Method for producing mps-compatible water gradient contact lenses

The present invention relates generally to weekly or monthly disposable water gradient contact lenses, and more particularly to durable, high moisture, soft, finger rub resistant silicone hydrogel contact lenses having a relatively thick hydrogel coating thereon and having a relatively high resistance to uptake of polycation-type antimicrobial agents.

A new class of soft contact lenses, water-gradient silicone hydrogel contact lenses, has been developed and successfully marketed as daily disposable contact lenses DAILIES® TOTAL1® (Alcon). This new class of silicone hydrogel contact lenses is characterized by a water-gradient structural form that increases the water content from the core to the surface from 33% to over 80% (see U.S. Pat. No. 8,480,227). This unique design provides a highly lubricated and extremely soft high-moisture lens surface, which can provide patients with better wearing comfort.

Such soft contact lenses can be manufactured according to the cost-effective method described in U.S. Pat. No. 8,529,057. Water-gradient silicone hydrogel contact lenses can be manufactured by forming an anchoring layer on each contact lens by dipping the contact lens into a coating solution of polyanionic polymer, followed by covalently bonding a water-soluble highly branched hydrophilic polymer material directly to the anchoring layer during autoclaving in the lens package. The water-soluble highly branched hydrophilic polymer material is prepared by partially reacting polyamidoamine-epichlorohydrin (PAE) with a wetting agent at various concentration ratios of PAE to wetting agent and reaction temperatures for a given reaction time that minimizes or eliminates surface defects (such as surface cracks) while achieving the desired lubricity of the surface gel.

Although the newly developed water-gradient silicone hydrogel contact lenses can provide patients with better wearing comfort due to their extremely soft, high moisture and relatively thick hydrogel coating, they may not be compatible with all lens care solutions on the market. For example, due to the presence of the anchoring layer of polyanionic material, these new contact lenses may take up (absorb) a large amount of polycation-type antibacterial agents (e.g., polyhexamethylene biguanide, polyquaternium-1 (also known as Polyquad®), etc., commonly found in most multi-purpose lens care solutions), and therefore may not be compatible with some multi-purpose lens care solutions on the market. These polycation-type antibacterial agents adsorbed by contact lenses may be released into the eye when the lenses are worn by patients, which may cause undesirable clinical symptoms such as diffuse corneal staining and product intolerance in some people. Due to incompatibility with some multi-purpose lens care solutions, newly developed water-gradient silicone hydrogel contact lenses, which must be cleaned and disinfected with lens care solutions on an almost daily basis, may not be suitable for use as weekly or monthly disposable contact lenses.

US Patent Application Publication Nos. 2015/0166205A1 and 2016/0326046A1 disclose a method for reducing the adhesion and deposition tendency of polycation-type antimicrobial agents on water-gradient contact lenses by adding one step involving the use of polyamidoamine-epichlorohydrin (PAE). However, these methods have some drawbacks. For example, although these methods can reduce the adhesion and deposition tendency of polycation-type antimicrobial agents on hydrogel-coated contact lenses, the lubricity, wettability, and/or hydrophilicity of the resulting contact lenses are also reduced at the same time, and the reduction in the adhesion and deposition of polycation-type antimicrobial agents may not be sufficient to make the contact lenses compatible with all multi-purpose lens care solutions on the market. Furthermore, contact lenses obtained by these methods may not be able to survive finger rubbing required in lens care regimes involving multipurpose lens care solutions, or inadvertent lens inversion during lens manufacture or handling, as finger rubbing and lens inversion can damage the hydrogel coating on the contact lens, as evidenced by crack lines visible to the eye under dark field after the contact lens is inverted or rubbed between fingers.

Thus, a need remains for disposable weekly or monthly aqueous gradient contact lenses that are highly resistant to finger rub yet are compatible with all lens care solutions, including multipurpose lens care solutions.

<p>In some embodiments, the present invention provides contact lenses that not only have a highly desirable water gradient structure morphology, but also have a polyquaternium-1 uptake rate ("PU") of about 0.4 micrograms/lens or less, and long-lasting surface hydrophilicity and wettability, characterized by a water-break-up time (WBUT) of at least 10 seconds after 30 cycles of finger rubbing (i.e., simulating a 30-day lens care regime) or after simulated abrasion cycling. The contact lenses of the present invention can provide better wearing comfort because they have a desired water gradient structure morphology and a relatively thick, highly flexible, and highly hydrated hydrogel surface layer. More importantly, the water gradient contact lenses of the present invention are compatible with multi-purpose lens care solutions available on the market and can withstand harsh lens care handling conditions (e.g., finger rubbing, inadvertent contact lens inversion, etc.) encountered in daily lens care regimes. Therefore, they are suitable for use as disposable contact lenses for one week or one month.</p><p>In another aspect, the present invention provides contact lenses that not only have an outer surface layer with desired flexibility, but also have a polyquaternium-1 uptake rate ("PU") of about 0.4 micrograms/lens or less, and long-lasting surface hydrophilicity and wettability, characterized by a water break-down time (WBUT) of at least 10 seconds after 30 cycles of finger rubbing (i.e., simulating a 30-day lens care regime). The contact lenses of the present invention have a relatively thick and extremely soft surface layer, which can provide better wearing comfort. More importantly, the contact lenses of the present invention are compatible with multi-purpose lens care solutions available on the market and can withstand harsh lens care handling conditions encountered in daily lens care regimes (e.g., finger rubbing, inadvertent contact lens inversion, etc.). Therefore, they are suitable for use as disposable contact lenses for one week or one month.</p><p>These and other aspects of the invention will become apparent from the following description of the presently preferred embodiments. The detailed description is merely illustrative of the invention and does not limit the scope of the invention, which is defined by the appended claims and their equivalents. As will be apparent to those skilled in the art, many variations and modifications of the invention are possible without departing from the spirit and scope of the novel concepts of the disclosure.</p>

<figref num="1">1 shows a schematic cross-sectional view of a structural form of a contact lens according to a preferred embodiment of the present invention.</figref><figref num="2">2 shows a schematic cross-sectional view of a structural form of a contact lens according to another preferred embodiment of the present invention;</figref><figref num="3">Schematic diagrams of a lens holder for performing a simulated lens polishing cycling process to determine the long-lasting lubricity and/or long-lasting wettability of the contact lenses of the present invention: A-oblique view, B-top view, C-side view, D-bottom view, and E-cross-sectional view.</figref><figref num="4">FIG. 1 shows a schematic of a lens holder for performing nanoindentation measurements on contact lenses with an Optics11 Puima nanoindentation instrument: A-top view, B-perspective view, and C-cross-section.</figref><figref num="5">1 shows the indentation force at 400 nm indentation depth as a function of bulk modulus of contact lenses as measured in the microindentation test of Example 20 using Bruker's Hysitron® BioSoft In-Situ Indenter.</figref><figref num="6">1 shows the indentation force at an indentation depth of 400 nm as a function of the bulk modulus of the contact lens as measured in the nanoindentation test of Example 42 using a nanoindentation instrument (Optics11 Puima).</figref>

Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. In general, the terms and experimental procedures used herein are well known and commonly used in the art. These procedures use conventional methods such as those provided in the art and various general references. Where a term is provided in the singular form, the inventors also intend the plural form of the same term. The terms used herein and the experimental procedures described below are well known and commonly used in the art.

As used herein, "about" means that a number referred to as "about" includes the recited number plus or minus 1 to 10% of the recited number.

"Contact lens" refers to a structure that may be placed on or in the eye of a wearer. A contact lens may, but need not, correct, improve, or modify the user's vision. A contact lens may be made of any suitable material known or later developed in the art and may be a hard lens, a rigid gas permeable lens, a soft lens, or a hybrid lens.

"Hard contact lens" refers to a contact lens that contains a hard plastic (eg, polymethyl methacrylate) as the bulk (core) material.

"Rigid gas permeable contact lens" refers to a contact lens that includes a gas permeable material (eg, a material made from fluorosilicone acrylate) as the bulk (core) material.

A soft contact lens may be a non-silicone hydrogel lens, a silicone hydrogel lens, or a silicone lens. "Hydrogel contact lens" refers to a contact lens that comprises a non-silicone hydrogel bulk (core) material. "Silicone hydrogel contact lens" refers to a contact lens that comprises a silicone hydrogel bulk (core) material. "Silicone contact lens" refers to a contact lens made from a crosslinked silicone material as its bulk (or core or base) material that has a three-dimensional polymer network (i.e., polymer matrix), is water insoluble, and can retain less than about 7.5% by weight (preferably less than about 5% by weight, more preferably less than about 2.5% by weight, and even more preferably less than about 1% by weight) of water when fully hydrated.

Hybrid contact lenses have a central optic zone made from a gas permeable lens material surrounded by a peripheral zone made from silicone hydrogel or standard hydrogel lens material.

"Hydrogel" or "hydrogel material" refers to a crosslinked polymeric material that is water-insoluble but can retain at least 10% by weight of water within its three-dimensional polymeric network (ie, polymer matrix) upon full hydration.

As used herein, the term "non-silicone hydrogel" refers to a hydrogel that is theoretically free of silicone.

As used herein, the term "silicone hydrogel" refers to a hydrogel containing silicone.Silicone hydrogels are typically obtained by copolymerizing a polymerizable composition comprising at least one silicone-containing vinyl monomer, or at least one silicone-containing vinyl macromer, or at least one silicone-containing prepolymer having ethylenically unsaturated groups.

As used herein, "hydrophilic" describes a material, or portion thereof, that associates with water more readily than with lipids.

"Vinyl monomer" refers to a compound that has one and only one ethylenically unsaturated group, is solvent soluble, and is polymerizable actinically or thermally.

The term "soluble" in reference to a compound or material in a solvent means that the compound or material dissolves in the solvent at room temperature (i.e., about 25±3°C) to provide a solution having a concentration of at least about 0.05% by weight.

The term "insoluble" in reference to a compound or material in a solvent means that the compound or material dissolves in the solvent at room temperature (as defined above) to give a solution having a concentration of less than 0.005% by weight.

As used herein, the term "ethylenically unsaturated group" is used broadly herein and is intended to encompass any group that contains at least one &gt;C=C&lt; group. Exemplary ethylenically unsaturated groups include (meth)acryloyl, <img file="JP7635289B2_D0001.tif" /> , allyl, vinyl, styrenyl, or other C=C containing groups.

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

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

As used herein, "actinically" in reference to curing, crosslinking, or polymerization of a polymerizable composition, prepolymer, or material means that the curing (e.g., crosslinking and/or polymerization) is effected by actinic radiation, such as, for example, UV/visible light radiation, ionizing radiation (e.g., gamma or x-ray radiation), microwave radiation, etc. Thermal curing or actinic curing methods are well known to those skilled in the art.

As used herein, "hydrophilic vinyl monomer" refers to a vinyl monomer that, typically as a homopolymer, results in a polymer that is water soluble or can absorb at least 10 weight percent water.

As used herein, "hydrophobic vinyl monomer" refers to a vinyl monomer that, typically as a homopolymer, results in a polymer that is water insoluble and can absorb less than 10 weight percent water.

The term "blending vinylic monomer" refers to a vinylic monomer that is capable of dissolving both the hydrophilic and hydrophobic polymerizable components of a polymerizable composition to form a solution.

"Acrylic monomer" refers to a vinyl monomer having only one (meth)acryloyl group.

"N-vinyl amide monomers" are monomers that have a vinyl group (-CH=CH) bonded directly to the nitrogen atom of an amide group.₂) refers to an amide compound having the formula:

"Macromer" or "prepolymer" refers to a compound or polymer that contains ethylenically unsaturated groups and has a number average molecular weight greater than 700 Daltons.

As used herein, the term "vinylic crosslinker" refers to a compound having at least two ethylenically unsaturated groups. "Vinyl crosslinking agent" refers to a subclass of vinyl crosslinkers each having a number average molecular weight of 700 Daltons or less.

As used herein, the term "polymer" refers to a material formed by polymerizing or crosslinking one or more monomers, macromers, prepolymers, and/or combinations thereof.

As used herein, the term "molecular weight" of a polymeric material (including monomeric or macromeric materials) means number average molecular weight, unless otherwise specified or dictated otherwise by the test conditions.

"Polysiloxane segment" means <img file="JP7635289B2_D0002.tif" /> refers to a polymer chain consisting of at least three consecutively and directly linked siloxane units (divalent radicals) each independent of the other, having the formula:₁' and R₂' is an independent C₁~C₁₀Alkyl, C₁~C₄Alkyl- or C₁~C₄-alkoxy substituted phenyl, C₁~C₁₀Fluoroalkyl, C₁~C₁₀Fluoroether, C₆~C₁₈Aryl radical, -alk-(OC₂H₄)_γ1-OR^o(Wherein, alk is C₁~C₆Alkyl diradical, R^ois H or C₁~C₄alkyl, and γ1 is an integer from 1 to 10), hydroxyl group (-OH), carboxyl group (-COOH), -NR₃'R₄', -NR₃'-amino bond, -CONR₃'-amide bond, -CONR₃'R₄' amide, -OCONH- urethane bond, and C₁~C₄C having at least one functional group selected from the group consisting of alkoxy groups₂~C₄₀Organic radicals, or linear hydrophilic polymer chains (wherein R₃' and R₄' is hydrogen or C₁~C₁₅and n is an integer from 1 to 2. The two substituents are selected from the group consisting of:

"Polysiloxane vinyl monomer" refers to a compound that contains at least one polysiloxane segment and only one ethylenically unsaturated group.

"Polysiloxane vinyl crosslinker" refers to a compound that contains at least one polysiloxane segment and at least two ethylenically unsaturated groups.

"Chain-extended polysiloxane vinyl crosslinker" refers to a compound that contains at least two ethylenically unsaturated groups and at least two polysiloxane segments, each pair of which is linked by a divalent radical.

What is "polycarbosiloxane"? <img file="JP7635289B2_D0003.tif" /> where n1 is an integer of 2 or 3, and R₁", R₂", R₃" and R₄" is C₁~C₆It is an alkyl radical, preferably methyl.

"Polycarbosiloxane vinyl monomer" refers to a compound that contains at least one polycarbosiloxane segment and only one ethylenically unsaturated group.

"Polycarbosiloxane vinyl crosslinker" refers to a compound that contains at least one polycarbosiloxane segment and at least two ethylenically unsaturated groups.

As used herein, the term "fluid" indicates that a material is capable of flowing like a liquid.

As used herein, the term "clear" in relation to a polymerizable composition means that the polymerizable composition is a transparent solution or liquid mixture (i.e., has a light transmittance of 85% or greater within the range of 400-700 nm).

The term "alkyl" refers to a monovalent radical obtained by removing a hydrogen atom from a straight-chain or branched-chain alkane compound. An alkyl group (radical) forms one bond with one other group in an organic compound.

The terms "alkylene diradical" or "alkylene diradical" or "alkyl diradical" refer interchangeably to a divalent radical obtained by removing one hydrogen atom from an alkyl. An alkylene diradical forms two bonds with other groups in an organic compound.

The term "alkyl triradical" refers to a trivalent radical obtained by removing two hydrogen atoms from an alkyl. An alkyl triradical forms three bonds with other groups in an organic compound.

The terms "alkoxy" or "alkoxyl" refer to a monovalent radical obtained by removing a hydrogen atom from the hydroxyl group of a straight- or branched-chain alkyl alcohol. An alkoxy group (radical) forms one bond with one other group in an organic compound.

As used herein, unless otherwise specified, the term "amino group" refers to a primary or secondary amino group of formula -NHR', where R' is hydrogen or C.₁~C₂₀is an unsubstituted or substituted straight or branched chain alkyl group of the formula:

In this application, the term "substituted" in relation to an alkyl diradical or alkyl radical refers to an alkyl diradical or alkyl radical that replaces one hydrogen atom of the alkyl diradical or alkyl radical and is substituted with hydroxy (-OH), carboxy (-COOH), -NH₂, sulfhydryl (-SH), C₁~C₄Alkyl, C₁~C₄Alkoxy, C₁~C₄Alkylthio(alkyl sulfide), C₁~C₄Acylamino, C₁~C₄Alkylamino, Di-C₁~C₄It is meant to contain at least one substituent selected from the group consisting of alkylamino, halogen atoms (Br or Cl), and combinations thereof.

In this application, "oxazoline" means <img file="JP7635289B2_D0004.tif" /> In the formula, R¹is hydrogen, methyl, ethyl, N-pyrrolidonylmethyl, N-pyrrolidonylethyl, N-pyrrolidonylpropyl, or -alk-(OC₂H₄)_m3-OR^”(Wherein, alk is C₁~C₄is an alkyl diradical, R is C₁~C₄alkyl (preferably methyl), and m3 is an integer from 1 to 10 (preferably 1 to 5) a monovalent radical.

In this application, the term "polyoxazoline" means <img file="JP7635289B2_D0005.tif" /> In the formula, R¹is hydrogen, methyl, ethyl, N-pyrrolidonylmethyl, N-pyrrolidonylethyl, N-pyrrolidonylpropyl, or -alk-(OC₂H₄)_m3-OR^”(Wherein, alk is C₁~C₄is an alkyl diradical, R is C₁~C₄m3 is an integer from 1 to 10 (preferably, 1 to 5), and x is an integer from 5 to 500) is a monovalent radical.

In this application, the term "poly(2-oxazoline-co-ethyleneimine)" means <img file="JP7635289B2_D0006.tif" /> or a polymer segment thereof having the formula:¹is hydrogen, methyl, ethyl, N-pyrrolidonylmethyl, N-pyrrolidonylethyl, N-pyrrolidonylpropyl, or -alk-(OC₂H₄)_m3-OR^”(Wherein, alk is C₁~C₄is an alkyl diradical, R is C₁~C₄m3 is an integer from 1 to 10 (preferably, 1 to 5), x is an integer from 5 to 500, and z is an integer equal to or less than x) monovalent radical. Poly(2-oxazoline-co-ethyleneimine) can be obtained by hydrolyzing polyoxazoline.

In this application, the term "poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin" refers to a polymer obtained by reacting poly(2-oxazoline-co-ethyleneimine) with epichlorohydrin to convert all or a substantial proportion (90%) of the secondary amine groups of poly(2-oxazoline-co-ethyleneimine) to azetidinium groups. Examples of poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin are disclosed in co-pending U.S. Patent Application Publication No. 2016/0061995 A1.

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

The term "polyamidoamine-epichlorohydrin" refers to epichlorohydrin-functionalized adipic acid-diethylenetriamine copolymers.

In this application, the term "azetidinium" or "3-hydroxyazetidinium" refers to <img file="JP7635289B2_D0007.tif" /> "Cationic" refers to a positively charged (i.e. cationic) divalent radical (or group or moiety) of the formula:

The term "thermally crosslinkable" in reference to a polymeric material or functional group means that the polymeric material or functional group is capable of undergoing a crosslinking (or coupling) reaction with another material or functional group at relatively high temperatures (about 40°C to about 140°C), while the polymeric material or functional group is not capable of undergoing the same crosslinking (or coupling) reaction with another material or functional group to a detectable extent at a temperature of about 5°C to about 15°C over a period of about 1 hour.

The term "azlactone" means a compound of the formula <img file="JP7635289B2_D0008.tif" /> where p is 0 or 1, and each p is independently³R and⁴R is C₁~C₈It is alkyl (preferably methyl).

The term "aziridine group" means a group of the formula <img file="JP7635289B2_D0009.tif" /> where R1 is hydrogen, methyl, or ethyl.

As used herein, the term "phosphorylcholine" refers to a compound of the formula <img file="JP7635289B2_D0010.tif" /> In the formula, n is an integer of 1 to 5, and each R₁, R₂, and R₃is C₁~C₈Alkyl or C₁~C₈It is a hydroxyalkyl.

As used herein, the term "reactive vinyl monomer" refers to any vinyl monomer having at least one reactive functional group selected from the group consisting of a carboxyl group, a primary amino group, and a secondary amino group.

As used herein, the term "non-reactive vinyl monomer" refers to any vinyl monomer (either hydrophilic or hydrophobic vinyl monomer) that does not contain a carboxyl group, a primary amino group, a secondary amino group, an epoxide group, an isocyanate group, an azlactone group, or an aziridine group.

A free radical initiator may be either a photoinitiator or a thermal initiator. "Photoinitiator" refers to a chemical that initiates a free radical crosslinking/polymerization reaction through the use of light. "Thermal initiator" refers to a chemical that initiates a radical crosslinking/polymerization reaction through the use of thermal energy.

"Spatial confinement of actinic radiation" refers to the act or process in which energy radiation in the form of light rays is directed, for example, by a mask or screen or a combination thereof, to impinge on an area having a well-defined peripheral boundary in a spatially confined manner. The spatial confinement of UV radiation is obtained by using a mask or screen having radiation (e.g., UV) transparent regions, radiation (e.g., UV) opaque regions surrounding the radiation transparent regions, and a projection contour that is the boundary between the radiation opaque and radiation transparent regions, as shown diagrammatically in the drawings of U.S. Pat. No. 6,800,225 (FIGS. 1-11), and U.S. Pat. Nos. 6,627,124 (FIGS. 1-9), 7,384,590 (FIGS. 1-6), and 7,387,759 (FIGS. 1-6). The mask or screen allows for spatial projection of a beam of radiation (e.g., UV radiation) having a cross-sectional profile defined by the projection contour of the mask or screen. The projected beam of radiation (e.g., UV radiation) limits the radiation (e.g., UV radiation) impinging on the lens formulation located on the path of the projected beam from the first molding surface to the second molding surface of the mold. The resulting contact lens comprises a front surface defined by the first molding surface, an opposing rear surface defined by the second molding surface, and a lens edge defined by the cross-sectional profile of the projected UV beam (i.e., the spatial limit of the radiation). The radiation used for crosslinking is radiant energy, in particular UV radiation, gamma radiation, electron beams or heat radiation, and in order to achieve good energy limiting on the one hand and efficient use of energy on the other hand, the radiant energy is preferably in the form of a substantially parallel beam.

The specific "oxygen permeability" of the material, Dk_iis the rate at which oxygen passes through the material. As used herein, the term "oxygen permeability (Dk)" in relation to a hydrogel (silicone or non-silicone) or contact lens refers to the corrected oxygen permeability (Dk) measured at about 34-35°C according to the procedure described in Example 1 of US Patent Application Publication No. 2012/0026457 A1 and corrected for the surface resistance to oxygen flow caused by boundary layer effects._cOxygen permeability is conventionally expressed in units of barrer, where "barrer" means [(cm³oxygen)(mm)/(cm²)(sec)(mmHg)]×10^-10It is defined as follows.

The "oxygen transmissibility" of a lens or material, Dk/t, is the rate at which oxygen passes through a particular lens or material having an average thickness t [in mm] over the area being measured. Oxygen transmissibility is conventionally expressed in units of barrer/mm, where "barrer/mm" is [(cm³oxygen)/(cm²)(sec)(mmHg)]×10^-9It is defined as follows.

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

The term "ophthalmically safe" in reference to a packaging solution for sterilizing and storing contact lenses means that a contact lens stored in the solution is safe to be placed directly on the eye without rinsing after autoclaving, and that the solution is safe and sufficiently comfortable for everyday contact with the eye through a contact lens. An ophthalmically safe packaging solution after autoclaving has an eye-compatible tonicity and pH, and is substantially free of eye-irritating or eye-cytotoxic materials according to international ISO standards and USFDA regulations.

As used herein, the term "water gradient" in relation to contact lenses means an increase in water content observed passing from the core to the surface of the contact lens, reaching a maximum water content in a region near and including the surface of the contact lens. It will be understood that the increase in water content from the core to the surface of the contact lens may be continuous and/or step-wise, so long as the maximum water content is in a region near and including the surface of the contact lens.

As used herein, the term "cross section" of a contact lens refers to a cross section of the lens obtained by cutting the lens with a knife or cutting tool at an angle substantially perpendicular to either the anterior or posterior surface of the lens. Those skilled in the art are familiar with the process of cutting a contact lens manually (i.e., by hand cutting) or with a cryosta microtome or lath to obtain a cross section of the contact lens. The resulting cross section of the contact lens can be polished using ion etching or similar techniques.

The term "modulus" or "elastic modulus" in relation to contact lenses or materials refers to the tensile modulus or Young's modulus, which is a measure of the stiffness of contact lenses or materials. Modulus can be measured using a method according to the ANSI Z80.20 standard. Those skilled in the art are familiar with the method of determining the modulus of elasticity of silicone hydrogel materials or contact lenses. For example, all commercially available contact lenses have a reported modulus value.

The terms "surface modulus", "surface flexibility", "surface elastic modulus", "surface Young's modulus" or "surface compressibility modulus" are used interchangeably herein and refer to nanomechanical properties (elastic properties) measured by atomic force microscopy (AFM) on the surface of a material or a contact lens cross section in a fully hydrated state (in phosphate buffer solution, pH about 7.3±0.2) using nanoindentation, as known to those skilled in the art. Jan Domke and Manfred Radmacher reported that the elastic properties of thin films can be measured by AFM (Langmuir 1998,14,3320-3325). The AFM nanoindentation method was reported by 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 Nanoindentation of contact lenses using nanoindentation with AFM, pp 554-559, A. Mendez-Vilas and J. Diaz (Eds.), Formatex Research Center, Badajoz, Spain (2010). It should be noted that the surface of the cross section of the contact lens (performed by Gonzalez-Meijome JM, Almeida JB and Parafita MA in these papers) is analyzed using nanoindentation with AFM, not the anterior or posterior surface of the contact lens. Nanoindentation, Peakforce QNM and Harmonic Force methods are described in the article by Kim Sweers, et al. in Nanoscale Research Letters 2011, 6:270, entitled Nanomechanical properties of a-synuclein amyloid fibrils: a comparative study by Nanoindentation, Harmonic Force Microscopy, and Peakforce QNM. It will also be appreciated that when measurements of surface modulus are performed using AFM from the anterior surface to the bulk or from the bulk to the posterior surface (or vice versa) of a cross-section of a fully hydrated contact lens, the surface modulus profile across the cross-section of the contact lens can be determined along the shortest line between the anterior and posterior surfaces of the cross-section of the contact lens. It will further be appreciated that, as a good approximation, any experimentally and directly measured quantity can be used to represent the surface modulus, so long as the measured quantity is proportional to the surface modulus. Alternatively, microindentation or nanoindentation techniques may be used where colloidal spheres of various sizes are used to measure the surface modulus.

As used herein, the terms "inner layer" or "bulk material" in relation to a contact lens refer interchangeably to the layer that has the three-dimensional shape of the contact lens, includes a central curved surface (dividing the contact lens into two portions, one containing the anterior surface and the other containing the posterior surface), and has a variable thickness.

As used herein, the term "outer surface hydrogel layer" in relation to a contact lens means the outermost hydrogel layer on the surface of the contact lens, which consists of a front outer hydrogel layer and a back outer hydrogel layer, and which completely covers the inner layer (or lens bulk material).

As used herein, the term "front outer hydrogel layer" in relation to a contact lens means a hydrogel layer that includes the front surface of a contact lens, that is substantially uniform in thickness (i.e., that varies in thickness by no more than about 20% from the average thickness of the layer), and that has an average thickness of at least about 0.25 μm.

As used herein, the term "posterior outer hydrogel layer" in relation to a contact lens means a hydrogel layer that comprises the posterior surface of a contact lens, that is substantially uniform in thickness (i.e., that varies in thickness by no more than about 20% from the average thickness of the layer), and that has an average thickness of at least about 0.25 μm.

As used herein, the term "transition layer" in the context of contact lenses means a layer of polymeric material located between the inner layer (or lens bulk material) and one of the anterior and posterior outer hydrogel layers. Each transition layer is substantially uniform in thickness (i.e., the thickness varies by no more than about 20% from the average thickness of that layer).

In this application, the "average thickness" of the anterior or posterior hydrogel layer or transition layer is simply referred to as the "anterior posterior hydrogel layer thickness," "posterior posterior hydrogel layer thickness," or "transition layer thickness" measured using an AFM on a cross-section of a contact lens in a specified state, e.g., in a fully hydrated state or when fully hydrated (i.e., in a phosphate buffer solution, pH about 7.3±0.2), or in a dry state (e.g., thoroughly oven dried).

FIG. 1 shows a schematic representation of a contact lens of the present invention according to a preferred embodiment. According to a preferred embodiment of the present invention, the contact lens 100 has an anterior surface (or front curve or convex surface) 101 and an opposing posterior surface (or base curve or concave surface) 102 that rests on the cornea of the eye when worn by a user. The contact lens 100 comprises an inner (or middle) layer (or lens bulk material) 110 and anterior and posterior outer hydrogel layers 120. The inner layer 110 is the bulk material of the contact lens 100 and has a three-dimensional shape that closely resembles the contact lens 100. The anterior and posterior outer hydrogel layers 120 are made of a substantially uniform thickness, substantially silicone-free (preferably silicone-free) hydrogel material with a higher water content than that of the inner layer 110. The anterior and posterior outer hydrogel layers 120 merge at the peripheral edge 103 of the contact lens 100 and completely cover the inner layer 110.

