg)]×10 -9 It is defined as follows.

[0042] The "ion permeability" of a lens is correlated with the ion flux diffusion coefficient. Ion flux diffusion coefficient D([mm 2 The time (in units of [ / minute]) is determined by applying Fick's Law as follows: D = -n' / (A × dc / dx) (In the formula, n' = rate of ion transport [mol / min]; A = area of ​​the exposed lens [mm²]) 2 ];dc=concentration difference [mol / L];dx=lens thickness [mm])

[0043] As used in this application, the term "ophthalmic compatibility" refers to a material or surface of a material that can be in close contact with the intraocular environment for an extended period without causing significant damage to the intraocular environment or severe discomfort to the user.

[0044] As used in this application, the term “ophthalmologically safe” is intended to mean, with respect to a packaging solution for sterilizing and preserving contact lenses, that the contact lenses stored in the solution are safe to place directly on the eye without rinsing after autoclaving, and that the solution is safe and sufficiently comfortable for daily contact with the eye via the contact lenses. An ophthalmologically safe packaging solution after autoclaving has an osmotic pressure and pH compatible with the eye and is substantially free of materials that are irritating or cytotoxic to the eye according to international ISO standards and US FDA regulations.

[0045] As used in this application, the term “cross-section” in SiHy contact lenses refers to the lens cross-section obtained by cutting the lens with a knife or cutting tool at an angle substantially perpendicular to the front or rear surface of the lens. Those skilled in the art are well aware that to obtain a cross-section of a contact lens, the contact lens may be cut manually (i.e., by hand) or with a Cryosta Microtome or lath. The resulting cross-section of the contact lens can be polished using ion etching or similar techniques.

[0046] The terms “surface modulus,” “surface flexibility,” “surface modulus,” “surface Young’s modulus,” or “surface compressibility” are used interchangeably in this application and refer to nanomechanical properties (elastic properties) measured by atomic force microscopy (AFM) of the surface of a fully hydrated material (in phosphate buffer, pH ~7.3 ± 0.2) or a cross-section of a contact lens, using the contact mode, nanoindentation method, Peakforce QNM method, or Harmonic Force method, as is known to those skilled in the art. Jan Domke and Manfred Radmacher reported that the elastic properties of thin layers can be measured by AMF (Langmuir 1998, 14, 3320-3325, the whole of which is incorporated herein by reference). AFM nanoindentation can be performed according to the experimental procedure described in Gonzalez-Meijome 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", pp554-559, A. Mendez-Vilas and J. Diaz (Eds.), Formatex Research Center, Badajoz, Spain (2010), which is incorporated herein by reference in its entirety. Note that the surface of the cross-section of the contact lens (as performed by Gonzalez-Meijome JM, Almeida JB and Parafita MA in these papers), rather than the front or back surface of the contact lens, is analyzed using nanoindentation with AFM.The nanoindentation method, Peakforce QNM method, and Harmonic Force method are described in Kim Sweers, et al. in Nanoscale Research Letters 2011, 6:270, under the title "Nanomechanical properties of a-synuclein amyloid fibrils: a comparative study by nanoindentation, harmonic force microscopy, and Peakforce QNM" (the entire paper is incorporated herein by reference). Furthermore, it should be understood that when surface modulus measurements are performed using AFM from the front to the bulk or from the bulk to the back (and vice versa) of a fully hydrated SiHy contact lens cross-section, the surface modulus profile across the contact lens cross-section can be determined along the shortest line between the front and back surfaces of the contact lens cross-section. Additionally, it should be understood that, as a good approximation, any experimentally and directly measured quantities can be used to represent the surface modulus to the extent that the measured quantity is proportional to the surface modulus.

[0047] As used in this application, the term “front external hydrogel layer” means, with respect to the SiHy contact lens of the present invention, a hydrogel layer including the front surface of the contact lens, having a substantially uniform thickness (i.e., thickness variation is less than or equal to about 10% of the average thickness of the layer), and having an average thickness of at least about 0.1 μm. The “average thickness” of the front external hydrogel layer is also referred to in this application simply as “thickness of the front external hydrogel layer.”

[0048] As used in this application, the term “rear outer hydrogel layer” means, with respect to the SiHy contact lens of the present invention, a hydrogel layer comprising the rear surface of the contact lens, having a substantially uniform thickness (i.e., thickness variation is less than or equal to about 10% of the average thickness of the layer), and having an average thickness of at least about 0.1 μm. The “average thickness” of the rear outer hydrogel layer is also referred to in this application simply as “thickness of the rear outer hydrogel layer.”

[0049] As used in this application, the term “internal layer” in relation to the SiHy contact lens of the present invention means a layer having a variable thickness, which includes a central curved surface (dividing the contact lens into two parts, one of which includes the front surface and the other including the rear surface).

[0050] As used in this application, the terms “crosslinked coating” or “hydrogel coating” are used interchangeably to refer to a crosslinked polymer material having a three-dimensional network structure that can contain water when fully hydrated. The three-dimensional network structure of the crosslinked polymer material can be formed via crosslinking links by crosslinking two or more linear or branched polymers.

[0051] As used in this application, the term "water expansion coefficient" is defined with respect to the front or rear outer hydrogel layer of the SiHy contact lens of the present invention, where WSR = L Wet / L Dry According to ×100%, this means the value determined by AFM (wherein WSR is the water expansion coefficient of one of the front and rear outer hydrogel layers, L Wet L is the average thickness of the outer hydrogel layer of a fully hydrated SiHy contact lens, measured by AFM on a cross-section of the SiHy contact lens in a fully hydrated state (i.e., in phosphate buffer, pH ~7.3 ± 0.2), and L Dry This is the average thickness of the outer hydrogel layer of a SiHy contact lens in a dry state (dried without retaining the porosity of the hydrogel material, e.g., vacuum dried) and when the cross-section of a SiHy contact lens in a substantially dry atmosphere is measured by AFM. The water expansion coefficient of each outer hydrogel layer (of the SiHy contact lens of the present invention) is proportional to the water content of each outer hydrogel layer, and is at least about 100% or

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[0052] As used in this application, the term “reduced surface coefficient” refers to either or both of the front and rear outer hydrogel layers of the SiHy contact lens of the present invention, as defined by the following formula:

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[0053] The "critical coefficient of friction" is the tangent of the critical angle, which is the maximum angle of inclination of the inclined surface at which the lens begins to slide after being pressed, but takes more than 10 seconds to stop or reach the edge. 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 correlates with its surface lubricity and can be used to quantify the surface lubricity of a contact lens.

[0054] As used in this application, the “positively charged particle adhesion test” refers to a test to characterize the surface concentration of negatively charged groups (e.g., carboxylic acid groups) on hydrated SiHy contact lenses. The positively charged particle adhesion test is performed as follows: DOWEX (trademark) 1×4 20~50 mesh resin (spherical type I strong basic resin (N + (CH3)3Cl -An aqueous dispersion of a styrene / divinylbenzene copolymer containing functional groups and 4% divinylbenzene is prepared by dispersing a predetermined amount of DOWEX® 1×4 20-50 mesh resin in phosphate-buffered saline (pH~7.3) to a resin concentration of 5% (by weight), and then thoroughly mixing by shaking, stirring, or vortexing at approximately 1000 rpm for 10 seconds. A hydrated silicone hydrogel contact lens is immersed in the aqueous dispersion of DOWEX® 1×4 20-50 mesh resin prepared above, vortexed at approximately 1000-1100 rpm for approximately 1 minute, then rinsed with DI water, and vortexed in DI water for approximately 1 minute. Next, the lens is placed in water in a glass petri dish, and an image of the lens is taken using a Nikon optical microscope with bottom illumination. The number of positively charged particles attached to each lens surface can be counted. The number of positively charged particles attached to the lens surface is proportional to the surface concentration of negatively charged groups on the contact lens.

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

[0056] The present invention relates to a SiHy contact lens having a layered structure and a unique water gradient from the inside to the outside of the SiHy contact lens: a lower water content silicone hydrogel core (or bulk material) completely covered by an outer (surface) hydrogel layer having a higher water content and a moderate thickness (at least about 0.1 μm) and substantially free of silicone (preferably completely free of silicone); and an outer hydrogel layer having a water content 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%) of the water content of the bulk material. Figure 1 schematically illustrates a SiHy contact lens having a layered structure according to 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 base curve or concave surface) 102 that rests on the cornea of ​​the eye when worn by the user. The SiHy contact lens 100 includes an inner (or intermediate) layer 110 and two outer layers 120. The inner layer 110 is the bulk material of the SiHy contact lens 100 and has a three-dimensional shape that is very close to the SiHy contact lens 100. The inner layer 110 preferably consists of a silicone hydrogel with a lower water content. The two substantially identical outer layers 120 are substantially of uniform thickness and consist of a substantially silicone-free (preferably completely silicone-free) hydrogel material having a higher water content than the inner layer 110. The two outer layers 120 fuse at the peripheral edge 103 of the contact lens 100 and completely cover the inner layer 110.

[0057] The SiHy contact lens having the layered structure of the present invention can offer several advantages compared to conventional contact lenses. First, such SiHy contact lenses can still have the high oxygen permeability necessary to maintain the health of the cornea of ​​the eye. Second, since the inner layer (bulk material) provides the bulk mechanical strength and rigidity required for the contact lens, the outer hydrogel layer can contain as much water as possible without being limited in terms of water content. Therefore, the outer hydrogel layer can provide a contact lens with a water content gradient (highest water content in the vicinity of and including the lens surface and lowest water content in the lens nucleus) in a water-rich membrane or lens structure. Third, the SiHy contact lens having the layered structure of the present invention has low intraocular dehydration, resulting in a less dry feeling in the eye and, as a result, improved all-day wearing comfort. The inner layer with low water content (i.e., the bulk material of the lens) is thought to control (limit) the diffusion rate of water from the posterior to the anterior surface of the lens and evaporation (water loss) at the anterior surface of the lens. Furthermore, the layered structure of the present invention may create an internal water concentration gradient (i.e., the water content decreases as you move inward from the front surface to the lens nucleus), which is considered undesirable for the diffusion of water from the rear surface to the front surface of the lens according to Fick's law of diffusion. Fourthly, the SiHy contact lens having the layered structure of the present invention can provide high biocompatibility because water is highly biocompatible with tear fluid, and the high water content in the outer hydrogel layer (for example, preferably >75%H2O) is located inside and near the front and rear surfaces where the eye makes direct contact and biocompatibility is maximized. Fifthly, the high water content in the outer hydrogel layer with a moderate thickness can provide a SiHy contact lens with a highly flexible surface, i.e., a "water cushion". Sixthly, the SiHy contact lens having the layered structure of the present invention can have a highly lubricating surface. The outer hydrogel layer with a very high water content and a moderate thickness is thought to provide a "water-loving" surface that can attract tear fluid spreading across the lens surface.The outer hydrogel layer, which has considerably higher flexibility than the bulk lens material (inner layer), is highly deformable under pressure (i.e., the shear force of the eyelid), and it is thought that such a SiHy contact lens can provide elastofluid lubrication when implanted in the eye. Seventh, the layered structure in the SiHy contact lens of the present invention can prevent silicone exposure. The three-dimensional mesh structure (i.e., polymer matrix) of the outer hydrogel layer with a moderate thickness is thought to be able to cover the silicone and prevent the 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), making it less susceptible to severe debris adhesion during patient handling and severe protein adhesion during wear (it is thought that most proteins in tears are positively charged).

[0058] In one embodiment, the present invention relates to a hydrated silicone hydrogel contact lens comprising a front (convex) surface and an opposite rear (concave) surface; and a layered structural shape from the front to the rear surface, wherein the layered structural shape comprises a front outer hydrogel layer, an inner layer of silicone hydrogel material, and a rear outer hydrogel layer, and the silicone hydrogel material has an oxygen permeability (Dk) of at least about 50, preferably at least about 60, more preferably at least about 70, even more preferably at least about 90, most preferably at least about 110 bars, and a first water content (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 The front and rear outer hydrogel layers are substantially uniform in thickness and are fused at the peripheral edge of the contact lens to completely enclose the inner layer of silicone hydrogel material, and the front and rear outer hydrogel layers are independent of each other, WC SiHyIf ≤45%, it must have a water expansion coefficient of 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 WC SiHy If it is >45%, then at least approximately

number

[0059] According to the present invention, the inner layer of the SiHy contact lens is substantially the bulk material of the lens. This can be derived directly from a pre-formed SiHy contact lens by a surface modification process in which two outer hydrogel layers are applied directly and / or indirectly to and bonded onto a pre-formed SiHy contact lens. The pre-formed SiHy contact lens may be any commercially available SiHy lens, e.g., one of the lenses described above. Alternatively, the pre-formed SiHy can be manufactured according to any method well known to those skilled in the art. For example, the pre-formed contact lens can be manufactured, for example, by conventional "spin-casting" as described in U.S. Patent No. 3,408,429, or by a static full-casting process as described in U.S. Patents No. 4,347,198; No. 5,508,317; No. 5,583,463; No. 5,789,464; and No. 5,849,810, or by lathe cutting of the silicone hydrogel base used in the manufacture of customized contact lenses. In cast molding, the lens formulation is typically dispensed into a mold for manufacturing contact lenses and cured (i.e., polymerized and / or crosslinked) in the mold. SiHy lens formulations for manufacturing pre-formed SiHy contact lenses, for cast molding or spin casting, or for manufacturing SiHy rods used in lathe cutting of contact lenses, generally contain, as is well known to those skilled in the art, at least one component selected from the group consisting of silicone-containing vinyl monomers, silicone-containing vinyl macromers, silicone-containing prepolymers, hydrophilic vinyl monomers, hydrophobic vinyl monomers, crosslinking agents (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.The SiHy contact lens formulation may also contain 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, leaching lubricants, leakable tear-stabilizing agents, and mixtures thereof. The resulting pre-formed SiHy contact lenses can then be subjected to an extraction and hydration process using an extraction solvent to remove non-polymerized components from the resulting lenses, as known to those skilled in the art. The pre-formed SiHy contact lenses may also be colored contact lenses (i.e., SiHy contact lenses having at least one printed color pattern, as well as well known to those skilled in the art).

[0060] Any suitable silicone-containing vinyl monomer can be used in the present invention. Examples of preferred silicone-containing vinyl monomers include N-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide, N-[tris(dimethylpropylsiloxy)-silylpropyl]-(meth)acrylamide, N-[tris(dimethylphenylsiloxy)silylpropyl](meth)acrylamide, N-[tris(dimethylethylsiloxy)silylpropyl](meth)acrylamide, and N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy) Propyl)-2-methylacrylamide; N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)acrylamide; N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]-2-methylacrylamide; N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]acrylamide; N-(2-hydroxy-3-(3-( Tris(trimethylsilyloxy)silyl)propyloxy)propyl)-2-methylacrylamide; N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)acrylamide; N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methylacrylamide; N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]acrylamide Rylamide; N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methylacrylamide; N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide; N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methylacrylamide; N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide;3-Methacryloxypropylpentamethyldisiloxane, Tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS), (3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane), (3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane, 3-methacryloxy-2-(2-hydroxyethoxy)-propyloxy)propylbis(trimethylsiloxy)methylsilane, N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl) This includes, but is not limited to, lylcarbamate, 3-(trimethylsilyl)propyl vinyl carbonate, 3-(vinyloxycarbonylthio)propyl-tris(trimethyl-siloxy)silane, 3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate, 3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate, 3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate, t-butyldimethyl-siloxyethyl vinyl carbonate; trimethylsilylethyl vinyl carbonate and trimethylsilylmethyl vinyl carbonate). The most preferred siloxane-containing (meth)acrylamide monomer of formula (1) is N-[tris(trimethylsiloxy)silylpropyl]acrylamide, TRIS, N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide or a combination thereof.

[0061] A preferred class of silicone-containing vinyl monomers or macromers is polysiloxane-containing vinyl monomers or macromers. Examples of such polysiloxane-containing vinyl monomers or macromers include monomethacrylate or monoacrylate polydimethylsiloxanes of various molecular weights (e.g., mono-3-methacrylateoxypropyl-terminated, mono-butyl-terminated polydimethylsiloxane or mono-(3-methacrylateoxy-2-hydroxypropyloxy)propyl-terminated, mono-butyl-terminated polydimethylsiloxane); dimethacrylate or diacrylate polydimethylsiloxanes of various molecular weights; vinyl carbonate-terminated polydimethylsiloxanes; vinyl carbamate-terminated polydimethylsiloxanes; vinyl-terminated polydimethylsiloxanes of various molecular weights; methacrylamide-terminated polydimethylsiloxanes; acrylamide-terminated polydimethylsiloxanes; acrylate-terminated poly Dimethylsiloxane; methacrylate-terminated polydimethylsiloxane; bis-3-methacrylateoxy-2-hydroxypropyloxypropyl polydimethylsiloxane; N,N,N',N'-tetrakis(3-methacrylateoxy-2-hydroxypropyl)-α,ω-bis-3-aminopropyl-polydimethylsiloxane; polysiloxanyl alkyl (meth)acrylic monomer; siloxane-containing macromers selected from the group consisting of macromer A, macromer B, macromer C and macromer D as described in U.S. Patent No. 5,760,100 (which is incorporated herein by reference in its entirety); reaction products of glycidyl methacrylate and amino-functionalized polydimethylsiloxane; hydroxyl-functionalized siloxane-containing vinyl monomers or macromers;U.S. Patent Nos. 4,136,250, 4,153,641, 4,182,822, 4,189,546, 4,343,927, 4,254,248, 4,355,147, 4,276,402, 4,327,203, 4,341,889, 4,486,577, No. 4,543,398, No. 4,605,712, No. 4,661,575, No. 4,684,538, No. 4,703,097, No. 4,833,218 No. 4,837,289, No. 4,954,586, No. 4,954,587, No. 5,010,141, No. 5,034,461, No. 5,070, Polysiloxane-containing macromers disclosed in U.S. Patent Nos. 170, 5,079,319, 5,039,761, 5,346,946, 5,358,995, 5,387,632, 5,416,132, 5,451,617, 5,486,579, 5,962,548, 5,981,675, 6,039,913 and 6,762,264 (all incorporated herein by reference); polysiloxane-containing macromers disclosed in U.S. Patent Nos. 4,259,467, 4,260,725 and 4,261,875 (all incorporated herein by reference). Di- and tri-block macromers consisting of polydimethylsiloxane and polyalkylene oxide can also be used. For example, to improve oxygen permeability, methacrylate-terminated polyethylene oxide-block-polydimethylsiloxane-block-polyethylene oxide may be used. Suitable monofunctionalized hydroxyl-functionalized siloxane-containing vinyl monomers / macromers and suitable polyfunctionalized hydroxyl-functionalized siloxane-containing vinyl monomers / macromers are commercially available from Gelest, Inc., Morrisville, PA.

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

[0063] Examples of preferred hydrophilic vinyl monomers include N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA), 2-acrylamidoglycolic acid, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, and 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, These include 1-tert-butyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl methacrylate (HEMA), 2-hydroxyethyl acrylate (HEA), hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), 2-hydroxypropyl methacrylate trimethylammonium hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate (DMAEMA), glycerol methacrylate (GMA), N-vinyl-2-pyrrolidone (NVP), allyl alcohol, vinylpyridine, C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight-average molecular weight of up to 1500, methacrylic acid, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, N-vinylcaprolactam, and mixtures thereof.

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

[0065] Examples of preferred crosslinking agents include tetraethylene glycol diacrylate, triethylene glycol diacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, tetraethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylopropane trimethacrylate, pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethylacrylamide, ethylenediamine diacrylamide, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, and 1,3-bis(methacrylamidopropyl)- This includes, but is not limited to, 1,1,3,3-tetrakis(trimethylsiloxy)disiloxane, N,N'-methylenebisacrylamide, N,N'-methylenebismethacrylamide, N,N'-ethylenebismethacrylamide, 1,3-bis(N-methacrylamidopropyl)-1,1,3,3-tetrakis-(trimethylsiloxy)disiloxane, 1,3-bis(methacrylamidobutyl)-1,1,3,3-tetrakis(trimethylsiloxy)-disiloxane, 1,3-bis(acrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane, 1,3-bis(methacryloxyethylureidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane, and combinations thereof. Preferred crosslinking agents are tetra(ethylene glycol) diacrylate, tri(ethylene glycol) diacrylate, ethylene glycol diacrylate, di(ethylene glycol) diacrylate, methylenebisacrylamide, triallyl isocyanurate, or triallyl cyanurate. The amount of crosslinking agent used is expressed as a weight percentage of the total polymer, preferably in the range of about 0.05% to about 4%, and more preferably in the range of about 0.1% to about 2%.

[0066] Suitable thermal initiators include, but are not limited to, 2,2'-azobis(2,4-dimethylpentanenitrile), 2,2'-azobis(2-methylpropanenitrile), 2,2'-azobis(2-methylbutanenitrile), and peroxides such as benzoyl peroxide. Preferably, the thermal initiator is 2,2'-azobis(isobutyronitrile) (AIBN).

[0067] Suitable photoinitiators include benzoin methyl ether, diethoxyacetophenone, benzoylphosphine oxide, 1-hydroxycyclohexylphenyl ketone, and Darocur and Irgacur types, preferably Darocur 1173® and Darocur 2959®. Examples of benzoylphosphine oxide initiators include 2,4,6-trimethylbenzoyldiphenylphosphine oxide; bis-(2,6-dichlorobenzoyl)-4-N-propylphenylphosphine oxide; and bis-(2,6-dichlorobenzoyl)-4-N-butylphenylphosphine oxide. Reactive photoinitiators that can be incorporated into macromers or used as special monomers are also suitable, for example. Examples of reactive photoinitiators are disclosed in European Patent Application No. 632 329 (which is incorporated herein by reference in its entirety). Polymerization can then be initiated by chemical beams, for example, light, particularly UV light of an appropriate wavelength. The spectral requirements can be controlled by adding an appropriate photosensitizer as needed.

[0068] Any suitable polymerizable UV absorber can be used in the present invention. Preferably, the polymerizable UV absorber contains a benzotriazole moiety or a benzophenone moiety. Examples of preferred polymerizable UV absorbers include 2-(2-hydroxy-5-vinylphenyl)-2H-benzotriazole, 2-(2-hydroxy-5-acrylyloxyphenyl)-2H-benzotriazole, 2-(2-hydroxy-3-methacrylamidomethyl-5-tertoctylphenyl)benzotriazole, 2-(2'-hydroxy-5'-methacrylamidophenyl)-5-chlorobenzotriazole, 2-(2'-hydroxy-5'-methacrylamidophenyl)-5-methoxybenzotriazole, and 2-(2'-hydroxy-5'-methacrylamidophenyl)-5-methoxybenzotriazole. This includes, but is not limited to, takryloxypropyl-3'-t-butylphenyl)-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, and 2-hydroxy-4-methacryloxybenzophenone.

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

[0070] Examples of leaching lubricants include, but are not limited to, mucin-like materials (e.g., polyglycolic acid) and non-crosslinked hydrophilic polymers (i.e., those not containing ethylene unsaturated groups). Any hydrophilic polymer or copolymer that does not contain any ethylenically unsaturated groups can be used as a leaching lubricant. Preferred examples of non-crosslinked 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 vinyl comonomers, homopolymers of acrylamide or methacrylamide, copolymers of acrylamide or methacrylamide with one or more hydrophilic vinyl monomers, polyethylene oxide (i.e., polyethylene glycol (PEG)), polyoxyethylene derivatives, poly-NN-dimethylacrylamide, polyacrylic acid, poly-2-ethyloxazoline, heparin polysaccharides, polysaccharides and mixtures thereof. Weight-average molecular weight M of non-crosslinked hydrophilic polymers w Preferably, this is between 5,000 and 100,000.