2 shows a schematic diagram of a contact lens of the present invention according to another preferred embodiment. The contact lens 100 comprises an inner (or intermediate) layer (or lens bulk material) 110, anterior and posterior outer hydrogel layers 120, and two transition layers 115. Each of the two transition layers 115 is located between the inner layer 110 and one of the two outer hydrogel layers 120.

As used herein, the term "equilibrium water content" in relation to a contact lens or polymeric material means the amount of water (expressed as weight percent) present in a contact lens or polymeric material when fully hydrated (equilibrium) in saline (about 0.79 wt % NaCl) and measured at room temperature (as defined above).

As used herein, the terms "crosslinked coating" or "hydrogel coating" or "hydrogel layer" on a contact lens are used interchangeably to refer to a crosslinked polymeric material having a three-dimensional network that can contain water when fully hydrated. The three-dimensional network of the crosslinked polymeric material can be formed by crosslinking two or more linear or branched polymers through crosslinking links.

As used herein, the term "water swelling ratio" in relation to the anterior or posterior outer hydrogel layer of the contact lens of the present invention means<math num="1"><img file="JP7635289B2_D0011.tif" /></math>where WSR is the water swelling ratio of one of the front and rear outer hydrogel layers, and L_Wetis the average thickness of the outer hydrogel layer on the anterior or posterior surface of a contact lens in a fully hydrated state (i.e., in a phosphate buffer solution at a pH of about 7.3±0.2) as measured by AFM on a cross section of the contact lens in a fully hydrated state (i.e., in a phosphate buffer solution at a pH of about 7.3±0.2), and L_Dryis the average thickness of the outer hydrogel layer of the anterior or posterior surface of a contact lens in its dry state as measured by AFM on a cross-section of a dry (oven dried) contact lens.

The water swelling rate of the outer surface hydrogel layer of a contact lens is considered to be proportional to the equilibrium water content of the outer surface hydrogel layer. The higher the water swelling rate of the outer surface hydrogel layer, the higher the equilibrium water content of the outer surface hydrogel layer. Furthermore, the water swelling rate of the outer surface hydrogel layer is considered to be proportional to the mesh size of the outer surface hydrogel layer, and therefore to the flexibility of the outer surface hydrogel layer. The mesh size of the hydrogel is inversely proportional to the crosslink density of the hydrogel, which in turn is proportional to the length of the crosslinked chain. The higher the water swelling rate of the outer surface hydrogel layer, the more flexible the outer surface hydrogel layer will be. Therefore, the water swelling rate can be a good indicator of both the equilibrium water content and flexibility of the outer surface hydrogel layer.

As used herein, the term "surface compressive force at an indentation depth of 400 nm" or "indentation force at an indentation depth of 400 nm" refers to the averaged normal force at the indentation depth along the loading curve, as measured in the microindentation or nanoindentation test described in Example 1.

As used herein, the term "reduction in intrusion force" or "Δ(IF)" in relation to contact lenses._400nm" means the difference between the predicted indentation force (μN) at an indentation depth of 400 nm based on the bulk elastic modulus (MPa) of the contact lens and the measured indentation force (μN) at an indentation depth of 400 nm of the contact lens in the microindentation or nanoindentation test described in Example 1, which can be calculated by the following equation:<math num="2"><img file="JP7635289B2_D0012.tif" /></math>In the formula, (IF)_tis the indentation force at an indentation depth of 400 nm measured in a microindentation or nanoindentation test of a contact lens, (IF)₀is the relationship between the bulk elastic modulus and the indentation force at an indentation depth of 400 nm measured in microindentation or nanoindentation tests, (IF)₀= kE' + b, where "k" and "b" are a correlation coefficient and an empirical correction coefficient, respectively, established in a series of micro- or nano-indentation tests on several contact lenses having no hydrogel coating thereon and different bulk moduli. When the micro-indentation test described in Example 1 is used, "k" is 13.98 and "b" is 0.62. When the nano-indentation test described in Example 1 is used, "k" is 2.12 and "b" is -0.38.

Every contact lens may have different mechanical properties at its surface, particularly when the contact lens has a soft hydrogel coating thereon. The mechanical properties of the region near and including the surface of the contact lens can be characterized by measuring the surface compressive or indentation force as a function of displacement in micro- or nano-indentation testing.

It has been found that for contact lenses that do not have any soft hydrogel coating thereon, the indentation force at a given displacement or indentation depth (e.g., 400 nm) correlates well with the bulk (Young's) modulus (i.e., there is a linear bulk modulus-indentation force relationship between bulk modulus and indentation force at an indentation depth of 400 nm), whereas for contact lenses that have a soft hydrogel coating thereon, the indentation force at a 400 nm indentation depth is much less than would be predicted based on the linear bulk modulus-indentation force relationship (i.e., a decrease in indentation force at a 400 nm indentation depth). The decrease in indentation force at a 400 nm indentation depth, i.e., Δ(IF),_400nmIt is believed that the above can be used to quantitatively characterize contact lenses having a water gradient structure morphology. When a contact lens has a sufficiently thick (0.25 μm) outer surface hydrogel layer thereon, this is equivalent to a reduction in indentation force (Δ(IF)) at an indentation depth of 400 nm of about 40% or more._400nm) The Δ(IF) of the water gradient contact lens_400nmThe value of Δ(IF) may depend on both the flexibility and thickness of the outer surface hydrogel layer on the contact lens._400nm) is proportional to the flexibility and/or thickness of the outer surface hydrogel layer (or outer surface layer) of the contact lens._400nmThe larger Δ(IF) is, the softer and/or thicker the outer surface hydrogel layer (or outer surface layer) is, and the smaller the force induced on the corneal surface._400nmcan be a good indicator of the combined effect of flexibility and thickness of the outer surface hydrogel layer (or outer surface layer) on a water gradient contact lens.

As used herein, the term "normalized surface compressive force" or "NSCF" in relation to contact lenses means the ratio of the surface compressive force or indentation force at an indentation depth of 400 nm of a contact lens (as determined by microindentation testing using a probe size of 1 mm as described in Example 1) to the elastic modulus of the contact lens, which has units of μN/MPa, i.e.,<math num="3"><img file="JP7635289B2_D0013.tif" /></math>It is.

It has been found that if a contact lens does not have an outer surface hydrogel layer thereon, it will have a normalized surface compressive force of about 14 μN/MPa or slightly higher as measured with a 1 mm colloidal probe, regardless of the bulk modulus of the contact lens. Therefore, it is believed that the normalization of the surface compressive force over the modulus of the contact lens is intended to equalize the contribution of the bulk material of the contact lens to the surface compressive force. However, if a contact lens has a sufficiently thick outer surface hydrogel layer thereon, it will have a normalized surface compressive force (at an indentation depth of 400 nm) of less than about 14 μN/MPa. Δ(IF)_400nmSimilarly, it is believed that the normalized surface compressive force at an indentation depth of 400 nm can be used to qualitatively and quantitatively characterize contact lenses having a water gradient structural form. If a contact lens has a sufficiently thick (0.25 μm) outer surface hydrogel layer thereon, it will have a normalized surface compressive force (at an indentation depth of 400 nm) of about 12 μN/MPa or less. It is also understood that the normalized surface compressive force (NSCF) at an indentation depth of 400 nm of a water gradient contact lens depends on both the flexibility and thickness of the outer surface hydrogel layer on the contact lens. The NSCF is proportional to the flexibility of the outer surface hydrogel layer (or outer surface layer) of the contact lens. The smaller the normalized surface compressive force at an indentation depth of 400 nm, the more flexible the outer surface hydrogel layer (or outer surface layer) is, and the smaller the force induced on the corneal surface. The NSCF is inversely proportional to the thickness of the outer surface hydrogel layer (or outer surface layer). The thicker the outer surface hydrogel layer (or outer surface layer), the smaller the normalized surface compressive force at an indentation depth of 400 nm.Therefore, the normalized surface compressive force at an indentation depth of 400 nm can be a good indicator of the combined effect of the flexibility and thickness of the outer surface hydrogel layer (or outer surface layer) on the water gradient contact lens.

As used herein, the term "Polyquaternium-1 Uptake" or "PU" in relation to contact lenses means the amount of Polyquaternium-1 absorbed by a contact lens, as measured according to the procedure described in Example 1.

As used herein, the term "long-lasting surface hydrophilicity and wettability" in relation to contact lenses means that the contact lenses have a water break down time (WBUT) of at least 10 seconds after 30 cycles of finger rubbing or simulated abrasion cycling. The determination of the WBUT of the contact lenses, the cycles of finger rubbing, and the simulated abrasion cycling are carried out according to the procedure described in Example 1.

As used herein, the term "long-lasting lubricity" in relation to contact lenses means that the contact lenses have a friction rating of about 2.0 or less after 30 cycles of finger rubbing or simulated abrasion cycling. The determination of the friction rating of the contact lenses, the cycles of finger rubbing, and the simulated abrasion cycling are carried out according to the procedures described in Example 1.

As used herein, the term "30 cycles of finger rubbing treatment" or "n cycles of finger rubbing treatment" means that a contact lens is subjected to 30 or n repeated finger rubbing procedures, which consist essentially of finger rubbing the contact lens with RENU® Multipurpose Lens Care Solution (or equivalent, i.e., the Multipurpose Lens Care Solution disclosed in Table I of U.S. Pat. No. 5,858,937) for 20 seconds (while wearing disposable powder-free latex gloves), followed by rinsing the finger-rubbed contact lens with phosphate buffered saline for at least 20 seconds. The 30 or n finger rubbing cycles can reasonably mimic the daily cleaning and disinfection of a 30-day or n-day lens care regime.

"UVA" refers to radiation occurring in the wavelengths between 315 and 380 nanometers, "UVB" refers to radiation occurring in the wavelengths between 280 and 315 nanometers, and "violet" refers to radiation occurring in the wavelengths between 380 and 440 nanometers.

"UVA Transmittance" (or "UVA %T"), "UVB Transmittance" or "UVB %T", and "Violet Transmittance" or "Violet %T" are calculated using the following formula:<math num="4"><img file="JP7635289B2_D0014.tif" /></math>where the luminescence %T is determined by the following formula:

Emission %T = average % transmittance from 780 to 380 nm.

The term "essentially wettable" in relation to silicone hydrogel contact lenses refers to a silicone hydrogel contact lens that, after the silicone hydrogel contact lens is formed by thermally or actinically polymerizing (i.e., curing) a silicone hydrogel lens formulation, has a water break-up time (WBUT) of about 10 seconds or more and a water contact angle (WCA) with trapped air bubbles of about 80 degrees or less without being subjected to any surface treatment._cbAccording to the present invention, WBUT and WCA_cbis measured according to the procedure described in Example 1.

As used herein, "surface modification" or "surface treatment" means that an article has been treated, either before or after formation of the article, with a surface treatment process (or surface modification process) that (1) applies a coating to the surface of the article, (2) adsorbs a chemical species to the surface of the article, (3) changes the chemical nature (e.g., electrostatic charge) of chemical groups on the surface of the article, or (4) otherwise modifies the surface properties of the article. Exemplary surface treatment processes include, but are not limited to, surface treatment with energy (e.g., plasma, electrostatic charge, irradiation, or other energy sources), chemical treatment, grafting of hydrophilic vinyl monomers or macromers onto the surface of the article, mold-transfer coating process disclosed in U.S. Pat. No. 6,719,929, incorporation of wetting agents into lens formulations for producing contact lenses as proposed in U.S. Pat. Nos. 6,367,929 and 6,822,016, enhanced mold transfer coating disclosed in U.S. Pat. No. 7,858,000, and hydrophilic coatings consisting of covalent bonding or physical vapor deposition of one or more layers of one or more hydrophilic polymers onto the surface of a contact lens as disclosed in U.S. Pat. Nos. 8,147,897 and 8,409,599, and U.S. Patent Publication Nos. 2011/0134387, 2012/0026457, and 2013/0118127.

"Post-cure surface treatment" in the context of a lens bulk material or contact lens refers to a surface treatment process that is performed after the lens bulk material or contact lens formed by curing (i.e., thermal or actinic polymerization) of a lens formulation. "Lens formulation" refers to a polymerizable composition that includes all polymerizable components necessary to manufacture a contact lens or lens bulk material as known to those skilled in the art.

"Organic-based solution" refers to a solution that is a homogeneous mixture of an organic solvent and one or more solutes dissolved in the organic solvent. Organic-based coating solution refers to an organic-based solution that contains at least one polymeric coating material as a solute in the solution.

"Organic solvent" is intended to mean a solvent system consisting of one or more organic solvents and less than about 40% by weight water, preferably less than about 30% by weight, more preferably less than about 20% by weight, even more preferably less than 10% by weight, and especially less than about 5% by weight water, based on the weight of the solvent system.

The present invention broadly relates to a disposable water gradient contact lens for one week or one month use, which has a layered structure morphology that provides a unique water gradient from the inside to the outside of the contact lens and relatively long-lasting wettability/hydrophilicity, but is also finger rub-resistant and compatible with lens care solutions, including multi-purpose lens care solutions. The layered structure morphology comprises an inner layer (i.e., lens bulk material) having an equilibrium water content of about 70% by weight or less, and an outer surface hydrogel layer (consisting of a front outer hydrogel layer and a rear outer hydrogel layer) that completely covers the inner layer (or lens bulk material), has an equilibrium water content of at least 1.2 times (preferably at least 80% by weight) the equilibrium water content of the inner layer (or lens bulk material), and has a sufficient thickness (about 0.25 μm to about 25 μm) when fully hydrated.

According to the present invention, the outer surface hydrogel layer must not only have a relatively high water swelling rate, but also have a sufficient thickness to provide better wearing comfort. The relatively high water swelling rate of the outer surface hydrogel layer can ensure that the contact lens has a very soft surface with a high equilibrium water content. However, if the outer surface hydrogel layer is too thin, the outer surface hydrogel layer will be easily completely collapsed against the lens bulk material by a slight compression force, and the advantages associated with the water gradient structure mechanism of the contact lens of the present invention will be lost. At a given high water swelling rate, it is believed that the wearing comfort provided by the contact lens of the present invention will improve with the increase in the thickness of its outer surface hydrogel layer, and then will plateau after a certain thickness value.

The present invention solves the problems existing in the prior art related to the incompatibility of water gradient contact lenses with multi-purpose lens care solutions and poor finger rub resistance. It has been found that a relatively thick anchor layer (i.e., reactive base coating) of reactive polyanionic polymer (e.g., carboxyl-containing polyanionic polymer) on the contact lens is necessary to form a thick outer surface hydrogel layer. The thicker the anchor layer, the thicker the outer surface hydrogel layer. However, a relatively thick anchor layer results in a higher concentration of reactive groups (e.g., carboxyl groups) in the anchor layer and a higher uptake rate of polycation-type antimicrobial agents present in the lens care solution. Past attempts to reduce the uptake rate of polycation-type antimicrobial agents by water gradient contact lenses have mainly relied on reducing the thickness of the anchor layer and using polyanionic materials with higher pKa values. Such approaches make the outer surface hydrogel layer too thin, which reduces the durability and/or lubricity of the outer surface hydrogel layer and impairs the wearing comfort provided by the resulting contact lens.

It has been found that the anchor layer and outer surface hydrogel layer of an in-manufacturing water gradient contact lens and/or a preformed water gradient contact lens can be treated with a small, flexible, hydrophilic charge neutralizer to convert most or most of the negatively charged groups in the water gradient contact lens to uncharged ester bonds and simultaneously crosslink the anchor layer to enhance the durability of the outer surface hydrogel layer on the contact lens with no or minimal effect on the wettability, hydrophilicity, and lubricity of the outer surface hydrogel layer on the contact lens.

It has also been found that the durability of hydrogel coatings on SiHy contact lenses is highly dependent on the processing conditions under which its underlying base coating, consisting of polyanionic polymer, is formed. When a base coating is applied to a SiHy contact lens in a single coating step (i.e., by contacting it with a sole coating solution of polyanionic polymer (pH&lt;4.5)) for a given coating period (e.g., 50 minutes) followed by one or more rinsing steps, the durability of the hydrogel coating formed on such a base coating may vary with the refractive power (i.e., center thickness) of the SiHy contact lens during coating. For example, the durability of the hydrogel coating on a coated SiHy contact lens having a refractive power of -10.0 diopters is inferior to that of a coated SiHy contact lens having a refractive power of -3.0 diopters. Increasing the coating period did not improve the variation in the durability of the hydrogel coating with the refractive power (center thickness) of the contact lens. However, it has been found that when a base coating is applied onto a SiHy contact lens by contacting the SiHy contact lens with one coating solution of a polyanionic polymer (having a low pH) even for a shorter coating period (e.g., 25 minutes), followed by rinsing with a buffered saline solution having a neutral or slightly basic pH, and then contacting the lens again with another coating solution of a polyanionic polymer (having a low pH) for a shorter period (e.g., 25 minutes), the durability of the hydrogel coating formed on such a base coating can be significantly improved and does not vary with the optical power (i.e., central thickness) of the SiHy contact lens being coated.

Furthermore, it has been found that the PU of a coated SiHy contact lens having a hydrogel coating thereon is highly dependent on the pH and/or salt concentration (i.e., ionic strength) of the buffered saline solution used to rinse the treated SiHy contact lens having a base coating (of a polyanionic polymer) thereon prior to forming a hydrogel coating on the base coating. Lower PUs can be achieved by using a rinse solution having a higher pH and/or higher ionic strength (higher salt concentration). Combined with the discovery described above regarding how to significantly improve the durability of hydrogel coatings on water gradient contact lenses, this discovery may enable the production of water gradient contact lenses with durable hydrogel coatings and minimized PU.

The present invention provides a water gradient contact lens that is compatible with multi-purpose lens care solutions and resistant to finger rub, making it suitable for use as a weekly or monthly disposable contact lens. The contact lens of the present invention has a desired water gradient structural morphology and a relatively thick, extremely soft, and high moisture hydrogel surface layer, which can provide better wearing comfort.

The present invention, in one aspect, provides a polyquaternium-1 uptake rate ("PU") of about 0.40 or 0.30 micrograms/lens or less (preferably about 0.20 micrograms/lens or less, more preferably about 0.15 micrograms/lens or less, even more preferably about 0.10 micrograms/lens or less, and most preferably about 0.05 micrograms/lens or less) and a saturation rate of at least 10 seconds (preferably at least 12.5 seconds, more preferably at least 15 seconds, and even more preferably at least 17.5 seconds) after 30 cycles of finger rubbing or simulated abrasion cycling. and/or long-lasting surface hydrophilicity and wettability, characterized by a water disintegration time of at least about 20 seconds, and most preferably at least 20 seconds, and/or long-lasting lubricity, characterized by a friction rating of 2.0 or less, preferably about 1.5 or less, more preferably about 1.0 or less, and even more preferably about 0.5 or less, the contact lens comprising an anterior surface and an opposite posterior surface, and a layered structural morphology comprising, in a direction from the anterior surface to the posterior surface, a front outer hydrogel layer, an inner layer of lens material, and a rear outer hydrogel layer, the inner layer having a first equilibrium water content of at most about 70% by weight.<u style="Single">having</u>The front and rear outer hydrogel layers are separate from each other and have a thickness of about 0.25 μm to about 25 μm.<u style="Single">and</u>and a second equilibrium water content higher than the first equilibrium water content, and the independent front and rear outer hydrogel layers have a water swelling rate of at least 140% (preferably at least 170%, more preferably at least 200%, even more preferably at least 250%, and most preferably at least 300%). Preferably, the contact lens is substantially free (i.e., less than three) and preferably free of surface crack lines visible under dark field after the contact lens is rubbed between a finger 10 times.

In another aspect, the present invention provides a surface hydrophilicity and wettability characterized by a polyquaternium-1 uptake rate ("PU") of about 0.40 or 0.30 micrograms/lens or less (preferably about 0.20 micrograms/lens or less, more preferably about 0.15 micrograms/lens or less, even more preferably about 0.10 micrograms/lens or less, and most preferably about 0.05 micrograms/lens or less) and a water disintegration time of at least 10 seconds (preferably at least 12.5 seconds, more preferably at least 15 seconds, even more preferably at least 17.5 seconds, and most preferably at least 20 seconds) after 30 cycles of finger rubbing or simulated abrasion cycling; and/or a friction rating of 2.0 or less (preferably about 1.5 or less, more preferably about 1.0 or less, even more preferably about 0.5 or less), and a water content gradient from the inside to the outside of the contact lens, the contact lens comprising a lens bulk material completely coated with an outer surface hydrogel layer having a thickness of about 0.25 μm to about 25 μm as measured by atomic force microscopy across a cross section from the posterior surface to the anterior surface of the contact lens in a fully hydrated state, the lens bulk material having a first equilibrium water content of about 70% by weight or less, and the outer surface hydrogel layer having a second equilibrium water content that is at least 1.2 times the first equilibrium water content and is at least 80% by weight. Preferably, the contact lens is substantially free (i.e., less than 3), or preferably free, of surface crack lines visible under dark field after the contact lens is rubbed between a finger 10 times.

In a further aspect, the present invention provides a polyquaternium-1 uptake ("PU") of about 0.40 or 0.30 micrograms/lens or less (preferably about 0.20 micrograms/lens or less, more preferably about 0.15 micrograms/lens or less, even more preferably about 0.10 micrograms/lens or less, and most preferably about 0.05 micrograms/lens or less) on the front surface and on the opposite rear surface, and a polyquaternium-1 uptake ("PU") of about 0.20 micrograms/lens or less, more preferably about 0.15 micrograms/lens or less, even more preferably about 0.10 micrograms/lens or less, and most preferably about 0.05 micrograms/lens or less for at least 10 seconds (preferably at least 12.5 seconds, more preferably at least 15 seconds, and even more preferably at least 17 seconds) after 30 cycles of finger rubbing or simulated abrasion cycling. and a structural morphology characterized by a cross-sectional surface-modulus profile along a shortest line between the anterior and posterior surfaces of the contact lens, the cross-sectional surface-modulus profile comprising an anterior-lateral zone including and proximal to the anterior surface, an inner zone including and peripheral to the central portion of the shortest line, and a posterior-lateral zone including and proximal to the posterior surface, the anterior-lateral zone having an average anterior surface modulus (<math num="5"><img file="JP7635289B2_D0015.tif" /></math>), while the posterolateral zone has a mean posterior surface modulus (<math num="6"><img file="JP7635289B2_D0016.tif" /></math>), and the inner zone has an average inner surface modulus (<math num="7"><img file="JP7635289B2_D0017.tif" /></math>)<math num="8"><img file="JP7635289B2_D0018.tif" /></math>is at least about 20%. Preferably, the contact lens is substantially free (i.e., less than 3), and preferably free, of surface crack lines visible under dark field after the contact lens is rubbed between a finger 10 times.

In another further aspect, the present invention provides a lens that has a normalized surface compression force at an indentation depth of 400 nm using a 1 mm microindentation probe of about 12 μN/MPa or less (preferably about 10 μN/MPa or less, more preferably about 8 μN/MPa or less, even more preferably about 6 μN/MPa or less, and most preferably about 4 μN/MPa or less), a Polyquaternium-1 uptake ("PU") of about 0.4 or 0.30 micrograms/lens or less (preferably about 0.20 micrograms/lens or less, more preferably about 0.15 micrograms/lens or less, even more preferably about 0.10 micrograms/lens or less, and most preferably about 0.05 micrograms/lens or less), and after 30 cycles of finger rubbing or simulated finger rubbing. and/or long-lasting surface hydrophilicity and wettability characterized by a water disintegration time of at least 10 seconds (preferably at least 12.5 seconds, more preferably at least 15 seconds, even more preferably at least 17.5 seconds, and most preferably at least 20 seconds) after abrasive cycling treatment, and/or long-lasting lubricity characterized by a friction rating of 2.0 or less (preferably about 1.5 or less, more preferably about 1.0 or less, and even more preferably about 0.5 or less), the contact lens comprising an anterior surface and an opposite posterior surface, and a layered structural morphology comprising, in a direction from the anterior surface to the posterior surface, a front outer hydrogel layer, an inner layer of lens material, and a rear outer hydrogel layer. Preferably, the contact lens is substantially free (i.e., less than 3), or preferably free, of surface crack lines visible under dark field after the contact lens is rubbed between a finger 10 times.

In still further aspects, the present invention provides a method for the preparation of a lens-based PET ... "); long-lasting surface hydrophilicity and wettability characterized by having a water disintegration time of at least 10 seconds (preferably at least 12.5 seconds, more preferably at least 15 seconds, even more preferably at least 17.5 seconds, and most preferably at least 20 seconds) after 30 cycles of finger rubbing or simulated abrasion cycling; and/or long-lasting lubricity characterized by having a friction rating of 2.0 or less (preferably about 1.5 or less, more preferably about 1.0 or less, and even more preferably about 0.5 or less), wherein the contact lens comprises a lens bulk material that is a polymeric material.

In yet another further aspect, the present invention provides a lens having a reduction in indentation force at an indentation depth of 400 nm, i.e., Δ(IF)400nm, of about 50% or more (preferably about 55% or more, more preferably about 60% or more, even more preferably about 65% or more, and most preferably about 70% or more), a polyquaternium-1 uptake ("PU") of about 0.4 or 0.30 micrograms/lens or less (preferably about 0.20 micrograms/lens or less, more preferably about 0.15 micrograms/lens or less, even more preferably about 0.10 micrograms/lens or less, and most preferably about 0.05 micrograms/lens or less), and after 30 cycles of finger rubbing or simulated abrasion cycling. and/or long-lasting surface hydrophilicity and wettability characterized by a water disintegration time of at least 10 seconds (preferably at least 12.5 seconds, more preferably at least 15 seconds, even more preferably at least 17.5 seconds, and most preferably at least 20 seconds), and/or long-lasting lubricity characterized by a friction rating of 2.0 or less (preferably about 1.5 or less, more preferably about 1.0 or less, and even more preferably about 0.5 or less), the contact lens comprising an anterior surface and an opposite posterior surface, and a layered structural morphology comprising, in a direction from the anterior surface to the posterior surface, a front outer hydrogel layer, an inner layer of lens material, and a rear outer hydrogel layer. Preferably, the contact lens is substantially free (i.e., less than 3), or preferably free, of surface crack lines visible under dark field after rubbing the contact lens between a finger 10 times.

In yet another further aspect, the present invention relates to a method for producing a 400 nm indentation depth reduction in indentation force, i.e., Δ(IF), of about 40% or more (preferably about 50% or more, more preferably about 55% or more, even more preferably about 60% or more, and most preferably about 65% or more)._400nmand a polyquaternium-1 uptake ("PU") of about 0.30 micrograms/lens or less (preferably about 0.20 micrograms/lens or less, more preferably about 0.15 micrograms/lens or less, even more preferably about 0.10 micrograms/lens or less, and most preferably about 0.05 micrograms/lens or less); and long-lasting surface hydrophilicity and wettability characterized by having a water disintegration time of at least 10 seconds (preferably at least 12.5 seconds, more preferably at least 15 seconds, even more preferably at least 17.5 seconds, and most preferably at least 20 seconds) after 30 cycles of finger rubbing or simulated abrasion cycling; and/or long-lasting lubricity characterized by having a friction rating of 2.0 or less (preferably about 1.5 or less, more preferably about 1.0 or less, and even more preferably about 0.5 or less), wherein the contact lens comprises a lens bulk material that is a polymeric material.

When the reduction in indentation force of a contact lens is determined in a nanoindentation test by using an Optics 11 Piuma and a Piuma probe with a tip radius of about 9.0 μm, the reduction in indentation force at an indentation depth of 400 nm, i.e., Δ(IF)_400nmteeth,<math num="9"><img file="JP7635289B2_D0019.tif" /></math>where: (IF)_tis the measured indentation force at an indentation depth of 400 nm for the contact lens, and E' is the bulk modulus of elasticity (E') of the contact lens.

The reduction in indentation force of the contact lens is determined by microindentation testing using a Bruker Hysitron® BioSoft In-Situ Indenter and a 1 mm hemispherical borosilicate glass probe, where the reduction in indentation force at an indentation depth of 400 nm, i.e., Δ(IF), is_400nmteeth,<math num="10"><img file="JP7635289B2_D0020.tif" /></math>where: (IF)_tis the measured indentation force at an indentation depth of 400 nm for the contact lens, and E' is the bulk modulus of elasticity (E') of the contact lens.

According to all of the various aspects of the present invention, the inner layer or lens bulk material of the contact lens of the present invention can be derived directly from a preformed contact lens. A preformed contact lens can be any contact lens that has not undergone any surface treatment after being manufactured according to any lens manufacturing process, any contact lens that has been plasma treated, or any commercially available contact lens, as long as it does not have a water gradient structure form. Those skilled in the art are familiar with the method of manufacturing a preformed contact lens. Those skilled in the art are familiar with the method of manufacturing a preformed contact lens. For example, a preformed contact lens can be manufactured in a conventional "spin casting mold" as described, for example, in U.S. Pat. No. 3,408,429, or by a static form full cast molding process as described in U.S. Pat. Nos. 4,347,198, 5,508,317, 5,583,463, 5,789,464, and 5,849,810, or by lathe cutting a button of polymeric material used in manufacturing customized contact lenses. In cast molding, a lens formulation is typically dispensed into a mold and cured (ie, polymerized and/or crosslinked) in the mold to produce a contact lens.

Lens molds for producing 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 mold (for cast molding) generally comprises at least two mold sections (or parts) or mold halves, namely a first and a second mold half. The first mold half defines a first molding (or optical) surface and the second mold half defines a second molding (or optical) surface. The first and second mold halves are configured to receive each other such that a lens-forming cavity is formed between the first and second molding surfaces. The molding surfaces of the mold halves are the cavity-forming surfaces of the mold and are in direct contact with the lens-forming material.

Methods of manufacturing mold sections for casting contact lenses are generally 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 mold forming method may be used in the present invention. The first and second mold halves can be formed by various techniques, such as injection molding or lathe cutting. Examples of suitable processes for forming the mold halves are disclosed in U.S. Patent Nos. 4,444,711, 4,460,534, 5,843,346, and 5,894,002.

To manufacture the mold for contact lens manufacturing, virtually all materials known in the art for mold manufacturing can be used.For example, polymeric materials such as polyethylene, polypropylene, polystyrene, PMMA, Topas® COC grade 8007-S10 (transparent amorphous copolymer of ethylene and norbornene, manufactured by Ticona GmbH, Frankfurt, Germany and Summit, New Jersey) can be used.Other materials that allow transmission of ultraviolet light, such as quartz glass and sapphire, can also be used.

In a preferred embodiment, a reusable mold is used, and the lens-forming composition is actinically cured under the spatial confinement of actinic radiation to form a contact lens. Examples of preferred reusable molds are those disclosed in U.S. Patent Nos. 6,627,124, 6,800,225, 7,384,590, and 7,387,759. Reusable molds can be made of fused silica, sapphire, CaF₂, cyclic olefin copolymers (e.g., Topas® COC grade 8007-S10 (a transparent amorphous copolymer of ethylene and norbornene) from Ticona GmbH (Frankfurt, Germany and Summit, New Jersey), Zeonex® and Zeonor® from Zeon Chemicals LP (Louisville, KY)), polymethyl methacrylate (PMMA), polyoxymethylene from DuPont (Delrin), Ultem® (polyetherimide) from GEPlastics, PrimoSpire®, and the like.

In accordance with the present invention, the polymerizable composition can be introduced (dispensed) into the cavity formed by the mold by any known method.

After the polymerizable composition is dispensed into the mold, it is polymerized to produce a contact lens. Crosslinking may be initiated thermally or actinically, preferably by exposing the lens-forming composition in the mold to the spatial confinement of actinic radiation to crosslink the polymerizable components in the polymerizable composition.

Opening the mould to enable the moulded article to be removed from it may be effected in a manner known per se.

The molded contact lenses may be subjected to lens extraction to remove unpolymerized polymerizable components. The extraction solvent may be any solvent known to those skilled in the art. Examples of suitable extraction solvents are described below.

In a preferred embodiment, the preformed contact lens is a hard contact lens comprising a hard plastic material as the bulk material of the lens. Preferably, the hard plastic material is crosslinked polymethyl acrylate. Those skilled in the art are familiar with methods for producing hard plastic materials comprising crosslinked polymethyl methacrylate.

In another preferred embodiment, the preformed contact lens is a rigid gas permeable contact lens.Those skilled in the art know how to make rigid gas permeable contact lenses.

In another preferred embodiment, the preformed contact lens is a hybrid contact lens having a central optic zone made from a rigid gas permeable lens material surrounded by a peripheral zone made from a hydrogel material.

In another preferred embodiment, preformed contact lens is a soft silicone contact lens, comprising crosslinked silicone material as lens bulk material.Useful crosslinked silicone material includes, but is not limited to, crosslinked polysiloxane, silicone elastomer, silicone rubber, etc., obtained by crosslinking silicone composition by any known method.Silicone contact lens can be prepared by any kind of conventional technique well known to those skilled in the art, such as lathe cutting manufacturing method, spin casting manufacturing method, cast molding manufacturing method, etc.

In another preferred embodiment, the preformed contact lenses are non-silicone hydrogel contact lenses (or so-called conventional hydrogel contact lenses).

Preformed non-silicone hydrogel contact lenses may be any commercially available non-silicone hydrogel contact lens or may be manufactured by any known method. For example, non-silicone hydrogel lens formulations for manufacturing preformed non-silicone hydrogel contact lenses, for cast molding or spin casting, or for manufacturing rods used in lathe cutting of contact lenses typically contain (1) (a) at least one hydrophilic vinyl monomer (e.g., hydroxyethyl methacrylate, glycerol methacrylate, N-vinylpyrrolidone, or combinations thereof) and (b) a crosslinker, hydrophobic vinyl monomer, lubricant (or so-called internal wetting agent incorporated into the lens formulation), free radical initiator (photoinitiator or thermal initiator), UV absorbing vinyl monomer, high energy visible light ("HEVL") absorbing vinyl monomer, visibility tinting agent, and/or other additives. or (2) an aqueous solution comprising one or more water-soluble prepolymers and at least one component selected from the group consisting of hydrophilic vinyl monomers, crosslinkers, hydrophobic vinyl monomers, lubricants (or so-called internal wetting agents incorporated into the lens formulation), free radical initiators (photoinitiators or thermal initiators), UV absorbing vinyl monomers, HEVL absorbing vinyl monomers, visibility colorants (e.g., reactive dyes, polymerizable dyes, pigments, or mixtures thereof), antimicrobial agents (e.g., preferably silver nanoparticles), bioactive agents, and combinations thereof. The resulting preformed hydrogel contact lens may then be subjected to extraction with an extraction solvent to remove unpolymerized components from the resulting lens, and a hydration process, as is well known to those skilled in the art. It will be appreciated that the lubricant present in a hydrogel lens formulation may improve the lubricity of a preformed hydrogel contact lens as compared to the lubricity of a control preformed hydrogel contact lens obtained from a control hydrogel lens formulation that does not contain a lubricant.

Examples of water-soluble prepolymers include water-soluble crosslinkable poly(vinyl alcohol) prepolymers described in U.S. Pat. Nos. 5,583,163 and 6,303,687, water-soluble vinyl-terminated polyurethane prepolymers described in U.S. Pat. No. 6,995,192, polyvinyl alcohol, polyethyleneimine, or polyvinylamine derivatives disclosed in U.S. Pat. No. 5,849,841, water-soluble crosslinkable polyurea prepolymers, crosslinkable polyacrylamides described in U.S. Pat. Nos. 6,479,587 and 7,977,430, vinyl lactams, MMA, and comonomers disclosed in U.S. Pat. No. 5,712,356, and the like. No. 5,665,840; polyether-polyester copolymers containing crosslinkable side chains as disclosed in U.S. Pat. No. 6,492,478; branched polyalkylene glycol-urethane prepolymers as disclosed in U.S. Pat. No. 6,165,408; polyalkylene glycol-tetra(meth)acrylate prepolymers as disclosed in U.S. Pat. No. 6,221,303; and crosslinkable polyallylamine gluconolactone prepolymers as disclosed in U.S. Pat. No. 6,472,489.

Numerous non-silicone hydrogel lens formulations have been described in numerous patents and patent applications published as of the filing date of this application and have been used to manufacture commercially available non-silicone hydrogel contact lenses. Examples of commercially available non-silicone hydrogel contact lenses include, but are not limited to, alfafilcon A, acofilcon A, deltafilcon A, etafilcon A, focofilcon A, helfilcon A, helfilcon B, hilafilcon B, hioxifilcon A, hioxifilcon B, hioxifilcon D, methafilcon A, methafilcon B, nelfilcon A, nesofilcon A, ocufilcon A, ocufilcon B, ocufilcon C, ocufilcon D, omafilcon A, phemfilcon A, polymacon, samfilcon A, telfilcon A, tetrafilcon A, and vifilcon A.

In a preferred embodiment, the inner layer is made of a non-silicone hydrogel material comprising at least 50 mole % of repeat units of at least one hydroxyl-containing vinyl monomer, preferably selected from the group consisting of hydroxyethyl (meth)acrylate, glycerol (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 3-amino-2-hydroxypropyl (meth)acrylate, N-2-hydroxyethyl (meth)acrylamide, N-3-hydroxypropyl (meth)acrylamide, N-2-hydroxypropyl (meth)acrylamide, N-2,3-dihydroxypropyl (meth)acrylamide, N-tris(hydroxymethyl)methyl (meth)acrylamide, vinyl alcohol, allyl alcohol, and combinations thereof, more preferably selected from the group consisting of hydroxyethyl (meth)acrylate, glycerol (meth)acrylate, and vinyl alcohol. The mole percentage of repeat units can be calculated based on the non-silicone hydrogel lens formulation for producing the non-silicone hydrogel contact lens.

In another preferred embodiment, the preformed contact lenses are non-silicone hydrogel contact lenses, preferably naturally wettable silicone hydrogel contact lenses.

The preformed silicone hydrogel contact lens may be any commercially available silicone hydrogel contact lens or may be manufactured by any known method. For example, the SiHy lens formulation for manufacturing preformed silicone hydrogel (SiHy) contact lenses, for casting or spin casting, or for manufacturing SiHy rods used in lathe cutting of contact lenses generally includes at least one component selected from the group consisting of silicone-containing vinyl monomers, silicone-containing vinyl crosslinkers, silicone-containing prepolymers, hydrophilic vinyl monomers, hydrophobic vinyl monomers, non-silicone vinyl crosslinkers, free radical initiators (photoinitiators or thermal initiators), silicone-containing prepolymers, and combinations thereof, as known to those skilled in the art. The resulting preformed SiHy contact lens may be subsequently subjected to extraction with an extraction solvent to remove unpolymerized components from the resulting lens, and a hydration process, as known to those skilled in the art. Furthermore, the preformed SiHy contact lens may be a colored contact lens (i.e., a SiHy contact lens having at least one color pattern printed thereon, as known to those skilled in the art).

According to the present invention, silicone-containing vinyl monomer can be any silicone-containing vinyl monomer known to those skilled in the art.Preferred examples of silicone-containing vinyl monomer include but are not limited to the vinyl monomer that each has bis(trialkylsilyloxy) alkylsilyl group or tris(trialkylsilyloxy) silyl group, polysiloxane vinyl monomer, polycarbosiloxane vinyl monomer, 3-methacryloxypropyl pentamethyldisiloxane, t-butyldimethyl-siloxyethyl vinyl carbonate, trimethylsilylethyl vinyl carbonate, and trimethylsilylmethyl vinyl carbonate, and combinations thereof.

Examples of preferred vinyl monomers each having a bis(trialkylsilyloxy)alkylsilyl group or a tris(trialkylsilyloxy)silyl group include tris(trimethylsilyloxy)silylpropyl(meth)acrylate, [3-(meth)acryloxy-2-hydroxypropyloxy]propylbis(trimethylsiloxy)methylsilane, [3-(meth)acryloxy-2-hydroxypropyloxy]propylbis(trimethylsiloxy)butylsilane, 3-(meth)acryloxy-2-(2-hydroxyethoxy)-propyloxy)propylbis(trimethylsiloxy)methylsilane, 3-(meth)acryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane, N-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide, N-(2-hydroxy-3-(3 -(Bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)-2-methyl(meth)acrylamide, N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)(meth)acrylamide, N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)-2-methylacrylamide, N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)(meth)acrylamide, N-[tris(dimethylpropylsiloxy)silylpropyl]-(meth)acrylamide, N-[tris(dimethylphenylsiloxy)silylpropyl]-(meth)acrylamide, N-[tris(dimethylethylsiloxy)silylpropyl](meth)acrylamide, N,N-bis[2-hydro N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]-2-methyl(meth)acrylamide, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl](meth)acrylamide, N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methyl(meth)acrylamide, N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methyl(meth)acrylamide, N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methyl(meth)acrylamide, N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl](meth)acrylamide arylamide, N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methyl(meth)acrylamide, N-2-(meth)acryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silylcarbamate, 3-(trimethylsilyl)propyl vinyl carbonate, 3-(vinylcarbonylthio)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, those disclosed in U.S. Pat. Nos. 9,097,840, 9,103,965, and 9,475,827, and mixtures thereof. The above preferred silicone-containing vinyl monomers can be obtained from commercial suppliers or can be prepared according to the procedures described in U.S. Pat. Nos. 7,214,809, 8,475,529, 8,658,748, 9,097,840, 9,103,965, and 9,475,827.

Examples of preferred polysiloxane vinyl monomers include, but are not limited to, mono-(meth)acryloyl-terminated, monoalkyl-terminated polysiloxanes of formula (I) include α-(meth)acryloxypropyl-terminated, ω-butyl (or ω-methyl)-terminated polydimethylsiloxane, α-(meth)acryloxy-2-hydroxypropyloxypropyl-terminated, ω-butyl (or ω-methyl)-terminated polydimethylsiloxane, α-(2-hydroxypropyloxypropyl)-terminated ... dipropyl)-ω-butyl-decamethylpentasiloxane, α-[3-(meth)acryloxyethoxy-2-hydroxypropyloxypropyl] end ω-butyl (or ω-methyl) polydimethylsiloxane, α-[3-(meth)acryloxy-propyloxy-2-hydroxypropyloxypropyl] end ω-butyl (or ω-methyl) polydimethylsiloxane, α-[3-(meth)acryloxyisopropyloxy-2-hydroxypropyloxypropyl] end ω-butyl (or ω-methyl) polydimethylsiloxane, α- [3-(meth)acryloxybutyloxy-2-hydroxypropyloxypropyl] ω-butyl (or ω-methyl) terminated polydimethylsiloxane, α-[3-(meth)acryloxyethylamino-2-hydroxypropyloxypropyl] ω-butyl (or ω-methyl) terminated polydimethylsiloxane, α-[3-(meth)acryloxypropylamino-2-hydroxypropyloxypropyl] ω-butyl (or ω-methyl) terminated polydimethylsiloxane, α-[3-(meth)acryloxy-butylamino-2-hydroxypropyloxypropyl] ω-butyl (or ω-methyl) terminated polydimethylsiloxane, polydimethylsiloxane having an α-(meth)acryloxy(polyethyleneoxy)-2-hydroxypropyloxypropyl end terminal, an α-(meth)acryloxy(polyethyleneoxy)-2-hydroxypropyloxypropyl end terminal, an α-(meth)acryloxy-2-hydroxypropyloxy-ethoxypropyl end terminal, an α-(meth)acryloxy-2-hydroxypropyloxy-ethoxypropyl end terminal, an α-(meth)acryloxy-2-hydroxypropyloxy-ethoxypropyl end terminal, an α-(meth)acryloxy-2-hydroxypropyl-N-ethylaminopropyl end terminal, an α-(meth)acryloxy-2-hydroxypropyl-N-ethylaminopropyl end terminal, α-[(meth)acryloxy-2-hydroxypropyl-aminopropyl]-terminated ω-butyl (or ω-methyl) polydimethylsiloxane, α-[(meth)acryloxy-2-hydroxypropyloxy-(polyethyleneoxy)propyl]-terminated ω-butyl (or ω-methyl) polydimethylsiloxane, α-(meth)acryloylamidopropyloxypropyl-terminated ω-butyl (or ω-methyl) polydimethylsiloxane, α-N-methyl-(meth)acryloylamidopropyloxypropyl-terminated ω-butyl (or ω-methyl) polydimethylsiloxane polydimethylsiloxane having an α-[3-(meth)acrylamidoethoxy-2-hydroxypropyloxypropyl] end group and an ω-butyl (or ω-methyl) end group, polydimethylsiloxane having an α-[3-(meth)acrylamidopropyloxy-2-hydroxypropyloxypropyl] end group and an ω-butyl (or ω-methyl) end group, polydimethylsiloxane having an α-[3-(meth)acrylamidopropyloxy-2-hydroxypropyloxypropyl] end group and an ω-butyl (or ω-methyl) end group, polydimethylsiloxane having an α-[3-(meth)acrylamidoisopropyloxy-2-hydroxypropyloxypropyl] end group and an ω-butyl (or ω-methyl) end group, polydimethylsiloxane having α-[3-(meth)acryloylamide-2-hydroxypropyloxypropyl] end group and ω-butyl (or ω-methyl) end group, polydimethylsiloxane having α-[3-[N-methyl-(meth)acryloylamide]-2-hydroxypropyloxypropyl] end group and ω-butyl (or ω-methyl) end group, polydimethylsiloxane having α-[3-[N-methyl-(meth)acryloylamide]-2-hydroxypropyloxypropyl] end group and ω-butyl (or ω-methyl) end group, polydimethylsiloxane having N-methyl-N'-(propyltetra(dimethylsiloxy)dimethylbutylsilane)(meth)acryloylamide These include, but are not limited to, acrylamide, N-(2,3-dihydroxypropane)-N'-(propyltetra(dimethylsiloxy)dimethylbutylsilane)(meth)acrylamide, (meth)acryloylamidopropyltetra(dimethylsiloxy)dimethylbutylsilane, monovinyl carbonate terminated monoalkyl terminated polydimethylsiloxane, monovinyl carbamate terminated monoalkyl terminated polydimethylsiloxane, those disclosed in U.S. Pat. Nos. 9,097,840 and 9,103,965, and mixtures thereof. The preferred polysiloxane vinyl monomers described above can be obtained from commercial suppliers (e.g., Shin-Etsu Chemical Co., Ltd., Gelest, etc.) or can be prepared according to procedures described in patents such as, for example, U.S. Pat. Nos. 6,867,245, 8,415,405, 8,475,529, 8,614,261, and 9,217,813, or based on coupling reactions well known to those skilled in the art, by reacting hydroxyalkyl (meth)acrylate or (meth)acrylamide or (meth)acryloxypolyethylene glycol with monoepoxypropyloxypropyl terminated polydimethylsiloxane, by reacting glycidyl (meth)acrylate with monocarbinol terminated polydimethylsiloxane, monoaminopropyl terminated polydimethylsiloxane, or monoethylaminopropyl terminated polydimethylsiloxane, or by reacting isocyanatoethyl (meth)acrylate with monocarbinol terminated polydimethylsiloxane.

Any polycarbosiloxane vinyl monomer can be used in the present invention. Examples of preferred polycarbosiloxane vinyl monomers include, but are not limited to, those disclosed in U.S. Patent Nos. 7,915,323 and 8,420,711, and U.S. Patent Application Publication Nos. 2012/244088A1 and 2012/245249A1.

Any suitable silicone-containing vinyl crosslinker can be used in the present invention. Examples of preferred silicone-containing vinyl crosslinkers include, but are not limited to, polysiloxane vinyl crosslinkers, polycarbosiloxane vinyl crosslinkers, and combinations thereof.

Any suitable polysiloxane vinyl crosslinker can be used in the present invention. Examples of preferred polysiloxane vinyl crosslinkers include di-(meth)acryloyl terminated polydimethylsiloxane, di-vinyl carbonate terminated polydimethylsiloxane, di-vinyl carbamate terminated polydimethylsiloxane, N,N,N',N'-tetrakis(3-methacryloxy-2-hydroxypropyl)-α,ω-bis-3-aminopropyl-polydimethylsiloxane, Macromer A, Macromer B, Macromer C, Macromer D, Macromer E, Macromer F, Macromer G, Macromer H, Macromer I ... Polysiloxane-containing macromers selected from the group consisting of Macromer C, Macromer D, U.S. Pat. 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, and 4,543,398. Specification, Specification No. 4605712, Specification No. 4661575, Specification No. 4684538, Specification No. 4703097, Specification No. 4833218, Specification No. 4837289, Specification No. 4954586, Specification No. Specification No. 4954587, Specification No. 5010141, Specification No. 5034461, Specification No. 5070170, Specification No. 5079319, Specification No. 5039761, Specification No. 5346946, Specification No. 535899. Nos. 5, 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; and U.S. Pat. Nos. 4,259,467, 4,260,725, and 4,261,875.

Examples of preferred di-(meth)acryloyloxy terminated polysiloxane vinyl crosslinkers include the reaction product of glycidyl methacrylate with di-amino terminated polydimethylsiloxane, the reaction product of glycidyl methacrylate with di-hydroxyl terminated polydimethylsiloxane, the reaction product of isocyantoethyl (meth)acrylate with di-hydroxyl terminated polydimethylsiloxane, the reaction product of isocyantoethyl (meth)acrylate with di-hydroxyl terminated polydimethylsiloxane, the reaction products of monovalent C dimethylsiloxanes each having one methyl substituent and 2-6 hydroxyl groups as disclosed in U.S. Pat. No. 1,008,1697, and the like.₄~C₄₀di-(meth)acryloyloxy terminated polysiloxane vinyl crosslinkers each having hydrophilized siloxane units having organic radical substituents, chain extended polysiloxabe vinyl crosslinkers as disclosed in U.S. Patent Application Publication Nos. 201008843A1 and 20120088844A1, U.S. Patent Nos. 5,034,461, 5,416,132, 5,449,729, 5,760,100, 7 chain-extended polysiloxane vinyl crosslinkers described in U.S. Patent Application Publication No. 423074 and No. 8529057; chain-extended polysiloxane vinyl crosslinkers described in U.S. Patent Application Publication No. 2018-0100053; chain-extended polysiloxane vinyl crosslinkers described in U.S. Patent Application Publication No. 2018-0100038; chain-extended polysiloxane vinyl crosslinkers described in U.S. Patent Application Publication No. 8993651; α,ω-bis[3-(meth)acrylamide] α,ω-bis[3-(meth)acryloxypropyl]terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxypropyl]terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxy-2-hydroxypropyloxypropyl]terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxyethoxy-2-hydroxypropyloxypropyl]terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxypropyloxy-2-hydroxypropyloxypropyl]terminated polydimethylsiloxane Methylsiloxane, α,ω-bis[3-(meth)acryloxy-isopropyloxy-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxybutyloxy-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α,ω-bis[3-(meth)acrylamideethoxy-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α,ω-bis[3-(meth)acrylamidepropyloxy-2- hydroxypropyloxypropyl] terminated polydimethylsiloxane, α,ω-bis[3-(meth)acrylamide isopropyloxy-2-hydroxypropyloxypropyl] terminated polydimethylsiloxane, α,ω-bis[3-(meth)acrylamide butyloxy-2-hydroxypropyloxypropyl] terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxyethylamino-2-hydroxypropyloxypropyl] terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxypropylamino-2-hydroxypropyloxypropyl] terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxypropylamino-2-hydroxypropyloxypropyl] terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxybutylamino-2-hydroxypropyloxypropyl] terminated polydimethylsiloxane, α,ω-bis[(meth)acrylamide ethylamino-2-hydroxypropyloxy-propyl] terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxypropylamino-2-hydroxypropyloxypropyl] terminated polydimethylsiloxane ] terminated polydimethylsiloxane, α,ω-bis[3-(meth)acrylamide-butylamino-2-hydroxypropyloxypropyl] terminated polydimethylsiloxane, α,ω-bis[(meth)acryloxy-2-hydroxypropyloxy-ethoxypropyl] terminated polydimethylsiloxane, α,ω-bis[(meth)acryloxy-2-hydroxypropyl-N-ethylaminopropyl] terminated polydimethylsiloxane, α,ω-bis[(meth)acryloxy-2-hydroxypropyl-aminopropyl] polydimethylsiloxane, α,ω-bis[(meth)acryloxy-2-hydroxypropyloxy-(polyethyleneoxy)propyl] terminated polydimethylsiloxane, α,ω-bis[(meth)acryloxyethylamino-carbonyloxy-ethoxypropyl] terminated polydimethylsiloxane, α,ω-bis[(meth)acryloxyethylamino-carbonyloxy-(polyethyleneoxy)propyl] terminated polydimethylsiloxane, but are not limited thereto.

Any polycarbosiloxane vinyl crosslinker can be used in the present invention. Examples of preferred polycarbosiloxane vinyl crosslinkers include, but are not limited to, those disclosed in U.S. Patent Nos. 7,915,323 and 8,420,711, and U.S. Patent Application Publication Nos. 2012/0244088 and 2012/0245249.

Any hydrophilic vinyl monomer can be used in the present invention. Examples of preferred hydrophilic vinyl monomers are alkyl (meth)acrylamides (described below), hydroxyl-containing acrylic monomers (described below), amino-containing acrylic monomers (described below), carboxyl-containing acrylic monomers (described below), N-vinylamide monomers (described below), methylene-containing pyrrolidone monomers (i.e., pyrrolidone derivatives having a methylene group attached to the pyrrolidone ring at the 3- or 5-position, respectively) (described below), C₁~C₄These include acrylic monomers having an alkoxyethoxy group (described below), vinyl ether monomers (described below), allyl ether monomers (described below), phosphorylcholine-containing vinyl monomers (described below), N-2-hydroxyethyl vinyl carbamate, N-carboxyvinyl-β-alanine (VINAL), N-carboxyvinyl-α-alanine, and combinations thereof.

Examples of alkyl(meth)acrylamides include, but are not limited to, (meth)acrylamide, N,N-dimethyl(meth)acrylamide, N-ethyl(meth)acrylamide, N,N-diethyl(meth)acrylamide, N-propyl(meth)acrylamide, N-isopropyl(meth)acrylamide, N-3-methoxypropyl(meth)acrylamide, and combinations thereof.

Examples of hydroxyl-containing acrylic monomers include, but are not limited to, N-2-hydroxylethyl (meth)acrylamide, N,N-bis(hydroxyethyl) (meth)acrylamide, N-3-hydroxypropyl (meth)acrylamide, N-2-hydroxypropyl (meth)acrylamide, N-2,3-dihydroxypropyl (meth)acrylamide, N-tris(hydroxymethyl)methyl (meth)acrylamide, 2-hydroxyethyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, glycerol methacrylate (GMA), di(ethylene glycol) (meth)acrylate, tri(ethylene glycol) (meth)acrylate, tetra(ethylene glycol) (meth)acrylate, poly(ethylene glycol) (meth)acrylate having a number average molecular weight of up to 1500, poly(ethylene glycol)ethyl (meth)acrylamide having a number average molecular weight of up to 1500, and combinations thereof.

Examples of amino-containing acrylic monomers include, but are not limited to, N-2-aminoethyl(meth)acrylamide, N-2-methylaminoethyl(meth)acrylamide, N-2-ethylaminoethyl(meth)acrylamide, N-2-dimethylaminoethyl(meth)acrylamide, N-3-aminopropyl(meth)acrylamide, N-3-methylaminopropyl(meth)acrylamide, N-3-dimethylaminopropyl(meth)acrylamide, 2-aminoethyl(meth)acrylate, 2-methylaminoethyl(meth)acrylate, 2-ethylaminoethyl(meth)acrylate, 3-aminopropyl(meth)acrylate, 3-methylaminopropyl(meth)acrylate, 3-ethylaminopropyl(meth)acrylate, 3-amino-2-hydroxypropyl(meth)acrylate, trimethylammonium 2-hydroxypropyl(meth)acrylate hydrochloride, dimethylaminoethyl(meth)acrylate, and combinations thereof.

Examples of carboxyl-containing acrylic monomers include, but are not limited to, 2-(meth)acrylamidoglycolic acid, (meth)acrylic acid, ethylacrylic acid, and combinations thereof.

Examples of preferred N-vinyl amide monomers include N-vinylpyrrolidone (also known as N-vinyl-2-pyrrolidone), N-vinyl-3-methyl-2-pyrrolidone, N-vinyl-4-methyl-2-pyrrolidone, N-vinyl-5-methyl-2-pyrrolidone, N-vinyl-6-methyl-2-pyrrolidone, N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone, N-vinyl-5,5-dimethyl-2-pyrrolidone, N-vinyl-3,3,5-trimethyl-2-pyrrolidone, N-vinylpiperidone (also known as N-vinyl-2-piperidone), N-vinyl-3-methyl-2-piperidone, N-vinyl-4-methyl-2-piperidone, N-vinyl-5-methyl-2-piperidone, N-vinyl-6-methyl-2-piperidone, N-vinyl-6-ethyl-2-piperidone, N-vinyl- These include, but are not limited to, 3,5-dimethyl-2-piperidone, N-vinyl-4,4-dimethyl-2-piperidone, N-vinyl caprolactam (also known as N-vinyl-2-caprolactam), N-vinyl-3-methyl-2-caprolactam, N-vinyl-4-methyl-2-caprolactam, N-vinyl-7-methyl-2-caprolactam, N-vinyl-7-ethyl-2-caprolactam, N-vinyl-3,5-dimethyl-2-caprolactam, N-vinyl-4,6-dimethyl-2-caprolactam, N-vinyl-3,5,7-trimethyl-2-caprolactam, N-vinyl-N-methylacetamide, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, and mixtures thereof. Preferably, the N-vinyl amide monomer is N-vinylpyrrolidone, N-vinyl-N-methylacetamide, or a combination thereof.

Preferred methylene-containing (=CH₂) Examples of pyrrolidone monomers include, but are not limited to, 1-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, and combinations thereof.