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

[0072] According to the present invention, the SiHy lens preparation may be a solution or a molten state 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 preparations can be prepared, as is known to those skilled in the art, by dissolving all desired components in any suitable solvent, such as water, a mixture of water and one or more miscible organic solvents, an organic solvent, or a mixture of one or more organic solvents.

[0074] Examples of preferred organic solvents include tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, ketones (e.g., acetone, methyl ethyl ketone, etc.), diethylene glycol n-butyl ether, diethylene glycol methyl ether, ethylene glycol phenyl ether, propylene glycol methyl ether, propylene glycol acetate methyl ether, dipropylene glycol acetate methyl ether, 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 methyl, dipropylene glycol dimethyl ether, polyethylene glycol, polypropylene glycol, ethyl acetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate, i-propyl lactate, methylene chloride, 2-butanol, 1-propanol, 2-propanol, menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, tert-butanol, tert-amyl alcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol, 2-2-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- This includes, but is not limited to, 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, t-amyl alcohol, isopropanol, 1-methyl-2-pyrrolidone, N,N-dimethylpropionamide, dimethylformamide, dimethylacetamide, dimethylpropionamide, N-methylpyrrolidinone and mixtures thereof.

[0075] Many SiHy lens formulations are described in numerous patents and patent applications published up to the filing date of this application. All of these can be used to produce SiHy materials having the Dk and water content specified above when obtaining pre-formed SiHy lenses that will form the inner layer of the SiHy contact lens of the present invention. Commercial SiHy lens formulations for manufacturing SiHy lenses such as lottrafilcon A, lotrafilcon B, balafilcon A, galyfilcon A, senofilcon A, narafilcon A, narafilcon B, comfilcon A, enfilcon A, asmofilcon A, and filcon II 3 can also be used in the manufacture of pre-formed SiHy contact lenses (the inner layer of the SiHy contact lens of the present invention).

[0076] Lens molding dies for manufacturing contact lenses are well known to those skilled in the art and are used, for example, in cast molding or spin casting. For example, a molding die (in the case of cast molding) generally comprises at least two molding die parts (or sections) or molding die halves, i.e., a first and a second molding die half. The first molding die half defines the first molding (or optical) surface, and the second molding die half defines the second molding (or optical) surface. The first and second molding die halves are arranged to meet each other so that a lens-forming cavity is formed between the first molding surface and the second molding surface. The molding surfaces of the molding die halves are the cavity-forming surfaces of the mold and are in direct contact with the lens-forming material.

[0077] Methods for manufacturing mold portions for casting contact lenses are generally well known to those skilled in the art. The process of the present invention is not limited to any particular mold forming method. In fact, any method for forming a mold can be used in the present invention. The first and second mold halves can be formed by various techniques such as injection molding or turning. Examples of suitable processes for forming mold halves are disclosed in U.S. Patents 4,444,711 (Schad); 4,460,534 (Boehm et al.); 5,843,346 (Morrill); and 5,894,002 (Boneberger et al.), which are also incorporated herein by reference.

[0078] In effect, molds for manufacturing contact lenses can be manufactured using all materials known in the art for manufacturing molds. For example, polymer materials such as polyethylene, polypropylene, polystyrene, PMMA, and Topas® COC grade 8007-S10 (a transparent amorphous copolymer of ethylene and norbornene, Ticona GmbH of Frankfurt, Germany and Summit, New Jersey) can be used. Other UV light-transmitting materials such as quartz glass and sapphire may also be used.

[0079] In preferred embodiments, SiHy contact lenses are formed by curing a silicone hydrogel lens-forming composition with a chemical beam under spatially restricted chemical beam conditions using a reusable mold. Examples of preferred reusable molds are disclosed in U.S. Patent Applications No. 08 / 274,942 (filed July 14, 1994), No. 10 / 732,566 (filed October 10, 2003), No. 10 / 721,913 (filed November 25, 2003), and U.S. Patent No. 6,627,124 (which is incorporated in whole by reference). Reusable molds can be manufactured from materials such as quartz, glass, sapphire, CaF2, cyclic olefin copolymers (e.g., Topas® COC grade 8007-S10 (transparent amorphous copolymer of ethylene and norbornene) (Ticona GmbH of Frankfurt, Germany and Summit, New Jersey), Zeonex® and Zeonor® (Zeon Chemicals LP, Louisville, KY)), polymethyl methacrylate (PMMA), DuPont's polyoxymethylene (Delrin), GE Plastics' Ultem® (polyetherimide), and PrimoSpire®.

[0080] According to the present invention, the inner layer silicone hydrogel (bulk material) has an oxygen permeability of at least about 50, preferably at least about 60, more preferably at least about 70, even more preferably at least about 90 bars, and most preferably at least about 110 bars. The silicone hydrogel material also has a (first) water content 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%, and most preferably about 15% to about 50% (by weight) WC. SiHyThe silicone hydrogel material may have a bulk modulus or bulk Young's modulus (hereinafter, the terms “flexibility,” “modulus,” and “Young's modulus” are used interchangeably in this application to mean bulk modulus when the term is not modified by the term “surface”) of about 0.3 MPa to about 1.8 MPa. The oxygen permeability, modulus, and water content of the inner layer of the silicone hydrogel material of the SiHy contact lens of the present invention can be determined by measuring the oxygen permeability, modulus, and water content of the pre-formed SiHy lens on which the inner layer is induced. It should be understood that, as a reasonable approximation, the modulus of the SiHy contact lens of the present invention can be considered to be the modulus of the silicone hydrogel material of the inner layer because the outer hydrogel layer is very thin. How to determine the modulus and water content of the silicone hydrogel material of the SiHy contact lens is well known to those skilled in the art. For example, the modulus and water content values ​​of all commercially available SiHy contact lenses have been reported.

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

[0082] The layered structure of the SiHy contact lens of the present invention can be determined, as described above, by analyzing the cross-section of the SiHy contact lens in a fully hydrated state (i.e., directly in water or buffered saline) using atomic force microscopy (AFM), as shown in the examples. To visualize any change in the surface coefficient from the rear to the front side of the cross-section, the cross-sectional surface coefficient can be characterized (imaged) using AFM (e.g., force-volume mode). A significant change in the surface coefficient observed (e.g., about 20% or more, preferably about 30% or more) (by examining the AFM image) along the shortest line between the front and rear sides across the cross-section of the fully hydrated SiHy contact lens, over 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 another. The average thickness of each outer hydrogel layer can be determined from the AFM image, as 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 are fused at the peripheral edge of the contact lens to completely incorporate the inner layer of silicone hydrogel material. The thickness of each outer hydrogel layer is about 0.1 μm to about 20 μm, preferably about 0.25 μm to about 15 μm, more preferably about 0.5 μm to about 12.5 μm, and most preferably about 1 μm to about 10 μm. The thickness of the outer hydrogel layer (or crosslinked coating) of the SiHy contact lens of the present invention is determined by AFM analysis of a cross section of the fully hydrated SiHy contact lens, as described above. In a more preferred embodiment, the thickness of each outer hydrogel layer is preferably up to about 30% (i.e., 30% or less), preferably up to about 20% (20% or less), and more preferably up to about 10% (10% or less), of the center thickness of the fully hydrated SiHy contact lens.

[0084] It should be understood that the layered structure shape of the SiHy contact lens of the present invention can also be qualitatively determined by analysis of the cross-section of the lyophilized SiHy contact lens using a scanning electron microscope (SEM), as shown in the examples. SEM can reveal the various compositions and / or structures of each layer in the cross-section of the lyophilized SiHy contact lens. Significant changes in composition (e.g., about 20% or more, preferably about 30% or more) and / or significant (visually prominent) changes in structure (by examining SEM images) observed over 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 across the cross-section of the lyophilized SiHy contact lens indicate a transition from one layer to another. However, the thickness values ​​based on SEM analysis of the cross-section of the lyophilized SiHy lens are typically lower than the actual values ​​due to the breakdown of the outer hydrogel layer, any transition layer, and inner layers after lyophilization.

[0085] According to this aspect of the present invention, the two outer hydrogel layers (front and rear outer hydrogel layers) of the SiHy contact lens of the present invention have a (first) water content (WC) of the inner layer of the silicone hydrogel material. SiHy ) needs to be higher, more specifically, the (first) water content (WC) of the inner layer of the silicone hydrogel material. SiHy The (second) water content must be at least about 1.2 times (i.e., 120%) of the (w) water content. The water expansion coefficient of each outer hydrogel layer is thought to correlate with its water content and can appropriately represent the water content of the outer hydrogel layer as a good approximation. In another preferred embodiment, the water content of the inner layer of the silicone hydrogel material (WC SiHy If the water content of the inner layer of the silicone hydrogel material is approximately 55% or less, the water expansion coefficient of each outer hydrogel layer is at least approximately 150%; the water content of the inner layer of the silicone hydrogel material is (WC SiHy ) If the water expansion coefficient of each outer hydrogel layer is approximately 60% or less, the water expansion coefficient of each outer hydrogel layer is at least approximately 200%; the water content of the inner layer of the silicone hydrogel material (WC SiHyIf the water content of the inner layers of the silicone hydrogel material is approximately 65% ​​or less, the water expansion coefficient of each outer hydrogel layer is at least approximately 250%; the water content of the inner layers of the silicone hydrogel material is (WC SiHy If the ratio is approximately 70% or less, the water expansion coefficient of each outer hydrogel layer is at least approximately 300%.

[0086] It should be understood that the water content of the front and rear external hydrogel layers (crosslinked coatings) can be determined more accurately by following the procedure described in Example 23. Alternatively, the water content of the two external hydrogel layers (crosslinked coatings) can be determined using an article comprising a non-water-absorbent thin substrate and a crosslinked coating thereon, where the crosslinked coating is applied to the non-water-absorbent thin substrate under substantially the same conditions, following the same coating process as the SiHy contact lens. Then, the water content of each external hydrogel layer can be determined based on the difference between the dry weight and hydrated weight of the article having the crosslinked coating.

[0087] According to the present invention, each of the two outer hydrogel layers is substantially silicone-free, preferably completely silicone-free. However, when X-ray photoelectron spectroscopy (XPS) is used to determine the presence or absence of silicon in the outer hydrogel layer (generally with a probe of 1.5 to 6 nm), it is well known that environmental silicon inevitably contaminates the sample, as demonstrated by silicon detection by XPS on the surface of samples that theoretically contain no silicon atoms at all, such as polyethylene sheets, DAILIES® AquaComfortPlus® contact lenses from CIBA Vision Corporation, or ACUVUE® Moist from Johnson & Johnson (see Example 21 below). Therefore, the term "substantially silicon-free" is used in this application to mean that the surface silicon atom percentage measured by XPS on the SiHy contact lens is less than about 200%, preferably less than about 175%, more preferably less than about 150%, and even more preferably less than about 125%, of the silicon atom percentage of a control sample (e.g., polyethylene sheet, DAILIES® AquaComfortPlus® contact lens from CIBA Vision Corporation, or ACUVUE® Moist from Johnson & Johnson) which is known to be originally (theoretically) silicon-free. Alternatively, each outer hydrogel layer of the SiHy contact lens of the present invention is substantially silicon-free, characterized in that, when the dry contact lens is measured by XPS analysis, it has a silicon atom percentage of about 5% or less, preferably about 4% or less, and even more preferably about 3% or less of the total elemental percentage. It should be understood that, as long as the surface properties (hydrophilicity, wetting, and / or lubricity) of the SiHy contact lens are not significantly reduced, a small proportion of silicone may be incorporated (but preferably not) into the polymer network structure of the outer hydrogel layer.

[0088] In preferred embodiments, the front and rear external hydrogel layers (crosslinked coatings) have a sufficiently low crosslinking density to provide a crosslinked coating or external hydrogel layer (i.e., SiHy contact lens) with high digital friction resistance, characterized by the absence of surface cracking lines under dark field after rubbing the SiHy contact lens between fingers. Surface cracking resulting from digital friction is thought to potentially reduce surface lubricity and / or fail to prevent migration (exposure) to the silicone surface. Surface cracking can also indicate an excessive crosslinking density in the surface layer, which may affect the surface modulus. Preferably, the non-silicone hydrogel material in the external hydrogel layer (crosslinked coating) includes crosslinking induced from azetidinium groups in a thermally induced coupling reaction.

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

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

[0091] In another preferred embodiment, the SiHy contact lens of the present invention further includes two transition layers of polymer material in its layered structure, as schematically illustrated in Figure 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 has a substantially uniform 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 are fused at the peripheral edges of the contact lens so as to completely enclose the inner layer of silicone hydrogel material. The presence and thickness of the transition layers can preferably be determined by AFM analysis of a cross-section of a fully hydrated SiHy contact lens, 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 prime) coatings applied to a pre-formed SiHy contact lens having a desired Dk, water content, and bulk modulus before the cross-linked coating (outer hydrogel layer) is applied. The transition layers (base coatings) function to fix / bond the outer hydrogel layer. Preferably, the transition layers are carboxyl (COOH)-containing polymers, preferably acrylic acid or methacrylic acid or C2-C 12This includes homopolymers or copolymers of alkylacrylic acids. It should be understood that carboxyl-containing polymers can penetrate the bulk material and extend into the outer hydrogel layer. If such penetration into the inner layers of the silicone hydrogel material occurs, each transition layer will contain the carboxyl-containing polymer and silicone hydrogel bound together. Furthermore, especially when a carboxyl-containing polymer is present, the presence of the transition layer is thought to give a thicker layer and / or a relatively high water content exceeding the water reservoir layer due to the high water-binding properties of the carboxyl groups. Moreover, even if the transition layer can contain many carboxylic acid groups, the adverse effect on the surface concentration of carboxylic acid groups in the SiHy contact lens will be minimal, as the surface concentration of carboxylic acid groups is mainly 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 the deposition of positively charged proteins from the tear fluid of the patient wearing the lens.

[0093] In another preferred embodiment, the front and rear outer hydrogel layers have a surface coefficient that 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% lower than that of the inner layer.

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

[0095] According to the present invention, a pre-formed SiHy contact lens originally contains amino groups and / or carboxyl groups on its surface and / or nearby, or can be modified to contain them.

[0096] If the pre-formed SiHy contact lens originally contains amino groups and / or carboxyl groups on and / or near its surface, this can be obtained by polymerizing a silicone hydrogel lens formulation containing a reactive vinyl monomer.

[0097] Examples of preferred reactive vinyl monomers include amino-C2-C6 alkyl(meth)acrylate, C1-C6 alkylamino-C2-C6 alkyl(meth)acrylate, allylamine, vinylamine, amino-C2-C6 alkyl(meth)acrylamide, C1-C6 alkylamino-C2-C6 alkyl(meth)acrylamide, acrylic acid, C1-C 12 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-phenylacrylic acid, β-acrylooxypropionic acid, sorbic acid, angelic 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 are included but not limited to these. Preferably, SiHy contact lenses include amino-C2-C6 alkyl (meth)acrylate, C1-C6 alkylamino-C2-C6 alkyl (meth)acrylate, allylamine, vinylamine, amino-C1-C6 alkyl (meth)acrylamide, C1-C6 alkylamino-C2-C6 alkyl (meth)acrylamide, acrylic acid, C1-C 12 It is produced from a lens formulation containing at least one reactive vinyl monomer selected from the group consisting of alkylacrylic acid, N,N-2-acrylamidoglycolic acid, and combinations thereof.

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

[0099] The pre-formed SiHy contact lenses can also be subjected to surface treatment to form a reactive base coating having amino groups and / or carboxyl groups on the surface of the contact lenses. Examples of surface treatment include, but are not limited to, surface treatment with energy (e.g., plasma, electrostatics, radiation or other energy sources), chemical treatment, chemical vapor deposition, grafting of hydrophilic vinyl monomers or macromers onto the surface of the article, and layer-by-layer coatings ("LbL coatings") obtained by following the methods described in U.S. Patents 6,451,871, 6,719,929, 6,793,973, 6,811,805 and 6,896,926 series and U.S. Patent Applications 2007 / 0229758A1, 2008 / 0152800A1 and 2008 / 0226922A1 (which are incorporated herein by reference in their entirety). As used herein, “LbL coating” refers to a coating that is not covalently bonded to the polymer matrix of a contact lens and is obtained through layer-by-layer ("LbL") deposition of charged or chargeable (by protonation or deprotonation) and / or uncharged material onto the lens. An LbL coating may consist of one or more layers.

[0100] Preferably, the surface treatment is an LbL coating process. In this preferred embodiment (i.e., an embodiment of a reactive LbL base coating), the resulting silicone hydrogel contact lens comprises a reactive LbL base coating (i.e., two transition layers) comprising at least one layer of reactive polymer (i.e., a polymer having pendant amino groups and / or carboxyl groups), the reactive LbL base coating is obtained by contacting the contact lens with a solution of the reactive polymer. Contact between the contact lens and the reactive polymer coating solution can be carried out by immersing the contact lens in the coating solution or by spraying the coating solution onto the contact lens. One contact process involves simply immersing the contact lens in a bath of the coating solution for a certain period of time, or by immersing the contact lens in a series of baths of the coating solution, with each bath having a shorter time. Another contact process involves simply spraying the coating solution. However, those skilled in the art can design many alternative methods, including various combinations of spraying and immersion steps. The contact time between the contact lens and the reactive polymer coating solution may be up to about 10 minutes, preferably about 5 to about 360 seconds, more preferably about 5 to about 250 seconds, and even more preferably about 5 to about 200 seconds.

[0101] According to this embodiment of the reactive LbL base coating, the reactive polymer can be a linear or branched polymer having pendant amino groups and / or carboxyl groups. Any polymer having pendant amino groups and / or carboxyl groups can be used as a reactive polymer 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 a reactive vinyl monomer and one or more non-reactive hydrophilic vinyl monomers (i.e., hydrophilic vinyl monomers that do not contain any carboxyl or (primary or secondary) amino groups); polyethyleneimines (PEI); polyvinyl alcohols having pendant amino groups; carboxyl-containing celluloses (e.g., carboxymethylcellulose, carboxyethylcellulose, carboxypropylcellulose); hyaluronic acid; chondroitin sulfate; poly(glutamic acid); poly(aspartic acid); and combinations thereof.

[0102] Any preferred reactive vinyl monomer described above can be used in this embodiment to form a reactive polymer for forming a reactive LbL-based coating.

[0103] Preferred examples of non-reactive hydrophilic vinyl monomers that do not contain carboxyl or amino groups include acrylamide (AAm), methacrylamide, N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA), N-vinylpyrrolidone (NVP), N,N-dimethylaminoethyl methacrylate (DMAEM), N,N-dimethylaminoethyl acrylate (DMAEA), N,N-dimethylaminopropyl methacrylamide (DMAPMAm), N,N-dimethylaminopropylacrylamide (DMAPAAm), glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2- This includes, but is not limited to, pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight-average molecular weight of up to 1500 daltons, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol (hydrolyzed forms of vinyl acetate in copolymers), phosphorylcholine-containing vinyl monomers (including (meth)acryloyloxyethyl phosphorylcholine and those described in U.S. Patent No. 5,461,433 (which is incorporated herein in whole by reference)) and combinations thereof.

[0104] Preferably, the reactive polymer for forming the reactive LbL base coating is polyacrylic acid, polymethacrylic acid, poly(C2-C) 12 Alkyl acrylic acid), poly(acrylic acid-co-methacrylic acid), poly[C2-C 12[Alkyl acrylic acid-co-(meth)acrylic acid], poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic acid-co-acrylamido], poly[(meth)acrylic acid-co-vinylpyrrolidone], poly[C2-C 12 [Alkyl acrylic acid-co-acrylamide], poly[C2-C 12 [Alkyl acrylate-co-vinylpyrrolidone], hydrolyzed poly[(meth)acrylate-co-vinyl acetate], hydrolyzed poly[C2-C 12 This includes alkylacrylic acid-co-vinyl acetate, polyethyleneimine (PEI), polyallylamine hydrochloride (PAH) homopolymer or copolymer, polyvinylamine homopolymer or copolymer, or a combination thereof.

[0105] Weight-average molecular weight M of reactive polymers for forming reactive LbL base coatings w This is at least about 10,000 Daltons, preferably at least about 50,000 Daltons, and more preferably about 100,000 to 5,000,000 Daltons.

[0106] A solution of a reactive polymer for forming a reactive LbL base coating on a contact lens can be prepared by dissolving one or more reactive polymers in water, a mixture of water and one or more miscible organic solvents, an organic solvent, or a mixture of one or more organic solvents. Preferably, the reactive polymer is dissolved in a mixture of water and one or more organic solvents, an organic solvent, or a mixture of one or more organic solvents. It is believed that a solvent system containing at least one organic solvent can cause the pre-formed SiHy contact lens to swell, thereby allowing some of the reactive polymer to penetrate into the pre-formed SiHy contact lens and increase the durability of the reactive base coating. Any of the above-mentioned organic solvents can be used to prepare the solution of the reactive polymer, as long as they can dissolve the reactive polymer.

[0107] In another preferred embodiment, the pre-formed SiHy contact lens originally contains amino groups and / or carboxyl groups on its surface and / or nearby, and is further subjected to surface treatment to form a reactive LbL base coating having amino groups and / or carboxyl groups therein.

[0108] In another preferred embodiment (reactive plasma-based coating), a pre-formed SiHy contact lens is subjected to plasma treatment to form a reactive plasma-based coating that covalently bonds to the contact lens. That is, one or more reactive vinyl monomers (any of those previously described) are polymerized under the action of plasma generated by an electrical discharge (so-called plasma-induced polymerization). The term "plasma" refers to an ionized gas generated by a glow discharge, which may consist, for example, electrons in the ground or any higher excited state, ions of any polarity, gas atoms and molecules, and photons. This is also called "low-temperature plasma."For an overview of plasma polymerization and its applications, see R. Hartmann, "Plasma polymerisation": Grundlagen, Technik und Anwendung, Jahrb. Oberflachentechnik (1993) 49, pp. 283-296, Battelle-Inst. eV Frankfurt / Main Germany; H. Yasuda, "Glow Discharge Polymerization", Journal of Polymer Science: Macromolecular Reviews, vol. 16 (1981), pp. 199-293; H. Yasuda, "Plasma Polymerization", Academic Press, Inc. (1985); Frank Jansen, "Plasma Deposition Processes", in "Plasma Deposited Thin Films", ed. by T. Mort and F. Jansen, CRC Press Boca Raton (19); O. Auciello et al. (ed.) "Plasma-Surface Interactions and Processing of Materials". See also N. Dilsiz and G. Akovali, "Plasma Polymerization of Selected Organic Compounds," Polymer, vol. 37 (1990), pp. 377-399, published by Kluwer Academic Publishers in NATO ASI Series; Series E: Applied Sciences, vol. 176 (1990), pp. 377-399; and N. Dilsiz and G. Akovali, "Plasma Polymerization of Selected Organic Compounds," Polymer, vol. 37 (1996), pp. 333-341. Preferably, the plasma-inducible polymerization is "post-glow" plasma-inducible polymerization, as described in WO98028026 (which is incorporated herein by reference in its entirety).In the case of "post-glow" 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 activated surface is exposed to a vinyl monomer having amino or carboxyl groups (any of the above-mentioned reactive vinyl monomers) while the plasma output is turned off. The activation causes plasma-induced radical generation on the surface, and in a subsequent step, polymerization of the vinyl monomer is initiated on it.