C₁~C₄Examples of preferred acrylic monomers having an alkoxyethoxy group include ethylene glycol methyl ether (meth)acrylate, di(ethylene glycol) methyl ether (meth)acrylate, tri(ethylene glycol) methyl ether (meth)acrylate, tetra(ethylene glycol) methyl ether (meth)acrylate, C methyl ether (meth)acrylate having a weight average molecular weight of up to 1500,₁~C₄These include, but are not limited to, alkoxy poly(ethylene glycol) (meth)acrylates, methoxy-poly(ethylene glycol) ethyl (meth)acrylamides having a number average molecular weight of up to 1500, and combinations thereof.

Examples of preferred vinyl ether monomers include, but are not limited to, ethylene glycol monovinyl ether, di(ethylene glycol) monovinyl ether, tri(ethylene glycol) monovinyl ether, tetra(ethylene glycol) monovinyl ether, poly(ethylene glycol) monovinyl ether, ethylene glycol methyl vinyl ether, di(ethylene glycol) methyl vinyl ether, tri(ethylene glycol) methyl vinyl ether, tetra(ethylene glycol) methyl vinyl ether, poly(ethylene glycol) methyl vinyl ether, and combinations thereof.

Examples of preferred allyl ether monomers include, but are not limited to, allyl alcohol, ethylene glycol monoallyl ether, di(ethylene glycol) monoallyl ether, tri(ethylene glycol) monoallyl ether, tetra(ethylene glycol) monoallyl ether, poly(ethylene glycol) monoallyl ether, ethylene glycol methyl allyl ether, di(ethylene glycol) methyl allyl ether, tri(ethylene glycol) methyl allyl ether, tetra(ethylene glycol) methyl allyl ether, poly(ethylene glycol) methyl allyl ether, and combinations thereof.

Examples of preferred phosphorylcholine-containing vinyl monomers include (meth)acryloyloxyethyl phosphorylcholine (also known as MPC, or 2-((meth)acryloyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate), (meth)acryloyloxypropyl phosphorylcholine (also known as 3-((meth)acryloyloxy)propyl-2'-(trimethylammonio)ethyl phosphate), 4-((meth)acryloyloxy)butyl-2'-(trimethylammonio)ethyl phosphate, 2-[(meth)acryloylamino]ethyl-2'-(trimethylammonio)ethyl phosphate, 3-[ (Meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 4-[(meth)acryloylamino]butyl-2'-(trimethylammonio)ethyl phosphate, 5-((meth)acryloyloxy)pentyl-2'-(trimethylammonio)ethyl phosphate, 6-((meth)acryloyloxy)hexyl-2'-(trimethylammonio)-ethyl phosphate, 2-((meth)acryloyloxy)ethyl-2'-(triethylammonio)ethyl phosphate, 2-((meth)acryloyloxy)ethyl-2'-(tripropylammonio)ethyl phosphate, 2- ((meth)acryloyloxy)ethyl-2'-(tributylammonio)ethyl phosphate, 2-((meth)acryloyloxy)propyl-2'-(trimethylammonio)-ethyl phosphate, 2-((meth)acryloyloxy)butyl-2'-(trimethylammonio)ethyl phosphate, 2-((meth)acryloyloxy)pentyl-2'-(trimethylammonio)ethyl phosphate, 2-((meth)acryloyloxy)hexyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy) )ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)-ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butenoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, and combinations thereof.

According to the present invention, any hydrophobic vinyl monomer can be in the present invention.Examples of preferred hydrophobic vinyl monomer include methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, cyclohexyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidene chloride, (meth)acrylonitrile, 1-butene, butadiene, vinyl toluene, vinyl ethyl ether, perfluorohexylethyl-thio-carbonyl-aminoethyl-methacrylate, isobornyl (meth)acrylate, trifluoroethyl (meth)acrylate, hexafluoro-isopropyl (meth)acrylate, hexafluorobutyl (meth)acrylate, and combinations thereof.

According to the present invention, any non-silicone vinyl crosslinker may be present in the present invention. Examples of preferred non-silicone vinyl crosslinkers include ethylene glycol di-(meth)acrylate, diethylene glycol di-(meth)acrylate, triethylene glycol di-(meth)acrylate, tetraethylene glycol di-(meth)acrylate, glycerol di-(meth)acrylate, 1,3-propanediol di-(meth)acrylate, 1,3-butanediol di-(meth)acrylate, 1,4-butanediol di-(meth)acrylate, glycerol 1,3-diglycerolate di-(meth)acrylate, 1,4-butanediol di-(meth)acrylate, 1,5-dimethylphenyl di-(meth)acrylate, 1,6-dimethylphenyl di-(meth)acrylate, 1,7-dimethylphenyl di-(meth)acrylate, 1,8-dimethylphenyl di-(meth)acrylate, 1,9-dimethylphenyl di-(meth)acrylate, 1,10-dimethylphenyl di-(meth)acrylate, 1,11-dimethylphenyl di-(meth)acrylate, 1,12-dimethylphenyl di-(meth)acrylate, 1,13-dimethylphenyl di-(meth)acrylate, 1,14-dimethylphenyl di-(meth)acrylate, 1,15-dimethylphenyl di-(meth)acrylate, 1,16-dimethylphenyl di-(meth)acrylate, 1,17-dimethylphenyl di-(meth)acrylate, 1,18-dimethylphenyl di-(meth)acrylate, 1,19-dimethylphenyl di-(meth)acrylate, 1,20-dimethylphenyl di-(meth)acrylate, 1,21-dimethylphenyl di-(meth)acrylate, 1,22-dimethylphenyl di-(meth)acrylate, 1,23-dimethylphenyl di-(meth)acrylate, 1,24-dimethylphenyl di-(meth)acrylate, 1,25-dimethylphenyl di-(meth)acrylate, 1,26-dimethylphenyl di-(meth)acrylate, 1,27-dimethylphenyl di-(meth) meth)acrylate, ethylene bis[oxy(2-hydroxypropane-1,3-diyl)]di-(meth)acrylate, bis[2-(meth)acryloxyethyl]phosphate, trimethylolpropane di-(meth)acrylate, and 3,4-bis[(meth)acryloyl]tetrahydrofuan, diacrylamide, dimethacrylamide, N,N-di(meth)acryloyl-N-methylamine, N,N-di(meth)acryloyl-N-ethylamine, N,N'-methylene bis These include, but are not limited to, (meth)acrylamide, N,N'-ethylene bis(meth)acrylamide, N,N'-dihydroxyethylene bis(meth)acrylamide, N,N'-propylene bis(meth)acrylamide, N,N'-2-hydroxypropylene bis(meth)acrylamide, N,N'-2,3-dihydroxybutylene bis(meth)acrylamide, 1,3-bis(meth)acrylamidopropan-2-yl dihydrogen phosphate, piperazine diacrylamide, tetraethylene glycol divinyl ether, triethylene glycol divinyl ether, diethylene glycol divinyl ether, ethylene glycol divinyl ether, triallyl isocyanurate, triallyl cyanurate, trimethylopropane trimethacrylate, pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, allyl methacrylate, allyl acrylate, N-allyl-methacrylamide, N-allyl-acrylamide, and combinations thereof. Preferred non-silicone vinyl crosslinkers are tetra(ethylene glycol) di-(meth)acrylate, tri(ethylene glycol) di-(meth)acrylate, ethylene glycol di-(meth)acrylate, di(ethylene glycol) di-(meth)acrylate, tetraethylene glycol divinyl ether, triethylene glycol divinyl ether, diethylene glycol divinyl ether, ethylene glycol divinyl ether, triallyl isocyanurate, triallyl cyanurate, and combinations thereof.

Any thermal polymerization initiator can be used in the present invention. Suitable thermal polymerization initiators are known to those skilled in the art and include, for example, peroxides, hydroperoxides, azo-bis(alkyl or cycloalkyl nitriles), persulfates, percarbonates, or mixtures thereof. Examples of preferred thermal polymerization initiators include benzoyl peroxide, t-butyl peroxide, t-amyl peroxybenzoate, 2,2-bis(tert-butylperoxy)butane, 1,1-bis(tert-butylperoxy)cyclohexane, 2,5-bis(tert-butylperoxy)-2,5-dimethylhexane, 2,5-bis(tert-butylperoxy)-2,5-dimethyl-3-hexane, bis(1-(tert-butylperoxy)-1-methylethyl)benzene, 1,1-bis(tert-butylperoxy)-3,3,5-trimethylcyclohexane, di-t-butyl diperoxyphthalate, t-butyl hydroperoxide, t-butyl peracetate, t-butyl peroxybenzoate, t-butyl peroxyisopropyl carbonate, acetyl peroxide, lauroyl peroxide, decanoyl peroxide, dicetyl peroxydicarbonate, di(4-t-butylcyclohexyl) peroxydicarbonate (Perkadox 16S), di(2-ethylhexyl) peroxydicarbonate, t-butyl peroxypivalate (Lupersol 11), t-butyl peroxy-2-ethylhexanoate (Trigonox 21-C50), 2,4-pentanedione peroxide, dicumyl peroxide, peracetic acid, potassium persulfate, sodium persulfate, ammonium persulfate, 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) (VAZO 33), 2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (VAZO 44), 2,2'-azobis(2-amidinopropane)dihydrochloride (VAZO 50), 2,2'-azobis(2,4-dimethylvaleronitrile) (VAZO 52), 2,2'-azobis(isobutyronitrile) (VAZO 64 or AIBN), 2,2'-azobis-2-methylbutyronitrile (VAZO 67), 1,1-azobis(1-cyclohexanecarbonitrile) (VAZO 88), 2,2'-azobis(2-cyclopropylpropionitrile), 2,2'-azobis(methylisobutyrate), 4,4'-azobis(4-cyanovaleric acid), and combinations thereof. Preferably, the thermal initiator is 2,2'-azobis(isobutyronitrile) (AIBN or VAZO 64).

Suitable photoinitiators are benzoin methyl ether, diethoxyacetophenone, benzoylphosphine oxide, 1-hydroxycyclohexylphenyl ketone, and Darocur and Irgacur types, preferably Darocur 1173® and Darocur 2959®, germanium-based Norrish type I photoinitiators, such as those described in U.S. Pat. No. 7,605,190. Examples of benzoylphosphine initiators include 2,4,6-trimethylbenzoyldiphenylophosphine oxide, bis-(2,6-dichlorobenzoyl)-4-N-propylphenylphosphine oxide, and bis-(2,6-dichlorobenzoyl)-4-N-butylphenylphosphine oxide. Reactive photoinitiators, which can be incorporated into macromers or used as special monomers, are also suitable. Examples of reactive photoinitiators are disclosed in EP 632,329.

Any silicone-containing prepolymer that contains hydrophilic and hydrophobic segments can be used in the present invention.Examples of such silicone-containing prepolymers include those described in US Patent No. 6,039,913, US Patent No. 7,091,283, US Patent No. 7,268,189, US Patent No. 7,238,750, US Patent No. 7,521,519, US Patent No. 8,383,744 and US Patent No. 8,642,712, and US Patent Publication No. 2008/0015315A1, US Patent No. 2008/0143958A1, US Patent No. 2008/0143003A1, US Patent No. 2008/0234457A1 and US Patent No. 2008/0231798A1.

The SiHy contact lens formulation may further include other essential ingredients known to those skilled in the art, such as, for example, UV absorbing vinyl monomers, HEVL absorbing vinyl monomers, visibility colorants (e.g., reactive dyes, polymeric dyes, pigments, or mixtures thereof, as known to those skilled in the art), antimicrobial agents (e.g., preferably silver nanoparticles), bioactive agents, leachable lubricants, leachable tear stabilizers, and mixtures thereof.

In accordance with a preferred embodiment of the present invention, the preformed silicone hydrogel contact lenses of the present invention may further comprise (but preferably include) repeat units of one or more UV absorbing vinyl monomers, and optionally (but preferably) one or more UV/HEVL absorbing vinyl monomers. The term "UV/HEVL absorbing vinyl monomers" refers to vinyl monomers that are capable of absorbing UV light and high energy visible light (i.e., light having wavelengths between 380 nm and 440 nm).

Any suitable UV absorbing and UV/HEVL absorbing vinyl monomers may be used in the polymerizable compositions to prepare the preformed SiHy contact lenses of the present invention. Examples of preferred UV absorbing and UV/HEVL absorbing vinyl monomers 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-methoxy ... 2-(2'-hydroxy-5'-methacryloxypropylphenyl)benzotriazole, 2-hydroxy-5-methoxy-3-(5-(trifluoromethyl)-2H-benzo[d][1,2,3]triazol-2-yl)benzyl methacrylate (WL-1), 2-hydroxy-5-methoxy-3-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)benzyl methacrylate (WL-5), 3-(5-fluoro-2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzyl methacrylate (WL-2), 3-(2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzyl methacrylate (WL-3), 3-(5-chloro-2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzyl methacrylate (WL-4), 2-hydroxy-5-methoxy-3-(5-methyl-2H-benzo[d][1,2,3]triazol-2-yl)benzyl methacrylate (WL-6), 2-hydroxy-5-methyl-3-(5-(trifluoromethyl)-2H-benzo[d][1,2,3]triazol-2-yl)benzyl Methacrylate (WL-7), 4-allyl-2-(5-chloro-2H-benzo[d][1,2,3]triazol-2-yl)-6-methoxyphenol (WL-8), 2-{2'-hydroxy-3'-tert-5'[3"-(4"-vinylbenzyloxy)propoxy]phenyl}-5-methoxy-2H-benzotriazole, phenol, 2-(5-chloro-2H-benzotriazol-2-yl)-6-(1,1-dimethylethyl)-4-ethenyl-(UVAM), 2-[2'-hydroxy-5'-(2-methacryloxyethyl)phenyl)]-2H-benzotriazole (2-propenoic acid, 2-methyl-, 2-[3-( 2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl ester, Norbloc), 2-{2'-hydroxy-3'-tert-butyl-5'-[3'-methacryloyloxypropoxy]phenyl}-2H-benzotriazole, 2-{2'-hydroxy-3'-tert-butyl-5'-[3'-methacryloyloxypropoxy]phenyl}-5-methoxy-2H-benzotriazole (UV13), 2-{2'-hydroxy-3'-tert-butyl-5'-[3'-methacryloyloxypropoxy]phenyl}-5-chloro-2H-benzotriazole (UV28), 2-[2'-hydroxy -3'-tert-butyl-5'-(3'-acryloyloxypropoxy)phenyl]-5-trifluoromethyl-2H-benzotriazole (UV23), 2-(2'-hydroxy-5-methacrylamidophenyl)-5-methoxybenzotriazole (UV6), 2-(3-allyl-2-hydroxy-5-methylphenyl)-2H-benzotriazole (UV9), 2-(2-hydroxy-3-methallyl-5-methylphenyl)-2H-benzotriazole (UV12), 2-3'-t-butyl-2'-hydroxy-5'-(3"-dimethylvinylsilylpropoxy)-2'-hydroxy-phenyl)-5-methoxybenzo Triazole (UV15), 2-(2'-hydroxy-5'-methacryloylpropyl-3'-tert-butyl-phenyl)-5-methoxy-2H-benzotriazole (UV16), 2-(2'-hydroxy-5'-acryloylpropyl-3'-tert-butyl-phenyl)-5-methoxy-2H-benzotriazole (UV16A), 2-Methylacrylic acid 3-[3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl]-propyl ester (16-100, CAS#96478-15-8), 2-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2 H-benzo[d][1,2,3]triazol-2-yl)phenoxy)ethyl methacrylate (16-102), Phenol, 2-(5-chloro-2H-benzotriazol-2-yl)-6-methoxy-4-(2-propen-1-yl) (CAS#1260141-20-5), 2-[2-hydroxy-5-[3-(methacryloyloxy)propyl]-3-tert-butylphenyl]-5-chloro-2H-benzotriazole, Phenol, 2-(5-ethenyl-2H-benzotriazol-2-yl)-4-methyl-, homopolymer (9CI) (CAS#83063-87-0). According to the present invention, the polymerizable composition comprises from about 0.1% to about 3.0% by weight, preferably from about 0.2% to about 2.5% by weight, and more preferably from about 0.3% to about 2.0% by weight, of one or more UV absorbing vinyl monomers, relative to the amount of all polymerizable components in the polymerizable composition.

When vinyl monomers capable of absorbing ultraviolet and high energy visible light (HEVL) are used in the present invention, a germanium-based Norrish type I photoinitiator and a light source comprising light in the range of about 400 to about 550 nm are preferably used to initiate free radical polymerization. Any germanium-based Norrish type I photoinitiator can be used in the present invention as long as it can initiate free radical polymerization under irradiation with a light source comprising light in the range of about 400 to about 550 nm. An example of a Germane-based Norrish type I photoinitiator is an acylgermanium compound described in U.S. Pat. No. 7,605,190.

A bioactive agent is any compound capable of preventing ocular disease or alleviating the symptoms of ocular disease. A bioactive agent may be a drug, an amino acid (e.g., taurine, glycine, etc.), a polypeptide, a protein, a nucleic acid, or any combination thereof. Examples of drugs useful herein include, but are not limited to, rebamipide, ketotifen, olaptidine, cromoglycolate, cyclosporine, nedocromil, levocabastine, lodoxamide, ketotifen, or pharma- ceutically acceptable salts or esters thereof. Other examples of bioactive agents include 2-pyrrolidone-5-carboxylic acid (PCA), alpha-hydroxyl acids (e.g., glycolic acid, lactic acid, malic acid, tartaric acid, mandelic acid, and citric acid and their salts), linoleic acid and gamma-linoleic acid, and vitamins (e.g., B5, A, B6, etc.).

Examples of leachable lubricants include, but are not limited to, mucin-like materials (e.g., polyglycolic acid) and non-crosslinkable hydrophilic polymers (i.e., without ethylenically unsaturated groups). Any hydrophilic polymer or copolymer that does not contain any ethylenically unsaturated groups can be used as a leachable lubricant. Preferred examples of non-crosslinkable hydrophilic polymers include, but are not limited to, polyvinyl alcohol (PVA), polyamides, polyimides, polylactones, homopolymers of vinyllactams, copolymers of at least one vinyllactam with or without 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, poly2-ethyloxazoline, heparin polysaccharides, polysaccharides, and mixtures thereof. The number average molecular weight M of the non-crosslinkable hydrophilic polymers is 0.01 to 0.01._nis preferably 5,000 to 1,000,000.

Examples of exudative tear stabilizers include, but are not limited to, phospholipids, monoglycerides, diglycerides, triglycerides, glycolipids, glyceroglycolipids, sphingolipids, sphingoglycolipids, fatty 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, fatty alcohol having 8 to 36 carbon atoms, or mixtures thereof.

The polymerizable composition (SiHy lens formulation) may be a solvent-free clear liquid prepared by mixing all the polymerizable components and other essential ingredients, or it may be a solution prepared by dissolving all the desired components in any suitable solvent known to those skilled in the art, such as a mixture of water and one or more organic solvents miscible with water, an organic solvent, or a mixture of one or more organic solvents. The term "solvent" refers to a chemical that cannot participate in a free radical polymerization reaction.

Solventless lens SiHy lens formulations typically contain at least one blending vinyl monomer as a reactive solvent to dissolve all other polymerizable components of the solventless SiHy lens formulation. Examples of preferred blending vinyl monomers include C₁~C₁₀Examples of suitable vinyl monomers include alkyl (meth)acrylates (e.g., methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, isopropyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, pentyl (meth)acrylate, hexyl (meth)acrylate, etc.), cyclopentyl acrylate, cyclohexyl methacrylate, cyclohexyl acrylate, isobornyl (meth)acrylate, styrene, 4,6-trimethylstyrene (TMS), t-butylstyrene (TBS), trifluoroethyl (meth)acrylate, hexafluoro-isopropyl (meth)acrylate, hexafluorobutyl (meth)acrylate, or combinations thereof. Preferably, methyl methacrylate is used as the blend vinyl monomer in the preparation of the solventless SiHy lens formulation.

Any solvent can be used in the present invention. 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 methyl ether acetate, dipropylene glycol methyl ether acetate, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, propylene glycol n-butyl ether, dipropylene glycol n-butyl ether, tripropylene glycol n-butyl ether, ... ethylene glycol phenyl ether 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-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 3-ethyl-3-pentanol, 1-ethylcyclopentanol, 3-hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol, 2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol, and 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl-2-propanol, t-amyl alcohol, isopropanol, 1-methyl-2-pyrrolidone, N,N-dimethylpropionamide, dimethylformamide, dimethylacetamide, dimethylpropionamide, N-methylpyrrolidinone, and mixtures thereof.

Numerous SiHy lens formulations have been described in numerous patents and patent applications published up to the filing date of this application and have been used to manufacture commercially available SiHy contact lenses. Examples of commercially available SiHy contact lenses include, but are not limited to, asmofilcon A, balafilcon A, comfilcon A, delefilcon A, efrofilcon A, enfilcon A, fanfilcon A, galyfilcon A, lotrafilcon A, lotrafilcon B, narafilcon A, narafilcon B, senofilcon A, senofilcon B, senofilcon C, smafilcon A, somofilcon A, and stenfilcon A.

The SiHy lens formulation (ie, the polymerizable composition) can be cured (polymerized) thermally or actinically, preferably in a mold for casting a contact lens, as is well known to those skilled in the art.

The thermal polymerization is conveniently carried out at a temperature of, for example, 25 to 120° C., preferably 40 to 100° C. The reaction time may vary within wide limits but is conveniently, for example, 1 to 24 hours, or preferably 2 to 12 hours. It is advantageous to previously degas the components and the solvent used in the polymerization reaction and to carry out the above copolymerization reaction under an inert atmosphere, for example under a nitrogen or argon atmosphere.

The actinic polymerization may then be triggered off by actinic radiation, e.g. light, in particular UV light or visible light of a suitable wavelength. The spectral requirements can be controlled, if appropriate, by the addition of suitable sensitizers.

In a preferred embodiment, the inner layer or lens bulk material is comprised of a silicone hydrogel material comprising at least one repeating unit of a polysiloxane vinyl monomer (preferably selected from those described above) and at least one repeating unit of a hydrophilic vinyl monomer (preferably selected from those described above).

In a preferred embodiment, the inner layer or lens bulk material is comprised of a silicone hydrogel material comprising at least one repeating unit of a polysiloxane vinyl crosslinker (preferably selected from those described above) and at least one repeating unit of a hydrophilic vinyl monomer (preferably selected from those described above).

In a preferred embodiment, the inner layer or lens bulk material is comprised of a silicone hydrogel material comprising at least one repeating unit of a polysiloxane vinyl monomer (preferably selected from those described above) and at least one repeating unit of a hydrophilic N-vinyl amide monomer (preferably selected from those described above).

In a preferred embodiment, the inner layer or lens bulk material is comprised of a silicone hydrogel material comprising at least one repeating unit of a polysiloxane vinyl crosslinker (preferably selected from those described above) and at least one repeating unit of a hydrophilic N-vinyl amide monomer (preferably selected from those described above).

In a preferred embodiment, the inner layer or lens bulk material is comprised of a silicone hydrogel material comprising at least one repeating unit of a polycarbosiloxane vinyl monomer (preferably selected from those described above) and at least one repeating unit of a hydrophilic vinyl monomer (preferably selected from those described above).

In a preferred embodiment, the inner layer or lens bulk material is comprised of a silicone hydrogel material comprising at least one repeating unit of a polycarbosiloxane vinyl crosslinker (preferably selected from those described above) and at least one repeating unit of a hydrophilic vinyl monomer (preferably selected from those described above).

In a preferred embodiment, the inner layer or lens bulk material is comprised of a silicone hydrogel material comprising at least one repeating unit of a polycarbosiloxane vinyl monomer (preferably selected from those described above) and at least one repeating unit of a hydrophilic N-vinyl amide monomer (preferably selected from those described above).

In a preferred embodiment, the inner layer or lens bulk material is comprised of a silicone hydrogel material comprising at least one repeating unit of a polycarbosiloxane vinyl crosslinker (preferably selected from those described above) and at least one repeating unit of a hydrophilic N-vinyl amide monomer (preferably selected from those described above).

In a preferred embodiment, the inner layer or lens bulk material consists of a silicone hydrogel material comprising at least one repeat unit of a silicone-containing vinyl monomer having a bis(trialkylsilyloxy)alkylsilyl or tris(trialkylsilyloxy)silyl group (preferably selected from those described above) and at least one repeat unit of a hydrophilic vinyl monomer (preferably selected from those described above).

In a preferred embodiment, the inner layer or lens bulk material is comprised of a silicone hydrogel material comprising repeating units of at least one polycarbosiloxane vinyl crosslinker (preferably selected from those described above), at least one repeating unit of a silicone-containing vinyl monomer having a bis(trialkylsilyloxy)alkylsilyl or tris(trialkylsilyloxy)silyl group (preferably selected from those described above), and at least one repeating unit of a hydrophilic vinyl monomer (preferably selected from those described above).

In a preferred embodiment, the inner layer or lens bulk material consists of a silicone hydrogel material comprising repeat units of at least one silicone-containing vinyl monomer having a bis(trialkylsilyloxy)alkylsilyl or tris(trialkylsilyloxy)silyl group (preferably selected from those described above) and at least one hydrophilic N-vinyl amide monomer repeat unit (preferably selected from those described above).

In a preferred embodiment, the inner layer or lens bulk material is comprised of a silicone hydrogel material comprising repeating units of at least one polycarbosiloxane vinyl crosslinker (preferably selected from those described above), at least one repeating unit of a silicone-containing vinyl monomer having a bis(trialkylsilyloxy)alkylsilyl or tris(trialkylsilyloxy)silyl group (preferably selected from those described above), and at least one repeating unit of a hydrophilic N-vinyl amide monomer (preferably selected from those described above).

According to any one of the preferred embodiments of the present invention, the inner layer or lens bulk material is comprised of a silicone hydrogel material further comprising repeat units of one or more blended vinyl monomers, preferably in an amount of about 25% by weight or less (preferably about 20% by weight or less, more preferably about 15% by weight or less) based on the dry weight of the inner layer of silicone hydrogel material. The amount of repeat units of the blended vinyl monomers can be calculated based on the amount of the blended vinyl monomers in the polymerizable composition used in the preparation of the pre-formed silicone hydrogel contact lens (i.e., the inner layer) relative to the total amount of all polymerizable components in the polymerizable composition.

According to any one of the preferred embodiments of the present invention, the inner layer or lens bulk material is comprised of a silicone hydrogel material further comprising one or more repeating units of a non-silicone vinyl crosslinker (preferably selected from those described above), preferably in an amount of about 1.0 wt.% or less (preferably about 0.8 wt.% or less, more preferably about 0.05 wt.% to about 0.6 wt.%) based on the dry weight of the inner layer. The amount of repeating units of a non-silicone vinyl crosslinker can be calculated based on the amount of the non-silicone vinyl crosslinker in the polymerizable composition used in preparing the pre-formed silicone hydrogel contact lens (i.e., the inner layer) relative to the total amount of all polymerizable components of the polymerizable composition.

According to any one of the preferred embodiments of the present invention, the inner layer or lens bulk material is made of a naturally wettable silicone hydrogel material (i.e., a preformed silicone hydrogel contact lens that is naturally wettable without being subjected to any post-curing surface treatment). Naturally wettable preformed SiHy contact lenses are disclosed in U.S. Patent Nos. 6,367,929, 6,822,016, 7,052,131, 7,249,848, 6,867,245, 7,268,198, 7,540,609, 7,572,841, and 7,750,079. Specification, Specification No. 7934830, Specification No. 8231218, Specification No. 8367746, Specification No. 8445614, Specification No. 8481662, Specification No. Specification No. 8487058, Specification No. 8513325, Specification No. 8703891, Specification No. 8820928, Specification No. 8865789, Specification No. 89371 Specification No. 10, Specification No. 8937111, Specification No. 9057821, Specification No. 9057822, Specification No. 9121998, Specification No. 9,125,808 Specification, Specification No. 9140825, Specification No. 9140908, Specification No. 9156934, Specification No. 9164298, Specification No. 9170349, Specification No. Nos. 9188702, 9217813, 9296159, 9322959, 9322960, 9360594, and 9529119, as well as U.S. Provisional Patent Application Nos. 16/000,930 and 16/000,933.

According to the present invention, the silicone hydrogel material of the inner layer (or of the lens 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 barrers, and most preferably at least about 110 barrers. The silicone hydrogel material may also have an equilibrium water content of about 10% to about 70% by weight, preferably about 10% to about 65% by weight, more preferably about 10% to about 60% by weight, even more preferably about 15% to about 55% by weight, and most preferably about 15% to about 50% by weight. The silicone hydrogel material may further have a bulk modulus or bulk Young's modulus of about 0.3 MPa to about 1.8 MPa, preferably about 0.4 MPa to about 1.5 MPa, and more preferably about 0.5 MPa to about 1.2 MPa (hereinafter, the terms "flexibility", "elastic modulus", and "Young's modulus" are used interchangeably in this application to mean bulk modulus, unless the term is modified by the word "surface"). The oxygen permeability, elastic modulus and water content of the inner layer of the silicone hydrogel material of the contact lens of the present invention can be determined by measuring the oxygen permeability, elastic modulus and water content of the preformed SiHy lens from which the inner layer is derived.It should be understood that, as a reasonable approximation, the elastic modulus of the SiHy contact lens of the present invention can be considered to be the elastic modulus of the silicone hydrogel material of the inner layer, since the outer hydrogel layer is much thinner.Those skilled in the art are familiar with the method of determining the elastic modulus and water content of silicone hydrogel material or SiHy contact lens.For example, all commercially available SiHy contact lenses have reported values of oxygen permeability, elastic modulus and water content.