[0109] According to the present invention, a water-soluble and crosslinkable hydrophilic polymer material for forming an external hydrogel layer (or crosslinked coating) comprises a crosslinkable group, preferably a thermally crosslinkable group, more preferably an azetidinium group. Preferably, the water-soluble and crosslinkable hydrophilic polymer material for forming an external hydrogel layer (or crosslinked coating) is a partially crosslinked polymer material comprising a three-dimensional network structure and a crosslinkable (preferably thermally crosslinkable) group, more preferably an azetidinium group, within the network structure. The term "partially crosslinked" means, with respect to polymer materials, that in the crosslinking reaction, the crosslinkable groups of the starting material for producing the polymer material are not completely consumed. Examples of crosslinkable groups include, but are not limited to, azetidinium groups, epoxy groups, isocyanate groups, aziridine groups, azulactone groups, and combinations thereof.

[0110] In a preferred embodiment, the water-soluble and crosslinkable hydrophilic polymer material for forming an outer hydrogel layer (or crosslinked coating) comprises (i) about 20% to about 95% (by weight) of a primary polymer chain derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, (ii) about 5% to about 80% (by weight) of a hydrophilic moiety or secondary polymer chain derived from at least one hydrophilicity enhancer having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups and combinations thereof (wherein the hydrophilic moiety or secondary polymer chain is covalently linked to the primary polymer chain via one or more covalent bonds formed between one azetidinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl, or thiol group of the hydrophilicity enhancer, respectively), and (iii) an azetidinium group that is part of the primary polymer chain or a pendant or terminal group covalently linked to the primary polymer chain.

[0111] Using such water-soluble and crosslinkable hydrophilic polymer materials, an outer hydrogel layer (or crosslinked coating) can be formed by simply heating a pre-formed SiHy contact lens (having amino and / or carboxyl groups, or a base coating containing amino and / or carboxyl groups, on and / or near the surface of the contact lens) in an aqueous solution in the presence of the hydrophilic polymer material at a temperature of about 40°C to about 140°C for a sufficient time to covalently link the hydrophilic polymer material to the surface of the contact lens via the covalent bonds formed between one azetidinium group of the hydrophilic polymer material and one amino and / or carboxyl group on and / or near the surface of the contact lens, thereby forming a crosslinked hydrophilic coating on the contact lens. It should be understood that any water-soluble and crosslinkable hydrophilic polymer material containing crosslinkable groups (e.g., those described above) can be used in the present invention to form the front and rear outer hydrogel layers of the SiHy contact lens.

[0112] The water-soluble and thermally crosslinkable hydrophilic polymer material containing an azetidinium group comprises about 20% to about 95%, preferably about 35% to about 90%, more preferably about 50% to about 85% (by weight) of a primary polymer chain derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, and about 5% to about 80%, preferably about 10% to about 65%, more preferably about 15% to about 50% (by weight) of a hydrophilic moiety or secondary polymer chain derived from at least one hydrophilicity enhancer having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups and combinations thereof (i.e., having a composition containing these). The composition of the hydrophilic polymer material is determined by the composition of the reaction mixture used to prepare the thermally crosslinkable hydrophilic polymer material according to the crosslinking reaction shown in Scheme I above (based on the total weight of the reactants). For example, if the reaction mixture contains about 75% (by weight) of an epichlorohydrin-functionalized polyamine or polyamidoamine and about 25% (by weight) of at least one hydrophilicity enhancer (based on the total weight of the reactants), the resulting hydrophilic polymer material contains about 75% (by weight) of a first polymer chain derived from the epichlorohydrin-functionalized polyamine or polyamidoamine, and about 25% (by weight) of a hydrophilic moiety or second polymer chain derived from the at least one hydrophilicity enhancer. The azetidinium groups in the thermally crosslinkable hydrophilic polymer material are azetidinium groups (of the epichlorohydrin-functionalized polyamine or polyamidoamine) that do not participate in the crosslinking reaction for preparing the thermally crosslinkable hydrophilic polymer material.

[0113] Epichlorohydrin-functionalized polyamines or polyamidoamines can be obtained by reacting epichlorohydrin with a polyamine polymer or a polymer containing a primary or secondary amino group. For example, poly(alkyleneimines) or poly(amidoamines), which are polycondensates derived from polyamines and dicarboxylic acids (e.g., adipic acid-diethylenetriamine copolymers), can be reacted with epichlorohydrin to form epichlorohydrin-functionalized polymers. Similarly, homopolymers or copolymers of aminoalkyl(meth)acrylates, mono-alkylaminoalkyl(meth)acrylates, aminoalkyl(meth)acrylamides, or mono-alkylaminoalkyl(meth)acrylamides can also be reacted with epichlorohydrin to form epichlorohydrin-functionalized polyamines. The reaction conditions for the epichlorohydrin-functionalization of polyamine or polyamidoamine polymers are taught in European Patent No. 1465931 (which is incorporated herein by reference in its entirety). Preferred epichlorohydrin-functionalized polymers include polyaminoamide-epichlorohydrin (PAE) (or polyamide-polyamine-epichlorohydrin or polyamide-epichlorohydrin) such as Hercules' Kymene® or Polycup® resin (epichlorohydrin-functionalized adipic acid-diethylenetriamine copolymer), or Servo / Delden's Polycup® or Servamine® resin.

[0114] Any suitable hydrophilicity enhancer can be used in the present invention, as long as it contains at least one amino group, at least one carboxyl group, and / or at least one thiol group.

[0115] Preferred classes of hydrophilicity enhancers include amino-, carboxyl-, or thiol-containing monosaccharides (e.g., 3-amino-1,2-propanediol, 1-thiolglycerol, 5-keto-D-gluconic acid, galactosamine, glucosamine, galacturonic acid, gluconic acid, glucosamic acid, mannosamine, sugar acid 1,4-lactone, saccharidic acid, ketodeoxynonulosonic acid) This includes, but is not limited to, amino-, carboxyl-, or thiol-containing disaccharides (e.g., chondroitin disaccharide sodium salt, di(β-D-xylopyranosyl)amine, digalacturonic acid, heparin disaccharide, hyaluronic acid disaccharide, lactobionic acid); and amino-, carboxyl-, or thiol-containing oligosaccharides (e.g., carboxymethyl-β-cyclodextrin sodium salt, trigalacturonic acid); and combinations thereof.

[0116] Another preferred class of hydrophilicity enhancers is a hydrophilic polymer having one or more amino, carboxyl, and / or thiol groups. More preferably, the content of monomer units having amino (-NHR', where R' is as defined above) carboxyl (-COOH) and / or thiol (-SH) groups in the hydrophilic polymer as a 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] One preferred class of hydrophilic polymers as hydrophilicity enhancers is, for example, carboxymethylcellulose (having a carboxyl content of about 40% or less, with repeating units -[C6H 10-m O5(CH2CO2H) m]-(wherein m is 1-3) is estimated based on the composition of carboxyethylcellulose (having a carboxyl content of approximately 36% or less, repeating units -[C6H 10-m O5(C2H4CO2H) m ]-(wherein m is 1-3) is estimated based on the composition of carboxypropylcellulose (having a carboxyl content of approximately 32% or less, repeating units -[C6H 10-m O5(C3H6CO2H) m ]-(wherein m is 1-3) is estimated based on the composition of hyaluronic acid (having a carboxyl content of approximately 11%, repeating units - (C 13 H 20 Based on the composition of O9NCO2H), chondroitin sulfate (having a carboxyl content of approximately 9.8%, repeating unit - (C) 12 H 18 O 13 It is an amino- or carboxyl-containing polysaccharide, such as (estimated based on the composition of NSCO2H)- or a combination thereof.

[0118] Another preferred class of hydrophilic polymers as hydrophilicity enhancers includes poly(ethylene glycol) (PEG) having mono-amino, carboxyl, or thiol groups (e.g., PEG-NH2, PEG-SH, PEG-COOH); H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; poly-PEG having one or more amino, carboxyl, or thiol groups; PEG dendrimers having one or more amino, carboxyl, or thiol groups; diamino- or non-reactive hydrophilic vinyl monomers. This includes, but is not limited to, dicarboxyl-terminated homopolymers or copolymers; monoamino- or monocarboxyl-terminated homopolymers or copolymers of non-reactive hydrophilic vinyl monomers; copolymers which are polymerization products of compositions comprising (1) one or more reactive vinyl monomers in about 60% (weight) or less, preferably about 0.1% to about 30%, more preferably about 0.5% to about 20%, and even more preferably about 1% to about 15% (weight) of a composition comprising (2) at least one non-reactive hydrophilic vinyl monomer and / or at least one phosphorylcholine-containing vinyl monomer; and combinations thereof. Reactive vinyl monomers and non-reactive hydrophilic vinyl monomers have been previously described.

[0119] More preferably, the hydrophilic polymer as a hydrophilicity enhancer is PEG-NH2; PEG-SH; PEG-COOH; H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; polyvariant PEG having one or more amino, carboxyl, or thiol groups; PEG dendrimers having one or more amino, carboxyl, or thiol groups; acrylamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, up to 400 daltons by weight average Monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homopolymer or copolymer of nonreactive hydrophilic vinyl monomers selected from the group consisting of C1-C4-alkoxy polyethylene glycol (meth)acrylate having molecular weight, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, N,N-dimethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylamide, (meth)acryloyloxyethyl phosphorylcholine and combinations thereof; (1) about 0.1% to about 30%, preferably about 0.5% to about 20%, more preferably about 1% to about 15% (by weight) of (meth)acrylic acid, C2-C 12The copolymer is a polymerization product of a composition comprising (2)(meth)acrylic acid, vinylamine, allylamine and / or amino-C2-C4 alkyl (meth)acrylate and (2)(meth)acryloyloxyethyl phosphorylcholine and / or 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, with at least one non-reactive hydrophilic vinyl monomer selected from the group.

[0120] Most preferably, the hydrophilicity enhancer is PEG-NH2; PEG-SH; PEG-COOH; monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated polyvinylpyrrolidone; monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated polyacrylamide; monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly(DMA); monoamino- or monocarboxyl-, diamino- or dicarboxyl-terminated poly(DMA-co-NVP); monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly(NVP-co-N,N-dimethylaminoethyl (meth)acrylate); monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly(vinyl alcohol); monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly[(meth)acryloyloxyethyl phosphorylcholine] homopolymer or copolymer; monoami No, monocarboxyl, diamino, or dicarboxyl-terminated poly(NVP-co-vinyl alcohol); monoamino, monocarboxyl, diamino, or dicarboxyl-terminated poly(DMA-co-vinyl alcohol); poly[(meth)acrylic acid-co-acrylamide] having about 0.1% to about 30%, preferably about 0.5% to about 20%, more preferably about 1% to about 15% (by weight) of (meth)acrylic acid; about 0.1% to about 30%, preferably about 0.5% Poly[(meth)acrylic acid-co-NVP] having approximately 20%, more preferably approximately 1% to approximately 15% (by weight) of (meth)acrylic acid; (1) (meth)acryloyloxyethyl phosphorylcholine; and (2) copolymers and combinations thereof that are polymerization products of compositions comprising approximately 0.1% to approximately 30%, preferably approximately 0.5% to approximately 20%, more preferably approximately 1% to approximately 15% (by weight) of carboxylic acid-containing vinyl monomers and / or amino acid-containing vinyl monomers.

[0121] Functionalized PEGs and multi-functionalized PEGs can be obtained from various suppliers, such as Polyscience and Shearwater Polymers, Inc.

[0122] Monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated homo- or copolymers of one or more nonreactive hydrophilic vinyl monomers or phosphorylcholine-containing vinyl monomers can be prepared by following the procedure described in U.S. Patent No. 6,218,508 (which is incorporated herein by reference in its entirety). For example, to prepare diamino- or dicarboxyl-terminated homo- or copolymers of nonreactive hydrophilic vinyl monomers, a nonreactive vinyl monomer, a chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropinic acid, thioglycolic acid, thiolactic acid, or other hydroxymercaptans, aminomercaptans, or carboxyl-containing mercaptans) and optionally other vinyl monomers are copolymerized (by heat or chemical rays) with a reactive vinyl monomer (having an amino or carboxyl group) in the presence of a free radical initiator. Generally, the molar ratio of the chain transfer agent to all vinyl monomers other than 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 such preparations, the chain transfer agent having an amino or carboxyl group is used to control the molecular weight of the resulting hydrophilic polymer, forming the ends of the hydrophilic polymer to give the hydrophilic polymer having one terminal amino or carboxyl group, while the reactive vinyl monomer provides the other terminal carboxyl or amino group to the resulting hydrophilic polymer. Similarly, to prepare monoamino- or monocarboxyl-terminated homo- or copolymers of non-reactive hydrophilic vinyl monomers, the non-reactive vinyl monomer, the chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid, or other hydroxymercaptans, aminomercaptans, or carboxyl-containing mercaptans) and optionally other vinyl monomers are copolymerized (by heat or chemical rays) in the absence of any reactive vinyl monomers.

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

[0124] Weight-average molecular weight M of a hydrophilic polymer (as a hydrophilicity enhancer) having at least one amino, carboxyl, or thiol group w Preferably, it is about 500 to about 1,000,000, and more preferably about 1,000 to about 500,000.

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

[0126] According to the present invention, the concentration of the hydrophilicity enhancer for epichlorohydrin-functionalized polyamines or polyamidoamines should be selected so as not to make the resulting hydrophilic polymer material water-insoluble (i.e., less than 0.005 g solubility per 100 ml of water at room temperature), and so as to consume about 99% or less, preferably about 98% or less, more preferably about 97% or less, and even more preferably about 96% or less of the azetidinium groups of the epichlorohydrin-functionalized polyamine or polyamidoamine.

[0127] According to the present invention, heating is preferably carried out by immersing a pre-formed SiHy contact lens, which includes amino and / or carboxyl groups on and / or near the surface of the contact lens, or a base coating containing amino and / or carboxyl groups, in a packaging solution (i.e., a buffered aqueous solution) containing a water-soluble, thermocrosslinkable, hydrophilic polymer material in a sealed lens package, and autoclaving it at a temperature of about 118°C to about 125°C for about 20 to 90 minutes. According to this embodiment of the present invention, the packaging solution is a buffered aqueous solution that is ophthalmologically safe after autoclaving. Alternatively, heating is preferably carried out by immersing a pre-formed SiHy contact lens, which includes a base coating and a layer of water-soluble, thermocrosslinkable, hydrophilic polymer material on top of the base coating, in a packaging solution (i.e., a buffered aqueous solution) in a sealed lens package, and autoclaving it at a temperature of about 118°C to about 125°C for about 20 to 90 minutes.

[0128] Lens packages (or containers) for autoclaving and storing soft contact lenses are well known to those skilled in the art. Any lens package can be used in the present invention. Preferably, the lens package is a blister package including a base and a cover. The cover is removably sealed to the base, which includes a cavity for receiving a sterile packaging solution and a contact lens.

[0129] Before being sold to the user, the lenses are packaged in individual packages, sealed, and sterilized (for example, by autoclaving at approximately 120°C or above for at least 30 minutes). Those skilled in the art will understand how to properly seal and sterilize lens packages.

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

[0131] The packaging solution contains a sufficient amount of buffer to maintain the pH of the packaging solution within a desired range, for example, preferably a physiologically acceptable range of about 6 to about 8.5. As is known, any physiologically suitable buffer can be used. Suitable buffers as components of the contact lens care composition according to the present invention are known to those skilled in the art. Examples include boric acid, borate, e.g., sodium borate; citric acid, citrate, e.g., potassium citrate; bicarbonate, e.g., sodium bicarbonate; TRIS (2-amino-2-hydroxymethyl-1,3-propanediol); bis-tris (bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane); bis-aminopolyol; triethanolamine; ACES (N-(2-hydroxyethyl)-2-aminoethanesulfonic acid); BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid); HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid); MES (2-(N-morpholino)ethanesulfonic acid) The buffers are 1,3-bis(tris[hydroxymethyl]-methylamino)propane (bis-TRIS-propane), 1,3-bis(tris[hydroxymethyl]methyl)propane (bis-TRIS-propane), 1,3-bis(tris[hydroxymethyl]methyl)propane (bis-TRIS-propane), 1,3-bis(tris[hydroxymethyl]methylamino)propane (bis-TRIS-propane), 1,3-bis(tris[hydroxymethyl]methylamino)propane (bis-TRIS-propane), 1,3-bis(tris[hydroxymethyl]methylamino)propane (bis-TRIS-propane). The amount of each buffer in the packaging solution is preferably 0.001% to 2%, preferably 0.01% to 1%; most preferably about 0.05% to about 0.30% (by weight).

[0132] The packaging solution has an osmotic pressure of about 200 to about 450 milliosmoles (mOsm), preferably about 250 to about 350 mOsm. The osmotic pressure of the packaging solution can be adjusted by adding organic or inorganic substances that affect the osmotic pressure. Suitable ophthalmologically acceptable isotonic agents include, but are not limited to, sodium chloride, potassium chloride, glycerol, propylene glycol, polyols, mannitol, sorbitol, xylitol, and mixtures thereof.

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

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

[0135] The packaging solution of the present invention may contain a viscosity-enhancing polymer. The viscosity-enhancing polymer is preferably nonionic. The increased viscosity of the solution provides a film on the lens that can enhance the comfort of wearing the contact lens. The viscosity-enhancing component can also function to mitigate the impact on the ocular surface during insertion and also helps to reduce irritation to the eye.

[0136] Preferred viscosity-enhancing 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 (PVAs), high molecular weight poly(ethylene oxide) having a molecular weight greater than about 2,000 (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 dialkylaminoalkyl (meth)acrylate having at least one 7-20 carbon atom, and combinations thereof. Water-soluble cellulose ethers and copolymers of vinylpyrrolidone and dimethylaminoethyl methacrylate are the most preferred viscosity-enhancing polymers. Copolymers of N-vinylpyrrolidone and dimethylaminoethyl methacrylate are commercially available, for example, ISP's Copolymer 845 and Copolymer 937.

[0137] The viscosity-enhancing polymer is present in the packaging solution in an amount of about 0.01% to about 5% (by weight), preferably about 0.05% to about 3% (by weight), and more preferably about 0.1% to about 1% (by weight), relative to the total amount of the packaging solution.

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

[0139] If at least one of the crosslinked coating and packaging solutions contains a polymer material having polyethylene glycol segments, the packaging solution preferably contains an α-oxo-multi-acid or a salt thereof in an amount sufficient to reduce the susceptibility of the polyethylene glycol segments to oxidative degradation. A concurrent patent application by the same owner (U.S. Patent Application No. 2004 / 0116564 A1, which is incorporated in whole hereof) discloses that an oxo-multi-acid or a salt thereof can reduce the susceptibility of PEG-containing polymer materials to oxidative degradation.

[0140] Typical α-oxopolyacids or their biocompatible salts include, but are not limited to, citric acid, 2-ketoglutaric acid, or malic acid or their biocompatible (preferably ophthalmically compatible) salts. More preferably, the α-oxopolyacid is citric acid or malic acid or their biocompatible (preferably ophthalmically compatible) salts (e.g., sodium, potassium, etc.).

[0141] According to the present invention, the packaging solution may further contain a mucin-like substance, an ophthalmologically beneficial substance, and / or a surfactant. Typical mucin-like substances, typical ophthalmologically beneficial substances, and typical surfactants described above can be used in this embodiment.

[0142] In preferred embodiments, the SiHy contact lenses of the present invention have a relatively long water decay time (WBUT). WBUT is the time required for the water film to decay (de-wet) and for the underlying lens material to be exposed under visual inspection. SiHy contact lenses with a longer WBUT can retain a water (tear film) film on their surface for a relatively long time when worn in the eye. This will reduce the likelihood of dry spots forming between blinks of the eyelids and enhance wearing comfort. WBUT can be measured according to the procedures described in the examples below. Preferably, the SiHy contact lenses of the present invention have surface hydrophilicity characterized by having a water decay time of at least about 10 seconds.

[0143] In a preferred embodiment, the SiHy contact lens of the present invention has 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.

[0144] In a preferred embodiment, the SiHy contact lens has an oxygen transfer rate of at least about 40, preferably at least about 60, more preferably at least about 80, even more preferably at least about 100, and most preferably at least about 120 bars / mm.

[0145] In this embodiment of the present invention, various embodiments, including preferred embodiments of the present invention, can be described separately, but it should be understood that these can be combined and / or used together in any desired manner to derive different embodiments of the silicone hydrogel contact lens of the present invention.

[0146] In another embodiment, 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 rear surface; the contact lens has an oxygen transfer coefficient of at least about 40, preferably at least about 60, more preferably at least about 80, and even more preferably at least about 110 barser / mm, and a cross-sectional surface coefficient profile (along the shortest line between the front and rear surfaces of the cross-sectional surface of the contact lens, including the front surface and the surrounding front outer region; including the center of the shortest line and the surrounding inner region; and including the rear surface and the surrounding rear outer region, the front outer region being the average front coefficient

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[0147] In preferred embodiments, the hydrated silicone hydrogel contact lens may have 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%, most preferably about 25% to about 55% (by weight); surface wetting 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, most preferably about 50 degrees or less; 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 rear surfaces have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups) characterized by attracting a maximum of about 200, preferably about 160, more preferably about 120, even more preferably about 90, and most preferably about 60 positively charged particles in a positively charged particle adhesion test. In order to have a low surface concentration of negatively charged groups (e.g., carboxylic acid groups), the front and rear outer hydrogel layers need to have a relatively low carboxylic acid content. Preferably, the front and rear outer hydrogel layers have a carboxylic acid content of 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.

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

[0150] In another preferred embodiment, the hydrated SiHy contact lens preferably has high digital friction resistance, characterized by the absence of surface cracking lines under dark field after rubbing the SiHy contact lens between fingers. Surface cracking resulting from digital friction is thought to reduce surface lubricity and / or may not prevent migration (exposure) to the silicone surface.

[0151] In another preferred embodiment, the hydrated SiHy contact lens of the present invention comprises an inner layer of silicone hydrogel material, a front outer hydrogel layer, and a rear outer hydrogel layer, wherein the front and rear outer hydrogel layers are substantially uniform in thickness and are fused at the peripheral edge of the contact lens to completely enclose the inner layer of silicone hydrogel material. It should be understood that the first and second outer regions in the cross-sectional surface coefficient profile correspond to the two outer hydrogel layers, and the inner region corresponds to the inner layer of silicone hydrogel material. As described above in other embodiments of the present invention, all of the various embodiments of the outer hydrogel layer (crosslinked coating) can be used as the outer hydrogel layer in this embodiment of the present invention, either alone or in any combination. As described above in other embodiments of the present invention, all of the various embodiments of the inner layer of silicone hydrogel material can be used as the inner layer of silicone hydrogel material in this embodiment of the present invention, either alone or in any combination.

[0152] According to this embodiment of the present invention, the outer hydrogel layer has a substantially uniform thickness, at least about 0.1 μm, preferably about 0.1 μm to about 20 μm, more preferably about 0.25 μm to about 15 μm, even more preferably about 0.5 μm to about 12.5 μm, and most preferably about 1 μm to about 10 μm. The thickness of each outer hydrogel layer of the SiHy contact lens of the present invention is determined by AFM analysis of the cross section of the fully hydrated SiHy contact lens, as described above. In a more preferred embodiment, the thickness of each outer hydrogel layer is at most about 30% (i.e., 30% or less) of the center thickness of the fully hydrated SiHy contact lens, preferably at most about 20% (20% or less), and more preferably at most about 10% (10% or less). Furthermore, each of the two outer hydrogel layers is substantially silicone-free (characterized by having about 5% or less, preferably about 4% or less, and more preferably about 3% or less of silicon atoms in the total elemental percentage when the contact lens in a dry state is measured by XPS analysis), and preferably completely silicone-free. It should be understood that a small proportion of silicone can be optionally incorporated (but preferably not incorporated) into the polymer network structure of the outer hydrogel layer, as long as it does not significantly reduce 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 have a water content (WC) of the hydrated silicone hydrogel contact lens. Lens It contains a higher moisture content (as indicated by WC), and more specifically, WC Lens It needs to be at least approximately 1.2 times (i.e., 120%). The water expansion coefficient of each outer hydrogel layer can be considered to approximately represent the water content of the outer hydrogel layer, as discussed above. WC Lens When the ratio is approximately 45% or less, the water expansion ratio 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%. LensIf it is higher than 45%, the water expansion rate of each outer hydrogel layer is at least approximately

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[0154] Preferably, the SiHy contact lens further includes a transition layer located between the silicone hydrogel material and the outer hydrogel layer. As described in earlier aspects of the present invention, all of the various embodiments of the transition layer can be used individually or in any combination in this embodiment of the present invention.

[0155] The hydrated SiHy contact lenses of the present invention can be prepared according to the method described above. All of the various embodiments of the inner layer (i.e., the silicone hydrogel material) described above can be used individually or in any combination as the silicone hydrogel nucleus in this embodiment of the present invention. As described in the earlier aspects of the present invention, all of the various embodiments can be used individually or in any combination as the present embodiment of the present invention.

[0156] In this embodiment of the present invention, various embodiments, including preferred embodiments of the present invention, can be described separately, but it should be understood that these can be combined and / or used together in any desired manner to derive different embodiments of the silicone hydrogel contact lens of the present invention. As described in the earlier aspects of the present invention, all of the various embodiments can be used in this embodiment of the present invention, individually or in any combination, in any desired manner.

[0157] In a further embodiment, 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 rear surface; the contact lens has surface lubricity characterized by (1) an oxygen transfer rate of at least about 40, preferably at least about 60, more preferably at least about 80, and even more preferably at least about 110 bars / mm, and (2) a critical coefficient of friction (represented as CCOF) of about 0.046 or less, preferably about 0.043 or less, and more preferably about 0.040 or less, and the front and rear surfaces have negatively charged groups such as carboxylic acid groups at a low surface concentration, characterized by attracting a maximum of about 200, preferably about 160, more preferably about 120, even more preferably about 90, and most preferably about 60 positively charged particles in a positively charged particle adhesion test.

[0158] In preferred embodiments, the hydrated silicone hydrogel contact lens has a modulus of elasticity (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%, most preferably about 25% to about 55% (by weight); surface wettability characterized by having an average water contact angle of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, even more preferably about 60 degrees or less, most preferably about 50 degrees or less; surface hydrophilicity characterized by having a WBUT of at least about 10 seconds; or a combination thereof.

[0159] In another preferred embodiment, the hydrated SiHy contact lens preferably has high digital friction resistance, characterized by the absence of surface cracking lines under dark field after rubbing the SiHy contact lens between fingers. Surface cracking resulting from digital friction is thought to reduce surface lubricity and / or may not prevent migration (exposure) to the silicone surface.

[0160] In another preferred embodiment, the hydrated SiHy contact lens of the present invention comprises an inner layer of silicone hydrogel material, a front outer hydrogel layer, and a rear outer hydrogel layer, the front and rear outer hydrogel layers having substantially uniform thickness and fused at the peripheral edge of the contact lens to completely enclose the inner layer of silicone hydrogel material. It should be understood that the first and second outer regions in the cross-sectional surface coefficient profile correspond to the two outer hydrogel layers, and the inner region corresponds to the inner layer of silicone hydrogel material. As described above in other embodiments of the present invention, all of the various embodiments of the outer hydrogel layer (crosslinked coating) can be used as the outer hydrogel layer in this embodiment of the present invention, either alone or in any combination. As described above in other embodiments of the present invention, all of the various embodiments of the inner layer of silicone hydrogel material can be used as the inner layer of silicone hydrogel material in this embodiment of the present invention, either alone or in any combination.

[0161] According to this embodiment of the present invention, the outer hydrogel layer has a substantially uniform thickness, having a thickness of at least about 0.1 μm, preferably about 0.1 μm to about 20 μm, more preferably about 0.25 μm to about 15 μm, even more preferably about 0.5 μm to about 12.5 μm, and most preferably about 1 μm to about 10 μm. The thickness of each outer hydrogel layer of the SiHy contact lens of the present invention is determined by AFM analysis of the cross section of the fully hydrated SiHy contact lens, as described above. In a more preferred embodiment, the thickness of each outer hydrogel layer is preferably up to about 30% (i.e., 30% or less) of the center thickness of the fully hydrated SiHy contact lens, preferably up to about 20% (20% or less), and more preferably up to about 10% (10% or less). Furthermore, each of the two outer hydrogel layers is substantially silicone-free (characterized by having about 5% or less, preferably about 4% or less, and more preferably about 3% or less of silicon atoms in the total elemental percent when the contact lens in a dry state is measured by XPS analysis), and preferably completely silicone-free. It should be understood that a small proportion of silicone can be optionally incorporated (but preferably not incorporated) into the polymer network structure of the outer hydrogel layer, as long as it does not significantly reduce 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 and rear outer hydrogel layers need to have a relatively low carboxylic acid content. Preferably, the front and rear outer hydrogel layers have a carboxylic acid content of about 20% (by weight) or less, preferably about 15% (by weight) or less, 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 have a water content (WC) of the hydrated silicone hydrogel contact lens. Lens It contains a higher water content (WC) than indicated by, and more specifically, the water content (WC) of hydrated silicone hydrogel contact lenses. LensIt needs to be at least approximately 1.2 times (i.e., 120%) of the original value. The water expansion coefficient of each outer hydrogel layer can be considered to approximate the water content of the outer hydrogel layer, as discussed above. WC Lens When the ratio is approximately 45% or less, the water expansion ratio 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%. Lens If it is higher than 45%, the water expansion rate of each outer hydrogel layer is at least approximately

number

number

number

number

[0163] In another preferred embodiment, the front and rear outer hydrogel layers have a surface coefficient that 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% lower than that of the inner layer.

[0164] Preferably, the SiHy contact lens further includes a transition layer located between the silicone hydrogel material and the outer hydrogel layer. As described in earlier aspects of the present invention, all of the various embodiments of the transition layer can be used individually or in any combination in this embodiment of the present invention.

[0165] The hydrated SiHy contact lens of the present invention can be prepared according to the method described above. All of the various embodiments of the inner layer (i.e., the silicone hydrogel material) described above can be used individually or in any combination as the silicone hydrogel nucleus in this embodiment of the present invention. As described in the earlier aspects of the present invention, all of the various embodiments can be used individually or in any combination as the present embodiment of the present invention.

[0166] In this embodiment of the present invention, various embodiments, including preferred embodiments of the present invention, can be described separately, but it should be understood that these can be combined and / or used together in any desired manner to derive different embodiments of the silicone hydrogel contact lens of the present invention. As described in the earlier aspects of the present invention, all of the various embodiments can be used in this embodiment of the present invention, individually or in any combination, in any desired manner.

[0167] With the foregoing disclosure, those skilled in the art will be able to implement the present invention. Various modifications, variations, and combinations can be made to the various embodiments described herein. It is suggested that readers refer to the following examples to better understand specific embodiments and their advantages. This description and examples are to be considered illustrative.

[0168] Various aspects and embodiments of the present invention are described using specific terms, apparatus, and methods, but such descriptions are for illustrative purposes only. The terms used are descriptive rather than restrictive. Those skilled in the art will understand that modifications and variations can be carried out without departing from the spirit and scope of the invention as set forth in the following claims. They will also understand that the aspects of the various embodiments can be replaced in whole or in part, or combined and / or used together in any way. Accordingly, the spirit and scope of the appended claims shall not limit the description of preferred versions contained herein.

[0169] Example 1 Measurement of oxygen permeability The apparent oxygen permeability of a lens and the oxygen transfer coefficient of the lens material are determined according to techniques similar to those described in U.S. Patent No. 5,760,100 and Winterton et al.'s paper (The Cornea: Transactions of the World Congress on the Cornea 111, HD Cavanagh Ed., Raven Press: New York 1988, pp273-280) (both of which are incorporated herein by reference in their entirety). The oxygen flux (J) is measured in a humidified cell (i.e., the gas flow is maintained at approximately 100% relative humidity) at 34°C using a Dk1000 instrument (available from Applied Design and Development Co., Norcross, GA) or a similar analytical instrument. A known oxygen % (e.g., 21%) airflow is subjected to a flow of approximately 10-20 cm². 3 A nitrogen stream is passed through one side of the lens at a speed of [number] minutes, and then approximately 10-20 cm of nitrogen is flowed through the other side of the lens. 3Pass at a speed of / minute. Before measurement, equilibrate the sample with the test medium (i.e., physiological saline or distilled water) at the predetermined test temperature for at least 30 minutes (but within 45 minutes). Equilibrate any test medium used as an overlayer at the predetermined test temperature for at least 30 minutes (but within 45 minutes) before measurement. Set the speed of the stirring motor to 1200 ± 50 rpm corresponding to the display setting 400 ± 15 of the stepping motor controller. The atmospheric pressure P measured around the system is measured. Determine the thickness (t) of the lens in the area exposed in the test by measuring about 10 locations using a Mitotoya micrometer VL-50 or a similar device, and take the average of the measured values. Measure the oxygen concentration of the nitrogen flow (i.e., the oxygen diffusing through the lens) using a DK1000 device. The apparent oxygen permeability Dk app of the lens material is determined from the following formula: Dk app = Jt / (P oxygen ) [where J = oxygen flux [O2 μl / cm 2 - minute] P oxygen = (P measured - P water vapor) = (O2% in the air stream) [mmHg] = partial pressure of oxygen in the air stream P measured = atmospheric pressure (mmHg) P water vapor = 0 mmHg (in the dry cell) at 34 °C (mmHg) P water vapor = 40 mmHg (in the wet cell) at 34 °C (mmHg) t = average thickness of the lens in the exposure test area (mm) Dk app is expressed in barrer units

[0170] The apparent oxygen transmission rate (Dk / t) of the material can be calculated by dividing the apparent oxygen permeability (Dk app ) by the average thickness (t) of the lens.

[0171] The above measurements are not corrected for the so-called boundary layer effect, which results from the use of water or saline baths on the upper part of the contact lens during oxygen flux measurement. The boundary layer effect causes the reported apparent Dk of the silicone hydrogel material to be lower than the actual intrinsic Dk value. Furthermore, the relative effect of the boundary layer effect is greater with thinner lenses than with thicker lenses. The net effect will appear to vary depending on the lens thickness when the reported Dk needs to be kept constant.

[0172] The intrinsic Dk value of a lens can be estimated based on the Dk value corrected for the surface resistance to the oxygen flux caused by the boundary layer effect, as shown below.

[0173] The apparent oxygen permeability value (single point) of a reference lotrafilcon A (Focus® N&D®, CIBA VISION CORPORATION) or lotrafilcon B (AirOptix®, CIBA VISION CORPORATION) lens is measured using the same apparatus. The reference lens has a similar refractive power to the test lens and is measured simultaneously with the test lens.

[0174] Following the apparent Dk measurement procedure described above, the oxygen flux passing through a series of thicknesses of the Lotrafilcon A or Lotrafilcon B (reference) lens is measured using the same apparatus to obtain the intrinsic Dk value (Dk) of the reference lens. i ) is obtained. The series of thicknesses shall satisfy a thickness range of approximately 100 μm or more. Preferably, the thickness range of the reference lens encompasses the thickness of the test lens (bracket). Dk of these reference lenses app The measurement should be performed using the same apparatus as the test lens, and ideally, simultaneously with the test lens. The apparatus settings and measurement parameters should be kept constant throughout the experiment. If desired, individual samples may be measured multiple times.

[0175] In the calculation, using Equation 1, the residual oxygen resistance R is obtained from the results of the reference lens. r To decide.

number

[0176] Using the residual oxygen resistance value determined above, the accurate oxygen permeability Dk of the test lens can be calculated based on Equation 2. c Calculate the (estimated unique Dk).

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[0177] Using the estimated intrinsic Dk of the test lens, the apparent Dk (Dk) for a standard thickness lens under the same test environment is calculated based on Equation 3. a_std ) can be calculated. The standard thickness (t) of lotrafilcon A can be calculated. std ) = 85 μm. Standard thickness of lotrafilcon B = 60 μm.

number

[0178] Measurement of ion permeability The ion transmittance of the lens is measured according to the procedure described in U.S. Patent No. 5,760,100 (which is incorporated herein by reference in its entirety). The ion transmittance values ​​shown in the following examples are relative to the ion flux diffusion coefficient (D / D) of the standard lens material Alsacon. ref Alsacon has an ionoflux diffusion coefficient of 0.314 × 10⁻⁶. -3 mm 2 / has a minute

[0179] Lubricity evaluation Lubricity ranking is a qualitative ranking system, with 0 assigned to the polyacrylic acid-coated control lens, 1 to the commercially available Oasys® / TruEye® lens, and 4 to the commercially available Air Optix® lens. Samples are rinsed at least three times with excess DI water, then transferred to PBS for evaluation. Before evaluation, hands are rinsed with soapy water, thoroughly rinsed with DI water, and then dried with a KimWipe® towel. Samples are handled between the fingers, and each sample is assigned a numerical value relative to the standard lenses described above. For example, if a lens is determined to be slightly better than an Air Optix® lens, these lenses are assigned a number of 3. To ensure consistency, all rankings are collected independently by the same two operators to avoid bias, and good qualitative agreement and consistency of evaluation are evident from the data.

[0180] Surface wetting test The water contact angle on a contact lens is a general measure of the surface wettability of the contact lens. In particular, a small water contact angle corresponds to a more wettable surface. The average contact angle (droplet method) of the contact lens is measured using a VCA 2500 XE contact angle measuring device from AST, Inc. in Boston, Massachusetts. This device enables the measurement of the advancing or receding contact angle or the sessile (static) contact angle. The measurement is carried out immediately after blot drying with a fully hydrated contact lens as follows. The contact lens is taken out of the vial and washed three times in ~200 ml of fresh DI water to remove weakly bound packaging additives from the lens surface. Next, the lens is placed on a soft clean cloth (Alpha Wipe TX1009), wiped thoroughly to remove surface water, placed on the contact angle measuring stage, air dried by blowing dry air, and finally, the droplet contact angle is automatically measured using the software provided by the manufacturer. The DI water used to measure the contact angle has a resistivity > 18 MΩcm and the droplet volume used is 2 μl. Typically, a non-coated silicone hydrogel lens (after autoclaving) has a droplet contact angle of about 120 degrees. Before contacting the contact lens, the tweezers and the stage are thoroughly washed with isopropanol and rinsed with DI water.

[0181] Water Breakup Time (WBUT) Test The surface hydrophilicity of the lens (after autoclaving) is evaluated by determining the time required for the water film on the lens surface to start to break down. Briefly, the lens is taken out of the vial and washed three times in ~200 ml of fresh DI water to remove weakly bound packaging additives from the lens surface. The lens is taken out of the solution, clamped with tweezers and held in front of a strong light source. Visually confirm the time required for the water film to break down (dewet) and expose the underlying lens material. Non-coated lenses typically break down immediately after removing the DI water, which is taken as WBUT 0 seconds. Lenses showing WBUT ≥ 5 seconds are considered to have good hydrophilicity and are expected to show the ability to maintain a tear film on the eye.

[0182] Coating Non-Damage Test The non-damage of the coating on the surface of the contact lens can be tested according to the Sudan Black staining test as follows. A contact lens having a coating (LbL coating, plasma coating or any other coating) is immersed in a Sudan Black dye solution (Sudan Black in vitamin E oil), and then thoroughly rinsed with water. Sudan Black dye is hydrophobic and tends to be adsorbed by hydrophobic substances or on hydrophobic spots on the hydrophobic lens surface or the partially coated surface of a hydrophobic lens (e.g., a silicone hydrogel contact lens). If the coating on the hydrophobic lens is non-damaged, no staining spots are observed on or inside the lens. All test lenses are fully hydrated.

[0183] Coating Durability Test Using Solo-care (registered trademark) multi-purpose lens care solution, rub the lens 30 times with a finger, and then rinse with physiological saline. Repeat the above procedure a predetermined number of times, e.g., 1 - 30 times (i.e., the number of times of a continuous digital friction test to reproduce the cleaning and immersion cycles). Then, subject the lens to the Sudan Black test (i.e., the above coating non-damage test) to test whether the coating is still non-damaged. If the lens withstands the digital friction test, no significant increase in staining spots is observed (e.g., the staining spots cover only about 5% of the entire lens surface). Measure the water contact angle to determine the coating durability.

[0184] Determination of Azetidinium Content The azetidinium content in PAE can be determined according to one of the following assays.

[0185] PPVS Assay The PAE charge density (i.e., azetidinium content) can be determined according to the PPVS assay of a colorimetric titration assay, where potassium vinyl sulfate (PPVS) is the titrator and toluidine blue is the indicator. See SK Kam and J. Gregory, "Charge determination of synthetic cationic polyelectrolytes by colloid titration," in Colloid & Surface A: Physicochem. Eng. Aspect, 159: 165-179 (1999). PPVS binds to positively charged species, such as toluidine blue and the azetidinium group of PAE. The decrease in absorption intensity of toluidine blue is an indicator of a proportional PAE charge density (azetidinium content).

[0186] PES-Na assay The PES-Na assay is another colorimetric titration assay for determining PAE charge density (azetidinium content). In this assay, the titrant is sodium polyethylene sulfonate (PES-Na) instead of PPVS. The assay is the same as the PPVS assay described above.

[0187] PCD assay The PCD assay is a potentiometric titration assay for determining PAE charge density (azetidinium content). The titrant is sodium polyethylene sulfonate (PES-Na), PPVS, or other titrants. The PAE charge is detected by an electrode using, for example, the Mutek PCD-04 particle charge detector from BTG. The measurement principle of this detector can be found on the BTG website (http: / / www.btg.com / products.asp?langage=1&appli=5&numProd=357&cat=prod).

[0188] NMR method The active positively charged moiety in PAEs is the azetidinium group (AZR). NMR ratio analysis is the ratio of AZR-specific protons to non-AZR-related protons. This ratio serves as an indicator of the charge or AZR density of the PAE.

[0189] Debris adhesion test Contact lenses with a highly charged surface may be more susceptible to increased debris adhesion during patient handling. Rub a paper towel with gloved hands, then rub both sides of the lens with your fingers to transfer debris to the lens surface. Rinse the lens briefly and then observe it under a microscope. Rank each lens using a qualitative ranking criterion from 0 (no debris adhesion) to 4 (debris adhesion equivalent to a PAA-coated control lens). Lenses with a score of "0" or "1" are considered acceptable.

[0190] Example 2 Preparation of CE-PDMS macromers In the first step, 49.85 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn=2000, Shin-Etsu, KF-6001a) is reacted 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), thereby capping the α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane with IPDI. The reaction is maintained at 40°C for 4.5 hours to form IPDI-PDMS-IPDI. In the second step, a mixture of 164.8 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn=3000, Shin-Etsu, KF-6002) and 50 g of dehydrated MEK is added dropwise to the IPDI-PDMS-IPDI solution to which an additional 0.063 g of DBTDL has been added. The reactor is maintained at approximately 40°C for 4.5 hours to form HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. Next, the MEK is removed under reduced pressure. In the third step, 7.77 g of isocyanatoethyl methacrylate (IEM) and an additional 0.063 g of DBTDL are added to cap the terminal hydroxyl groups with methacryloyloxyethyl groups in the third step, forming IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM (i.e., CE-PDMS terminated with methacrylate groups).

[0191] Alternative preparation method for CE-PDMS macromers having terminal methacrylate groups 240.43g of KF-6001 was added to a 1-L reactor equipped with a stirring bar, thermometer, cryostat, dropping funnel, and nitrogen / vacuum inlet adapter, and then a high vacuum (2 × 10⁻¹⁰) was applied. -2Dry by applying mBar. Next, under a dry nitrogen atmosphere, add 320g of distilled MEK to the reactor and stir the mixture thoroughly. Add 0.235g of DBTDL to the reactor. After warming the reactor to 45°C, add 45.86g of IPDI to the reactor over 10 minutes with moderate stirring through an addition funnel. Maintain the reaction at 60°C for 2 hours. Next, add 630g of KF-6002 dissolved in 452g of distilled MEK and stir until a homogeneous solution is formed. Add approximately 0.235g of DBTDL and keep the reactor overnight under a dry nitrogen blanket at approximately 55°C. The next day, remove MEK by flash distillation. Cool the reactor and then add 22.7g of IEM, followed by approximately 0.235g of DBTDL to the reactor. After about 3 hours, add an additional 3.3g of IEM and allow the reaction to proceed overnight. The following day, the reaction mixture was cooled to approximately 18°C ​​to obtain a CE-PDMS macromer having terminal methacrylate groups.

[0192] Example 3 Preparation of lens formulations The lens preparation is prepared by dissolving the components in 1-propanol to have the following composition: 33% (by weight) CE-PDMS macromer prepared in Example 2, 17% (by weight) N-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24% (by weight) N,N-dimethylacrylamide (DMA), 0.5% (by weight) N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt) (L-PEG), 1.0% (by weight) Darocur 1173 (DC1173), 0.1% (by weight) visitint (5% copper phthalocyanine blue pigment dispersion in tris(trimethylsiloxy)silylpropyl methacrylate (TRIS)), and 24.5% (by weight) 1-propanol.

[0193] Lens preparation The lenses are prepared by casting from the lens mixture prepared above using a reusable mold similar to the molds shown in U.S. Patent No. 7,384,590 (Figures 1-6) and No. 7,387,759 (Figures 1-6). The mold includes a female half made of CaF2 and a male half made of PMMA. The UV irradiation source has an intensity of approximately 4 mW / cm² with a WG335 + TM297 cutoff filter. 2 This is a Hamamatsu lamp. The lens preparation in the molding mold is irradiated with UV light for approximately 25 seconds. The cast lens is extracted with isopropanol (or methyl ethyl ketone, MEK), rinsed with water, and coated with polyacrylic acid (PAA) by immersion in a propanol solution of PAA (0.1% (by weight), acidified to pH approximately 2.5 with formic acid), and then hydrated with water. The lens having the resulting reactive PAA-LbL base coating is determined to have the following properties: ion permeability of approximately 8.0 to approximately 9.0 compared to Alsacon lens material; apparent Dk (single point) of approximately 90 to 100; water content of approximately 30% to approximately 33%; and bulk surface modulus of approximately 0.60 MPa to approximately 0.65 MPa.

[0194] Example 4 In-package coated (IPC) saline is prepared by adding 0.2% polyamidoamine-epichlorohydrin (PAE) (Ashland's Kymene (aqueous solution), used as is; NMR assay indicates an azetidinium content of 0.46%) to phosphate-buffered saline (PBS, as specified below) (approximately 0.044 w / w% NaH2PO4·H2O, approximately 0.388 w / w% Na2HPO4·2H2O, approximately 0.79 w / w% NaCl), and then adjusting the pH to 7.2-7.4.

[0195] The lens from Example 3 is placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the IPC saline is added before inserting the lens). The blister is then sealed with aluminum foil and autoclaved at 121°C for approximately 30 minutes to form a cross-linked coating (PAA-x-PAE coating) on ​​the lens.

[0196] Next, the adhesion of lens debris, surface cracking, lubricity, contact angle, and water breakdown time (WBUT) are evaluated. The test lenses (lenses packaged / autoclaved in IPC saline, i.e., lenses having a PAA-x-PAE coating thereon) have no debris adhesion after being rubbed with a paper towel, while the control lenses (lenses packaged / autoclaved in PBS, i.e., lenses having a PAA-LbL base coating thereon) show severe debris adhesion. The water contact angle (WCA) of the test lenses is small (~20 degrees), and the WBUT is less than 2 seconds. When observed under a dark-field microscope, severe cracking lines are seen after handling the lenses (inverting the lens and rubbing the lens between the fingers). When judged by a qualitative finger friction test, the test lenses are much less slippery than the control lenses.