According to various aspects of the present invention, the thicknesses of the outer surface hydrogel layer, the anterior outer surface hydrogel layer, and the posterior outer surface hydrogel layer vary depending on the inner layer or lens bulk material of the contact lens of the present invention, to ensure biocompatibility of the contact lens, provide sufficient wearing comfort, and prevent exposure of the underlying lens bulk material to the eye.

When the inner layer or lens bulk material is a rigid plastic material (preformed hard contact lenses) or a rigid gas permeable lens material (i.e., preformed rigid gas permeable contact lenses), the thickness of the outer surface hydrogel layer, the front outer surface hydrogel layer, and the rear outer surface hydrogel layer is from about 1.0 μm to about 20 μm, preferably from about 2.0 μm to about 15 μm, more preferably from about 2.0 μm to about 10 μm, and even more preferably from about 2.5 μm to about 8 μm.

When the inner layer or lens bulk material is a crosslinked silicone material (i.e., a preformed silicone contact lens), the thickness of the outer surface hydrogel layer, the front outer surface hydrogel layer, and the rear outer surface hydrogel layer is from about 2.0 μm to about 25 μm, preferably from about 3.0 μm to about 25 μm, more preferably from about 4.0 μm to about 20 μm, and even more preferably from about 5.0 μm to about 20 μm.

When the inner layer or lens bulk material is a crosslinked non-silicone hydrogel material (i.e., a preformed non-silicone hydrogel contact lens), the thickness of the outer surface hydrogel layer, the anterior outer surface hydrogel layer, and the posterior outer surface hydrogel layer is from about 0.25 μm to about 20 μm, preferably from about 0.50 μm to about 15 μm, more preferably from about 0.5 μm to about 10 μm, and even more preferably from about 0.5 μm to about 6 μm.

When the inner layer or lens bulk material is a silicone hydrogel material that is not naturally wettable (i.e., a preformed silicone hydrogel contact lens), the thickness of the outer surface hydrogel layer, the anterior outer surface hydrogel layer, and the posterior outer surface hydrogel layer is from about 0.5 μm to about 25 μm, preferably from about 1.0 μm to about 20 μm, more preferably from about 1.0 μm to about 15 μm, and even more preferably from about 1.5 μm to about 10 μm.

When the inner layer or lens bulk material is a naturally wettable crosslinked silicone hydrogel material (i.e., a preformed silicone hydrogel contact lens), the thickness of the outer surface hydrogel layer, the anterior outer surface hydrogel layer, and the posterior outer surface hydrogel layer is from about 0.25 μm to about 20 μm, preferably from about 0.5 μm to about 20 μm, more preferably from about 0.5 μm to about 15 μm, and even more preferably from about 1.0 μm to about 10 μm.

The anterior and posterior outer hydrogel layers of the present contact lenses are preferably substantially identical to one another (ie, resulting in the outer surface hydrogel layers) and are crosslinked coatings that are applied onto a preformed contact lens.

In a preferred embodiment, the front and rear exterior hydrogel layers, independent of one another, and the outer surface hydrogel layer, are comprised of at least 25 mol % (preferably at least 35 mol %, more preferably at least 45 mol %, and even more preferably at least 55 mol %) of an alkyl(meth)acrylamide (any one of the above), N-2-dimethylaminoethyl(meth)acrylamide, dimethylaminoethyl(meth)acrylate, hydroxyl-containing acrylic monomer (any one of the above), N-vinylamide monomer (any one of the above), methylene-containing pyrrolidone monomer (i.e., pyrrolidone derivatives each having a methylene group attached to the pyrrolidone ring at the 3 or 5 position) (any one of the above), C₁~C₄The monomers are selected from the group consisting of (meth)acrylate monomers having an alkoxyethoxy group (any one of the above), vinyl ether monomers (any one of the above), allyl ether monomers (any one of the above), and combinations thereof (preferably, (meth)acrylamide, dimethyl(meth)acrylamide, N-2-hydroxyethyl(meth)acrylamide, N,N-bis(hydroxyethyl)(meth)acrylamide, N-2,3-dihydroxypropyl(meth)acrylamide, N-tris(hydroxymethyl)methyl(meth)acrylamide, 2-hydroxyethyl(meth)acrylate, glycerol methacrylate (GMA), tetra(ethylene glycol) (meth)acrylamide, ... poly(ethylene glycol) (meth)acrylate, poly(ethylene glycol) ethyl (meth)acrylamide having a number average molecular weight of up to 1500, poly(ethylene glycol) (meth)acrylate having a number average molecular weight of up to 1500, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, N-vinylformamide, N-vinylacetamide, 1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, tetra(ethylene glycol) methyl ether (meth)acrylate, methoxypoly(ethylene glycol) ethyl (meth)acrylamide having a number average molecular weight of up to 1500, C having a weight average molecular weight of up to 1500₁~C₄-alkoxy polyethylene glycol (meth)acrylate, tetra(ethylene glycol) monovinyl ether, poly(ethylene glycol) monovinyl ether, tetra(ethylene glycol) methyl vinyl ether, poly(ethylene glycol) methyl vinyl ether, tetra(ethylene glycol) monoallyl ether, poly(ethylene glycol) monoallyl ether, tetra(ethylene glycol) methyl allyl ether, poly(ethylene glycol) methyl allyl ether, vinyl alcohol, allyl alcohol, and combinations thereof, more preferably (meth)acrylamide, dimethyl(meth)acrylamide, N-2-hydroxyethyl ether, N ... propylethyl (meth)acrylamide, N,N-bis(hydroxyethyl) (meth)acrylamide, N-2,3-dihydroxypropyl (meth)acrylamide, N-tris(hydroxymethyl)methyl (meth)acrylamide, 2-hydroxyethyl (meth)acrylate, glycerol methacrylate (GMA), poly(ethylene glycol)ethyl (meth)acrylamide having a number average molecular weight of up to 1500, poly(ethylene glycol) (meth)acrylate having a number average molecular weight of up to 1500, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, methoxypoly(ethylene glycol)ethyl (meth)acrylamide having a number average molecular weight of up to 1500 amide, methoxypolyethylene glycol (meth)acrylate having a weight average molecular weight of up to 1500, poly(ethylene glycol) monovinyl ether, poly(ethylene glycol) methyl vinyl ether, poly(ethylene glycol) monoallyl ether, poly(ethylene glycol) methyl allyl ether, vinyl alcohol, allyl alcohol, and combinations thereof, and even more preferably selected from the group consisting of (meth)acrylamide, dimethyl(meth)acrylamide, N-2-hydroxyethyl(meth)acrylamide, N,N-bis(hydroxyethyl)(meth)acrylamide, N-2,3-dihydroxypropyl(meth)acrylamide, A crosslinked polymeric material comprising repeating monomer units of at least one hydrophilic vinyl monomer selected from the group consisting of N-tris(hydroxymethyl)methyl(meth)acrylamide, poly(ethylene glycol)ethyl(meth)acrylamide having a number average molecular weight of up to 1500, poly(ethylene glycol)(meth)acrylate having a number average molecular weight of up to 1500, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, methoxypoly(ethylene glycol)ethyl(meth)acrylamide having a number average molecular weight of up to 1500, methoxypolyethylene glycol(meth)acrylate having a weight average molecular weight of up to 1500, and combinations thereof.

In a preferred embodiment, the front and rear exterior hydrogel layers, as well as the outer surface hydrogel layer, independent of one another, are crosslinked polymeric materials comprising at least 25 mol % (preferably at least 35 mol %, more preferably at least 45 mol %, even more preferably at least 55 mol %) of repeating monomer units of at least one phosphrylcholine-containing vinyl monomer, preferably selected from the group consisting of (meth)acryloyloxyethyl phosphorylcholine, (meth)acryloyloxypropyl phosphorylcholine, 4-((meth)acryloyloxy)butyl-2'-(trimethylammonio)ethyl phosphate, 2-[(meth)acryloylamino]ethyl-2'-(trimethylammonio)ethyl phosphate, 3-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 4-[(meth)acryloylamino]butyl-2'-(trimethylammonio)ethyl phosphate, and combinations thereof.

In a preferred embodiment, the independent front and rear exterior hydrogel layers and the outer surface hydrogel layer are crosslinked polymeric materials comprising poly(ethylene glycol) chains. The poly(ethylene glycol) chains are preferably (1)-NH₂(2) pol (ethylene glycol) with one unique functional group: -NH₂(3) poly(ethylene glycol) having two terminal functional groups selected from the group consisting of -NH₂, -COOH, -SH, and combinations thereof; and (4) multi-arm poly(ethylene glycol)s having one or more functional groups selected from the group consisting of -COOH, -SH, and combinations thereof.

According to a preferred embodiment, the anterior and posterior outer hydrogel layers of the present contact lenses are identical to one another and are substantially uniform in thickness, merge at the edges of the contact lens to completely cover the inner layers, and have an equilibrium water content of at least 80% by weight, preferably at least 85% by weight, more preferably at least about 90% by weight, and even more preferably at least 95% by weight.

According to a preferred embodiment, the outer surface hydrogel layer of the present contact lenses comprises an equilibrium water content of at least 80% by weight, preferably at least 85% by weight, more preferably at least about 90% by weight, and even more preferably at least 95% by weight.

According to the present invention, each of the front and rear outer hydrogel layers is substantially free of silicone, preferably completely free of silicone. However, when X-ray photoelectron spectroscopy (XPS) is used to verify the presence or absence of silicon in the outer hydrogel layer (typically with a probing depth of 1.5-6 nm), it is well known that the sample is inevitably contaminated by silicon in the environment, as shown by the detection of silicon by XPS on the surface of a sample that theoretically does not contain any silicon atoms, such as polyethylene sheet from Goodfellow (1.3±0.2%), DAILIES® AquaComfortPlus® contact lens from Alcon (1.7±0.9%), or ACUVUE® Moist from Johnson &amp; Johnson (2.8±0.9%). Thus, the term "substantially silicon-free" is used herein to mean that the surface silicon atomic concentration measured by XPS on a 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 atomic concentration of a control sample known to be inherently (theoretically) silicon-free (e.g., polyethylene sheet, DAILIES® AquaComfortPlus contact lens from Alcon, or ACUVUE® Moist from Johnson &amp; Johnson). Alternatively, each outer hydrogel layer of the SiHy contact lens of the present invention is substantially silicon-free, as characterized by having a silicon atomic concentration of about 5% or less, preferably about 4% or less, and even more preferably about 3% or less of the total elemental percentage as measured by XPS analysis of the contact lens in the dry state. It will be appreciated that, optionally (though not preferred), a small percentage of silicone may be incorporated into the polymer network of the outer hydrogel layer so long as it does not significantly degrade the surface properties (hydrophilicity, wettability, and/or lubricity) of the contact lens.

In a preferred embodiment, each of the front and rear outer hydrogel layers (crosslinked coatings) has high finger-rubbing resistance, as characterized by no visible surface crack lines under dark field after rubbing the contact lens between fingers.It is believed that surface cracks caused by finger rubbing may reduce surface lubricity and/or may not prevent silicone from migrating (exposing) on the surface.Surface cracks also indicate the presence of excessive crosslink density in the surface layer, which may affect the surface modulus.Preferably, the non-silicone hydrogel material in the outer hydrogel layer (crosslinked coating) contains crosslinks from azetidinium groups during thermally induced coupling reaction.

In another preferred embodiment, the contact lens of the present invention further comprises two transition layers of polymeric material in its layered structure form. Each of the two transition layers is located between the inner layer and one of the anterior and posterior outer hydrogel layers. Each transition layer is substantially uniform in thickness. Each transition layer has a thickness of at least about 0.05 μm, preferably about 0.05 μm to about 10 μm, more preferably about 0.1 μm to about 7.5 μm, and even more preferably about 0.15 μm to about 5 μm. The transition layers merge at the peripheral edge of the contact lens and completely surround the inner layer of lens material.

As is well known to those skilled in the art, the layered structure morphology of the contact lenses of the present invention can be established by atomic force microscopy (AFM) analysis of cross-sections of contact lenses in a fully hydrated state (i.e., directly in water or buffered saline). As is well known to those skilled in the art, the average thickness of each outer hydrogel layer can be determined from the AFM images.

The two transition layers of the contact lenses of the present invention are essentially base (or primer or anchor) coatings (or layers) that are applied to the preformed contact lens before the crosslinked coating (outer hydrogel layer) is applied onto the preformed contact lens. The transition layer (base coating or anchor layer) serves to anchor/attach the outer hydrogel layer. Preferably, the transition layer comprises a carboxyl (COOH) containing polymer crosslinked with polyaziridine, preferably acrylic or methacrylic acid or C crosslinked with polyaziridine.₂~C₁₂The transition layers include homo- or copolymers of alkylacrylic acids. It will be appreciated that the carboxyl-containing polymer may permeate into the bulk material and extend into the outer hydrogel layers. If such permeation occurs into the inner layers of the lens material, each transition layer will contain carboxyl-containing polymer and lens material entangled together.

In another preferred embodiment, each of the independent front and back outer hydrogel layers has a reduced surface modulus relative to the inner layer of at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, and most preferably at least about 40%.

The surface modulus of the cross section can be characterized (imaged) by AFM (for example, according to nanoindentation) to visualize any change in surface modulus from the posterior surface side to the anterior surface side across the cross section.A significant change (for example, about 30% or more) observed in surface modulus (by inspecting the AFM image) along the shortest line between the anterior surface and the posterior surface across the cross section of the fully hydrated contact lens indicates a transition from one layer to another layer.

In any one of the above-described preferred embodiments of the various aspects of the present invention, the contact lenses of the present invention have a friction rating of about 2 or less (preferably about 1.5 or less, more preferably about 1.0 or less, and even more preferably about 0.5 or less) after 30 cycles of manual rubbing testing.

In any one of the above-described preferred embodiments of the various aspects of the present invention, the contact lenses of the present invention have a UVB transmittance of about 10% or less (preferably about 5% or less, more preferably about 2.5% or less, and even more preferably about 1% or less) from 280 to 315 nanometers, a UVA transmittance of about 30% or less (preferably about 20% or less, more preferably about 10% or less, and even more preferably about 5% or less) from 315 to 380 nanometers, and a violet transmittance of 0% to about 70%, preferably 5% to about 60%, more preferably 5% to about 50%, and even more preferably 5% to about 40% from 380 nm to 440 nm.

The contact lenses of the present invention may be obtained or developed by any method known to those skilled in the art.

For example, the contact lenses of the present invention can be obtained by neutralizing a preformed water gradient contact lens with a polyaziridine having a number average molecular weight of about 2000 daltons or less (preferably 250 daltons to 1500 daltons, more preferably 300 daltons to 1000 daltons, and even more preferably 350 daltons to about 800 daltons) and at least two aziridine groups.

Preformed water gradient contact lenses are described in U.S. Pat. Nos. 8,480,227, 8,529,057, and 9,505,184, as well as U.S. Patent Application Publication Nos. 2017/0068018A1, 2017/0068019A1, 2017/0165932A1, 2018/0079157A1, 2018/0079158A1, and 2018/0079159A1. Similar to the procedures described in 018/0081197 A1, 2018/0113236 A1 and 2018/0120590 A1, a contact lens precursor comprising an anchor layer (or base coating) of a polyanionic polymer having reactive functional groups (e.g., carboxyl groups) can be obtained by heating in an aqueous solution comprising a thermally crosslinkable hydrophilic polymer material.

A contact lens precursor having an anchor layer thereon can be obtained by contacting a preformed contact lens with a polyanionic polymer solution having a pH of about 1.0 to about 3.0 for a length of time sufficient to form an anchor layer of the polyanionic polymer having the desired thickness.

Contacting the preformed contact lens with the polymeric coating solution can occur by dipping it into the coating solution or by spraying it with the coating solution. One contacting process involves simply dipping the contact lens into a bath of coating solution for a period of time, or alternatively, dipping the contact lens sequentially into a series of baths of coating solution for a shorter predefined period of time in each bath. Another contacting process involves simply spraying the coating solution. However, numerous alternative methods involve various combinations of spraying and dipping steps that can be envisioned by one skilled in the art.

Any polyanionic polymer can be used to form the anchor layer on the preformed contact lens as long as it contains at least 60 mole % of one or more carboxyl-containing acrylic monomer repeat units (any one of those described above). Examples of preferred polyanionic polymers include, but are not limited to, polyacrylic acid, polymethacrylic acid, poly(ethylacrylic acid), poly(acrylic acid-co-methacrylic acid), poly[ethylacrylic acid-co-(meth)acrylic acid], poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone], poly[ethylacrylic acid-co-acrylamide], poly[ethylacrylic acid-co-vinylpyrrolidone], poly[(meth)acrylic acid-co-vinyl acetate], poly[ethylacrylic acid-co-vinyl acetate], or combinations thereof. Preferably, the polyanionic polymer is polyacrylic acid, polymethacrylic acid, or combinations thereof.

According to the present invention, the number average molecular weight M of a polyanionic polymer for forming an anchor layer (or base coating) on a preformed contact lens with or without a plasma coating is_nis at least about 25,000 daltons, preferably at least about 50,000 daltons, and more preferably from about 100,000 daltons to about 5,000,000 daltons.

The solution of polyanionic polymer for forming an anchor layer (or base coating) on a preformed contact lens with or without plasma coating can be prepared by dissolving one or more polyanionic polymers in water, a mixture of water and one or more organic solvents miscible with water, an organic solvent, or a mixture of one or more organic solvents. Preferably, the polyanionic 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 swell the preformed contact lens, so that a portion of the polyanionic polymer can penetrate into the preformed contact lens to increase the durability and thickness of the anchor layer (base coating). Any of the above organic solvents can be used to prepare the polyanionic polymer solution as long as they can dissolve the polyanionic polymer.

The concentration of the polyanionic polymer is about 0.001% by weight to about 2.5% by weight, preferably about 0.002% by weight to about 1.5% by weight, and more preferably 0.003% by weight to about 0.75% by weight, based on the total weight of the organic solution.

As known to those skilled in the art, the thickness of the anchor layer (base coating) can be adjusted by varying the concentration of the polyanionic polymer, the contact time of the preformed contact lens with the polyanionic polymer solution, the solvent system (e.g., the amount of one or more organic solvents), or a combination thereof.

Alternatively, the contact lens precursor comprising an anchor layer thereon can be obtained by grafting a polyanionic polymer onto the surface of a preformed contact lens based on any graft polymerization technique known to those skilled in the art. For example, a preformed contact lens in a dry state is first subjected to plasma treatment with a compound having at least one reactive functional group (e.g., a vinyl monomer having a primary or secondary amino group, a carboxyl group, an epoxy group, an azlactone group, an aziridine group, or an isocyanate group) in a plasma atmosphere to form a plasma coating having reactive functional groups. The plasma-treated contact lens is reacted with a compound having a free radical initiator moiety (e.g., a thermal initiator or a photoinitiator) or preferably a living polymerization initiator moiety (e.g., an atom transfer radical polymerization (ATRP) initiator or a reversible addition-fragmentation chain transfer polymerization (RAFT) initiator) and a functional group that is co-reactive with the functional group of the plasma coating on the contact lens in the presence or absence of a coupling agent under coupling reaction conditions known to those skilled in the art. The resulting contact lens having free radical initiator moieties thereon is immersed in a solution of one or more carboxyl-containing vinyl monomers, preferably the carboxyl-containing acrylic monomers described above, and subjected to conditions which initiate free radical polymerization of these carboxyl-containing vinyl monomers to form a layer of graft-from polyanionic polymer of the carboxyl-containing vinyl monomers.

According to the present invention, the thermally crosslinkable hydrophilic polymeric material for forming the outer surface hydrogel layer or the front and rear outer hydrogel layers (i.e., crosslinked hydrophilic coating) comprises crosslinkable groups, preferably thermally crosslinkable groups (e.g., epoxy groups, azetidinium groups, or a combination thereof), more preferably azetidinium groups. Preferably, the water-soluble and crosslinkable hydrophilic polymeric material is a partially crosslinked polymeric material comprising a three-dimensional network and thermally crosslinkable groups, preferably azetidinium groups, within or attached to the network. The term "partially crosslinked" in relation to the polymeric material means that the crosslinkable groups of the starting material for producing the polymeric material are not completely consumed in the crosslinking reaction. For example, such a thermally crosslinkable hydrophilic polymeric material comprises azetidinium groups and is a partial reaction product of at least one azetidinium-containing polymer and at least one hydrophilic enhancer (i.e., wetting agent) having at least one carboxyl, primary amine, secondary amine, or thiol group, based on the crosslinking reaction shown in Scheme I: <img file="JP7635289B2_D0021.tif" /> In the formula, X₁is -S-*, -OC(=O)-*, or -NR'-*, where R' is hydrogen or C₁~C₂₀where * represents an organic radical.

Any suitable azetidinium-containing polymer can be used in the present invention. Examples of azetidinium-containing polymers include, but are not limited to, epichlorohydrin-functionalized polyamines, homopolymers of azetidinium-containing vinyl monomers, and copolymers of azetidinium-containing vinyl monomers with one or more vinyl monomers.

Preferably, the azetidinium-containing polymer is an epichlorohydrin-functionalized polyamine. The epichlorohydrin-functionalized polyamine can be obtained by reacting epichlorohydrin with a polyamine polyamine or a secondary amino group-containing polymer. For example, poly(alkyleneimine) or poly(amidoamine), which is a polycondensate derived from a polyamine and a dicarboxylic acid (e.g., adipic acid-diethylenetriamine copolymer), can be reacted with epichlorohydrin to form an epichlorohydrin-functionalized polymer; homopolymers or copolymers of mono-alkylaminoalkyl(meth)acrylates or mono-alkylaminoalkyl(meth)acrylamides can also be reacted with epichlorohydrin to form epichlorohydrin-functionalized polyamines; poly(2-oxazoline-c o-Ethyleneimine copolymers can be reacted with epichlorohydrin to form epichlorohydrin-functionalized polyamines (i.e., poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin). Reaction conditions for epichlorohydrin functionalization of polyamine or polyamidoamine polymers are taught in EP 1465931. A preferred epichlorohydrin-functionalized polyamine is polyamidoamine-epichlorohydrin (PAE), or poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin.

Polyamidoamine-epichlorohydrin is commercially available, for example, Kymene® or Polycup® resins (epichlorohydrin functionalized adipic acid-diethylenetriamine copolymers) from Hercules.

Poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin can be prepared according to the procedures described in US Patent Application Publication No. 2016/0061995A1.

Homopolymers and copolymers of azetidinium-containing vinyl monomers can be obtained according to the procedures described in US 2013/0337160 A1.

Any suitable hydrophilicity enhancers can be used in the present invention so long as they are ophthalmically compatible and contain at least one amino group, at least one carboxyl group, and/or at least one thiol group, preferably at least one carboxyl group, at least one thiol group, or a combination thereof.

Preferred classes of hydrophilicity enhancers include primary amino, secondary 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, glucosamine acid, mannosamine, sugar acid 1,4-lactone, saccharidic acid, ketodeoxynonulosonic ... acid), N-methyl-D-glucamine, 1-amino-1-deoxy-β-D-galactose, 1-amino-1-deoxysorbitol, 1-methylamino-1-deoxysorbitol, N-aminoethyl gluconamide), primary amino, secondary 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 primary amino, secondary amino, carboxyl, or thiol-containing oligosaccharides (e.g., carboxymethyl-β-cyclodextrin sodium salt, trigalacturonic acid), and combinations thereof.

Another preferred class of hydrophilic enhancers is hydrophilic polymers having one or more (primary or secondary) amino, carboxyl, and/or thiol groups.More preferably, the content of amino (-NHR' (R' is as defined above)), carboxyl (-COOH), and/or thiol (-SH) groups in the hydrophilic polymer as hydrophilic 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.

One preferred class of hydrophilic polymers as hydrophilic enhancers is, for example, carboxymethylcellulose (repeating unit -[C₆H_10-mO₅(CH₂CO₂H)_m]- (wherein m is 1 to 3), carboxyethyl cellulose (having a carboxyl content of about 40% or less estimated based on the composition of the repeating unit -[C₆H_10-mO₅(C₂H₄CO₂H)_m]- (wherein m is 1 to 3), carboxypropyl cellulose (having a carboxyl content of about 36% or less estimated based on the composition of the repeating unit -[C₆H_10-mO₅(C₃H₆CO₂H)_m]- (wherein m is 1 to 3), hyaluronic acid (with a carboxyl content of about 32% or less estimated based on the composition of the repeating unit -(C₁₃H₂₀O₉NCO₂H)-), chondroitin sulfate (with a carboxyl content of about 11% estimated based on the composition of the repeating unit -(C₁₂H₁₈O₁₃NSCO₂H)-) having an estimated carboxyl content of about 9.8% based on the composition of (primary or secondary) amino, or carboxyl-containing polysaccharides, such as saccharides of the formula (I)-(H)-(H), (I), (II), or combinations thereof.

Another preferred class of hydrophilic polymers as hydrophilicity enhancers includes poly(ethylene glycol)s (PEGs) (e.g., PEG-NH₂, PEG-SH, PEG-COOH), H₂N-PEG-NH₂, HOOC-PEG-COOH, HS-PEG-SH, H₂N-PEG-COOH, HOOC-PEG-SH, H₂These include, but are not limited to, N-PEG-SH, multi-arm PEG having one or more amino (primary or secondary), carboxyl, or thiol groups, PEG dendrimers having one or more amino (primary or secondary), carboxyl, or thiol groups, diamino (primary or secondary) or dicarboxyl terminated homo- or copolymers of non-reactive hydrophilic vinyl monomers, monoamino (primary or secondary) or monocarboxyl terminated homo- or copolymers of non-reactive hydrophilic vinyl monomers, (1) copolymers that are the polymerization product of a composition comprising up to about 60% by weight, preferably from about 0.1% to about 30% by weight, more preferably from about 0.5% to about 20% by weight, and even more preferably from about 1% to about 15% by weight of one or more reactive vinyl monomers, and (2) at least one non-reactive hydrophilic vinyl monomer, and combinations thereof.

According to the present invention, the reactive vinyl monomer may be a carboxyl-containing vinyl monomer, a primary amino-containing vinyl monomer, or a secondary amino-containing vinyl monomer.

Examples of preferred carboxyl-containing vinyl monomers include, but are not limited to, acrylic acid, methacrylic ethylacrylic acid, N-2-(meth)acrylamidoglycolic acid, and combinations thereof.

Examples of preferred primary and secondary amino-containing vinyl monomers include, but are not limited to, N-2-aminoethyl(meth)acrylamide, N-2-methylaminoethyl(meth)acrylamide, N-2-ethylaminoethyl(meth)acrylamide, N-3-aminopropyl(meth)acrylamide, N-3-methylaminopropyl(meth)acrylamide, 2-aminoethyl(meth)acrylate, 2-methylaminoethyl(meth)acrylate, 2-ethylaminoethyl(meth)acrylate, 3-aminopropyl(meth)acrylate, 3-methylaminopropyl(meth)acrylate, 3-ethylaminopropyl(meth)acrylate, 3-amino-2-hydroxypropyl(meth)acrylate, and combinations thereof.

According to the present invention, the non-reactive vinyl monomer is a vinyl monomer that does not contain any carboxyl group, primary amino group, secondary amino group, epoxide group, isocyanate group, azlactone group, or aziridine group. The non-reactive vinyl monomer is preferably a non-charged hydrophilic vinyl monomer that does not contain a carboxyl group or an amino group (any of the above-described can be used herein), a phosphorylcholine-containing vinyl monomer (any of the above-described can be used herein), or a combination thereof.