[0197] Example 5 Poly(acrylamide-co-acrylic acid) (or PAAm-PAA or poly(AAm-co-AA) or p(AAm-co-AA)) partial sodium salt (~80% solids content, poly(AAm-co-AA) (80 / 20), Mw 520,000, Mn 150,000) is purchased from Aldrich and used as is.

[0198] IPC saline is prepared by dissolving 0.02% poly(AAm-co-AA) (80 / 20) and 0.2% PAE (Kymene from Ashland (aqueous solution), used as is, azetidinium content 0.46 according to NMR assay) in PBS. Adjust the pH to 7.2 - 7.4. PBS is prepared by dissolving 0.76% NaCl, 0.044% NaH2PO4·H2O, and 0.388% Na2HPO4·2H2O in water.

[0199] The lens having the PAA-LbL base coating prepared in Example 3 is placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). Next, the blister is sealed with aluminum foil and autoclaved at approximately 121°C for approximately 30 minutes. It is believed that a cross-linked coating consisting of three layers of PAA-x-PAE-x-poly(AAm-co-AA) is formed on the lens during autoclaving.

[0200] The test lens (packaged in IPC saline / autoclaved, i.e., a lens with a PAA-x-PAE-x-poly(AAm-co-AA) crosslinked coating on it) showed no residue after rubbing with a paper towel. The test lens had a WBUT of more than 10 seconds. When observed under a dark-field microscope, cracking lines were visible after rubbing the test lens. The test lens was much smoother than the test lens of Example 4, but still not as smooth as the control lens packaged in PBS.

[0201] Example 6 IPC saline is prepared by dissolving 0.02% poly(AAm-co-AA)(80 / 20) and 0.2% PAE (Ashland's Kymene (aqueous solution), used as is; NMR assay indicates an azetidinium content of 0.46%) in PBS and adjusting the pH to 7.2-7.4. Next, the saline is heated to approximately 70°C and treated by heating at that temperature for 4 hours (heat pretreatment). During this heat pretreatment, poly(AAm-co-AA) and PAE are partially crosslinked with each other (i.e., not all azetidinium groups of PAE are consumed), forming a water-soluble and heat-crosslinkable hydrophilic polymer material containing azetidinium groups within the branched polymer network structure of the IPC saline. After the heat pretreatment, the final IPC saline is filtered using a 0.22 micron polyethersulfone (PES) membrane filter and cooled again to room temperature.

[0202] The lens having the PAA-LbL base coating prepared in Example 3 is placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). The blister is then sealed with aluminum foil and autoclaved at approximately 121°C for approximately 30 minutes to form a cross-linked coating (PAA-x-hydrophilic polymer material) on the lens.

[0203] The test lens (packaged in heat-pre-treated IPC saline, i.e., a lens with a PAA-x-hydrophilic polymer material coating on it) showed no residue adhesion after rubbing with a paper towel, while the control lens (packaged in PBS, i.e., a lens with a non-covalent layer of PAA on it) showed severe residue adhesion. The test lens had a WBUT of more than 10 seconds. No cracking lines were observed after rubbing the test lens under a dark-field microscope. The test lens was very smooth in the finger friction test, comparable to the control lens.

[0204] A series of experiments were conducted to study the effect of the heat pretreatment conditions (duration and / or temperature) of IPC saline on the surface properties of lenses coated with the obtained IPC saline. Heat treatment times of approximately 6 hours or more at approximately 70°C resulted in lenses that were susceptible to residue adhesion similar to the control lens. Longer heat pretreatment may consume most of the azetidinium groups, and therefore, the number of azetidinium groups remaining in the branched polymer network structure of the resulting water-soluble polymer material is considered insufficient to adhere the polymer material to the PAA coating. Heat treatment of only 4 hours at 50°C resulted in lenses that showed cracking lines on the surface under a dark-field microscope after rubbing between fingers, similar to the test lens in Example 5 where the IPC saline was not heat pretreated. Shorter heat pretreatment may consume a small amount of azetidinium groups, and therefore, a large number of azetidinium groups remaining in the branched polymer network structure of the resulting water-soluble polymer material is considered, and thus, the crosslinked coating (PAA-x-hydrophilic polymer material) on the resulting lens may have a very high crosslinking density.

[0205] Example 7 Poly(acrylamide-co-acrylic acid) partial sodium salt (~90% solid content, poly(AAm-co-AA)90 / 10, Mw200,000) is purchased from Polysciences, Inc. and used as is.

[0206] IPC saline is prepared by dissolving 0.07% PAAm-PAA(90 / 10) and 0.2% PAE (Ashland's Kymene (aqueous solution), used as is; NMR assay indicates an azetidinium content of 0.46%) in PBS and adjusting the pH to 7.2-7.4. Next, the saline is pre-treated by heating at approximately 70°C for approximately 4 hours (heat pretreatment). During this heat pretreatment, poly(AAm-co-AA) and PAE are partially crosslinked with each other (i.e., not all azetidinium groups of PAE are consumed), forming a water-soluble and heat-crosslinkable hydrophilic polymer material containing azetidinium groups within the branched polymer network structure of the IPC saline. After heat pretreatment, the IPC saline is filtered using a 0.22 micron polyethersulfone [PES] membrane filter and cooled again to room temperature.

[0207] Lenses having the PAA-LbL base coating prepared in Example 3, and uncoated Lotrafilcon B lenses (CIBA Vision Corporation) immersed in an acidic propanol solution of PAA (approximately 0.1%, pH ~2.5), are placed in a polypropylene lens packaging shell along with 0.6 mL of preheated IPC saline (half of the IPC saline is added before inserting the lens). The blister is then sealed with aluminum foil and autoclaved at 121°C for approximately 30 minutes to form a cross-linked coating (PAA-x-hydrophilic polymer material) on the lens.

[0208] The test lenses (both Lotrafilcon B, which has a PAA-x-hydrophilic polymer on it, and the lens from Example 3) showed no residue after rubbing with a paper towel. The test lenses had a WBUT of more than 10 seconds. When observed under a dark-field microscope, no cracking lines were seen after rubbing the lenses between fingers. The lenses were very smooth in the qualitative finger friction test.

[0209] Example 8 In the Design of Experiment (DOE), IPC saline was prepared containing approximately 0.05% to 0.09% PAAm-PAA and approximately 0.075% to 0.19% PAE (Ashland's Kymene (aqueous solution), used as is; NMR assay showed an azetidinium content of 0.46%) in PBS. The IPC saline was heat-treated at 60°C for 8 hours, and the lenses from Example 3 were packaged in the heat-pre-treated IPC saline. No differences were observed in the surface properties of the final lenses; all lenses exhibited excellent lubricity, resistance to debris adhesion, and excellent wettability, and no surface cracking was observed.

[0210] Example 9 In the Design of Experiment (DOE), IPC saline is prepared to contain sufficient PAE to obtain an initial azetidinium content of approximately 0.07% PAAm-PAA and approximately 8.8 mmol equivalents / liter (~0.15% PAE). The heating pretreatment conditions are varied from 50°C to 70°C in the central composite design, and the pre-reaction time is varied from approximately 4 to approximately 12 hours. A pre-reaction time of 24 hours at 60°C is also tested. Next, 10 ppm hydrogen peroxide is added to the saline to prevent bioburden increase, and the IPC saline is filtered using a 0.22 micron polyethersulfone [PES] membrane filter.

[0211] The lenses from Example 3 were packaged in IPC saline solution that had been preheated, and the blisters were then autoclaved at 121°C for 45 minutes. All lenses exhibited excellent lubricity, wettability, and surface cracking resistance. As shown in Table 1, some lenses showed adhesion of residue from paper towels.

[0212] [Table 1]

[0213] Example 10 Methacryloyloxyethyl phosphorylcholine (MPC) copolymers containing one carboxyl-containing vinyl monomer (CH2=CH(CH3)C(O)OC2H4OC(O)C2H4COOH(MS), methacrylic acid (MA)) are evaluated in an in-package coating system in combination with PAE, either in the absence or presence of butyl methacrylate (BMA).

[0214] Prepare PBS containing NaCl (0.75% by weight), NaH2PO4·H2O (0.0536% by weight), Na2HPO4·2H2O (0.3576% by weight), and DI water (97.59% by weight), and add 0.2% PAE (polycup 3160). Adjust the pH to approximately 7.3.

[0215] Next, one of several 0.25% MPC copolymers is added to prepare IPC saline, which is then pre-treated by heating at 70°C for 4 hours (heat pre-treatment). During this heat pre-treatment, the MPC and PAE are partially crosslinked with each other (i.e., not all azetidinium groups of the PAE are consumed), forming a water-soluble and heat-crosslinkable hydrophilic polymer material containing azetidinium groups within the branched polymer network structure of the IPC saline. After 4 hours, the pre-treated IPC saline is filtered through a 0.2 micron polyethersulfone [PES] membrane filter (Fisher Scientific catalog #09-741-04, Thermo Scientific nalgene #568-0020) (250 ml).

[0216] Lenses having the PAA-LbL base coating prepared in Example 3 were packaged in IPC physiological saline that had been preheated, and autoclaved at 121°C for approximately 30 minutes. Table 2 shows that all lenses exhibited excellent surface properties.

[0217] [Table 2]

[0218] Example 11 PAA coated lenses The cast lenses 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: three MEK baths (22, 78, and 224 seconds); a DI water bath (56 seconds); two PAA coating solution baths (prepared by dissolving 3.6 g of PAA (MW: 450 kDa, Lubrizol) in 975 ml of 1-propanol and 25 ml of formic acid) for 44 and 56 seconds, respectively; and three DI water baths for 56 seconds each.

[0219] PAE / PAA coated lenses The lens having the PAA base coating prepared above is immersed in the following baths in succession: two PAE coating solution baths (prepared by dissolving 0.25 wt% PAE (Polycup 172, Hercules) in DI water, adjusting the pH to approximately 5.0 using sodium hydroxide, and finally filtering the resulting solution using a 5 μm filter) for 44 and 56 seconds, respectively; and three DI water baths for 56 seconds each. After this treatment, the lens will have one layer of PAA and one layer of PAE.

[0220] Lenses with PAA-x-PAE-x-CMC coating on them. Lenses, each having one layer of PAA and one layer of PAE in a batch, are packaged in 0.2% sodium carboxymethylcellulose (CMC, product no. 7H 3SF PH, Ashland Aqualon) in phosphate-buffered saline (PBS), and the pH is then adjusted to 7.2-7.4. The blister packs are then sealed and autoclaved at 121°C for approximately 30 minutes to form a cross-linked coating (PAA-x-PAE-x-CMC) on the lenses.

[0221] Lenses with PAA-x-PAE-x-HA coating on them. Lenses having one layer of PAA and one layer of PAE from a separate batch are packaged in 0.2% hyaluronic acid (HA, product number 6915004, Novozymes) in phosphate-buffered saline (PBS), and the pH is then adjusted to 7.2-7.4. The blister packs are then sealed and autoclaved at 121°C for approximately 30 minutes to form a cross-linked coating (PAA-x-PAE-x-HA) on the lenses.

[0222] Lenses having either the obtained PAA-x-PAE-x-CMC coating or the PAA-x-PAE-x-HA coating do not show Sudan black staining, residue adhesion, or cracking under microscopic examination. Lenses with the PAA-x-PAE-x-CMC coating have an average contact angle of 30 ± 3 degrees, and lenses with the PAA-x-PAE-x-HA coating have an average contact angle of 20 ± 3 degrees.

[0223] Example 12 Preparation of IPC solution The reaction mixture is prepared by dissolving 2.86% (by weight) of mPEG-SH2000 (methoxy-poly(ethylene glycol)-thiol, Avg MW 2000, product number MPEG-SH-2000, Laysan Bio Inc.) in PBS along with 2% (by weight) of PAE (Ashland's Kymene (aqueous solution), used as is, azetidinium content 0.46 according to NMR assay), and adjusting the final pH to 7.5. The solution is heat-treated at 45°C for approximately 4 hours (heat pretreatment). During this heat pretreatment, mPEG-SH2000 and PAE react with each other to form a water-soluble and heat-crosslinkable hydrophilic polymer material containing azetidinium groups, as well as chemically grafted polyethylene glycol polymer chains. After heat treatment, the solution is diluted 10-fold with PBS containing 0.25% sodium citrate, the pH is adjusted to 7.2-7.4, and then filtered using a 0.22 micron polyethersulfone (PES) membrane filter. The final IPC physiological saline contains 0.286% (by weight) of hydrophilic polymer material (consisting of approximately 59% (by weight) of MPEG-SH-2000 chains and approximately 41% (by weight) of PAE chains) and 0.25% sodium citrate dihydrate. PBS is prepared by dissolving 0.74% NaCl, 0.053% NaH2PO4·H2O, and 0.353% Na2HPO4·2H2O in water.

[0224] Lenses having a cross-linked coating on them The PAA-coated lens of Example 11 was packaged in the above IPC saline solution in a polypropylene lens packaging shell, and then autoclaved at approximately 121°C for approximately 30 minutes to form a cross-linked coating on the lens. The final lens showed no residue or cracking lines after rubbing the lens. The lens was very smooth in a finger friction test, similar to the control PAA-coated lens.

[0225] A series of experiments were conducted to study the effects of various conditions (reaction time and mPEG-SH2000 solution concentration (with a constant PAE concentration of 2%)) on the surface properties of lenses coated with the obtained IPC physiological saline. The results are shown in Table 3.

[0226] [Table 3]

[0227] As the solution concentration of mPEGSH2000 increases, the lubricity of the lens increases. The increase in the surface contact angle is thought to be due to the increase in the density of terminal methyl groups on the surface as the graft density increases. At a high graft density corresponding to a solution concentration of 0.6%, the contact angle is comparable to the measurements obtained on a polyethylene glycol (PEG) monolayer grafted flat substrate (reference: Langmuir 2008, 24, 10646-10653).

[0228] Example 13 A series of experiments were conducted to study the effect of the molecular weight of mPEG-SH. IPC saline was prepared in the same manner as described in Example 12. However, the following mPEG-SH were used to prepare the saline: mPEG-SH1000, mPEG-SH2000, mPEG-SH5000, and mPEG-SH20000. All saline solutions were subjected to heat treatment at 45°C for 4 hours and then diluted 10-fold. The results and reaction conditions are shown below:

[0229] [Table 4]

[0230] Example 14 The reaction mixture is prepared by dissolving 2.5% mPEG-SH2000, 10% PAE (Ashland's Kymene (aqueous solution), used as is, with an azetidinium content of 0.46% according to NMR assay) and 0.25% sodium citrate dihydrate in PBS. Next, the pH of this solution is adjusted to 7.5, and the mixture is further degassed by bubbling nitrogen gas through the container for 2 hours. Subsequently, this solution is heat-treated at 45°C for approximately 6 hours to react with the azetidinium groups in the PAE, forming a thermo-crosslinkable hydrophilic polymer material containing chemically grafted mPEG-SH-2000 groups on the polymer. After heat treatment, the solution is diluted 50-fold with PBS containing 0.25% sodium citrate, the pH is adjusted to 7.2-7.4, and then filtered using a 0.22 micron polyethersulfone (PES) membrane filter. The final IPC physiological saline contains approximately 0.30% (by weight) of polymer material (composed of approximately 17% wt. mPEG-SH-2000 and approximately 83% wt. PAE) and 0.25% sodium citrate dihydrate.

[0231] The PAA-coated lens of Example 11 is packaged in the above-mentioned IPC physiological saline solution in a polypropylene lens packaging shell, and then autoclaved at approximately 121°C for approximately 30 minutes to form a cross-linked coating on the lens.

[0232] The final lens shows no residue or cracking lines after friction. The test lens is extremely smooth in the finger friction test, similar to the control PAA coated lens.

[0233] Example 15 The reaction mixture is prepared by dissolving 3.62% mPEG-NH2550 (methoxy-poly(ethylene glycol)-amine, MW-550 (product number MPEG-NH2-550, Laysan Bio Inc.)) in PBS along with 2% PAE (Ashland's Kymene (aqueous solution), used as is, with an azetidinium ratio of 0.46 when assayed by NMR), and adjusting the final pH to 10. The solution is heat-treated at 45°C for approximately 4 hours to react with the azetidinium groups in the PAE, forming a thermo-crosslinkable hydrophilic polymer material containing chemically grafted MPEG-NH2-550 groups on the polymer. After heat treatment, the solution is diluted 10-fold with PBS containing 0.25% sodium citrate. The solution is diluted, the pH is adjusted to 7.2-7.4, and then filtered using a 0.22 micron polyethersulfone (PES) membrane filter. The final IPC saline contains approximately 0.562% wt. polymer material (composed of 64% wt. MPEG-SH-2000 and approximately 36% wt. PAE) and 0.25% sodium citrate dihydrate. PBS is prepared by dissolving 0.74% NaCl, 0.053% NaH2PO4·H2O, and 0.353% Na2HPO4·2H2O in water.

[0234] The PAA-coated lens of Example 11 is packaged in the above-mentioned IPC physiological saline solution in a polypropylene lens packaging shell, and then autoclaved at approximately 121°C for approximately 30 minutes to form a cross-linked coating on the lens.

[0235] The final lens shows no residue or cracking lines after digital (finger) friction of the lens.

[0236] Example 16 Poloxamer 108 (sample) and Nelfilcon A (CIBA VISION) are used as is. Nelfilcon A is a polymerizable polyvinyl alcohol obtained by modifying polyvinyl alcohol (e.g., Gohsenol KL-03 from Nippon Gohsei) with N-(2,2-dimethoxyethyl)acrylamide under cyclic acetal formation reaction conditions (Buhler et al., CHIMIA, 53 (1999), 269-274, the whole of which is incorporated herein by reference). Approximately 2.5% of the vinyl alcohol units in Nelfilcon A are modified with N-(2,2-dimethoxyethyl)acrylamide.

[0237] IPC saline is prepared by dissolving 0.004% poloxamer 108, 0.8% Nelfilcon A, 0.2% PAE (Kymene, Polycup 3160), 0.45% NaCl, and 1.1% disodium hydrogen phosphate (dihydrate) in DI water. The saline is pre-treated by heating at approximately 65-70°C for 2 hours. After pre-treatment, the saline is cooled to room temperature and then filtered using a 0.2 μm PES filter.

[0238] The lens prepared in Example 3 is placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). Next, the blister is sealed with aluminum foil and autoclaved at 121°C for approximately 30 minutes.

[0239] The test lens showed no residue after rubbing with a paper towel. The lens had a WBUT of over 10 seconds. When observed under a dark-field microscope, no cracking lines were observed after rubbing the lens between fingers. The lens was much smoother than the lens of Example 4, but still not as smooth as the PAA-coated control lens packaged in PBS.

[0240] Example 17 A. Synthesis of 80% ethylenically functionalized chain elongated polysiloxanes KF-6001A (α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane, Mn=2000, Shin-Etsu) and KF-6002A (α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane, Mn=3400, Shin-Etsu) are dried separately in a necked flask under high vacuum at approximately 60°C for 12 hours (or overnight). The OH molar equivalents of KF-6001A and KF-6002A are determined by titration of the hydroxyl groups, and these are used to calculate the millimolar equivalents to be used in synthesis.

[0241] Vacuum a 1-liter reaction vessel overnight to remove moisture, then interrupt the vacuum and replace with dry nitrogen. Add 75.00 g (75 meq) of dry KF6001A to the reactor, then add 16.68 g (150 meq) of freshly distilled IPDI. Purge the reactor with nitrogen and heat to 45°C with stirring, then add 0.30 g of DBTDL. Seal the reactor and maintain a positive nitrogen flow. Exothermic reaction occurs, then cool the reaction mixture and stir at 55°C for 2 hours. After exothermic reaction is reached, add 248.00 g (150 meq) of dry KF6002A to the reactor at 55°C, then add 100 μL of DBTDL. Stir the reactor for 4 hours. Interrupt heating and cool the reactor overnight. Interrupt nitrogen bubbling, open the reactor to air, and stir moderately for 30 minutes. A hydroxyl-terminal chain elongated polysiloxane HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH (or HO-CE-PDMS-OH) with three polysiloxane segments is produced.

[0242] For 80% ethylenically functionalized polysiloxane, add 18.64 g (120 meq) of IEM to the reactor along with 100 μL of DBTDL. Stir the reactor for 24 hours, then decant the product (CE-PDMS capped with 80% IEM) and store it under freezing.

[0243] B: Synthesis of non-UV absorbing amphiphilic branched-chain polysiloxane prepolymers A 1L jacketed reactor is equipped with a 500mL addition funnel, overhead stirrer, reflux condenser with nitrogen / vacuum inlet adapter, thermometer, and sampling adapter. 45.6g of 80% IEM capped CE-PDMS prepared above is added to the reactor and sealed. A solution of 0.65g of hydroxyethyl methacrylate (HEMA), 25.80g of DMA, and 27.80g of (tris(trimethylsilyl))-siloxypropyl) methacrylate (TRIS) in 279g of ethyl acetate is added to the addition funnel. The reactor is degassed using a high vacuum pump at <1mbar and room temperature for 30 minutes. The monomer solution is degassed in three cycles of 10 minutes each at 100mbar and room temperature, with the vacuum replaced by nitrogen during the degassing cycles. Next, the monomer solution is added to the reactor, the reaction mixture is stirred, and the mixture is heated to 67°C. While heating, add 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 to an addition funnel, and deoxygenate three times at 100 mbar and room temperature for 10 minutes each time. When the reactor temperature reaches 67°C, add the initiator / CTA solution to the PDMS / monomer solution in the reactor. Allow the reaction to proceed for 8 hours, then stop heating and allow the reactor temperature to return to room temperature within 15 minutes.

[0244] Next, the resulting reaction mixture is drawn up into a dry, necked flask with an airtight lid, and 4.452 g of IEM is added along with 0.21 g of DBTDL. The mixture is stirred at room temperature for 24 hours to produce a non-UV absorbing amphiphilic branched-chain polysiloxane prepolymer. To this mixture, 100 μL of hydroxytetramethylenepiperonyloxy solution in ethyl acetate (2 g / 20 mL) is added. The solution is then concentrated to 200 g (~50%) at 30°C using a rotary evaporator (rota-vap) and filtered through 1 μm pore size filter paper. After replacing the solvent with 1-propanol, the solution is further concentrated to the desired concentration.

[0245] C. Synthesis of UV-absorbing amphiphilic branched-chain polysiloxane prepolymers A 1L jacketed reactor is equipped with a 500mL addition funnel, overhead stirrer, reflux condenser with nitrogen / vacuum inlet adapter, thermometer, and sampling adapter. Next, 45.98g of 80% IEM capped CE-PDMS prepared above is added to the reactor and the reactor is sealed. A solution of 0.512g HEMA, 25.354g DMA, 1.38g Norbloc methacrylate, and 26.034g TRIS in 263g ethyl acetate is added to the addition funnel. The reactor is degassed using a high vacuum pump at <1mbar and room temperature for 30 minutes. The monomer solution is degassed in three cycles of 10 minutes each at 100mbar and room temperature, with the vacuum replaced by nitrogen during the degassing cycle. Next, the monomer solution is added to the reactor, the reaction mixture is stirred, and the mixture is heated to 67°C. While heating, add 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 to an addition funnel and deoxygenate three times at 100 mbar and room temperature for 10 minutes each time. When the reactor temperature reaches 67°C, add the initiator / CTA solution to the PDMS / monomer solution in the reactor. Allow the reaction to proceed for 8 hours, then stop heating and allow the reactor temperature to return to room temperature within 15 minutes.

[0246] Next, the resulting reaction mixture is drawn up into a dry, airtight flask and 3.841 g of isocyanatoethyl acrylate is added along with 0.15 g of DBTDL. The mixture is stirred at room temperature for 24 hours to produce a UV-absorbing amphiphilic branched-chain polysiloxane prepolymer. To this mixture, 100 μL of hydroxytetramethylenepiperonyloxy solution in ethyl acetate (2 g / 20 mL) is added. The solution is then concentrated to 200 g (~50%) at 30°C using a rotary evaporator and filtered through 1 μm pore size filter paper.

[0247] D-1: Lens formulation containing non-UV absorbing polysiloxane prepolymer Add 4.31 g of the synthetic macromer solution (82.39% in 1-propanol) prepared above to a 100 mL amber flask. Dissolve 0.081 g of TPO and 0.045 g of 1,2-dimiristoyl-sn-glycero-3-phosphocholine (DMPC) in 10 g of 1-propanol in a 20 mL vial, then transfer to the macromer solution. Concentrate the mixture to 5.64 g at 30°C using a rotary evaporator, then add 0.36 g of DMA and homogenize the preparation at room temperature. 6 g of clear lens preparation D-1 is obtained.

[0248] D-2: Lens formulation containing UV-absorbing polysiloxane prepolymer (4% DMA) Add 24.250 g of the macromer solution (43.92% in ethyl acetate) prepared above to a 100 mL amber flask. Dissolve 0.15 g of TPO and 0.75 g of DMPC in 20 g of 1-propanol in a 50 mL vial, then transfer to the macromer solution. Remove 20 g of solvent at 30°C using a rotary evaporator, then add 20 g of 1-propanol. After two cycles, concentrate the mixture to 14.40 g. Add 0.6 g of DMA to this mixture and homogenize the preparation at room temperature. 15 g of clear lens preparation D-2 is obtained.

[0249] D-3: Lens formulation containing UV-absorbing polysiloxane prepolymer (2% DMA / 2% HEA) Add 24.250 g of the macromer solution (43.92% in ethyl acetate) prepared above to a 100 mL amber flask. Dissolve 0.15 g of TPO and 0.75 g of DMPC in 20 g of 1-propanol in a 50 mL vial, then transfer to the macromer solution. Remove 20 g of solvent at 30°C using a rotary evaporator, then add 20 g of 1-propanol. After two cycles, concentrate the mixture to 14.40 g. Add 0.3 g of DMA and 0.3 g of HEA to this mixture and homogenize the preparation at room temperature. 15 g of clear lens preparation D-3 is obtained.

[0250] Example 18 Example E: Covalent bonding of modified PAE coated polymers Monomers containing amine groups, such as N-(3-aminopropyl)methacrylamide hydrochloride (APMAA-HCl) or N-(2-aminoethyl)methacrylamide hydrochloride (AEMAA-HCl), are purchased from Polysciences and used as is. An aqueous solution of poly(amideamine epichlorohydrin) (PAE) is obtained from Ashland and used as is. Poly(acrylamide-co-acrylic acid) (poly(AAm-co-AA)(90 / 10)) from Polysciences, mPEG-SH from Laysan Bio, and poly(MPC-co-AeMA) from NOF (i.e., copolymers of methacryloyloxyethyl phosphorylcholine (MPC) and aminoethyl methacrylate (AeMA)) are used as is.

[0251] The APMAA-HCl monomer was dissolved in methanol and added to lens formulations D-1, D-2, and D-3 (prepared in Example 17) to achieve a concentration of 1 wt%.

[0252] Reactive packaging saline is prepared by dissolving the components listed in Table 4 in DI water along with an appropriate buffer salt. The saline is pre-treated by heat by stirring at approximately 60°C for 8 hours. After heat pre-treatment, the saline is cooled to room temperature and then filtered using a 0.2 μm PES filter.

[0253] [Table 5]

[0254] Lens formulation D-1 prepared in Example 17 was modified by adding APMAA-HCl monomer (APMAA-HCl stock solution in 1:1 methanol:propanol), resulting in a 16 mW / cm² output. 2 The lens formulations D-2 and D-3 prepared in Example 17 are modified by adding APMAA-HCl monomer, resulting in a curing rate of 4.6 mW / cm². 2 It is then cured by a 380nm filter.

[0255] DSM lens Fill the female part of the polypropylene lens molding mold with approximately 75 μl of the lens mixture prepared above, and close the molding mold with the male part (base curve type) of the polypropylene lens molding mold. The closed molding mold is then exposed to a UV irradiation source (with a 330 nm cutoff filter and an intensity of approximately 16 mW / cm²). 2 By curing the lens using a Hamamatsu lamp for approximately 5 minutes, a contact lens can be obtained.

[0256] LS lens The LS lens is prepared by casting from the lens compound prepared above using a reusable mold similar to the molds shown in U.S. Patent No. 7,384,590 (Figures 1-6) and No. 7,387,759 (Figures 1-6). The mold includes a female half made of quartz and a male half made of PMMA. The UV irradiation source has an intensity of approximately 4.6 mW / cm² with a 380 nm cutoff filter. 2 This is a Hamamatsu lamp. The lens mixture inside the molding mold is irradiated with UV light for approximately 30 seconds.

[0257] Lens formulation D-1 modified with APMAA-HCl is cured according to the DSM and LS methods described above, and lens formulation D-2 or D-3 is cured according to the LS method described above.

[0258] The molded lenses are extracted with methyl ethyl ketone, hydrated, and packaged in one of the saline solutions listed in Table 4. The lenses are placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). The blister is then sealed with aluminum foil and autoclaved at 121°C for 30 minutes.

[0259] Evaluation of the lens surface indicates that no residue adheres to any of the test lenses after rubbing with a paper towel. When observed under a dark-field microscope, no cracking lines are observed after rubbing the lenses between fingers.

[0260] The wettability (WBUT), lubricity, and contact angle of the lens surface were measured, and the results are summarized in Table 5. Unless otherwise specified, the lenses were manufactured according to the DSM method. Lubricity was graded on a qualitative scale from 0 to 5, with lower numbers indicating greater lubricity. Generally, all properties were shown to improve after the application of in-package coatings.

[0261] [Table 6]

[0262] Example 19 Preparation of lens formulations The lens preparation is prepared by dissolving the components in 1-propanol to have the following composition: approximately 32% (by weight) of CE-PDMS macromer prepared in Example 2, approximately 21% (by weight) of TRIS-Am, approximately 23% (by weight) of DMA, approximately 0.6% (by weight) of L-PEG, approximately 1% (by weight) of DC1173, approximately 0.1% (by weight) of visitint (5% copper phthalocyanine blue pigment dispersion in TRIS), approximately 0.8% (by weight) of DMPC, approximately 200 ppm of H-tempo, and approximately 22% (by weight) of 1-propanol.

[0263] Lens preparation The lenses are prepared by casting from the lens mixture prepared above using a reusable mold (quartz female half and glass male half) similar to the molds shown in U.S. Patent No. 7,384,590 (Figures 1-6) and No. 7,387,759 (Figures 1-6). The lens mixture inside the mold is then subjected to UV irradiation (13.0 mW / cm²). 2 ) irradiate for approximately 24 seconds.

[0264] PAA coating solution A PAA coating solution is prepared by dissolving a certain amount of PAA (MW: 450 kDa, Lubrizol) in a predetermined amount of 1-propanol to have a concentration of approximately 0.36% (by weight), and the pH is adjusted to approximately 2.0 with formic acid.

[0265] PAA coated lenses The cast contact lenses are extracted as described above and coated by immersion in the following series of baths: DI water bath (approximately 56 seconds); six MEK baths (approximately 44, 56, 56, 56, 56, and 56 seconds, respectively); DI water bath (approximately 56 seconds); one PAA coating solution bath in 100% 1-propanol (approximately 0.36% by weight, acidified to pH approximately 2.0 with formic acid) (approximately 44 seconds); one water / 1-propanol 50% / 50% mixture bath (approximately 56 seconds); four DI water baths, each approximately 56 seconds; one PBS bath for approximately 56 seconds; and one DI water bath for approximately 56 seconds.

[0266] IPC saline solution Poly(AAm-co-AA)(90 / 10) partial sodium salt (~90% solid content, poly(AAm-co-AA)90 / 10, Mw200,000) is purchased from Polysciences, Inc. and used as is. PAE (Kymene, azetidinium content 0.46% according to NMR assay) is purchased as an aqueous solution from Ashland and used as is. IPC physiological saline is prepared by dissolving approximately 0.07% w / w poly(AAm-co-AA)(90 / 10) and approximately 0.15% PAE (approximately 8.8 mmol initial azetidinium millimolar equivalent) in PBS (approximately 0.044 w / w %NaH2PO4·H2O, approximately 0.388 w / w / %Na2HPO4·2H2O, approximately 0.79 w / w / %NaCl) and adjusting the pH to 7.2-7.4. Next, the IPC saline solution is pre-treated by heating at approximately 70°C for approximately 4 hours (heat pre-treatment). During this heat pre-treatment, poly(AAm-co-AA) and PAE are partially crosslinked with each other (i.e., not all azetidinium groups of PAE are consumed), forming a water-soluble and heat-crosslinkable hydrophilic polymer material containing azetidinium groups within the branched polymer network structure of the IPC saline solution. After the heat pre-treatment, the IPC saline solution is filtered using a 0.22 micron PES membrane filter and cooled again to room temperature. Next, 10 ppm hydrogen peroxide is added to the final IPC saline solution to prevent an increase in bioburden, and the IPC saline solution is filtered using a 0.22 micron PES membrane filter.

[0267] Application of cross-linked coatings The lens having the PAA-LbL base coating prepared above is placed in a polypropylene lens packaging shell (one lens per shell) with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). Next, the blister is sealed with aluminum foil and autoclaved at approximately 121°C for approximately 30 minutes to produce a SiHy contact lens having a cross-linked coating (PAA-x-hydrophilic polymer material) on it.

[0268] Characterization of SiHy lenses SiHy contact lenses having the resulting cross-linked coating (PAA-x-hydrophilic polymer material) on them show no residue adhesion after rubbing with a paper towel, while control lenses (packaged in PBS, i.e., lenses having a non-covalent layer of PAA on them) show severe residue adhesion. The lenses have an oxygen permeability of 146 bars (Dk c It has an estimated intrinsic Dk, a bulk surface modulus of 0.76 MPa, a water content of approximately 32% (by weight), a relative ion transmittance of approximately 6 (compared to Alsacon lenses), a contact angle of approximately 34-47 degrees, and a WBUT of over 10 seconds. When observed under a dark-field microscope, no cracking lines were observed after rubbing the test lens. The lens is very smooth, comparable to the control lens in finger friction tests.

[0269] Example 20 The SiHy lenses and IPC saline in the autoclaved lens packages prepared in Examples 6, 14, and 19 were subjected to the following biocompatibility studies.

[0270] In vitro cytotoxicity assessment SiHy lenses were evaluated using the USP Direct Contact Material Assay. Lens extracts were evaluated using the USP MEM elution and ISO CEN cell proliferation inhibition assays, and IPC saline in the autoclaved package was evaluated using a modified elution method. All evaluated lenses and lens extracts were well within the acceptable limits for each test, and no unacceptable cytotoxicity was observed.

[0271] in vivo trial The ISO systemic toxicity study in mice shows that no systemic toxicity was observed in mice using the lens extract. The ISO intraocular irritation study in rabbits shows that the lens extract is not considered an irritant to rabbit eye tissue. The ISO intraocular irritation study in rabbits shows that IPC saline during packaging after autoclaving is not considered an irritant to rabbit eye tissue. Lenses worn for 22 consecutive days in a daily disposable form showed low irritation to the rabbit model, with eyes treated with the test lens being similar to those treated with the control lens. The ISO sensitization study (guinea pig maximization test of packaging solution) shows that IPC saline after autoclaving does not cause a delay in skin contact sensitization in guinea pigs. The ISO sensitization study (guinea pig maximization test of lens extract) shows that sodium chloride and sesame oil extract in the lens do not cause a delay in skin contact sensitization in guinea pigs.

[0272] Genotoxicity testing When IPC saline and SiHy lens extract from lens packages were tested using a microbial reverse mutation assay (Ames test), the lens extract and IPC saline were found to be nonmutagenic to Salmonella typhimurium test strains TA98, TA100, TA1535, and TA1537, as well as Escherichia coli WPuvrA. When SiHy lens extract was tested using a mammalian erythrocyte micronucleus assay, it did not exhibit chromosomal aberration-inducing activity and was negative in the mouse bone marrow micronucleus assay. In Chinese hamsters, when IPC saline from lens packages was tested according to a chromosomal aberration assay, IPC saline was negative for induction of structural and numerical chromosomal aberrations in assays using CHO cells in both inactivation and S9 activation assay systems. When SiHy lens extract was tested according to a cell gene mutation assay (mouse lymphoma mutagenesis assay), the lens extract was shown to be negative in the mouse lymphoma mutagenesis assay.

[0273] Example 21 The surface compositions of pre-formed SiHy contact lenses (i.e., SiHy contact lenses without any coatings and before the application of the PAA-based coating), SiHy contact lenses with a PAA coating (i.e., lenses sealed in a lens package with IPC saline and before autoclaving), and SiHy contact lenses with a cross-linked coating (all of which were prepared according to the procedure described in Example 19) were determined by characterizing the vacuum-dried contact lenses by X-ray photoelectron spectroscopy (XPS). XPS is a method for measuring the surface composition of lenses at a sampling depth of approximately 10 nm. The surface compositions of the three types of lenses are reported in Table 6.

[0274] [Table 7]

[0275] Table 6 shows that when a PAA coating is applied to a SiHy lens (pre-formed without coating), the silicon atom composition decreases significantly (from 12.1% to 4.5%), and the nitrogen atom composition also decreases (from 6.2% to 1.6%). When a crosslinked coating is further applied on top of the PAA coating, the surface composition is dominated by three types of atoms: carbon, nitrogen, and oxygen (excluding hydrogen, as XPS does not count hydrogen in the surface composition). These results suggest that the outermost layer of a SiHy contact lens with a crosslinked coating is likely composed of a hydrophilic polymer material which is a reaction product of poly(AAm-co-AA)(90 / 10)(60%C, 22%O, and 18%N) and PAE.

[0276] The following commercially available SiHy lenses, which were vacuum-dried, were also subjected to XPS analysis. The surface compositions of these commercially available SiHy contact lenses are reported in Table 7.

[0277] [Table 8]

[0278] The SiHy contact lenses of the present invention are found to have a nominal silicon content of approximately 1.4% in the surface layer, which is considerably lower than commercially available SiHy lenses without plasma coating (Acuvue® Advance®, Acuvue® Oasys®, TruEye®, Biofinity®, Avaira®), PureVision® (with plasma oxidation), and Premio® (with unknown plasma treatment), and even lower than SiHy lenses with a plasma deposition coating of approximately 25 nm thickness (N&D® Aqua® and Air Optix® Aqua®). This extremely low Si% value is comparable to the silicon atom percentage of the control sample Goodfellow polyethylene (LDPE, d=0.015 mm; LS356526SDS; ET31111512; 3004622910). These results suggest that the extremely low XPS analysis values ​​of the vacuum-dried SiHy contact lenses of the present invention may be due to contaminants incorporated during the preparation process, including the vacuum drying process and XPS analysis, as evidenced by the observation of fluorine content in non-fluorine-containing lenses. In the SiHy contact lenses of the present invention, silicone is successfully shielded from XPS analysis.

[0279] XPS analysis will also be performed on the SiHy contact lenses of the present invention (prepared according to the procedure described in Example 19), commercially available SiHy contact lenses (CLARITI® 1 Day, ACUVUE® TruEye® (narafilcon A and narafilcon B)), Goodfellow polyethylene sheets (LDPE, d=0.015mm; LS356526 SDS; ET31111512; 3004622910), DAILIES® (polyvinyl alcohol hydrogel lenses, i.e., non-silicone hydrogel lenses), and ACUVUE® Moist (polyhydroxyethyl methacrylate hydrogel lenses, i.e., non-silicone hydrogel lenses). All lenses will be vacuum dried. The polyethylene sheets, DAILIES®, and ACUVUE® Moist will be used as controls as they do not contain silicon. The silicon atom composition in the surface layer of the test samples is as follows: 1.3±0.2 (polyethylene sheet); 1.7±0.9 (DAILIES®); 2.8±0.9 (ACUVUE® Moist); 3.7±1.2 (three types of 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 conventional hydrogels than to silicone hydrogels.

[0280] Example 22 Fluorescein-labeled PAA (PAA-F) PAA-F is synthesized in-house by covalently bonding 5-aminofluorescein to PAA (Mw450k). The degree of labeling of fluorescein is a few percent, for example, about 2 mol% (or n / (m+n)=2% as shown in the formula below). [ka]

[0281] Lens preparation The lenses are prepared by casting from the lens mixture prepared in Example 19 above using a reusable mold (quartz female half and glass male half) similar to the molds shown in U.S. Patent No. 7,384,590 (Figures 1-6) and No. 7,387,759 (Figures 1-6). The lens mixture in the mold is then subjected to UV irradiation (13.0 mW / cm²). 2 ) irradiate for approximately 24 seconds.

[0282] PAA-F coating solution The PAA-F coating solution is prepared by dissolving a certain amount of the PAA-F prepared above in a predetermined amount of 1-PrOH / water (95 / 5) solvent mixture to a concentration of approximately 0.36% (by weight), and adjusting the pH to approximately 2.0 with formic acid. Approximately 5% water is used to dissolve the PAA-F.

[0283] PAA coated lenses Cast contact lenses are extracted and coated by immersion in the following series of baths: DI water bath (approximately 56 seconds); six MEK baths (approximately 44, 56, 56, 56, 56, and 56 seconds, respectively); DI water bath (approximately 56 seconds); one PAA-F coating solution bath in a 1-PrOH / water (95 / 5) solvent mixture (approximately 0.36% by weight, acidified to approximately pH 2.0 with formic acid) (approximately 44 seconds); one water / 1-propanol 50% / 50% mixture bath (approximately 56 seconds); four DI water baths, each approximately 56 seconds; one PBS bath for approximately 56 seconds; and one DI water bath for approximately 56 seconds.

[0284] Application of cross-linked coatings The lens having the PAA-LbL base coating prepared above is placed in a polypropylene lens packaging shell (one lens per shell) with 0.6 mL of IPC saline (half of the saline is added before inserting the lens) prepared according to the procedure described in Example 19. The blister is then sealed with aluminum foil and autoclaved at approximately 121°C for approximately 30 minutes to produce a SiHy contact lens having a cross-linked coating (PAA-x-hydrophilic polymer material) on it.

[0285] Confocal laser fluorescence microscopy A cross-section of a hydrated SiHy lens (prepared as described above) with a cross-linked coating is cut and placed between two glass coverslips, and images are taken with a confocal laser fluorescence microscope (model #Zeiss LSM 510 Vis). The image is scanned from the front curve side of the lens to the base curve side (and vice versa). The presence of PAA-F is indicated by green fluorescence, and a confocal laser fluorescence microscope image can be obtained. From the examination of the confocal laser fluorescence microscope images, it is clear that layers rich in PAA-F exist on both sides (front and back) of the lens surface and at the peripheral edges, while PAA-F is not observed in the bulk material of the hydrated lens.

[0286] The fluorescence intensity profile was investigated across the entire cross-section of the lens, traversing both the rear and front surfaces and along a line perpendicular to the rear surface. Figure 3 shows two representative fluorescence intensity profiles along two lines traversing the lens cross-section (one at a point where the lens thickness is approximately 100 μm (Panel A), and the other at a point where the lens thickness is approximately 200 μm (Panel B)). The origin in Figure 3 is the midpoint between the front and rear surfaces along that line. In Figure 3, it can be noted that a layer rich in PAA-F exists near the outermost surface of the SiHy lens with a cross-linked coating, PAA-F is absent in the lens bulk, and the coating thickness is similar in these two cross-sections regardless of the cross-sectional thickness.

[0287] The thickness of the PAA-F-rich layer (i.e., the sum of the injection depth into the outer hydrogel layer and the penetration depth of PAA-F into the bulk material (i.e., the inner layer)) or the thickness of the transition layer (see Figure 2 for a schematic diagram, transition layer 115) can be estimated from the fluorescence intensity profile shown in Figure 3. The possible thickness of the transition layer (PAA-F-rich layer) is estimated by the distance from zero intensity, across the peak intensity, and back to zero intensity. Considering possible contributions from unknown factors (such as scattering) to the fluorescence intensity, the minimum layer thickness is the thickness at which at least 10% of the maximum peak intensity of fluorescence intensity is retained. Based on such predictions, the minimum thickness of the PAA-F-rich layer would be at least about 5 microns. Note that if the thickness of the SiHy lens with the PAA coating in the above-described example is greater, the PAA concentration used is likely to be 10 times higher than the PAA-F concentration used in this example. Lenses with thicker coatings can also be prepared using immersion coating times longer than 44 seconds, which was the immersion coating time for the PAA-F used in this example. Lenses with thicker coatings can also be prepared using PAAs of different molecular weights.

[0288] Example 23 This example illustrates a method for determining the water content of a crosslinked coating (two outer hydrogel layers) on SiHy according to the present invention. In the effort to determine the potential water content of the crosslinked coating of the SiHy lens of Example 19, a sample of the polymer composed of the coating components is prepared for evaluation. The resulting gel is then hydrated and tested to determine the water content.

[0289] A solution is prepared using the two polymer components of the crosslinked coating formed in Example 19: poly(AAm-co-AA)(90 / 10) and PAE to have the following composition: 12.55% w / w PAE, 6.45% w / w poly(AAm-co-AA)(90 / 10) and 81% w / w water. The PAE / poly(AAm-co-AA) ratio is the same as that of the IPC saline in Example 19, but the individual concentrations of the components are higher to allow the gel to form during autoclaving.

[0290] Next, the solution is autoclaved at 121°C for approximately 45 minutes, after which the sample gels. Then, gel samples are prepared to determine the water content by testing the hydrated samples (n=3). Hydrated samples are prepared by immersing the gel samples in SoftWear physiological saline for at least approximately 6 hours (i.e., overnight).

[0291] The hydrated sample is blot-dried, and the mass of the hydrated state is recorded according to the mass balance. After recording the mass of the hydrated state, all samples are placed in a vacuum oven set to approximately 50°C and dried overnight under a vacuum of <1 inch Hg.

[0292] After drying overnight, the dried sample is removed from the vacuum oven, and its dry mass is measured and recorded. The moisture content is calculated using the following formula: Moisture content = (wet mass - dry mass) / wet mass x 100% The water content of the sample is determined to be 84.6 ± 0.4 w / w / %.

[0293] This water content of the PAE / poly(AAm-co-AA) hydrogel is thought to represent the outer hydrogel layer (crosslinked coating) of the SiHy contact lens in Example 19 for the following reasons. Firstly, it can be estimated to some extent that the hydrophobic bulk lens polymer (silicone hydrogel) is not present in the outer surface layer. This is considered a very good assumption based on the XPS data. According to the XPS data of Example 21, the silicon content on the surface of the SiHy lens with the crosslinked coating is zero or very low, which indicates that the outer surface layer is composed almost entirely of the coating polymer (PAE and PAAm-PAA). Secondly, the polyacrylic acid (PAA)-based coating (transition layer) probably has the smallest effect on the water content of the surface layer. This assumption may not be certain. However, if any charged PAA is present in the outer surface layer, the water content will increase further, exceeding 84.6%. Thirdly, much higher concentrations of PAE and PAAm-PAA than those used in IPC saline in Example 19 are required to produce the PAE / poly(AAm-co-AA) hydrogel. This may result in a PAE / poly(AAm-co-AA) hydrogel with a higher crosslinking density, potentially giving an artificially lower water content result. Both the presence of PAA in the outer hydrogel layer and the lower crosslinking density may result in a surface layer (outer hydrogel layer) with an even higher water content than measured in the tests of this example, due to the lower concentration of polymer material during crosslinking (in Example 19). It can be inferred that the outer coating layer of the SiHy contact lens in Example 19 contains at least 80% water, and may be even higher if fully hydrated.