More preferably, the hydrophilic polymer as the hydrophilic enhancer is a -NH₂Poly(ethylene glycol) with one unique functional group: -NH₂, -COOH, -SH, and combinations thereof; poly(ethylene glycol);₂, -COOH, -SH, and combinations thereof; monoamide, monocarboxyl, diamino, or dicarboxyl terminated homo- or copolymers of non-reactive hydrophilic vinyl monomers; (1) from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1% to about 15% by weight of acrylic acid, methacrylic acid, ethylacrylic acid, 2-(meth)acrylamidoglycolic acid, N-2-aminoethyl(meth)acrylamide, N-2-methylaminoethyl(meth)acrylamide, N-2-ethylaminoethyl(meth)acrylamide, N-3-aminopropyl(meth)acrylamide, N-3-methyl ... (meth)acrylamide, 2-aminoethyl (meth)acrylate, 2-methylaminoethyl (meth)acrylate, 2-ethylaminoethyl (meth)acrylate, 3-aminopropyl (meth)acrylate, 3-methylaminopropyl (meth)acrylate, 3-amino-2-hydroxypropyl (meth)acrylate, or a combination thereof, and (2) acryamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, (meth)acryloyloxyethyl phosphorylcholine, N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C having a weight average molecular weight of up to 400 Daltons.₁~C₄- a copolymer that is the polymerization product of a composition comprising at least one non-reactive hydrophilic vinyl monomer selected from the group consisting of alkoxy polyethylene glycol (meth)acrylates, vinyl alcohol, and combinations thereof, wherein the non-reactive hydrophilic vinyl monomer is selected from the group consisting of alkyl (meth)acrylamides (any one of the above), N-2-dimethylaminoethyl (meth)acrylamide, dimethylaminoethyl (meth)acrylate, hydroxyl-containing acrylic monomers (any one of the above), N-vinyl amide monomers (any one of the above), methylene-containing pyrrolidone monomers (i.e., pyrrolidone derivatives each having a methylene group attached to the pyrrolidone ring at the 3 or 5 position) (any one of the above), C₁~C₄The monomer is selected from the group consisting of an acrylic monomer having an alkoxyethoxy group (any one of the above), a vinyl ether monomer (any one of the above), an allyl ether monomer (any one of the above), a phosphorylcholine-containing vinyl monomer (any one of the above), and a combination thereof (preferably, (meth)acryloyloxyethyl phosphorylcholine, (meth)acryloyloxypropyl phosphorylcholine, 4-((meth)acryloyloxy)butyl-2'-(trimethylammonio)ethyl phosphate, 2-[(meth)acryloylamino]ethyl-2'-(trimethylammonio)ethyl phosphate, 3-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 4-[(meth)acryloylamino]butyl-2'-(trimethylammonio)ethyl phosphate, (meth)acrylamide, dimethyl(meth)acrylamide, N-2-hydroxyethyl(meth)acrylamide, N,N-bis( hydroxyethyl)(meth)acrylamide, N-2,3-dihydroxypropyl(meth)acrylamide, N-tris(hydroxymethyl)methyl(meth)acrylamide, 2-hydroxyethyl(meth)acrylate, glycerol methacrylate (GMA), tetra(ethylene glycol)(meth)acrylate, poly(ethylene glycol)ethyl(meth)acrylamide having a number average molecular weight of up to 1500, poly(ethylene glycol)(meth)acrylate having a number average molecular weight of up to 1500, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, N-vinylformamide, N-vinylacetamide, 1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, tetra(ethylene glycol) methyl ether(meth)acrylate, methoxypoly(ethylene glycol)ethyl(meth)acrylamide having a number average molecular weight of up to 1500, C having a weight average molecular weight of up to 1500₁~C₄-alkoxy polyethylene glycol (meth)acrylate, tetra(ethylene glycol) monovinyl ether, poly(ethylene glycol) monovinyl ether, tetra(ethylene glycol) methyl vinyl ether, poly(ethylene glycol) methyl vinyl ether, tetra(ethylene glycol) monoallyl ether, poly(ethylene glycol) monoallyl ether, tetra(ethylene glycol) methyl allyl ether, poly(ethylene glycol) methyl allyl ether, vinyl alcohol, allyl alcohol, and combinations thereof, more preferably selected from the group consisting of (meth)acryloyloxyethyl phosphorylcholine, (meth)acryloyloxypropyl phosphorylcholine, 4-((meth)acryloyloxy)butyl-2'-(trimethylammonio)ethyl phosphate, 2-[(meth)acryloylamino]ethyl ... '-(trimethylammonio)ethyl phosphate, 3-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 4-[(meth)acryloylamino]butyl-2'-(trimethylammonio)ethyl phosphate, (meth)acrylamide, dimethyl(meth)acrylamide, N-2-hydroxyethyl(meth)acrylamide, N,N-bis(hydroxyethyl)(meth)acrylamide, N-2,3-dihydroxypropyl(meth)acrylamide, N-tris(hydroxymethyl)methyl(meth)acrylamide, 2-hydroxyethyl(meth)acrylate, glycerol methacrylate (GMA), poly(ethylene glycol)ethyl(meth)acrylamide having a number average molecular weight of up to 1500, poly(ethylene glycol)(meth)acrylate having a number average molecular weight of up to 1500, N-vinyl butyl(meth)acrylamide having a number average molecular weight of up to 1500, lolidone, N-vinyl-N-methylacetamide, methoxypoly(ethylene glycol)ethyl (meth)acrylamide having a number average molecular weight of up to 1500, methoxypolyethylene glycol (meth)acrylate having a weight average molecular weight of up to 1500, poly(ethylene glycol) monovinyl ether, poly(ethylene glycol) methyl vinyl ether, poly(ethylene glycol) monoallyl ether, poly(ethylene glycol) methyl allyl ether, vinyl alcohol, allyl alcohol, and combinations thereof, and even more preferably selected from the group consisting of (meth)acryloyloxyethyl phosphorylcholine, (meth)acryloyloxypropyl phosphorylcholine, 2-[(meth)acryloylamino]ethyl-2'-(trimethylammonio)ethyl phosphate, 3-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 4-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 5-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 6-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 7-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 8-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 9-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 10-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 11-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 12-[(meth)acryloylamino]propyl-2'-(trimethylammonio)ethyl phosphate, 13-[(meth)acryloylamino]propyl-2'-(trimethylammon N-vinyl-N-methylacetamide, methoxypoly(ethylene glycol)ethyl (meth)acrylamide having a number average molecular weight of up to 1500, methoxypolyethylene glycol (meth)acrylate having a number average molecular weight of up to 1500, and combinations thereof.

Functionalized PEG and functionalized multi-arm PEG can be obtained from a variety of commercial suppliers, such as Creative PEGWorks, Polyscience, and Shearwater Polymers.

Monoamino-, monocarboxyl-, diamino-, or dicarboxyl-terminated homo- or copolymers of one or more non-reactive hydrophilic vinyl monomers or phosphorylcholine-containing vinyl monomers can be prepared according to the procedures described in U.S. Pat. No. 6,218,508. For example, to prepare diamino- or dicarboxyl-terminated homo- or copolymers of non-reactive hydrophilic vinyl monomers, a non-reactive vinyl monomer, a chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, The vinyl monomers (such as hydroxymercaptans, aminomercaptans, or carboxyl-containing mercaptans) and optionally other vinyl monomers are copolymerized (thermally or actinically) with reactive vinyl monomers (having amino or carboxyl groups) in the presence of a free radical initiator. Typically, the molar ratio of the chain transfer agent to all vinyl monomers other than the reactive vinyl monomer is about 1:5 to about 1:100, where the molar ratio of the chain transfer agent to the reactive vinyl monomer is 1:1. In such preparations, the chain transfer agent having amino or carboxyl groups is used to control the molecular weight of the resulting hydrophilic polymer and form the ends of the resulting hydrophilic polymer, thereby imparting one terminal amino or carboxyl group to the resulting hydrophilic polymer, while the reactive vinyl monomer imparts the other terminal carboxyl or amino group to the resulting hydrophilic polymer. Similarly, to prepare monoamino- or monocarboxyl-terminated homo- or copolymers of nonreactive hydrophilic vinyl monomers, the nonreactive vinyl monomer, a chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid, or other hydroxymercaptans, aminomercaptans, or carboxyl-containing mercaptans), and optionally other vinyl monomers are copolymerized (thermally or actinically) in the absence of any reactive vinyl monomer.

Copolymers containing non-reactive hydrophilic vinyl monomers and reactive vinyl monomers (e.g., carboxyl-containing vinyl monomers, primary amino group-containing vinyl monomers, or secondary amino group-containing vinyl monomers) can be prepared according to any well-known radical polymerization method or obtained from commercial suppliers. Copolymers containing methacryloyloxyethyl phosphorylcholine and carboxyl-containing vinyl monomers (or amino-containing vinyl monomers) can be obtained from NOF Corporation (e.g., LIPIDURE®-A and -AF) or prepared according to the procedure described in U.S. Pat. No. 9,127,099.

The weight average molecular weight M of a hydrophilic polymer (as a hydrophilic enhancer) having at least one amino, carboxyl, or thiol group_wis preferably about 500 to about 5,000,000, more preferably about 1,000 to about 2,000,000, and even more preferably about 5,000 to about 1,000,000 daltons.

Water-soluble and thermally crosslinkable hydrophilic polymeric materials can be prepared according to the processes disclosed in US Patent Application Publication Nos. 2016/0061995 A1 and 2013/0337160 A1, and US Pat. No. 8,529,057.

In a preferred embodiment, the water-soluble thermally crosslinkable polymeric material can be obtained by heating a reactive aqueous solution containing at least one azetidinium-containing polymer and at least one hydrophilicity enhancer (i.e., wetting agent) having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof, to a temperature of about 35°C to about 85°C and maintaining the temperature for a sufficient period of time (about 8 hours or less, preferably about 5 hours, more preferably about 2 hours to about 4 hours). The reactive aqueous solution preferably contains about 70 mM to about 170 mM (preferably about 90 mM to about 150 mM, more preferably about 100 mM to about 130 mM) of one or more ionic compounds and a pH of at least 8.0 (preferably at least 8.5, more preferably at least 9.0, even more preferably at least 9.5). It is understood that the reaction time should be long enough to covalently bond the hydrophilic enhancer onto the polymer chain of the azetidinium-containing polymer, but short enough not to consume all of the azetidinium groups of the azetidinium-containing polymer and not form too many crosslinks between the azetidinium-containing polymer and the hydrophilic enhancer to form a gel (i.e., not water soluble). The resulting polymeric material is a lightly crosslinked polymeric material with a highly branched structure that still contains thermally crosslinkable azetidinium groups.

Those skilled in the art will appreciate that, for example, bases (e.g., NaOH, KOH, NH₄OH, or mixtures thereof) or acids (e.g., HCl, H₂SO₄, H₃PO₄In one embodiment, the present invention relates to a process for adjusting the pH of a reactive mixture by adding an acid such as acetic acid, citric acid, acetic acid, boric acid, or a mixture thereof.

According to the present invention, any ionic compound can be used in the reactive mixture. Preferably, the ionic compounds are those used as ionic tonicity adjusters and ionic buffers in ophthalmic solutions. Examples of preferred ionic tonicity adjusters include, but are not limited to, sodium chloride, potassium chloride, and combinations thereof. Examples of preferred ionic buffers include various salts of phosphates (e.g., NaH₂PO₄, Na₂HPO₄, Na₃PO₄, K.H.₂PO₄, K₂HPO₄, K₃PO₄, or mixtures thereof), various salts of boric acid (e.g., sodium borate, potassium borate, or mixtures thereof), various salts of citric acid (e.g., monosodium citrate, disodium citrate, trisodium citrate, monopotassium citrate, dipotassium citrate, tripotassium citrate, or mixtures thereof), various salts of carbonate (e.g., Na₂CO₃, NaHCO₃, K₂CO₃, K.H.C.O.₃or a mixture thereof).

A reactive aqueous solution for preparing a water-soluble thermally crosslinkable polymeric material can be prepared by dissolving a desired amount of an azetidinium-containing polymer, a desired amount of a hydrophilicity enhancing agent having at least one reactive functional group, and a desired amount of other components (e.g., ionic buffers, ionic tonicity adjusters, etc.) in water (or a mixture of water and a small amount of a water-soluble organic solvent) to form an aqueous solution, and then adjusting the pH of the aqueous solution as necessary.

According to the present invention, the concentration ratio of the hydrophilicity enhancing agent to the azetidinium-containing polymer in the reactive aqueous solution must be selected so as not to render the resulting water-soluble thermally crosslinkable polymer material water-insoluble (i.e., solubility of less than 0.005 g per 100 mL of water at room temperature) and not to consume more than about 99%, preferably about 98%, more preferably about 97%, and even more preferably about 96% of the azetidinium groups of the azetidinium-containing polymer.

In a preferred embodiment, the reactive aqueous solution contains 0.01% by weight to about 10% by weight (preferably 0.05% by weight to about 5% by weight, more preferably 0.08% by weight to about 1% by weight, and even more preferably 0.1% by weight to about 0.4% by weight) of an azetidinium-containing polymer and about 0.01% by weight to about 10% by weight (preferably 0.02% by weight to about 5% by weight, more preferably 0.05% by weight to about 2% by weight, and even more preferably 0.08% by weight to about 1.0% by weight) of a hydrophilicity enhancer having at least one reactive functional group (carboxyl, primary amino, secondary amino group), and the concentration ratio of the azetidinium-containing polymer to the hydrophilicity enhancer is about 1000:1 to 1:1000 (preferably about 500:1 to about 1:500, more preferably about 250:1 to about 1:250, and even more preferably about 100:1 to about 1:100).

In a preferred embodiment, the water-soluble thermally crosslinkable polymeric material comprises (i) about 20% to about 95% by weight of a first polymer chain derived from polyamidoamine-epichlorohydrin or poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin, and (ii) about 5% to about 80% by weight of a hydrophilic portion or second polymer chain derived from at least one hydrophilicity enhancer having at least one reactive functional group selected from the group consisting of an amino group, a carboxyl group, a thiol group, and combinations thereof, preferably a carboxyl or thiol group, wherein the hydrophilic portion or second polymer chain is an azetidium group of polyamidoamine-epichlorohydrin or poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin, respectively. (iii) an azetidinium group that is part of the first polymer chain or is a pendant or terminal group covalently attached to the first polymer chain. The composition of the chemically modified poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin or chemically modified polyamidoamine-epichlorohydrin is determined by the composition of the reaction mixture (based on the total weight of reactants) used for such polymers according to the crosslinking reaction shown in Scheme I above. For example, if the reaction mixture contains about 75% by weight of polyamidoamine-epichlorohydrin and about 25% by weight of at least one hydrophilic enhancing agent based on the total weight of the reactants, the resulting chemically modified polyamidoamine-epichlorohydrin will contain about 75% by weight of the first polymer chain derived from the polyamioamine-epichlorohydrin and about 25% by weight of the hydrophilic portion or second polymer chain derived from the at least one hydrophilic enhancing agent.

In accordance with the present invention, a preformed contact lens having an anchor layer thereon is heated in an aqueous solution containing a thermally crosslinkable hydrophilic polymeric material having azetidinium groups and, optionally but preferably, amino groups, thiol groups, carboxyl groups, or combinations thereof, at a temperature of from about 60° C. to about 140° C. for a period of time sufficient to crosslink the thermally crosslinkable hydrophilic polymeric material and simultaneously covalently bond the crosslinked thermally crosslinkable hydrophilic polymeric material onto the anchor layer to form a water gradient contact lens.

Preferably, the heating step is carried out by autoclaving the preformed contact lens with the anchor layer thereon, immersed in the aqueous coating solution, which is a packaging solution (i.e., a buffered aqueous solution having a pH of 6.7 to 7.6) in a sealed lens package, at a temperature of about 115° C. to about 125° C. for about 20 to 90 minutes. During autoclaving, those azetidinium groups that are not involved in the crosslinking reaction are converted to 2,3-dihydroxypropyl (HO-CH₂-CH(OH)-CH₂It is believed that the azetidinium-containing polymeric materials present in the lens packaging solution can be hydrolyzed to - groups, and, where applicable, converted to non-reactive polymeric wetting agents that can improve the insertion comfort of the lens. As a result, the aqueous second coating solution is ophthalmically safe after autoclaving.

Those skilled in the art are familiar with lens packages (or containers) for autoclaving and storing contact lenses. 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 being removably sealed to the base, and the base including a cavity for receiving a sterile packaging solution and a contact lens.

The lenses are packaged in individual packages, sealed, and sterilized (e.g., by autoclaving at or above about 120° C. under pressure for at least 30 minutes) before being distributed to users. Those skilled in the art will be familiar with methods of sealing and sterilizing lens packages.

In accordance with the present invention, the packaging solution contains at least one buffer and one or more other ingredients known to those skilled in the art, including, but not limited to, tonicity agents, surfactants, antibacterial agents, preservatives, and lubricants (e.g., cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone).

The packaging solution contains a sufficient amount of buffering agent to maintain the pH of the packaging solution within a desired range, e.g., within a physiologically acceptable range, preferably from about 6.5 to about 7.5. Any known physiologically compatible buffering agent may be used. Buffering agents suitable as components of the contact lens care compositions of the present invention are known to those skilled in the art. Examples include boric acid, borates, e.g., sodium borate, citric acid, citrates, e.g., potassium citrate, bicarbonates, e.g., sodium bicarbonate, tris (i.e., 2-amino-2-hydroxymethyl-1,3-propanediol), bis-tris [i.e., bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane], bis-trispropane [i.e., 1,3-bis(tris(hydroxymethyl)methylamino)propane], bis-aminopolyols, triethanolamine, ACES [i.e., N-(2-hydroxyethyl)-2-amino-1,3-propanediol], bis-tris-[ ...-[i.e., 1,3-bis(tris(hydroxymethyl)methylamino)propane], bis-aminopolyols, triethanolamine, ACES [i.e., N-(2-hydroxyethyl)-2-amino-1,3-propanediol], bis-tris- aminoethanesulfonic acid], BES [i.e., N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid], HEPES [i.e., 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid], MES [i.e., 2-(N-morpholino)ethanesulfonic acid], MOPS [i.e., 3-[N-morpholino]-propanesulfonic acid], PIPES [i.e., piperazine-N,N'-bis(2-ethanesulfonic acid], TES {i.e., N-[tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid}, salts thereof, phosphate buffer solutions, e.g., Na₂HPO₄, NaH₂PO₄, and K.H.₂PO₄or mixtures thereof. The amount of each buffer in the packaging solution is preferably 0.001% to 2% by weight, preferably 0.01% to 1% by weight, and most preferably about 0.05% to about 0.30% by weight.

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

The packaging solution of the present invention has a viscosity of about 1 centipoise to about 5 centipoise at 25°C.

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

The resulting water gradient contact lens can then be heated at a temperature between 40° C. and 140° C. in an aqueous solution containing a polyaziridine having a number average molecular weight of about 2000 Daltons or less and at least two aziridine groups in an amount sufficient to provide a water gradient contact lens having a PU of about 0.40 or 0.30 micrograms/lens or less (preferably about 0.20 micrograms/lens or less, more preferably about 0.15 micrograms/lens or less, even more preferably about 0.10 micrograms/lens or less, and most preferably about 0.05 micrograms/lens or less). Preferably, the aqueous solution is a lens packaging solution containing the necessary polyaziridine in addition to all of the necessary components described above with respect to the lens packaging solution.

Any polyaziridine can be used in the present invention to neutralize the negative charge present in water gradient contact lenses. Examples of preferred polyaziridines include, but are not limited to, trimethylolpropane tris(2-methyl-1-aziridinepropionate) (also known as PZ-28), pentaerythritol tris[3-(1-aziridinyl)propionate] (also known as PZ-33), trimethylolpropane tris(3-aziridinopropionate), Michael reaction products of vinyl crosslinkers having at least two (meth)acryloyl groups and 2-methylaziridine (or aziridine), and combinations thereof. Preferably, polyaziridines containing at least methyl-aziridinyl groups are used in the present invention.

In an alternative process for manufacturing the contact lenses of the present invention, in a process for preparing a water gradient contact lens, a contact lens precursor having an anchor layer thereon is heated in an aqueous solution containing a thermally crosslinkable hydrophilic polymeric material (any one of those described above) in the presence of a polyaziridine having a number average molecular weight of about 2000 Daltons or less and at least two aziridine groups. For example, a preformed contact lens having an anchor layer thereon is first contacted with a solution containing such a polyaziridine at or below room temperature to add the polyaziridine to the preformed contact lens, and then the polyaziridine-loaded contact lens having an anchor layer thereon is heated in an aqueous solution containing a thermally crosslinkable hydrophilic polymeric material (any one of those described above) at a temperature of about 60°C to about 140°C to form the contact lens of the present invention. Alternatively, a preformed contact lens having an anchor layer thereon is heated in an aqueous solution containing a thermally crosslinkable hydrophilic polymeric material (any one of those described above) and polyaziridine at a temperature of from about 60°C to about 140°C to form a contact lens of the present invention.

Several alternative processes for manufacturing the contact lenses of the present invention are illustrated in the Examples section.

Although various embodiments of the present invention have been described using specific terms, devices, and methods, such description is for illustrative purposes only. The words used are words of description rather than of limitation. As will be apparent to those skilled in the art, many variations and modifications of the present invention are possible without departing from the spirit and scope of the novel concepts of the present disclosure. Furthermore, it should be understood that the aspects of the various embodiments of the present invention may be interchangeable in whole or in part, or may be combined and/or used together in any manner, as set forth below.

A contact lens having a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less) and a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing or simulated abrasion cycling, the contact lens comprising an anterior surface and an opposing posterior surface, and a layered structural morphology comprising, in a direction from the anterior surface to the posterior surface, a front outer hydrogel layer, an inner layer of lens material, and a posterior outer hydrogel layer, the inner layer having a first equilibrium water content of about 70% by weight or less.<u style="Single">having</u>The separate front and rear outer hydrogel layers have a thickness of about 0.25 μm to about 25 μm when fully hydrated.<u style="Single">and</u>a second equilibrium water content greater than the first equilibrium water content, and the separate anterior and posterior outer hydrogel layers have a water swelling rate of at least 140%.

Embodiment 2: A contact lens having a polyquaternium-1 uptake ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less) and a friction rating of about 2.0 or less after 30 cycles of finger rubbing or simulated abrasion cycling, the contact lens comprising an anterior surface and an opposing posterior surface, and a layered structural morphology comprising, in a direction from the anterior surface to the posterior surface, a front outer hydrogel layer, an inner layer of lens material, and a posterior outer hydrogel layer, the inner layer having a first equilibrium water content of about 70% by weight or less.<u style="Single">having</u>The separate front and rear outer hydrogel layers have a thickness of about 0.25 μm to about 25 μm when fully hydrated.<u style="Single">and</u>a second equilibrium water content greater than the first equilibrium water content, and the separate anterior and posterior outer hydrogel layers have a water swelling rate of at least 140%.

Embodiment 3. The contact lens of embodiment 1 or 2, wherein the separate anterior and posterior outer hydrogel layers have a water swelling rate of at least 170%.

Embodiment 4. The contact lens of embodiment 1 or 2, wherein the separate anterior and posterior outer hydrogel layers have a water swelling rate of at least 200%.

Embodiment 5. The contact lens of embodiment 1 or 2, wherein the separate anterior and posterior outer hydrogel layers have a water-swelling ratio of at least 250%.

Embodiment 6. The contact lens of embodiment 1 or 2, wherein the separate anterior and posterior outer hydrogel layers have a water swelling rate of at least 300%.

Embodiment 7: A contact lens having a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less), a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing or simulated abrasion cycling, and a water content gradient that increases from the inside to one of the front or back surfaces of the contact lens, the contact lens comprising a lens bulk material completely covered with a front outer hydrogel layer and a rear outer hydrogel layer, the independent front and rear outer hydrogel layers having a thickness of about 0.25 μm to about 25 μm when fully hydrated, the lens bulk material having a first equilibrium water content of about 70% by weight or less, and the independent front and rear outer hydrogel layers having a second equilibrium water content that is at least 1.2 times the first equilibrium water content and is at least 80% by weight.

Embodiment 8: A contact lens having a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less), a friction rating of about 2.0 or less after 30 cycles of finger rubbing or simulated abrasion cycling, and a water content gradient that increases from the inside to the outside of the contact lens, the contact lens comprising a lens bulk material completely covered with a front outer hydrogel layer and a rear outer hydrogel layer, the independent front and rear outer hydrogel layers having a thickness of about 0.25 μm to about 25 μm when fully hydrated, the lens bulk material having a first equilibrium water content of about 70% by weight or less, and the independent front and rear outer hydrogel layers having a second equilibrium water content that is at least 1.2 times the first equilibrium water content and is at least 80% by weight.

Embodiment 9: A contact lens having a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less) and a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing or simulated abrasion cycling, the contact lens comprising an anterior surface and an opposing posterior surface, and a layered structural morphology comprising, in a direction from the anterior surface to the posterior surface, a front outer hydrogel layer, an inner layer of lens material, and a rear outer hydrogel layer, each of the anterior and rear outer hydrogel layers independent of one another having a reduced surface modulus of elasticity of at least about 20% compared to the inner layer.

Embodiment 10: A contact lens having a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less) and a friction rating of about 2.0 or less after 30 cycles of finger rubbing or simulated abrasion cycling, the contact lens comprising an anterior surface and an opposing posterior surface, and a layered structural morphology comprising, in a direction from the anterior surface to the posterior surface, a front outer hydrogel layer, an inner layer of lens material, and a rear outer hydrogel layer, each of the anterior and rear outer hydrogel layers independent of one another having a surface modulus that is reduced by at least about 20% compared to the inner layer.

Embodiment 11. A contact lens according to embodiment 9 or 10, wherein each of the separate anterior and posterior outer hydrogel layers has a surface modulus that is reduced by at least 25% compared to the inner layer.

Embodiment 12. A contact lens according to embodiment 9 or 10, wherein each of the separate anterior and posterior outer hydrogel layers has a surface modulus that is reduced by at least 30% compared to the inner layer.

Embodiment 13. The contact lens of embodiment 9 or 10, wherein each of the separate anterior and posterior outer hydrogel layers has a reduced surface modulus of at least about 35% compared to the inner layer.

Embodiment 14. A contact lens according to embodiment 9 or 10, wherein each of the separate anterior and posterior outer hydrogel layers has a surface modulus that is reduced by at least 40% compared to the inner layer.

Embodiment 1: A contact lens having a normalized surface compressive force at an indentation depth of 400 nm of about 12 μN/MPa or less as measured by microindentation testing using a 51 mm microindentation probe, a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less), and a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing or simulated abrasion cycling, the contact lens comprising an anterior surface, an opposing posterior surface, and a layered structural morphology, the layered structural morphology comprising, in a direction from the anterior surface to the posterior surface, a front outer hydrogel layer, an inner layer of lens material, and a rear outer hydrogel layer.

A contact lens having a normalized surface compressive force at an indentation depth of 400 nm of about 12 μN/MPa or less as measured by microindentation testing using a 61 mm microindentation probe, a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less), and a friction rating of about 2.0 or less after 30 cycles of finger rubbing or simulated abrasion cycling, the contact lens comprising an anterior surface, an opposing posterior surface, and a layered structural morphology, the layered structural morphology comprising, in a direction from the anterior surface to the posterior surface, a front outer hydrogel layer, an inner layer of lens material, and a rear outer hydrogel layer.

Embodiment 1: A contact lens having a normalized surface compressive force at an indentation depth of 400 nm of about 12 μN/MPa or less as measured by microindentation testing using a 71 mm microindentation probe, a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less), and a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing or simulated abrasion cycling, wherein the contact lens comprises a lens bulk material that is a polymeric material.

Embodiment 1: A contact lens having a normalized surface compressive force at an indentation depth of 400 nm of about 12 μN/MPa or less as measured by microindentation testing using a 1 mm microindentation probe, a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less), and a friction rating of about 2.0 or less after 30 cycles of finger rubbing or simulated abrasion cycling, wherein the contact lens comprises a lens bulk material that is a polymeric material.

Embodiment 19. The contact lens of any one of embodiments 15-18, wherein the contact lens has a normalized surface compressive force at an indentation depth of 400 nm of about 10 μN/MPa or less.

The contact lens of any one of embodiments 15-18, wherein the contact lens has a normalized surface compressive force at an indentation depth of 400 nm of about 8 μN/MPa or less.

Embodiment 21. The contact lens of any one of embodiments 15-18, wherein the contact lens has a normalized surface compressive force at an indentation depth of 400 nm of about 6 μN/MPa or less.

Embodiment 22. The contact lens of any one of embodiments 15-18, wherein the contact lens has a normalized surface compressive force at an indentation depth of 400 nm of about 4 μN/MPa or less.

Embodiment 23 A reduction in indentation force at an indentation depth of 400 nm, i.e., Δ(IF), of about 50% or more (preferably about 55% or more, more preferably about 60% or more, even more preferably about 65% or more, and most preferably about 70% or more)._400nmand a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less), and a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing or simulated abrasion cycling, wherein the contact lens comprises an anterior surface, an opposing posterior surface, and a layered structural morphology, the layered structural morphology comprising, in a direction from the anterior surface to the posterior surface, a front outer hydrogel layer, an inner layer of lens material, and a rear outer hydrogel layer.

Embodiment 24 A reduction in indentation force at an indentation depth of 400 nm, i.e., Δ(IF), of about 50% or more (preferably about 55% or more, more preferably about 60% or more, even more preferably about 65% or more, and most preferably about 70% or more)._400nmand a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less), and a friction rating of about 2.0 or less after 30 cycles of finger rubbing or simulated abrasion cycling, wherein the contact lens comprises an anterior surface, an opposing posterior surface, and a layered structural morphology, the layered structural morphology comprising, in a direction from the anterior surface to the posterior surface, a front outer hydrogel layer, an inner layer of lens material, and a rear outer hydrogel layer.

Embodiment 25 A reduction in indentation force at an indentation depth of 400 nm, i.e., Δ(IF), of about 50% or more (preferably about 55% or more, more preferably about 60% or more, even more preferably about 65% or more, and most preferably about 70% or more)._400nmand a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less), and a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing or simulated abrasion cycling, wherein the contact lens comprises a lens bulk material that is a polymeric material.

Embodiment 26 A reduction in indentation force at an indentation depth of 400 nm, i.e., Δ(IF), of about 50% or more (preferably about 55% or more, more preferably about 60% or more, even more preferably about 65% or more, and most preferably about 70% or more)._400nmand a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less), and a friction rating of about 2.0 or less after 30 cycles of finger rubbing or simulated abrasion cycling, wherein the contact lens comprises a lens bulk material that is a polymeric material.

Embodiment 27Δ(IF)_400nmwas determined by nanoindentation testing using a probe with a tip radius of about 9.0±0.9 μm,<math num="11"><img file="JP7635289B2_D0022.tif" /></math>where: (IF)_t27. The contact lens of any one of embodiments 23-26, wherein E is the measured indentation force at an indentation depth of 400 nm of the contact lens, and E' is the bulk modulus (E') of the contact lens.

Embodiment 28Δ(IF)_400nmwas determined by microindentation testing using a 1 mm hemispherical borosilicate glass probe,<math num="12"><img file="JP7635289B2_D0023.tif" /></math>where: (IF)_t27. The contact lens of any one of embodiments 23-26, wherein E is the measured indentation force at an indentation depth of 400 nm of the contact lens, and E' is the bulk modulus (E') of the contact lens.

Embodiment 29Δ(IF)_400nmThe contact lens of any one of embodiments 23 to 28, wherein the .lambda. is about 55% or greater.

Embodiment 30Δ(IF)_400nmThe contact lens of any one of embodiments 23 to 28, wherein the refractive index is about 60% or greater.

Embodiment 31Δ(IF)_400nmThe contact lens of any one of embodiments 23 to 28, wherein the .lambda. is about 65% or greater.

Embodiment 32Δ(IF)_400nmThe contact lens of any one of embodiments 23 to 28, wherein the luminance is about 70% or more.

Embodiment 33. A contact lens according to any one of embodiments 1 to 32, wherein the contact lens has a polyquaternium-1 uptake rate ("PU") of about 0.20 micrograms/lens or less.

Embodiment 34. A contact lens according to any one of embodiments 1 to 32, wherein the contact lens has a polyquaternium-1 uptake rate ("PU") of about 0.15 micrograms/lens or less.

Embodiment 35. The contact lens of any one of embodiments 1 to 32, wherein the contact lens has a polyquaternium-1 uptake rate ("PU") of about 0.10 micrograms/lens or less.

Embodiment 36. The contact lens of any one of embodiments 1-32, wherein the contact lens has a polyquaternium-1 uptake rate ("PU") of about 0.075 micrograms/lens or less.

Embodiment 37. The contact lens of any one of embodiments 1 to 32, wherein the contact lens has a polyquaternium-1 uptake rate ("PU") of about 0.050 micrograms/lens or less.

Embodiment 38. The contact lens of any one of embodiments 1 to 37, wherein the contact lens has a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing.

Embodiment 39. The contact lens of any one of embodiments 1 to 37, wherein the contact lens has a water disintegration time of at least 12.5 seconds after 30 cycles of finger rubbing.

Embodiment 40. The contact lens of any one of embodiments 1 to 37, wherein the contact lens has a water disintegration time of at least 15 seconds after 30 cycles of finger rubbing.

Embodiment 41. The contact lens of any one of embodiments 1 to 37, wherein the contact lens has a water disintegration time of at least 17.5 seconds after 30 cycles of finger rubbing.

Embodiment 42. The contact lens of any one of embodiments 1 to 37, wherein the contact lens has a water disintegration time of at least 20 seconds after 30 cycles of finger rubbing.

Embodiment 43. A contact lens according to any one of embodiments 1 to 37, wherein the contact lens has a water disintegration time of at least 10 seconds after a simulated abrasion cycling treatment.

Embodiment 44. The contact lens of any one of embodiments 1 to 37, wherein the contact lens has a water disintegration time of at least 12.5 seconds after a simulated abrasion cycling treatment.

Embodiment 45. The contact lens of any one of embodiments 1 to 37, wherein the contact lens has a water disintegration time of at least 15 seconds after a simulated abrasion cycling treatment.

Embodiment 46. The contact lens of any one of embodiments 1 to 37, wherein the contact lens has a water disintegration time of at least 17.5 seconds after a simulated abrasion cycling treatment.

Embodiment 47. The contact lens of any one of embodiments 1 to 37, wherein the contact lens has a water disintegration time of at least 20 seconds after a simulated abrasion cycling treatment.

Embodiment 48. A contact lens according to any one of embodiments 1 to 47, wherein the inner layer or lens bulk material is a preformed hard contact lens made essentially of a hard plastic material.

Embodiment 49. The contact lens of embodiment 48, wherein the hard plastic material is a crosslinked polymethacrylate.

Embodiment 50. A contact lens according to any one of embodiments 1 to 47, wherein the inner layer or lens bulk material is a preformed rigid gas permeable contact lens made essentially of a rigid gas permeable lens material.

Embodiment 51. A contact lens according to any one of embodiments 48 to 50, wherein each separate front and rear outer hydrogel layer has a thickness of about 1.0 μm to about 20 μm when fully hydrated.

Embodiment 52. A contact lens according to any one of embodiments 48 to 50, wherein the separate anterior and posterior outer hydrogel layers have a thickness of from about 2.0 μm to about 15 μm when fully hydrated.

Embodiment 53. A contact lens according to any one of embodiments 48 to 50, wherein the separate anterior and posterior outer hydrogel layers have a thickness of from about 2.0 μm to about 10 μm when fully hydrated.

Embodiment 54. A contact lens according to any one of embodiments 48 to 50, wherein the separate anterior and posterior outer hydrogel layers have a thickness of from about 2.5 μm to about 8 μm when fully hydrated.

Embodiment 55. A contact lens according to any one of embodiments 1 to 47, wherein the inner layer or lens bulk material is a preformed soft silicone contact lens made essentially of crosslinked silicone material.

Embodiment 56: The contact lens of embodiment 55, wherein the separate anterior and posterior outer hydrogel layers have a thickness of about 2.0 μm to about 25 μm when fully hydrated.

Embodiment 57: A contact lens as described in embodiment 55, wherein the separate anterior and posterior outer hydrogel layers have a thickness of about 3.0 μm to about 25 μm when fully hydrated.

Embodiment 58: The contact lens of embodiment 55, wherein the separate anterior and posterior outer hydrogel layers have a thickness of about 4.0 μm to about 20 μm when fully hydrated.

Embodiment 59: A contact lens as described in embodiment 55, wherein the separate anterior and posterior outer hydrogel layers have a thickness of about 5.0 μm to about 20 μm when fully hydrated.

Embodiment 60. A contact lens according to any one of embodiments 1 to 47, wherein the inner layer or lens bulk material is a preformed hybrid contact lens having a central optical zone made essentially of a hard gas permeable lens material, surrounded by a peripheral zone made essentially of a non-silicone hydrogel material.

Embodiment 61. A contact lens according to any one of embodiments 1 to 47, wherein the inner layer or lens bulk material is a preformed non-silicone hydrogel contact lens made essentially of a non-silicone hydrogel material.

Embodiment 62. The contact lens of embodiment 60 or 61, wherein the non-silicone hydrogel material comprises at least 50 mol % of repeat units of at least one hydroxyl-containing vinyl monomer.

Embodiment 63: The contact lens of embodiment 62, wherein the at least one hydroxyl-containing vinyl monomer is selected from the group consisting of hydroxyethyl (meth)acrylate, glycerol (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 3-amino-2-hydroxypropyl (meth)acrylate, N-2-hydroxyethyl (meth)acrylamide, N-3-hydroxypropyl (meth)acrylamide, N-2-hydroxypropyl (meth)acrylamide, N-2,3-dihydroxypropyl (meth)acrylamide, N-tris(hydroxymethyl)methyl (meth)acrylamide, vinyl alcohol, allyl alcohol, and combinations thereof.

Embodiment 64. The contact lens of embodiment 62, wherein the at least one hydroxyl-containing vinyl monomer is selected from the group consisting of hydroxyethyl (meth)acrylate, glycerol (meth)acrylate, and vinyl alcohol.

Embodiment 65. A contact lens according to any one of embodiments 60 to 64, wherein the separate anterior and posterior outer hydrogel layers have a thickness of about 0.25 μm to about 20 μm when fully hydrated.

Embodiment 66. A contact lens according to any one of embodiments 60 to 64, wherein the separate anterior and posterior outer hydrogel layers have a thickness of from about 0.50 μm to about 15 μm when fully hydrated.

Embodiment 67. A contact lens according to any one of embodiments 60 to 64, wherein the separate anterior and posterior outer hydrogel layers have a thickness of about 0.5 μm to about 10 μm when fully hydrated.

Embodiment 68. A contact lens according to any one of embodiments 60 to 64, wherein the separate anterior and posterior outer hydrogel layers have a thickness of from about 0.5 μm to about 6 μm when fully hydrated.

Embodiment 69: A contact lens according to any one of embodiments 1 to 47, wherein the inner layer and the lens bulk material, which are separate from each other, are a preformed contact lens made essentially from a silicone hydrogel material.

Embodiment 70. The contact lens of embodiment 69, wherein the silicone hydrogel material comprises at least one polysiloxane vinyl monomer repeat unit.

Embodiment 71. The contact lens of embodiment 69 or 70, wherein the silicone hydrogel material comprises at least one repeating unit of a polysiloxane vinyl crosslinker.

Embodiment 72. A contact lens according to any one of embodiments 69 to 71, wherein the silicone hydrogel material comprises at least one repeating unit of a hydrophilic vinyl monomer.

Embodiment 73. A contact lens according to any one of embodiments 69 to 72, wherein the silicone hydrogel material comprises at least one repeating unit of a hydrophilic N-vinylamide monomer.

Embodiment 74. A contact lens according to any one of embodiments 69 to 73, wherein the silicone hydrogel material comprises at least one polycarbosiloxane vinyl monomer repeat unit.

Embodiment 75. A contact lens according to any one of embodiments 69 to 74, wherein the silicone hydrogel material comprises at least one repeating unit of polycarbosiloxane vinyl crosslinker.

Embodiment 76. The contact lens of any one of embodiments 69 to 75, wherein the silicone hydrogel material comprises repeating units of at least one silicone-containing vinyl monomer having a bis(trialkylsilyloxy)alkylsilyl or tris(trialkylsilyloxy)silyl group.

Embodiment 77. A contact lens according to any one of embodiments 69 to 76, wherein the silicone hydrogel material comprises repeat units of one or more blended vinyl monomers.

Embodiment 78. A contact lens according to any one of embodiments 69 to 76, wherein the silicone hydrogel material comprises repeat units of one or more blended vinyl monomers in an amount of about 25% by weight or less based on the dry weight of the inner layer of the silicone hydrogel material.

Embodiment 79. A contact lens according to any one of embodiments 69 to 76, wherein the silicone hydrogel material comprises repeat units of one or more blended vinyl monomers in an amount of about 20% by weight or less based on the dry weight of the inner layer of the silicone hydrogel material.

Embodiment 80. A contact lens according to any one of embodiments 69 to 76, wherein the silicone hydrogel material comprises repeat units of one or more blended vinyl monomers in an amount of about 15% by weight or less based on the dry weight of the inner layer of the silicone hydrogel material.

Embodiment 81. A contact lens according to any one of embodiments 69 to 80, wherein the silicone hydrogel material comprises repeating units of one or more non-silicone vinyl crosslinkers.

Embodiment 82. A contact lens according to any one of embodiments 69 to 80, wherein the silicone hydrogel material comprises one or more repeating units of a non-silicone vinyl crosslinker in an amount of about 1.0% by weight or less based on the dry weight of the inner layer.

Embodiment 83. A contact lens according to any one of embodiments 69 to 80, wherein the silicone hydrogel material comprises one or more repeating units of a non-silicone vinyl crosslinker in an amount of about 0.8% by weight or less based on the dry weight of the inner layer.

Embodiment 84. A contact lens according to any one of embodiments 69 to 80, wherein the silicone hydrogel material comprises one or more repeating units of a non-silicone vinyl crosslinker in an amount of about 0.05% by weight to about 0.6% by weight based on the dry weight of the inner layer.

Embodiment 85. A contact lens according to any one of embodiments 69 to 84, wherein the silicone hydrogel material has an oxygen permeability of at least about 50 barrer.

Embodiment 86. A contact lens according to any one of embodiments 69 to 84, wherein the silicone hydrogel material has an oxygen permeability of at least about 60 barrer.

Embodiment 87. A contact lens according to any one of embodiments 69 to 84, wherein the silicone hydrogel material has an oxygen permeability of at least about 70 barrer.

Embodiment 88. A contact lens according to any one of embodiments 69 to 84, wherein the silicone hydrogel material has an oxygen permeability of at least about 90 barrer.

Embodiment 89. A contact lens according to any one of embodiments 69 to 84, wherein the silicone hydrogel material has an oxygen permeability of at least about 110 barrer.

Embodiment 90. The contact lens of any one of embodiments 69 to 89, wherein the silicone hydrogel material has an equilibrium water content of about 10% to about 70% by weight.

Embodiment 91. A contact lens according to any one of embodiments 69 to 89, wherein the silicone hydrogel material has an equilibrium water content of about 10% to about 65% by weight.

Embodiment 92. A contact lens according to any one of embodiments 69 to 89, wherein the silicone hydrogel material has an equilibrium water content of about 10% to about 60% by weight.

Embodiment 93. A contact lens according to any one of embodiments 69 to 89, wherein the silicone hydrogel material has an equilibrium water content of about 15% to about 55% by weight.

Embodiment 94. A contact lens according to any one of embodiments 69 to 89, wherein the silicone hydrogel material has an equilibrium water content of about 15% to about 50% by weight.

Embodiment 95. A contact lens according to any one of embodiments 69 to 94, wherein the silicone hydrogel material is not naturally wettable and the separate anterior and posterior outer hydrogel layers have a thickness of from about 0.5 μm to about 25 μm when fully hydrated.

Embodiment 96. A contact lens according to any one of embodiments 69 to 94, wherein the silicone hydrogel material is not naturally wettable and the separate anterior and posterior outer hydrogel layers have a thickness of from about 1.0 μm to about 20 μm when fully hydrated.

Embodiment 97. A contact lens according to any one of embodiments 69 to 94, wherein the silicone hydrogel material is not naturally wettable and the separate anterior and posterior outer hydrogel layers have a thickness of from about 1.0 μm to about 15 μm when fully hydrated.

Embodiment 98. A contact lens according to any one of embodiments 69 to 94, wherein the silicone hydrogel material is not naturally wettable and the separate anterior and posterior outer hydrogel layers have a thickness of about 1.5 μm to about 10 μm when fully hydrated.

Embodiment 99: A contact lens described in any one of embodiments 69 to 98, wherein the silicone hydrogel material is naturally wettable and the independent anterior and posterior outer hydrogel layers have a thickness of about 0.25 μm to about 20 μm when fully hydrated.

Embodiment 100. A contact lens according to any one of embodiments 69 to 98, wherein the silicone hydrogel material is naturally wettable and the separate anterior and posterior outer hydrogel layers have a thickness of about 0.5 μm to about 20 μm when fully hydrated.

Embodiment 101 A contact lens described in any one of embodiments 69 to 98, wherein the silicone hydrogel material is naturally wettable and the independent anterior and posterior outer hydrogel layers have a thickness of about 0.5 μm to about 15 μm when fully hydrated.

Embodiment 102 A contact lens described in any one of embodiments 69 to 98, wherein the silicone hydrogel material is naturally wettable and the independent anterior and posterior outer hydrogel layers have a thickness of about 1.0 μm to about 10 μm when fully hydrated.

[0046] Embodiment 103 The front and rear outer hydrogel layers, which are independent of each other, are made of alkyl (meth)acrylamides, N-2-dimethylaminoethyl (meth)acrylamides, dimethylaminoethyl (meth)acrylates, hydroxyl-containing acrylic monomers, N-vinylamide monomers, methylene-containing pyrrolidone monomers, C₁~C₄103. The contact lens of any one of embodiments 1-102, which is a crosslinked hydrophilic polymeric material comprising at least 25 mol % of repeating monomer units of at least one hydrophilic vinyl monomer selected from the group consisting of (meth)acrylate monomers having alkoxyethoxy groups, vinyl ether monomers, allyl ether monomers, and combinations thereof.

[0043] Embodiment 104 The front and rear outer hydrogel layers, which are independent of each other, are made of alkyl (meth)acrylamides, N-2-dimethylaminoethyl (meth)acrylamides, dimethylaminoethyl (meth)acrylates, hydroxyl-containing acrylic monomers, N-vinylamide monomers, methylene-containing pyrrolidone monomers, C₁~C₄103. The contact lens of any one of embodiments 1-102, which is a crosslinked hydrophilic polymeric material comprising at least 35 mol % of repeating monomer units of at least one hydrophilic vinyl monomer selected from the group consisting of (meth)acrylate monomers having alkoxyethoxy groups, vinyl ether monomers, allyl ether monomers, and combinations thereof.

[0046] Embodiment 105 The front and rear outer hydrogel layers, which are independent of each other, are made of alkyl (meth)acrylamides, N-2-dimethylaminoethyl (meth)acrylamides, dimethylaminoethyl (meth)acrylates, hydroxyl-containing acrylic monomers, N-vinylamide monomers, methylene-containing pyrrolidone monomers, C₁~C₄103. The contact lens of any one of embodiments 1-102, which is a crosslinked hydrophilic polymeric material comprising at least 45 mol % of repeating monomer units of at least one hydrophilic vinyl monomer selected from the group consisting of (meth)acrylate monomers having alkoxyethoxy groups, vinyl ether monomers, allyl ether monomers, and combinations thereof.

[0023] Embodiment 106 The front and rear outer hydrogel layers, which are independent of each other, are made of alkyl (meth)acrylamides, N-2-dimethylaminoethyl (meth)acrylamides, dimethylaminoethyl (meth)acrylates, hydroxyl-containing acrylic monomers, N-vinylamide monomers, methylene-containing pyrrolidone monomers, C₁~C₄103. The contact lens of any one of embodiments 1-102, which is a crosslinked hydrophilic polymeric material comprising at least 55 mol % of repeating monomer units of at least one hydrophilic vinyl monomer selected from the group consisting of (meth)acrylate monomers having alkoxyethoxy groups, vinyl ether monomers, allyl ether monomers, and combinations thereof.

Embodiment 107. A contact lens according to any one of embodiments 1 to 102, wherein the anterior and posterior outer hydrogel layers, which are independent of each other, are crosslinked hydrophilic polymeric materials comprising at least 25 mol % repeating monomer units of at least one phosphrylcholine-containing vinyl monomer.

Embodiment 108. A contact lens according to any one of embodiments 1 to 102, wherein the anterior and posterior outer hydrogel layers, which are independent of each other, are crosslinked hydrophilic polymeric materials comprising at least 35 mol % of repeating monomer units of at least one phosphirylcholine-containing vinyl monomer.

Embodiment 109: A contact lens according to any one of embodiments 1 to 102, wherein the anterior and posterior outer hydrogel layers, which are independent of each other, are crosslinked hydrophilic polymeric materials comprising at least 45 mol % repeating monomer units of at least one phosphirylcholine-containing vinyl monomer.

Embodiment 110. A contact lens according to any one of embodiments 1 to 102, wherein the anterior and posterior outer hydrogel layers, which are independent of each other, are crosslinked hydrophilic polymeric materials comprising at least 55 mol % repeating monomer units of at least one phosphirylcholine-containing vinyl monomer.

Embodiment 111 A contact lens according to any one of embodiments 1 to 102, wherein the anterior and posterior outer hydrogel layers, which are separate from each other, are crosslinked hydrophilic polymeric materials comprising poly(ethylene glycol) chains.

[0046] Embodiment 112 The front and rear outer hydrogel layers, which are independent of each other, are (1)-NH₂(2) pol (ethylene glycol) with one unique functional group: -NH₂(3) poly(ethylene glycol) having two terminal functional groups selected from the group consisting of -NH₂, -COOH, -SH, and combinations thereof; or (3) a crosslinked hydrophilic polymeric material comprising a poly(ethylene glycol) chain derived directly from a multi-arm poly(ethylene glycol) having one or more functional groups selected from the group consisting of: -COOH, -SH, and combinations thereof.

Embodiment 113 A contact lens described in any one of embodiments 1 to 112, wherein the front and rear outer hydrogel layers are identical to each other, are substantially uniform in thickness, and merge at the edge of the contact lens to completely cover the inner layer.

Embodiment 114. A contact lens according to any one of embodiments 1 to 113, wherein the separate anterior and posterior outer hydrogel layers have an equilibrium water content of at least 80% by weight.

Embodiment 115. A contact lens according to any one of embodiments 1 to 113, wherein the separate anterior and posterior outer hydrogel layers have an equilibrium water content of at least 85% by weight.

Embodiment 116 A contact lens according to any one of embodiments 1 to 113, wherein the separate anterior and posterior outer hydrogel layers have an equilibrium water content of at least about 90% by weight.

Embodiment 117 A contact lens described in any one of embodiments 1 to 113, wherein the independent anterior and posterior outer hydrogel layers have an equilibrium water content of at least 95% by weight.

Embodiment 118. A contact lens according to any one of embodiments 1 to 117, wherein the separate anterior and posterior outer hydrogel layers are substantially free of silicone.

Embodiment 119: A contact lens according to any one of embodiments 1 to 117, wherein the separate anterior and posterior outer hydrogel layers are completely free of silicone.

The contact lens of embodiment 120 further comprises two transition layers of polymeric material, each of the two transition layers being located between the inner layer or lens bulk material and one of the anterior and posterior outer hydrogel layers. A contact lens as described in any one of embodiments 1 to 119.

A contact lens as described in embodiment 120, wherein the two transitional layers are united at the peripheral edge of the contact lens and completely surround an internal layer of lens material or lens bulk material.

Embodiment 122A contact lens according to embodiment 120 or 121, wherein the two transitional layers have a thickness of at least about 0.05 μm when fully hydrated.

Embodiment 123 The contact lens of embodiment 120 or 121, wherein the two transitional layers have a thickness of about 0.05 μm to about 10 μm when fully hydrated.

[0046] Embodiment 124: The contact lens of embodiment 120 or 121, wherein the two transitional layers have a thickness of about 0.1 μm to about 7.5 μm when fully hydrated.

[0041] Embodiment 125: The contact lens of embodiment 120 or 121, wherein the two transitional layers have a thickness of about 0.1 μm to about 5 μm when fully hydrated.

Embodiment 126 A contact lens described in any one of embodiments 120 to 125, wherein each of the two transitional layers is a layer of a polyanionic polymer neutralized and crosslinked with a polyaziridine having at least two aziridine groups and a number average molecular weight of 2000 Daltons or less.

Embodiment 127. The contact lens of embodiment 126, wherein the polyanionic polymer is a carboxyl-containing polymer that contains at least 60 mole % of repeat units of one or more carboxyl-containing acrylic monomers.

Embodiment 128: The contact lens of embodiment 126, wherein the polyanionic polymer is polyacrylic acid, polymethacrylic acid, poly(ethylacrylic acid), poly(acrylic acid-co-methacrylic acid), poly[ethylacrylic acid-co-(meth)acrylic acid], poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone], poly[ethylacrylic acid-co-acrylamide], poly[ethylacrylic acid-co-vinylpyrrolidone], poly[(meth)acrylic acid-co-vinyl acetate], poly[ethylacrylic acid-co-vinyl acetate], or a combination thereof.

Embodiment 129: A contact lens according to embodiment 126, wherein the polyanionic polymer is a graft polymer grafted onto an inner layer or lens bulk material, the graft polymer comprising repeating units of at least one carboxyl-containing vinyl monomer.

Embodiment 130: The contact lens of embodiment 127, wherein the polyanionic polymer is a graft polymer grafted onto the inner layer or lens bulk material, the graft polymer comprising repeat units of at least one carboxyl-containing acrylic monomer.

Embodiment 131: The contact lens of any one of embodiments 126 to 130, wherein the polyaziridine is trimethylolpropane tris(2-methyl-1-aziridinepropionate), pentaerythritol tris[3-(1-aziridinyl)propionate], trimethylolpropane tris(3-aziridinopropionate), a Michael reaction product of a vinyl crosslinker having at least two (meth)acryloyl groups and 2-methylaziridine or aziridine, or a combination thereof.

Embodiment 132 A contact lens described in any one of embodiments 1 to 131, wherein the independent anterior and posterior outer hydrogel layers have a surface modulus reduced by at least about 25% compared to the inner layer.

Embodiment 133. A contact lens according to any one of embodiments 1 to 131, wherein the separate anterior and posterior outer hydrogel layers have a surface modulus reduced by at least about 30% compared to the inner layer.

Embodiment 134 A contact lens described in any one of embodiments 1 to 131, wherein the independent anterior and posterior outer hydrogel layers have a surface modulus reduced by at least about 35% compared to the inner layer.

Embodiment 135. A contact lens according to any one of embodiments 1 to 131, wherein the separate anterior and posterior outer hydrogel layers have a surface modulus reduced by at least about 40% compared to the inner layer.

Embodiment 136. The contact lens of any one of embodiments 1 to 135, wherein the contact lens has a friction rating of about 1.5 or less after 30 cycles of finger rubbing.

Embodiment 137. The contact lens of any one of embodiments 1 to 135, wherein the contact lens has a friction rating of about 1.0 or less after 30 cycles of finger rubbing.

Embodiment 138. The contact lens of any one of embodiments 1 to 135, wherein the contact lens has a friction rating of about 0.5 or less after 30 cycles of finger rubbing.

A contact lens having an anterior surface and an opposing posterior surface; a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less); a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing or after simulated abrasion cycling; and a structural morphology characterized by having a cross-sectional surface-modulus profile along a shortest line between the anterior and posterior surfaces of a cross-sectional surface of the contact lens, the cross-sectional surface-modulus profile comprising an anterior-lateral zone that includes and is proximal to the anterior surface, an inner zone that includes and is central to and at the periphery of the shortest line, and a posterior-lateral zone that includes and is proximal to the posterior surface, the anterior-lateral zone having an average anterior surface modulus of about 0.02 to about 0.02 micrograms/lens.<math num="13"><img file="JP7635289B2_D0024.tif" /></math>while the posterolateral zone has an average posterior surface modulus<math num="14"><img file="JP7635289B2_D0025.tif" /></math>and the inner zone has an average inner surface modulus<math num="15"><img file="JP7635289B2_D0026.tif" /></math>having<math num="16"><img file="JP7635289B2_D0027.tif" /></math>At least one of the contact lenses is at least about 20%.

Embodiment 140. The contact lens of embodiment 139, wherein the contact lens has a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing treatment.

Embodiment 141. The contact lens of embodiment 139, wherein the contact lens has a water disintegration time of at least 12.5 seconds after 30 cycles of finger rubbing treatment.

Embodiment 142. The contact lens of embodiment 139, wherein the contact lens has a water disintegration time of at least 15 seconds after 30 cycles of finger rubbing treatment.

Embodiment 143. The contact lens of embodiment 139, wherein the contact lens has a water disintegration time of at least 17.5 seconds after 30 cycles of finger rubbing treatment.

Embodiment 144. The contact lens of embodiment 139, wherein the contact lens has a water disintegration time of at least 20 seconds after 30 cycles of finger rubbing treatment.

Embodiment 145. The contact lens of embodiment 139, wherein the contact lens has a water disintegration time of at least 10 seconds after a simulated polishing cycle treatment.

Embodiment 146. The contact lens of embodiment 139, wherein the contact lens has a water disintegration time of at least 12.5 seconds after a simulated abrasion cycling treatment.

Embodiment 147. The contact lens of embodiment 139, wherein the contact lens has a water disintegration time of at least 15 seconds after a simulated abrasion cycling treatment.

Embodiment 148. The contact lens of embodiment 139, wherein the contact lens has a water disintegration time of at least 17.5 seconds after a simulated polishing cycle treatment.

Embodiment 149. The contact lens of embodiment 139, wherein the contact lens has a water disintegration time of at least 20 seconds after a simulated abrasion cycling treatment.

A contact lens having an anterior surface and an opposite posterior surface, a polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms/lens or less (or about 0.30 micrograms/lens or less), a friction rating of about 2.0 or less after 30 cycles of finger rubbing or simulated abrasion cycling, and a structural morphology characterized by having a cross-sectional surface-modulus profile along a shortest line between the anterior and posterior surfaces of the cross-sectional surface of the contact lens, the cross-sectional surface-modulus profile comprising an anterior-lateral zone that includes and is proximal to the anterior surface, an inner zone that includes and is central to and at the periphery of the shortest line, and a posterior-lateral zone that includes and is proximal to the posterior surface, the anterior-lateral zone having an average anterior surface modulus of about 0.02 to about 0.02 micrograms/lens.<math num="17"><img file="JP7635289B2_D0028.tif" /></math>while the posterolateral zone has an average posterior surface modulus<math num="18"><img file="JP7635289B2_D0029.tif" /></math>and the inner zone has an average inner surface modulus<math num="19"><img file="JP7635289B2_D0030.tif" /></math>having<math num="20"><img file="JP7635289B2_D0031.tif" /></math>At least one of the contact lenses is at least about 20%.