[0294] Example 24 The Abbe refractometer is commonly used to measure the refractive index of contact lenses. The difference in refractive index between the test lens and the instrument's prism generates a specific angle of total internal reflectance, which produces a dark visible shadow. The angle at which this shadow appears is directly related to the refractive index of the test lens. Most contact lenses (including the uncoated SiHy contact lens prepared in Example 19) produce a clear shadow on the Abbe refractometer, but the SiHy with the cross-linked coating (i.e., the outer hydrogel layer) in Example 19 does not produce a clear shadow. This phenomenon is thought to be due to the decrease in the refractive index of the lens at the surface compared to the bulk, and the fact that the transition from bulk to surface is not abrupt. Furthermore, it is thought that the water content begins to increase near the lens surface, locally decreasing the refractive index of the lens. This would, in fact, generate shadows at multiple angles simultaneously, resulting in a blurred image of the shadows.

[0295] The Abbe data demonstrates that the outer surface layer is characterized by an increase in water content near the lens surface, consistent with the results described in Example 23.

[0296] Example 25 SiHy contact lenses with the cross-linked coating (i.e., outer hydrogel layer) prepared in Example 19 are desalted in ultrapure water and individually placed in 50 mL disposable beakers with 50 mL of ultrapure water. The beakers are then frozen by placing them in a bath containing dry ice and isopropyl alcohol. The beakers are wrapped in aluminum foil and placed on a VirTis Freezemobile 35EL with a vacuum pressure of 30 μbar and a condenser temperature of -70 °C. After 24 hours, the aluminum foil is removed to enhance heat conduction, and the flask is left for a further 24–48 hours to remove any remaining moisture. The flask is sealed to prevent moisture from entering from the air until analysis. The lens sample is cut in half, and then each of the two sections is cut from the center, with their ends fixed to image the cross-section. The sample is then sputter-coated with Au / Pd for approximately 1 minute and examined by SEM using a Bruker Quantax Microanalysis System (JEOLJSM-800LV SEM). The sample stand is tilted at approximately 0-60° at the analyst's discretion to obtain the desired sample orientation.

[0297] When SiHy contact lenses are freeze-dried, it is possible that the hydrated surface structure of the lens may be preserved or fixed to some extent. Panel A of Figure 4 shows a top view of the SEM image of the surface of the freeze-dried SiHy contact lens prepared in Example 19. It is clear from Figure 4 that the freeze-dried SiHy contact lens has a sponge-like surface structure which is predicted to be a hydrogel with a high water content. Furthermore, this result confirms that the SiHy contact lens of the present invention contains two outer hydrogel layers with a high water content. Panels B and C of Figure 4 show side views at two different angles of the cross-section of the freeze-dried SiHy contact lens shown in Panel A. Panels B and C show a thick inner layer with a smooth surface, a lighter colored transition layer (PAA layer) above the inner layer, and an outer hydrogel layer with a sponge-like structure above the transition layer. From the data shown in Panels B and C, the thickness of the freeze-dried outer hydrogel layer is estimated to be approximately 2 μm to 2.5 μm.

[0298] Example 26 Fluorescein-labeled poly(AAm-co-AA)(90 / 10) (also known as PAAm-PAA-F) PAAm-PAA-F is synthesized in-house by covalently bonding 5-aminofluorescein to PAAm-PAA(90 / 10) using the same procedure as for the preparation of PAA-F. Poly(AAm-co-AA)(90 / 10) partial sodium salt (~90% solid content, poly(AAm-co-AA)90 / 10, Mw200,000) is purchased from Polysciences, Inc. and used as is. The labeling degree of fluorescein is approximately 0.04 mol%.

[0299] IPC saline modified with PAAm-PAA-F This physiological saline solution is prepared using the same IPC preparation procedure as described in Example 19, except that PAAm-PAA is replaced with PAAm-PAA-F.

[0300] PAA coated lenses Lenses are prepared by casting from the lens compound prepared in Example 19 above into a reusable mold (quartz female half and glass male half) similar to the molds shown in U.S. Patent No. 7,384,590 (Figures 1-6) and No. 7,387,759 (Figures 1-6). The lens compound in the mold is then subjected to UV irradiation (13.0 mW / cm²). 2 Irradiate for approximately 24 seconds. Extract the cast contact lenses and coat them by immersing them in the following series of baths: DI water bath (approximately 56 seconds); six MEK baths (approximately 44, 56, 56, 56, 56, and 56 seconds, respectively); DI water bath (approximately 56 seconds); one PAA coating solution bath in 1-PrOH solvent (approximately 0.36% by weight, acidified to pH approximately 2.0 with formic acid) (approximately 44 seconds); one water / 1-propanol 50% / 50% mixture bath (approximately 56 seconds); four DI water baths, each approximately 56 seconds; one PBS bath for approximately 56 seconds; and one DI water bath for approximately 56 seconds.

[0301] Application of cross-linked coatings The lens having the PAA base coating prepared above is placed in a polypropylene lens packaging shell (one lens per shell) with 0.6 mL of modified IPC saline prepared above using PAAm-PAA-F (half of the saline is added before inserting the lens). Next, the blister is sealed with aluminum foil and autoclaved at approximately 121°C for approximately 30 minutes to produce a SiHy contact lens having a cross-linked coating (PAA-x-hydrophilic polymer material) on it.

[0302] Confocal laser fluorescence microscopy A hydrated SiHy lens (prepared as described above) with a single cross-linked coating is placed between two glass coverslips, and images are taken using a confocal laser fluorescence microscope (model # Zeiss LSM 510 Vis). The image is scanned from the front curve side of the lens to the base curve side (and vice versa). The presence of PAAm-PAA-F is indicated by green fluorescence, and a confocal laser fluorescence microscope image can be obtained. From the examination of the confocal laser fluorescence microscope images, it is clear that layers rich in PAAm-PAA-F (i.e., the outer hydrogel layer) are present on both sides (front and back) and the peripheral edges of the lens surface, while PAAm-PAA-F is not observed in the bulk material of the lens.

[0303] The fluorescence intensity profile is investigated across the entire cross-section of the lens, traversing both the rear and front surfaces and along a line perpendicular to the rear surface. The thickness of the PAAm-PAA-F-rich layer can be estimated from the overall fluorescence intensity profile of the lens. The possible thickness of the outer hydrogel layer (the PAAm-PAA-F-rich layer) is estimated by the distance from zero intensity, across the peak intensity, and back to zero intensity. Considering possible contributions from unknown factors (such as scattering) to the fluorescence intensity, the minimum thickness of the layer is the thickness at which at least 10% of the maximum peak intensity of fluorescence intensity is retained. Based on such predictions, the minimum thickness of the PAAm-PAA-F-rich layer (hydrated outer hydrogel layer) would be at least approximately 5 microns.

[0304] Example 27 Lenses are prepared using lens formulation D-2 (Example 17), to which APMAA monomer is added to a concentration of 1%. LS lenses are prepared by casting from the lens formulation prepared above using a reusable mold similar to the molds shown in U.S. Patent Nos. 7,384,590 (Figures 1-6) and 7,387,759 (Figures 1-6). The mold includes a female half made of glass and a male half made of quartz. The UV irradiation source has an intensity of approximately 4.6 mW / cm² with a 380 nm cutoff filter. 2 This is a Hamamatsu lamp. It irradiates the lens mixture inside the molding mold with UV light for approximately 30 seconds.

[0305] The cast lenses are extracted with methyl ethyl ketone (MEK), rinsed with water, and coated with polyacrylic acid (PAA) by immersion in a propanol solution of PAA (0.0044% by weight, acidified to pH approximately 2.5 with formic acid), and then hydrated with water.

[0306] IPC saline is prepared according to the composition described in Example 9, under pre-reaction conditions of approximately 60°C for 8 hours. The lens is placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). The blister is then sealed with aluminum foil and autoclaved at 121°C for 30 minutes.

[0307] The lens surface evaluation indicates that all test lenses are free of debris. When observed under a dark-field microscope, no cracking lines were observed after rubbing the lenses between fingers. The lens surface wettability (WBUT) was over 10 seconds, lubricity was ranked as "1", and the contact angle was approximately 20°.

[0308] Example 28 Cast-molded SiHy contact lenses (without any coating) prepared in Example 19 were used. All lenses were extracted overnight in MEK to ensure that all residual monomers were removed. The first group of lenses (lenses with a hydrated crosslinking coating) were immersed overnight in a PAA coating solution (0.36% (by weight) PAA in 1-propanol, adjusted to pH 1.7-2.3 with formic acid), and the second group of lenses (control) were immersed overnight in 1-propanol for the same period. Both groups of lenses were packaged in IPC saline prepared in Example 19 and autoclaved. The autoclaved lenses were tested using gravimetric analysis (in five groups) to determine the weights of the dry and wet contact lenses (N=14 for the first group of contact lenses; N=18 for the second group of contact lenses). The results are shown in Table 8.

[0309] [Table 9]

[0310] Compared to the control lens (uncoated), the presence of a hydration crosslinking coating in the contact lens resulted in a statistically significant difference (7 mg) in wet weight between the first and second contact lens groups. However, the difference in dry weight between the first and second contact lens groups was approximately 0.3 mg, which is not statistically significant. The water content of the coated lens can be estimated to be ~96% according to the calculation below.

number

[0311] Example 29 This embodiment describes a method for quantifying the lubricity of SiHy contact lenses according to the inclined plate method ("Derby friction test"). The inclined plate method is a simple test set up as shown in Figure 5. The inclined plate setup consists of a plastic reservoir or tank 501 filled with phosphate-buffered saline (PBS, pH ~7.3) 502, a borosilicate glass plate 503, and a shim 506 with an adjustable height of 5 mm ~ 20 mm. Both the borosilicate glass plate 503 and the shim 506 are immersed in the phosphate-buffered saline 502 in the plastic reservoir or tank 501. In the test, the contact lens 504 is placed on the borosilicate glass plate, and then a stainless steel ferrule 505 is placed on top of it (to apply physiologically appropriate pressure). Critical friction coefficient = F t / F N =tanθ(where θ is the critical angle, F) N F is the normal force. t (where θ is the tangential force). The maximum angle at which a lens continues to slide after being pushed, but takes more than 10 seconds to stop or reach the edge, 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 will not exceed the CCOF, and a lens that does not stop within the distance traveled will exceed the CCOF. Angles that exceed or do not exceed the CCOF are excluded from the analysis. The Derby friction test can provide a direct method for measuring the coefficient of kinetic friction.

[0312] For the inclined plate method test, all lenses are soaked in PBS solution for at least one night (>6 hours) before testing to remove any residual packaging solution. The glass plates (6"×4" borosilicate glass) are washed with soapy water (1% Micro-90) and wiped (AlphaWipe TX1009). Each plate is thoroughly rinsed with DI water for about 2 minutes. The resistance of the plate cross-section is checked by rubbing with a finger to ensure all soapy water is removed. The water is wiped off with a paper towel (KimTech Kimwipe #34705) and the glass is inspected under light for any remaining foreign matter. The glass plates are placed on shims of various heights in a plastic reservoir or tank, and the height of this surface is measured and recorded with a micrometer. The reservoir is filled with phosphate-buffered saline (PBS) so that the lenses are completely submerged (28 mm deep).

[0313] Place each lens on the "start line" and place a 0.79g ferrule (1 / 4" stainless steel, to apply physiologically appropriate pressure) on the lens surface. Allow the lens to slide down the plate and record the time it takes for the lens to travel 96mm.

[0314] Before retesting, remove the weight and move the lens back to its starting position. This "pre-loading" effect should be minimized to achieve the best reproducibility. The lens can be tested at multiple angles to obtain the ideal CCOF.

[0315] Sixteen commercially available contact lenses and the silicone hydrogel contact lens prepared in Example 19 were tested for CCOF, and the results are reported in Table 9. These results demonstrate that the SiHy contact lens of the present invention (prepared in Example 19 with a cross-linked coating) has the lowest CCOF among commercially available and all classes of silicone hydrogel lenses tested, and therefore possesses the best lubricity.

[0316] [Table 10]

[0317] Example 30 This embodiment describes a method for characterizing the loaded electrosurface of a SiHy contact lens according to a positive charge particle adhesion test.

[0318] The surface charge of a lens surface can be detected indirectly through interaction with charged particles or beads. A loaded surface will attract positively charged particles. A surface that is free of or substantially free of negative charge will not attract positively charged particles, or will attract only a small amount of positively charged particles.

[0319] Uncoated SiHy contact lenses (i.e., cast and extracted with MEK as described in Example 19), PAA-coated SiHy contact lenses (as prepared in Example 19), and SiHy contact lenses having a cross-linked coating thereon (as prepared in Examples 14 and 19) are tested as follows. The PAA coating of the PAA-coated contact lenses has a surface concentration of approximately 62.5% (by weight) of carboxylic acid groups (M COOH / M AA )(where M COOH M is the mass of the carboxylic acid group. AA (where is the mass of acrylic acid). The crosslinked coating of the contact lens in Example 14 theoretically does not contain carboxylic acid groups, but the crosslinked coating of the contact lens in Example 19 has a low surface concentration of carboxylic acid groups.

number

[0320] DOWEX (trademark) 1x4 20-50 mesh resin is purchased from Sigma-Aldrich and used as is. DOWEX (trademark) 1x4 20-50 mesh resin is a spherical type I strong base anionic resin, N + (CH3)3Cl -This is a styrene / divinylbenzene copolymer containing functional groups and 4% divinylbenzene. 5% of 1×4 20-50 mesh resin is dispersed in PBS and thoroughly mixed by stirring or vortexing at approximately 1000 rpm for 10 seconds. The lens is immersed in this dispersion and vortexed at 1000-1100 rpm for 1 minute, then rinsed with DI water and vortexed for 1 minute. Next, the lens is placed in water in a glass petri dish and an image of the lens is taken using a Nikon optical microscope with bottom illumination. As shown in Figure 6, almost the entire surface of the PAA coated lens is covered with attached positively charged particles (Figure 6a), while a total of approximately 50 positively charged particles are attached to the lens with the cross-linked coating prepared in Example 19 (Figure 6B), and no positively charged particles are attached to the lens with the cross-linked coating prepared in Example 14 (Figure 6C). Some weakly attached particles fall off the lens surface and can be found in the water surrounding the lens.

[0321] It should be understood that if larger positively charged particles (i.e., DOWEX® monosphere ion exchange resin, cross-linked polystyrene beads, chloride form, ~590 micron size, Sigma-Aldrich) are used in the test, the number of particles adhering to the particles may decrease. Approximately 30% of these DOWEX monosphere resins are dispersed in PBS. The lens is immersed in this dispersion for about 1 minute, then rinsed with DI water. Next, the lens is placed in water in a glass petri dish, and an image of the lens is taken using a Nikon optical microscope with bottom illumination. It is found that many particles (approximately 200 particles) adhere to the PAA coated lens, while no particles adhere to the lens with the cross-linked coating. Several commercially available contact lenses are also tested. No particles are observed on the following lenses: Acuvue® TruEye®, Acuvue® Advance®, Acuvue® Oasys®, Avaira®, Biofinity®, Air Optix®, and Focus® Night&Day®. Particles are observed on the following four types of lenses (in increasing order of particle count): PureVision®, 1 Day Acuvue® Moist®, Proclear 1 day, and Acuvue® (Etafilcon A) lens. Almost the entire surface of the Acuvue® (Etafilcon A) lens is covered with attached positively charged particles.

[0322] The negatively charged resin (Amberlite CG50) was purchased from Sigma and used as is. 5% of these Amberlite CG50 beads were dispersed in PBS and vortexed at approximately 1000 rpm for 10 seconds. The PAA-coated lens was immersed in this dispersion and vortexed at 1000-1100 rpm for 1 minute, then rinsed with DI water and vortexed for 1 minute. Next, the lens was placed in water in a glass petri dish and an image of the lens was taken using a Nikon optical microscope with bottom illumination. No Amberlite particles (load charge) were found on the PAA-coated lens.

[0323] This experiment uses load beads (Amberlite CG50) coated with polyethyleneimine (PEI, a positively charged electrolyte). The PEI coating procedure is as follows: PEI (Lupasol SK, 24% aqueous solution, Mw~2,000,000) is purchased from BASF and used as is. Prepare an aqueous dispersion of 1% Amberlite particles and 5% PEI. Adjust the pH to 7 and mix the solution thoroughly (e.g., stir for 30 minutes). Then, suspend the dispersion in a large amount of water 2-3 times and filter 2-3 times to collect the particles (PEI-coated Amberlite). Disperse 5% of the PEI-coated Amberlite CG50 particles in PBS and vortex at approximately 1000 rpm for 10 seconds. Immerse the lens in this dispersion and vortex at 1000-1100 rpm for 1 minute, then rinse with DI water and vortex for 1 minute. Next, the lenses were placed in water in a glass petri dish, and images of the lenses were taken using a Nikon optical microscope with bottom illumination. A large number of PEI-coated Amberlite particles (positively charged particles, due to the presence of PEI) were observed adhering to the PAA-coated lens (Example 19). However, substantially, PEI-coated Amberlite particles were not adhering to the uncoated SiHy contact lens (Example 19), the SiHy contact lens with a cross-linked coating (Example 19), or the PAExPAA-coated lens (Example 4).

[0324] Example 31 Sample preparation: AFM studies were performed on SiHy contact lenses (prepared in Example 19) in both hydrated and dry states. The lenses were removed from their blister packs (sealed and autoclaved) and their cross-sections were cut (e.g., using a razor blade). As shown in Figure 7, the cross-sectional pieces of the lenses were placed vertically on a metal clamp. A small piece of the lens was allowed to protrude from the top of the holder, and the lens was scanned with an AFM tip (on the lens cross-section in Figure 7).

[0325] AFM experiment: The lens cross-section is characterized using two separate AFM instruments. In both cases (except for dry samples), the AFM scanning is performed under phosphate buffer (PBS containing or without NaCl, but with substantially the same osmotic pressure as physiological saline) to maintain the hydrogel sample in a fully hydrated state.

[0326] The primary AFM system is a Veeco BioScope AFM equipped with a Nanoscope IV controller. Data is acquired using a triangular silicon cantilever with a spring constant of 0.58 N / m and a nominal tip radius of 20–60 nm curvature. Scanning is performed in continuous contact (force-volume) mode at a probe speed of 30 microns / second and a force-volume scanning frequency of 0.19 Hz. Topographic and force-volume data are acquired simultaneously. Each force curve consists of approximately 30 data points. The lens is fully immersed in PBS during AFM scanning. A scan size of up to 20 microns is typically used to achieve sufficiently high resolution for obtaining force-volume images. 128 × 128 pixel force plots are acquired over approximately 3 hours per image.

[0327] AFM images of the cross-section of a SiHy contact lens (Example 19) having a fully hydrated cross-linked coating were obtained by force-volume method and are shown in Figure 8. In the images, the darker region 420 represents the coating, and the brighter region 410 represents the bulk material of the lens. The average thickness of the cross-linked coating (i.e., the front and rear outer layers) of the SiHy contact lens (Example 19) is determined to be approximately 5.9 μm (standard deviation 0.8 μm), as obtained from seven images of the four lenses.

[0328] AFM technology allows for the determination of the surface coefficient (surface flexibility) at specific locations on the lens cross-section. Figure 9 shows the cross-sectional surface coefficient profile of a SiHy contact lens (prepared in Example 19) with a fully hydrated cross-linked coating. Since the surface coefficient of a material is proportional to the cantilever deflection, the cross-sectional surface coefficient profile of a contact lens can be approximately obtained by plotting the cantilever deflection value (as a measure of the surface coefficient of the material at specific locations on the lens cross-section) as a function of the distance from the side (front or back) of the cross-section along two lines traversing the cross-section shown in Figure 8. As shown in Figure 9, the cross-linked coating (front and back outer layers of the contact lens in Example 19) is softer than the bulk (inner layer) silicone hydrogel lens material. As we move along the two lines, the surface coefficient initially remains almost constant over the 0–approximately 5.9 micron region with an average cantilever deflection (i.e., average surface coefficient) of approximately 52 nm, then gradually increases until it reaches a maximum further inside the lens, and then remains almost constant (plateau) over the region beyond approximately 7 microns with an average cantilever deflection (i.e., average surface coefficient) of approximately 91 nm. The transition from the softer crosslinked coating to the harder bulk SiHy material occurs gradually over a range of several microns, indicating that a morphological or compositional (water content) gradient may exist between the coating surface and the lens bulk. The surface coefficient in the 5.9–approximately 7 micron region, i.e., the region near the boundary between the outer hydrogel layer and the inner layer of the silicone hydrogel material, is not used in the calculation of the average surface coefficient. The front and rear outer hydrogel layers (crosslinked coating) of the SiHy contact lens (Example 19) showed a surface coefficient reduction of approximately 43%.

number

number

number

[0329] SiHy contact lenses (prepared in Example 19) are studied using a second AFM instrument. Scanning is performed using a Bruker Icon AFM in quantitative nanomechanical measurement (PeakForce QNM) mode, using either fully hydrated (PBS containing glycerol but no NaCl to achieve similar osmotic pressure) or dry lenses. The lens cross section is placed in a metal clamp as described above. Test conditions include a spring constant of 1.3 N / m, a tip radius of 33.3 nm, a sensitivity of 31 nm / V, a scanning frequency of 0.4 Hz, and a scanning resolution of 512 × 512.

[0330] AFM images of cross-sections of the SiHy contact lens (Example 19) in a fully hydrated and dry state were obtained according to the PeakForce QNM method. By analyzing the obtained images, it was determined that the thickness of the cross-linked coating in the fully hydrated state was approximately 4.4 microns, while the thickness of the cross-linked coating in the dry state was approximately 1.2 microns for the vacuum-dried sample and approximately 1.6 microns for the oven-dried sample. Water expansion coefficient L of the cross-linked coating of the SiHy contact lens (prepared in Example 19) wet / L Dry ×100% (in the formula, L Wet L is the average thickness of the outer hydrogel layer of a fully hydrated SiHy contact lens. Dry The average thickness of the outer hydrogel layer of a dry SiHy contact lens is calculated to be approximately 277% (oven-dried sample) or approximately 369% (vacuum-dried sample).

[0331] Example 32 Preparation of lens formulations Preparation I is prepared by dissolving the components in 1-propanol to have the following composition: 33% (by weight) CE-PDMS macromer prepared in Example 2, 17% (by weight) N-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24% (by weight) N,N-dimethylacrylamide (DMA), 0.5% (by weight) N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt) (L-PEG), 1.0% (by weight) Darocur 1173 (DC1173), 0.1% (by weight) visitint (5% copper phthalocyanine blue pigment dispersion in tris(trimethylsiloxy)silylpropyl methacrylate (TRIS)), and 24.5% (by weight) 1-propanol.

[0332] Preparation II is prepared by dissolving the components in 1-propanol to have the following composition: approximately 32% (by weight) of CE-PDMS macromer prepared in Example 2, approximately 21% (by weight) of TRIS-Am, approximately 23% (by weight) of DMA, approximately 0.6% (by weight) of L-PEG, approximately 1% (by weight) of DC1173, approximately 0.1% (by weight) of visitint (5% copper phthalocyanine blue pigment dispersion in TRIS), approximately 0.8% (by weight) of DMPC, approximately 200 ppm of H-tempo, and approximately 22% (by weight) of 1-propanol.

[0333] Lens preparation The lenses are prepared by casting from the lens mixture prepared above using reusable molds (a quartz female half and a glass male half) similar to those shown in U.S. Patent Nos. 7,384,590 (Figures 1-6) and 7,387,759 (Figures 1-6). The UV irradiation source has an intensity of approximately 4 mW / cm² and is equipped with a WG335 + TM297 cutoff filter. 2 This is a Hamamatsu lamp. The lens mixture in the molding mold is irradiated with UV light for approximately 25 seconds. The cast lens is extracted with methyl ethyl ketone (MEK) (or propanol or isopropanol).

[0334] Application of PAA Prime Coating to SiHy Contact Lenses The polyacrylic acid coating solution (PAA-1) is prepared by dissolving a certain amount of PAA (MW: 450 kDa, Lubrizol) in a predetermined amount of 1-propanol to have a concentration of approximately 0.36% (by weight), and adjusting the pH to approximately 2.0 with formic acid.

[0335] Another PAA coating solution (PAA-2) is prepared by dissolving a certain amount of PAA (MW: 450 kDa, Lubrizol) in a predetermined amount of organic solvent (50 / 50 1-propanol / H2O) to a concentration of approximately 0.39% (by weight), and adjusting the pH to approximately 2.0 with formic acid.

[0336] The SiHy contact lenses obtained above are subjected to one of the immersion processes shown in Tables 10 and 11.

[0337] [Table 11]

[0338] [Table 12]

[0339] Application of crosslinked hydrophilic coatings Poly(acrylamide-co-acrylic acid) partial sodium salt, poly(AAm-co-AA)(90 / 10) (~90% solid content, poly(AAm-co-AA)90 / 10, Mw200,000) is purchased from Polysciences, Inc. and used as is. PAE (Kymene, azetidinium content 0.46 according to NMR assay) is purchased as an aqueous solution from Ashland and used as is. In-package cross-linked (IPC) saline is prepared by dissolving approximately 0.07% w / w poly(AAm-co-AA)(90 / 10) and approximately 0.15% PAE (approximately 8.8 mmol initial azetidinium millimolar equivalent) in phosphate-buffered saline (PBS) (approximately 0.044 w / w% NaH2PO4·H2O, approximately 0.388 w / w / % Na2HPO4·2H2O, approximately 0.79 w / w% NaCl) and adjusting the pH to 7.2-7.4. Next, the IPC saline is pre-treated by heating at approximately 70°C for approximately 4 hours (heat pre-treatment). During this heat pretreatment, poly(AAm-co-AA) and PAE are partially crosslinked with each other (i.e., not all azetidinium groups of PAE are consumed), forming a water-soluble and heat-crosslinkable hydrophilic polymer material containing azetidinium groups within the branched polymer network structure in IPC saline. After the heat pretreatment, the IPC saline is filtered using a 0.22 micron polyethersulfone [PES] membrane filter and cooled again to room temperature. Next, 10 ppm hydrogen peroxide is added to the final IPC saline to prevent bioburden increase, and the IPC saline is filtered using a 0.22 micron polyethersulfone [PES] membrane filter.

[0340] The lens having the PAA prime coating prepared above is placed in a polypropylene lens packaging shell (one lens per shell) with 0.6 mL of IPC saline (half of the saline is added before inserting the lens). Next, the blister is sealed with aluminum foil and autoclaved at approximately 121°C for approximately 30 minutes to produce a SiHy contact lens having a crosslinked hydrophilic coating on it.

[0341] Characterization of SiHy lenses The resulting cross-linked hydrophilic coating is present on the SiHy contact lens, which has a central thickness of approximately 0.95 microns and an oxygen permeability of approximately 142 to 150 bars (Dk). c It has an estimated intrinsic Dk, a bulk surface modulus of approximately 0.72 to 0.79 MPa, a water content of approximately 30% to 33% (by weight), a relative ion transmittance of approximately 6 (relative to Alsacon lenses), and a contact angle of approximately 34 to 47 degrees.

[0342] Characterization of the nanotexture surface of contact lenses Transmission Differential Interference Contrast (TDIC) Method The contact lens is placed on a glass slide and flattened by compressing the lens between the slide and the glass coverslip. The surface of the contact lens is then set up and tested using a Nikon ME600 microscope with a transmission differential interference contrast optical system, focusing through the lens with a 40× objective lens. The resulting TDIC image is then evaluated to determine the presence of a wrinkled surface pattern (e.g., a random and / or regular worm-like pattern).

[0343] Reflectance differential interference contrast (RDIC) method Place the lens on a glass slide and flatten it to create four straight lines approximately 90 degrees apart. Use compressed air to blow off excess saline solution from the surface. Using a Nikon Optiphot-2 reflection differential interference contrast optical system, test the lens surface with 10×, 20×, and 50× objective lenses if wrinkle-like surface patterns are present on the contact lens surface. Acquire a representative image of each slide using a 50× objective lens. Next, flip the contact lens over, remove the excess saline solution, and similarly examine the other side of the contact lens. Then, evaluate the obtained RDIC images to determine the presence of wrinkle-like surface patterns (e.g., random and / or regular worm-like patterns).

[0344] Dark-field optical microscopy (DFLM) DFLM (Dark Field Illumination) is generally based on dark-field illumination and is a method for enhancing the contrast of a sample being observed. This technique consists of a light source outside or obscured from the observer's field of view to illuminate the sample at an angle relative to light transmitted perpendicularly. Since the non-scattered light from the light source is not collected by the objective lens, it is not part of the image, and the background of the image appears dark. When a light source illuminates a sample at a certain angle, the light observed in the sample image is scattered by the sample toward the observer, and contrast is then generated between this scattered light from the sample and the dark background of the image. This contrast effect results in dark illumination that is particularly useful for observing scattering phenomena such as haze.

[0345] DFLM is used to evaluate contact lens haze as follows: Because the darkfield setting includes scattered light, darkfield data is considered to provide the worst-case assessment of haze. In an 8-bit grayscale digital image, each image pixel is assigned a grayscale intensity (GSI) value ranging from 0 to 255. Zero represents a pixel that is completely black, and 255 represents a pixel that is completely white. An increase in scattered light captured in the image will produce pixels with higher GSI values. This GSI value can then be used as a means to quantify the amount of scattered light observed in the darkfield image. Haze is represented by averaging the GSI values ​​of all pixels in the area of ​​interest (AOI) (e.g., the entire lens or the lenticular zone or optical part of the lens). The experimental setup consists of a microscope or equivalent optical system, an accompanying digital camera, and a darkfield stand with a ring light and a variable intensity light source. The optical system is designed / positioned so that the entire contact lens being observed falls within the field of view (typically a field of view of ~15mm × 20mm). The illumination is set to an appropriate level to observe the desired changes in the sample in question. The light intensity is adjusted / calibrated to the same level for each setting of the sample using a density / light scattering standard as known to those skilled in the art. For example, the standard consists of two overlapping plastic cover slips (homogeneous and slightly or moderately cloudy). Such a standard consists of three regions with different mean GSIs, including two regions with intermediate grayscale levels and saturated white (edge). The black region represents the dark field of the sky. The black and saturated white regions can be used to verify the camera's gain and offset (contrast and brightness) settings. The intermediate gray level can provide three points for verifying the camera's linear response. The light intensity is adjusted so that the mean GSI of the dark field of the sky reaches 0 and the mean GSI of the specified AOI in the digital image of the standard is the same each time within ±5 GSI units. After calibrating the light intensity, the contact lens is immersed in phosphate-buffered saline filtered through 0.2 μm in a quartz petri dish or a dish of similar clarity placed on a DFLM stand.Next, an 8-bit grayscale digital image of the lens is acquired visually using calibrated lighting, and the average GSI of the specified AOI within a portion of the image containing the lens is determined. This is repeated for each set of contact lens samples. Light intensity calibration is periodically re-evaluated throughout the test to maintain consistency. The level of haze under DFLM testing refers to DFLM haze GSI / 255 × 100%.

[0346] SiHy contact lenses with PAA prime coating obtained according to either immersion process 20-0 or 80-0 were determined to have an average DFLM haze of approximately 73% and exhibit a wrinkled surface pattern (random worm-like pattern) that can be observed by the eye by testing the hydrated contact lenses according to either the RDIC or TDIC method described above. However, the wrinkled surface pattern does not actually have a detrimental effect on the light transmittance of the contact lenses.

[0347] SiHy contact lenses with PAA prime coating obtained according to any of the immersion processes 20-1 to 20-4 were determined to have a low average DFLM haze of approximately 26% (presumably due to the presence of visiting pigment particles) and did not exhibit a prominent wrinkle surface pattern (random worm-like pattern) when tested with either RDIC or TDIC as described above.

[0348] High percentage SiHy contact lenses with PAA prime coating obtained according to either of the immersion processes 20-5 were determined to have a moderate average DFLM haze of approximately 45% and exhibit a slightly noticeable wrinkled surface pattern when tested with either RDIC or TDIC as described above. However, the wrinkled surface pattern does not actually have a detrimental effect on the light transmittance of the contact lens.

[0349] SiHy contact lenses with PAA prime coating obtained according to any of the immersion processes 80-1, 80-2, 80-3, 80-5, and 80-6 do not exhibit a noticeable wrinkle surface pattern when tested with either the RDIC or TDIC as described above. However, SiHy contact lenses with PAA prime coating obtained according to any of the immersion processes 80-0 and 80-4 exhibit a noticeable wrinkle surface pattern when tested with either the RDIC or TDIC as described above. However, the wrinkled surface pattern does not actually have a detrimental effect on the light transmittance of the contact lens.

[0350] Example 33 Synthesis of UV-absorbing amphiphilic branched-chain copolymers A 1L jacketed reactor is equipped with a 500mL addition funnel, overhead stirrer, reflux condenser with nitrogen / vacuum inlet adapter, thermometer, and sampling adapter. 89.95g of 80% partially ethylenically functionalized polysiloxane prepared in Example 17A is added to the reactor and then degassed at room temperature for about 30 minutes under a vacuum of less than 1mbar. A monomer solution prepared by mixing 1.03g of HEMA, 50.73g of DMA, 2.76g of Norbloc methacrylate, 52.07g of TRIS, and 526.05g of ethyl acetate is added to a 500mL addition funnel and then degassed at room temperature for 10 minutes under a vacuum of 100mbar, and then refilled with nitrogen gas. The monomer solution is degassed for two more cycles under the same conditions. Next, the monomer solution is added to the reactor. The reaction mixture is heated to 67°C with moderate stirring. While heating, a solution consisting of 2.96 g of mercaptoethanol (chain transfer agent, CTA), 0.72 g of dimethyl 2,2'-azobis(methyl 2-propionate) (V-601-initiator), and 76.90 g of ethyl acetate is added to an addition funnel, and then the same degassing process as for the monomer solution is carried out. When the reactor temperature reaches 67°C, the initiator / CTA solution is also added to the reactor. The reaction is carried out at 67°C for 8 hours. After copolymerization is complete, the reactor temperature is cooled to room temperature.

[0351] Synthesis of UV-absorbing amphiphilic branched-chain prepolymers The copolymer solution prepared above is ethylenically 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-chain prepolymer. The mixture is stirred under sealed conditions at room temperature for 24 hours. Next, the prepared prepolymer is stabilized with 100 ppm of hydroxytetramethylenepiperonyloxy, and the solution is concentrated to 200 g (~50%) and filtered through 1 μm pore size filter paper. The reaction solvent is replaced with 1-propanol by repeating evaporation and dilution cycles, and the solution is prepared for use in formulations. The solid content is measured by removing the solvent in a vacuum oven at 80°C.

[0352] Preparation of lens formulations The lens preparation is prepared to have the following composition: 71% (by weight) of the prepolymer prepared above; 4% (by weight) of DMA; 1% (by weight) of TPO; 1% (by weight) of DMPC; 1% (by weight) of Brij 52 (Sigma-Aldrich); and 22% (by weight) of 1-PrOH.

[0353] Lens preparation The lenses are manufactured by casting the lens preparations prepared above using spatially limited UV irradiation, with reusable molds similar to those shown in U.S. Patent No. 7,384,590 (Figures 1-6) and No. 7,387,759 (Figures 1-6). The molds include a female half made of glass and a male half made of quartz. The UV irradiation source has an intensity of approximately 4.6 mW / cm² with a 380 nm cutoff filter. 2 This is a Hamamatsu lamp. It irradiates the lens mixture inside the molding mold with UV light for approximately 30 seconds.

[0354] The cast lenses are extracted with methyl ethyl ketone (MEK), rinsed with water, and coated with polyacrylic acid (PAA) by immersion in a propanol solution of PAA (0.004% by weight, acidified to approximately pH 2.0 with formic acid), and then hydrated with water.

[0355] IPC saline is prepared from a composition containing approximately 0.07% PAAm-PAA and sufficient PAE (~0.15% PAE) to provide an initial azetidinium content of approximately 8.8 mmol equivalents / liter, under pre-reaction conditions of approximately 6 hours at approximately 60°C. Next, 5 ppm hydrogen peroxide is added to the IPC saline to prevent bioburden increase, and the IPC saline is filtered using a 0.22 micron polyethersulfone [PES] membrane filter. The lens is placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the saline is added before lens insertion). The blister is then sealed with aluminum foil and autoclaved at 121°C for 30 minutes.

[0356] Determining Lens Characteristics The resulting lens has the following characteristics: E'~0.82MPa; DK c ~159.4 (using Lotrafilcon B as the reference lens, with an average center thickness of 80 μm and intrinsic Dk110); IP ~2.3; Water % ~26.9; and UVA / UVB % T ~4.6 / 0.1. When observed under a dark-field microscope, no cracking lines were observed after rubbing the test lens. The lens is very smooth, comparable to the control lens in the finger friction test.

Claims

1. Front and opposite rear; and A hydrated silicone hydrogel contact lens having a layered structure shape from the front to the back, The layered structure includes a front outer hydrogel layer and a rear outer hydrogel layer, each independently having a second water content, and an inner layer having a first water content. In the water content gradient from the inner layer to the front or rear outer hydrogel layer of the aforementioned structural shape, the second water content is higher than the first water content. Hydrated silicone hydrogel contact lenses have an oxygen transfer coefficient of at least 40 bars / mm, a Young's modulus of 0.3 MPa to 1.8 MPa, an average water contact angle of 80 degrees or less, and a water decay time of at least 10 seconds. Hydrated silicone hydrogel contact lenses are immersed in a Sudan Black dye solution, then thoroughly rinsed with water, and after that, they are free of stained spots on their surface. The inner layer is a bulk material for a hydrated silicone hydrogel contact lens and is composed of a silicone hydrogel material comprising (i) repeating units derived from silicone-containing vinyl monomers, silicone-containing vinyl macromers, silicone-containing prepolymers or combinations thereof, and (ii) repeating units derived from hydrophilic vinyl monomers. Each of the front and rear outer hydrogel layers is composed of a crosslinked polymer material comprising a polymer chain derived from a copolymer which is a polymerization product of a composition containing (i) at least one reactive vinyl monomer in an amount of 60% by weight or less and (ii) at least one phosphorylcholine-containing vinyl monomer. The at least one reactive vinyl monomer is a vinyl monomer having a carboxyl group, a primary amino group, or a secondary amino group. The at least one reactive vinyl monomer is selected from the group consisting of amino-C2-C6 alkyl (meth)acrylate, C1-C6 alkylamino-C2-C6 alkyl (meth)acrylate, allylamine, vinylamine, amino-C2-C6 alkyl (meth)acrylamide, C1-C6 alkylamino-C2-C6 alkyl (meth)acrylamide, acrylic acid, C1-C12 alkylacrylic acid, N,N-2-acrylamidoglycolic acid, β-methylacrylic acid, α-phenylacrylic acid, β-acrylooxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenylbutadiene-1,3, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof, in a hydrated silicone hydrogel contact lens.

2. The at least one reactive vinyl monomer is (meth)acrylic acid, C ２ -C １２ Alkyl acrylic acid, vinylamine, allylamine, amino-C ２ -C ４ A hydrated silicone hydrogel contact lens according to claim 1, selected from the group consisting of alkyl (meth)acrylates and combinations thereof.

3. The hydrated silicone hydrogel contact lens according to claim 1, wherein the at least one phosphorylcholine-containing vinyl monomer comprises (meth)acryloyloxyethyl phosphorylcholine.

4. The hydrated silicone hydrogel contact lens according to claim 2, wherein the at least one phosphorylcholine-containing vinyl monomer comprises (meth)acryloyloxyethyl phosphorylcholine.

5. The hydrated silicone hydrogel contact lens according to claim 4, wherein the hydrated silicone hydrogel contact lens has an oxygen transfer rate of at least 60 bars / mm and / or an average water contact angle of 70 degrees or less.

6. The hydrated silicone hydrogel contact lens according to claim 4, wherein the hydrated silicone hydrogel contact lens has an oxygen transfer rate of at least 80 bars / mm and / or an average water contact angle of 60 degrees or less.

7. The hydrated silicone hydrogel contact lens according to claim 4, wherein the hydrated silicone hydrogel contact lens has an oxygen transfer rate of at least 100 bars / mm and / or an average water contact angle of 50 degrees or less.

8. The hydrated silicone hydrogel contact lens according to claim 1, wherein the hydrated silicone hydrogel contact lens has an oxygen transfer rate of at least 60 bars / mm and / or an average water contact angle of 70 degrees or less.

9. The hydrated silicone hydrogel contact lens according to claim 1, wherein the hydrated silicone hydrogel contact lens has an oxygen transfer rate of at least 80 bars / mm and / or an average water contact angle of 60 degrees or less.

10. The hydrated silicone hydrogel contact lens according to claim 1, wherein the hydrated silicone hydrogel contact lens has an oxygen transfer rate of at least 100 bars / mm and / or an average water contact angle of 50 degrees or less.

11. A hydrated silicone hydrogel contact lens according to any one of claims 1 to 10, wherein the silicone hydrogel material comprises repeating units derived from a polysiloxane-containing vinyl monomer, a polysiloxane-containing vinyl macromer, or a combination thereof.

12. The hydrated silicone hydrogel contact lens according to claim 11, wherein the polysiloxane-containing vinyl monomer or macromer is monomethacrylate or monoacrylate polydimethylsiloxane; vinyl carbonate-terminated polydimethylsiloxane; vinyl carbamate-terminated polydimethylsiloxane; vinyl-terminated polydimethylsiloxane; methacrylamide-terminated polydimethylsiloxane; acrylamide-terminated polydimethylsiloxane; acrylate-terminated polydimethylsiloxane; methacrylate-terminated polydimethylsiloxane; bis-3-methacrylateoxy-2-hydroxypropyloxypropyl polydimethylsiloxane; N,N,N',N'-tetrakis(3-methacrylateoxy-2-hydroxypropyl)-α,ω-bis-3-aminopropyl-polydimethylsiloxane; polysiloxanyl alkyl (meth)acrylic monomer; or a reaction product of glycidyl methacrylate and amino-functionalized polydimethylsiloxane.

13. The silicone hydrogel material includes N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, 2-acrylamidoglycolic acid, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, 2-hydroxypropyl methacrylate trimethylammonium hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate, glycerol methacrylate, allyl alcohol, and C with a weight-average molecular weight of up to 1500. １ -C ４ - Alkoxy polyethylene glycol (meth)acrylate, 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 A hydrated silicone hydrogel contact lens according to claim 11, comprising repeating units derived from hydrophilic vinyl monomers selected from the group consisting of ropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, N-vinyl-2-pyrrolidone, vinylpyridine, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, N-vinylcaprolactam, and mixtures thereof.

14. The silicone hydrogel material is tetraethylene glycol diacrylate, triethylene glycol diacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, tetraethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylopropane trimethacrylate, pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethylacrylamide, ethylenediamine diacrylamide, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1,3-bis(methacrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy) A hydrated silicone hydrogel contact lens according to claim 13, further comprising repeating units derived from a crosslinking agent selected from the group consisting of disiloxane, N,N'-methylenebisacrylamide, N,N'-methylenebismethacrylamide, N,N'-ethylenebismethacrylamide, 1,3-bis(N-methacrylamidopropyl)-1,1,3,3-tetrakis-(trimethylsiloxy)disiloxane, 1,3-bis(methacrylamidobutyl)-1,1,3,3-tetrakis(trimethylsiloxy)-disiloxane, 1,3-bis(acrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane, 1,3-bis(methacryloxyethylureidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane, and combinations thereof.

15. The silicone hydrogel material includes N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, 2-acrylamidoglycolic acid, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, 2-hydroxypropyl methacrylate trimethylammonium hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate, glycerol methacrylate, allyl alcohol, and C with a weight-average molecular weight of up to 1500. １ -C ４ - Alkoxy polyethylene glycol (meth)acrylate, 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 A hydrated silicone hydrogel contact lens according to any one of claims 1 to 10, comprising repeating units derived from a hydrophilic vinyl monomer selected from the group consisting of -methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, N-vinyl-2-pyrrolidone, vinylpyridine, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, N-vinylcaprolactam, and mixtures thereof.

16. The silicone hydrogel material includes tetraethylene glycol diacrylate, triethylene glycol diacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, tetraethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylopropane trimethacrylate, pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethylacrylamide, ethylenediamine diacrylamide, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, and 1,3-bis(methacrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxy A hydrated silicone hydrogel contact lens according to any one of claims 1 to 10, further comprising repeating units derived from a crosslinking agent selected from the group consisting of sun, N,N'-methylenebisacrylamide, N,N'-methylenebismethacrylamide, N,N'-ethylenebismethacrylamide, 1,3-bis(N-methacrylamidopropyl)-1,1,3,3-tetrakis-(trimethylsiloxy)disiloxane, 1,3-bis(methacrylamidobutyl)-1,1,3,3-tetrakis(trimethylsiloxy)-disiloxane, 1,3-bis(acrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane, 1,3-bis(methacryloxyethylureidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane and combinations thereof.

17. Silicone hydrogel bulk materials include N-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide, N-[tris(dimethylpropylsiloxy)silylpropyl]-(meth)acrylamide, N-[tris(dimethylphenylsiloxy)silylpropyl](meth)acrylamide, N-[tris(dimethylethylsiloxy)silylpropyl](meth)acrylamide, and N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl) -2-methylacrylamide; N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)acrylamide; N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]-2-methylacrylamide; N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]acrylamide; N-(2-hydroxy-3-(3-(tris (trimethylsilyloxy)silyl)propyloxy)propyl)-2-methylacrylamide; N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)acrylamide; N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methylacrylamide; N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]acrylic Amides; N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methylacrylamide; N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide; N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methylacrylamide; N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide;3-Methacryloxypropylpentamethyldisiloxane, Tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS), (3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane), (3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane, 3-methacryloxy-2-(2-hydroxyethoxy)-propyloxy)propylbis(trimethylsiloxy)methylsilane, N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silylcarbamate, 3-(trimethylsilyl)propyl vinyl carbonate, 3-( A hydrated silicone hydrogel contact lens according to any one of claims 1 to 10, comprising repeating units derived from a silicone-containing vinyl monomer selected from the group consisting of vinyloxycarbonylthio)propyl-tris(trimethyl-siloxy)silane, 3-[tris(trimethylsiloxy)silyl]propyl vinylcarbamate, 3-[tris(trimethylsiloxy)silyl]propyl allylcarbamate, 3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate, t-butyldimethyl-siloxyethyl vinyl carbonate; trimethylsilylethyl vinyl carbonate, trimethylsilylmethyl vinyl carbonate, and combinations thereof.

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