The contact lens of embodiment 150, wherein the contact lens has a friction rating of about 2.0 or less after 30 cycles of finger rubbing.

Embodiment 152. The contact lens of embodiment 150, wherein the contact lens has a friction rating of about 1.5 or less after 30 cycles of finger rubbing.

Embodiment 153. The contact lens of embodiment 150, wherein the contact lens has a friction rating of about 1.0 or less after 30 cycles of finger rubbing.

Embodiment 154. The contact lens of embodiment 150, wherein the contact lens has a friction rating of about 0.5 or less after 30 cycles of finger rubbing.

Embodiment 155. The contact lens of embodiment 150, wherein the contact lens has a friction rating of about 2.0 or less after a simulated abrasion cycling treatment.

Embodiment 156. The contact lens of embodiment 150, wherein the contact lens has a friction rating of about 1.5 or less after a simulated abrasion cycling treatment.

Embodiment 157. The contact lens of embodiment 150, wherein the contact lens has a friction rating of about 1.0 or less after a simulated abrasion cycling treatment.

Embodiment 158. The contact lens of embodiment 150, wherein the contact lens has a friction rating of about 0.5 or less after a simulated abrasion cycling treatment.

EMBODIMENT 159<math num="21"><img file="JP7635289B2_D0032.tif" /></math>The contact lens of any one of embodiments 139 to 158, wherein at least one of the above is at least 25%.

Embodiment 160<math num="22"><img file="JP7635289B2_D0033.tif" /></math>The contact lens of any one of embodiments 139 to 158, wherein at least one of the above is at least 30%.

EMBODIMENT 161<math num="23"><img file="JP7635289B2_D0034.tif" /></math>The contact lens of any one of embodiments 139 to 158, wherein at least one of the above is at least 35%.

EMBODIMENT 162<math num="24"><img file="JP7635289B2_D0035.tif" /></math>The contact lens of any one of embodiments 139 to 158, wherein at least one of the above is at least 40%.

Embodiment 163. A contact lens according to any one of embodiments 139 to 162, wherein the contact lens has a polyquaternium-1 uptake rate ("PU") of about 0.20 micrograms/lens or less.

Embodiment 164. A contact lens according to any one of embodiments 139 to 162, wherein the contact lens has a polyquaternium-1 uptake rate ("PU") of about 0.15 micrograms/lens or less.

Embodiment 165. A contact lens according to any one of embodiments 139 to 162, wherein the contact lens has a polyquaternium-1 uptake rate ("PU") of about 0.10 micrograms/lens or less.

Embodiment 166. A contact lens according to any one of embodiments 139 to 162, wherein the contact lens has a polyquaternium-1 uptake rate ("PU") of about 0.075 micrograms/lens or less.

Embodiment 167. A contact lens according to any one of embodiments 139 to 162, wherein the contact lens has a polyquaternium-1 uptake rate ("PU") of about 0.050 micrograms/lens or less.

Embodiment 168. The contact lens of any one of embodiments 1 to 167, wherein the contact lens has a UVB Transmittance of about 10% or less from 280 to 315 nanometers, a UVA Transmittance of about 30% or less from 315 to 380 nanometers, and a Violet Transmittance of 0% to about 70% from 380 nm to 440 nm.

The contact lens of embodiment 169, wherein the contact lens has a UVB transmittance of about 5% or less from 280 to 315 nanometers.

The contact lens of embodiment 170 is the contact lens of embodiment 168, having a UVB transmittance of about 2.5% or less from 280 to 315 nanometers.

The contact lens of embodiment 171, wherein the contact lens has a UVB transmittance of about 1% or less from 280 to 315 nanometers.

Embodiment 172. A contact lens according to any one of embodiments 168 to 171, wherein the contact lens has a UVA transmittance of about 20% or less at 315 to 380 nanometers.

Embodiment 173. The contact lens of any one of embodiments 168 to 171, wherein the contact lens has a UVA transmittance of about 10% or less at 315 to 380 nanometers.

Embodiment 174. The contact lens of any one of embodiments 168 to 171, wherein the contact lens has a UVA transmittance of about 5% or less at 315 to 380 nanometers.

The contact lens of any one of embodiments 168 to 174, wherein the contact lens has a violet transmittance of 5% to about 60% at 380 to 440 nanometers.

The contact lens of any one of embodiments 168 to 174, wherein the contact lens has a violet transmittance of 5% to about 50% at 380 to 440 nanometers.

The contact lens of any one of embodiments 168 to 174, wherein the contact lens has a violet transmittance of about 5% to about 40% at 380 to 440 nanometers.

Embodiment 178: A contact lens described in any one of embodiments 1 to 177, wherein the contact lens is substantially free (i.e., less than three) of surface crack lines visible under dark field after rubbing the contact lens between a finger 10 times.

Embodiment 179: A contact lens according to any one of embodiments 1 to 177, wherein the contact lens does not contain any surface crack lines visible under dark field after rubbing the contact lens between fingers 10 times.

The above disclosure will enable those skilled in the art to practice the present invention. Various modifications, variations and combinations can be made to the various embodiments described herein. In order to allow the reader to better understand certain embodiments and their advantages, reference to the following examples is suggested. It is intended that the specification and examples be considered as illustrative.

<p>Example 1 Chemicals The following abbreviations are used in the examples below: AMA stands for allyl methacrylate, NVP stands for N-vinylpyrrolidone, DMA stands for N,N-dimethylacrylamide, VMA stands for N-vinyl-N-methylacetamide, MMA stands for methyl methacrylate, TEGDMA stands for triethylene glycol dimethacrylate, TEGDVE stands for triethylene glycol divinyl ether, EGMA stands for ethylene glycol methyl ether methacrylate, VAZO64 stands for 2,2-dimethyl-2,2 azodipropioninitrile, Nobloc is 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate from Aldrich, UV28 stands for 2-{2'-hydroxy-3'-tert-butyl-5'-[3'-methacryloyloxypropoxy]phenyl}-5-chloro-2H-benzotriazole, RB246 is Reactive Blue 246, and RB247 is Reactive Blue 247, TAA stands for tert-amyl alcohol, PrOH stands for 1-propanol, IPA stands for isopropanol, PAA stands for polyacrylic acid, PMAA stands for polymethacrylic acid, PAE stands for polyamidoamine-epichlorohydrin (also known as polyamine-epichlorohydrin), MPC stands for 2-methacryloyloxyethyl phosphorylcholine, poly(AAm-co-AA) stands for poly(acrylamide-co-acrylic acid), PZ-28 stands for trimethylol PZ-33 stands for pentaerythritol tris[3-(1-aziridinyl)propionate]; BTP or bis-tris-propane stands for bis[tris(hydroxymethyl)methylamino]propane; Tris-HCl stands for tris(hydroxymethyl)aminomethane hydrochloride; EDTA stands for ethylenediaminetetraacetic acid; PBS has a pH of 7.2±0.2 at 25° C. and contains approximately 0.044% by weight of NaHCO.₂PO₄H₂O, about 0.388% by weight of Na₂HPO₄2H₂% NaCl, and about 0.79 wt % NaCl, where wt % represents weight percent, mSi1 represents monobutyl-terminated monomethacryloxypropyl-terminated polydimethylsiloxane (Mw: about 600-800 g/mol: manufactured by Gelest), D9 represents monobutyl-terminated monomethacryloxypropyl-terminated polydimethylsiloxane (Mw: about 984 g/mol: manufactured by Shin-Etsu Chemical Co., Ltd.), and LM-CEPDMS is a PDMS segment bonded by diurethane bonds between two PDMS segments and two urethane bonds, each of which is located between one terminal methacrylate group and one PDMS segment. The "GA" macromer represents a dimethacrylate-terminated chain extended polydimethylsiloxane (Mn: about 6000 g/mol) having three polydimethylsiloxane (PDMS) segments combined and prepared according to a method similar to that described in Example 2 of U.S. Pat. No. 8,529,057; the "GA" macromer represents a dimethacryloyloxypropyl-terminated polysiloxane (Mn: about 6,800 g/mol, OH content: about 1.2 meq/g) of formula (A); and the "G4" macromer represents a dimethacryloyloxypropyl-terminated polysiloxane (Mn: about 13,500 g/mol, OH content: about 1.8 meq/g) of formula (A).</p><p><img file="JP7635289B2_D0036.tif" /></p><p>Measurement of oxygen permeability The apparent oxygen permeability (Dk_app), apparent oxygen transmissibility (Dk/t), specific (or edge-corrected) oxygen permeability (Dk_c) is determined according to the procedure described in Example 1 of US Patent Application Publication No. 2012/0026457A1.</p><p>Finger Rub Treatment The lens is finger rubbed with RENU® Multipurpose Lens Care Solution (or another multipurpose lens care solution) for 20 seconds (while wearing disposable powder-free latex gloves) followed by rinsing with saline. The above procedure is repeated i times (i.e., i cycles of finger rubs) to mimic daily cleaning in an i-day lens care regime, 7 times (i.e., 7 cycles of finger rubs) to mimic daily cleaning and disinfection in a 7-day lens care regime, or 30 times (i.e., 30 cycles of finger rubs) to mimic daily cleaning and disinfection in a 30-day lens care regime.</p><p>Simulated Polishing Cycling Process To simulate the worst case scenario of manual cycling, a simulated polishing technique is used to ensure constant pressure and shear conditions. To do this, a customized lens holder is manufactured to clamp the lens and simultaneously shear it. The lens (part 1) is placed on a rubber insert (part 2) into which a central shaft (part 3) with a diameter of 7.7 mm is axially fitted, as shown in FIG. 3. The top clip (part 4) is clipped onto the bottom clip (part 5), which holds the lens firmly against the silicone gasket. The central shaft is then stretched so that the lens protrudes above the outer body surface, exposing the circumferential area of the lens around the center of the lens. Optionally, a piece of fabric (i.e., Twillx1622 (Berkshire)) may be placed between the central shaft and the contact lens to improve polishing visualization.</p><p>The entire lens holder is placed onto the mounting end of a Taber linear abrasive system (Taber Industries, model 5750, http://www.taberindustries.com/linear-abraser). Without any additional weight attached, the total weight of the support arm and lens holder (230g normal force) is 47mm²100 mm contact lens area and 49 kPa is applied to the counter surface. For the counter surface, a sheet of silicone rubber (10 A, ¼ inch thick) is placed under the support arm and the reservoir channel is clipped onto the silicone rubber. The reservoir is then filled with room temperature PBS.</p><p>During the experiment, the lens holder is slowly lowered onto the counter surface and the lens is polished 20 times at a frequency of 75 cycles per minute (3 inches per stroke, 6 inches total travel per cycle). The lens surface can be analyzed using the water disintegration time method, lubricity evaluation, and/or Sudan Black staining test.</p><p>Although this technique applies shear forces significantly beyond those experienced by typical contact lenses, this controlled shear technique (i.e., simulated abrasive cycling treatment) has been found to be a reasonable equivalent to 30 cycles of finger rubbing treatment, ensuring that these contact lenses can handle even the most severe mechanical cycling.</p><p>Lubricity Assessment The lubricity of contact lenses is assessed by using a finger-felt lubricity test, which qualitatively characterizes the slipperiness of the lens surface on a friction rating scale of 0 to 4. The higher the friction rating, the less slipperiness (or lubricity).</p><p>Commercially available lenses, DAILIES® TOTAL 1®, ACUVUE® OASYS, ACUVUE® ADVANCE PLUS, DAILIES® Aqua Comfort Plus®, and AIR OPTIX®, are assigned friction ratings (hereinafter referred to as "FR") of 0, 1, 2, 3, and 4, respectively, which are used as standard lenses to determine the friction ratings of the lenses under test.</p><p>The samples are placed in PBS for at least two rinses of 30 minutes each, then transferred to fresh PBS before evaluation. Before evaluation, hands are rinsed with soap solution and rinsed thoroughly with DI water, then dried with a KimWipe towel. The samples are handled between fingers and each sample is assigned a numerical value relative to the standard lens described above. For example, if the lens is determined to be slightly better than the AIR OPTIX lens, a numerical value of 3 is assigned. The friction rating value is obtained by averaging the results of at least two friction ratings of the contact lens by two or more people, and/or by averaging the friction ratings of two or more contact lenses (from the same batch of lens production) by one person.</p><p>The finger lubricity (i.e., friction score) of contact lenses can be determined either out-of-pack (OOP) (but after immersion in PBS for 30 minutes or more), or after i cycles (e.g., 7, 14, 21, or 30 cycles) of finger rubbing according to the above procedure, or after simulated abrasion cycling.</p><p>Surface Wettability Testing The water contact angle (WCA) on contact lenses is a common measure of the surface wettability of contact lenses. Specifically, a lower water contact angle corresponds to a more wettable surface. The dynamic trapped air bubble contact angle of contact lenses is measured by FDS Future Digital Scientific The contact angles are measured using an FDS instrument manufactured by Sigma-Aldrich Corp. The FDS instrument is capable of measuring advancing and receding contact angles. Measurements are performed at room temperature on hydrated contact lenses. The contact lenses are removed from the vial and immersed in approximately 40 mL of fresh PBS and shaken for at least 30 minutes, followed by a replacement with fresh PBS, immersed, and shaken for another 30 minutes unless otherwise specified. The contact lenses are then placed on lens paper, tapped to remove surface water, and then placed on a lens holder with the front curve facing upwards, followed by screwing the top of the lens holder. The fixed lens holder is placed in a glass cell cuvette filled with filtered PBS. The glass cell cuvette is placed on the platform of the FDS instrument. The platform and needle height are adjusted to dispense air bubbles onto the lens surface. Three dispense/withdraw cycles are repeated for all lenses to obtain advancing and receding contact angles. Receding contact angles are reported in the examples below.</p><p>Water Breakdown Time (WBUT) The surface hydrophilicity of test lenses (after autoclaving) is evaluated by determining the time required for the water film to begin to break down on the lens surface. Lenses exhibiting a WBUT of 10 seconds or greater are considered to have a hydrophilic surface and are expected to exhibit sufficient wettability (ability to support a tear film) on the eye.</p><p>Lenses are prepared for aqueous disintegration measurements by removing them from their blisters with soft plastic tweezers (e.g., from Menicon) and placing them in test tubes containing phosphate buffered saline. The tubes contain 10 mL of phosphate buffered saline per lens, one lens per tube. Lenses are allowed to soak overnight (at least 16 hours) before testing.</p><p>WBUT is measured at room temperature as follows: A lens is removed from the test tube and placed on a pedestal submerged in PBS. The pedestal is then raised out of the PBS solution (t=0) and a video camera monitors the fluid running off the lens surface. When the fluid on the lens surface breaks down, this WBUT time is recorded. Optionally, a stopwatch may be used to measure the time between when the pedestal is raised out of the PBS solution and when the fluid on the lens surface breaks down. As the pedestal is raised, it pulls the lens under the surface of the PBS. At least three points per lens are measured and at least three lenses are measured to obtain an average WBUT measurement for each group of lenses.</p><p>Equilibrium Water Content The equilibrium water content (EWC) of a contact lens is determined as follows.</p><p>Determine the amount of water (expressed as weight %) present in hydrated hydrogel contact lenses that are fully equilibrated in saline at room temperature. Blot the lenses with a cloth, then quickly stack the lenses and transfer the stack of lenses to an aluminum dish on an analytical balance. The number of lenses in each sample dish is typically five. Record the hydrated weight of the dishes and lenses. Cover the dishes with aluminum foil. Place the dishes in a laboratory oven at 100 ± 2 °C to dry for 16-18 hours. Remove the dishes and lenses from the oven and cool in a desiccator for at least 30 minutes. Remove a single dish from the desiccator and discard the aluminum foil. Weigh the dishes and dry lens sample on an analytical balance. Repeat for all changes. The wet and dry weights of the lens samples can be calculated by subtracting the weight of the empty weighing dish.</p><p>Elastic Modulus The elastic modulus of contact lenses is determined using an MTS insight instrument. First, the contact lenses are cut into 3.12 mm wide strips using a Precision Concept two-stage cutter. Five thickness values within a 6.5 mm gauge length are measured. The strips are placed on the grips of the instrument and submerged in PBS with a temperature controlled at 21±2°C. Typically, a 5 N load cell is used for testing. A constant force and rate is applied to the sample until it collapses. Force and displacement data are collected using TestWorks software. The elastic modulus value, which is the slope of the stress in the elastic displacement region or the tangent to the stress vs. strain curve near zero elongation, is calculated by the TestWorks software.</p><p>Mechanical Properties of Contact Lens Surfaces Every contact lens can have different mechanical properties at its surface, particularly if the contact lens has a soft hydrogel coating thereon. The mechanical properties of the region near and including the surface of a contact lens can be characterized by measuring the surface compressive or indentation force as a function of displacement in micro- or nano-indentation tests.</p><p>It has been found that for contact lenses that do not have any soft hydrogel coating thereon, the indentation force at a given displacement or indentation depth (e.g., 400 nm) correlates well with the bulk (Young's) modulus (i.e., there is a linear bulk modulus-indentation force relationship between the bulk modulus and indentation force at a given displacement), whereas for contact lenses that have a soft hydrogel coating thereon, the indentation force at a given displacement is much smaller than would be predicted based on the linear bulk modulus-indentation force relationship. Such deviations can be used as a good indicator of the soft hydrogel coating on a contact lens.</p><p>Microindentation Test The surface compressive force of a contact lens at an indentation depth of 400 nm is measured by the following microindentation test. The contact lens to be tested is rinsed and placed in PBS overnight. The lens is then placed on a hemispherical platform submerged in PBS and indented using a pressure-driven quasistatic transducer indentation system (Bruker Hysitron® BioSoft In-Situ Indenter) equipped with a 1 mm hemispherical borosilicate glass probe. Between experiments, the probe is cleaned using a plasma cleaner (e.g., oxygen, air, or argon plasma cleaner) and inflated with F-127. The lens is coated with Pluronic (by dipping in an aqueous solution of F-127 at a concentration above the CMC of F-127, e.g., about 0.1 wt %). The probe is attached to the indentation system and pulled down at a constant indentation rate of 1 μm/s along typical load and unload curves (i.e., normal force vs. indentation depth). The normal force and displacement position (or indentation depth) are measured simultaneously at a rate of 125 Hz by a quasi-static transducer. The above procedure is repeated 20 times (i.e., 20 indentations) per lens. The surface compressive force (in micronewtons (μN)) at a indentation depth of 400 nm is obtained by averaging all the normal forces at a indentation depth of 400 nm along each of the 20 indentation load curves. The normalized surface compressive force (NSCF) is obtained by dividing the obtained surface compressive force at a indentation depth of 400 nm by the elastic modulus of the contact lens under test.</p><p>Nanoindentation Test The indentation force of a contact lens at an indentation depth of 400 nm is measured by the following microindentation test.</p><p>The indentation force is determined as a function of displacement using the Optics11 Piuma instrument. Prior to performing the indentation, the Piuma probe was attached to a LifeStyle The lens is calibrated in PuriLens Plus, a sterile and preservative-free saline solution manufactured by Piuma Company, Inc. (Freehold, NJ). This calibration consists of first calibrating the optical sensor by submerging the probe in PuriLens Plus but not engaging the surface of the substrate. A second cantilever calibration is then performed by forming a test indentation on a glass slide. The lens is rinsed in PuriLens Plus to remove excess lens packaging solution, followed by blotting dry. The lens is then placed in a 3D printed lens holder with the front curve facing down (Figure 4). The base curve is then partially filled with PuriLens Plus to place the lens in place, but the amount of PuriLens Plus added should not be so much that the base curve overflows during testing. Finally, the Piuma probe is moved just above the lens surface and a nanoindentation routine is performed according to the manufacturer's typical procedure. The indentation routine consists of a 10 μm indentation at a speed of 1 μm/s with a sampling rate of 100 Hz. The probe is moved to the surface where the contact point is determined by the first deflection detected by the cantilever.</p><p>Two different Piuma probes were used to collect the data, the first one with a stiffness of 0.500 N/m and a tip radius of 9.500 μm, and the other with a stiffness of 4.710 N/m and a tip radius of 9.000 μm. Both probes penetrate to the same depth (400 nm), so the contact areas are slightly different. The contact areas (S_cap) can be calculated by the following formula:_cap= 2πRh where "R" is the tip radius and h is the indentation depth. Therefore, the two probe tips have a 23.9 μm²and 22.6 μm²0.01 μm, or only a 5% difference. The resulting pressure of the 9 μm tip should be only 5% higher than the 9.5 μm tip. This small pressure difference should have little effect on the measured forces compared between these tips.</p><p>It should be understood that it is more desirable to use a single type of Piuma probe for all nanoindentation experiments, however, if multiple Piuma probes are needed to optimize measurements for contact lenses with a wide range of bulk moduli (e.g., 0.2 MPa to 1.5 MPa), Piuma probes with tip radius differences of about 10% or less can be used.</p><p>Once the indentation is performed, both the indentation depth and the indentation force are recorded. Five lenses per lens type are tested, with three measurements per lens, resulting in a total of 15 data points per lens group.</p><p>All raw data is processed using MATLAB and analyzed using Excel. The indentation force value at 400 nm indentation depth is determined by interpolating between the two closest force values. For each lens group, all indentation forces at 400 nm indentation depth are averaged, and the averaged indentation force at 400 nm indentation depth is used to characterize the contact lenses of that lens group.</p><p>Transmission contact lenses are manually placed into a custom sample holder or similar that is capable of retaining the shape of the lens when placed on the eye. The holder is then submerged into a quartz cell with a 1 cm path length containing PBS as a standard. A UV/Visible spectrophotometer such as a Varian Cary 3E UV-Visible spectrophotometer with a LabSphere DRA-CA-302 beam splitter or similar can be used for this measurement. The percent transmission spectrum is collected over the wavelength range of 250-800 nm, with T values collected at 0.5 nm intervals. This data is transferred onto an Excel spreadsheet and used to determine if the lens meets Class 1 UV absorbance. Transmission is calculated using the following formula:<math num="25"><img file="JP7635289B2_D0037.tif" /></math>where luminance %T is the average % transmittance from 380 to 780.</p><p>Determination of polyquaternium-1 uptake rate (PU).</p><p>The rate of polyquaternium-1 uptake by contact lenses is determined according to the DNA intercalation method based on the PicoGreen dsDNA assay kit (i.e., Quanti-iT PicoGreen dsDNA kit (ThermoFisher)). The rate of polyquaternium-1 uptake by contact lenses is determined as follows.</p><p>A basis solution is prepared by dissolving the following components in purified water, 5 ppm myristamidopropyl dimethylamine, 1000 ppm sodium decanoylethylenediamine triacetate, 83 ppm sodium citrate dehydrate, 1000 ppm NaCl, 1000 ppm Tetronic 1304, 1150 ppm sodium borate decahydrate, and 10000 ppm propylene glycol, followed by adjusting the pH to about 7.8.</p><p>Prepare polyquaternium-1 (PQ) test solutions by dissolving the desired amount in the standard solution prepared above to have 5 ppm PQ, followed by adjusting the pH to approximately 7.8 if necessary. Prepare a series of PQ standard solutions, each with a range of concentrations, to establish a calibration curve between 0 and 6 ppm (or higher) of PQ.</p><p>The contact lenses are removed from their individual lens packages and shaken in 25 mL of PBS per lens for 30 minutes. The PBS-soaked lenses are blotted with a paper towel of constant weight (i.e., 0.6 kg) (preferably Kimberly Clark W4 polypropylene towels) and then incubated overnight.</p><p>A 24-well plate is used in the overnight incubation experiment. The wells are divided into the following categories: negative control wells, each containing 0.5 mL of standard solution and two blotted contact lenses fully immersed therein, positive control wells, each containing 0.5 mL of polyquaternium-1 test solution, sample wells, each containing 0.5 mL of polyquaternium-1 test solution and two blotted contact lenses fully immersed therein, standard wells, each containing 0.5 mL of one of the standard solutions. The 24-well plate is then shaken on an orbital shaker for 20 minutes and then placed on the benchtop at room temperature overnight (16-20 hours).</p><p>Add 25 µL aliquots from each well of the overnight incubated 24-well plate to cell wells of a 96-well plate (e.g., DNA LoBind (Eppendorf)) containing 450 µL of lambda DNA solution (1 µg/mL lambda DNA, 10 mM Tris-HCl, 1 mM EDTA, pH 7.5). Mix the solution and incubate for 60 min at 700-800 rpm on an orbital shaker.</p><p>A 100 μL aliquot from each DNA-incubated cell well is transferred to a 96-well plate (e.g., black opaque, medium binding (Grenier)). 100 μL of PicoGreen solution (ThermoFisher, diluted in Tris-EDTA buffer [10 mM Tris-HCl, 1 mM EDTA, pH 7.5] according to kit instructions) is then added to each of these wells and mixed. The cell wells are then incubated for 5 minutes on an orbital shaker at 250 rpm. Each plate is read using a fluorescent plate reader (e.g., Victor X5 Plate Reader (Perkin Elmer)) using standard fluorescent excitation and emission wavelengths for PicoGreen. Read on a 350°C centrifuge (Elmer). Compare each sample to a linear fit of the standard curve to obtain the final PQ concentration in each solution. The amount of PQ uptake per lens is obtained by multiplying by the incubation volume and dividing by the number of lenses incubated. The percentage of PQ uptake by lenses is calculated as the difference in [polyquaternium-1] between the DNA-incubated positive control and the sample solutions multiplied by the incubation volume (0.5 mL) and divided by 2.</p><p>Surface Crack (SC) Test The test to assess surface cracks is performed as follows: Remove the lens from the package. Gently evert the lens (i.e., place the lens in an inverted configuration) by holding the edge of the lens between the thumb and index finger of one hand. The concave side of the lens should be facing the body of the experimenter. With the thumb and/or index finger of the other hand, hold the lens in the inverted configuration. The lens is gently bent over the index finger holding the lens until the lens inverts. Subsequently, gently fold the lens in two halves and apply slight pressure to the folded lens. The lens is then returned to its original form before inverting the lens and the above steps are repeated. The lens is placed in a Petri dish and inspected using a dark field stereo microscope. The lens is inspected for surface cracks first at low magnification (i.e. 10-20x) focusing on the center of the lens, and if no crack lines are discernible, the lens is further inspected at high magnification (e.g. 35-45x). If no cracks are observed at 45x magnification, the lens receives a surface crack rating of zero (0). If cracks are observed, a crack rating is obtained by counting the number of split lines, with a rating of 1 being 2-4 lines in the field of view, a rating of 2 being 5-8 lines, and a rating of 3 being 8 or more lines.</p><p>Coating Intactness Test The coating integrity on the surface of a contact lens can be tested according to the Sudan Black staining test as follows: A contact lens with a coating (LbL coating, plasma coating, hydrogel coating, or any other coating) is immersed in a Sudan Black dye solution (Sudan Black in a mixture of about 80% mineral oil and about 20% Vitamin E oil). Sudan Black dye is hydrophobic and has a high tendency to be adsorbed by hydrophobic materials or onto hydrophobic lens surfaces or onto hydrophobic spots on partially coated surfaces of hydrophobic lenses (e.g. silicone hydrogel contact lenses). If the coating on the hydrophobic lens is intact, no staining spots should be observed on or in the lens. All lenses under test are fully hydrated. Visible fine lines on the lens surface may indicate the presence of cracks in the crosslinked coating.</p><p>Comparative Example The method disclosed in US Patent Application Publication No. 2016/0326046A1 is used in this example to reduce the uptake rate of positively charged antimicrobial agents by water gradient contact lenses.</p><p>PMAA coating solution. A polymethacrylic acid (PMAA) coating solution is prepared by dissolving a certain amount of PMAA (Mn: 300-600 kDa (Polysciences, Inc.)) in a given volume of 1-propanol/water (90%/10% wt/wt) mixture to a concentration of about 0.011 wt%, and the pH is adjusted to about 2.0 using formic acid.</p><p>PAE Solution-1. The PAE solution is prepared by dissolving a certain amount of polyamidoamine epichlorohydrin (Kymene) in a certain volume of water to a concentration of about 0.5% by weight, and the pH is adjusted to the desired pH (e.g., 2.0, 3.5, 7, or 9).</p><p>PAE Solution-2. The PAE solution is prepared by dissolving a certain amount of polyamidoamine epichlorohydrin (Kymene) in a given volume of a mixture of water (68 wt%) and 1-propanol (32 wt%) to a concentration of about 0.5 wt%, and the pH is adjusted to pH 2.0.</p><p>Preparation of In-Package Coating (IPC) Saline (IPC-1) Approximately 90 mol % 2-methacryloyloxyethyl phosphorylcholine (MPC) and approximately 10 mol % <img file="JP7635289B2_D0038.tif" /> (Wherein, X is -CH₂CH(OH)CH₂SCH₂CH₂NH₂or -CH₂CH(CH₂OH)SCH₂CH₂NH₂The MPC-containing copolymer (Mw: 230-320 kD) containing is prepared according to a procedure similar to that described in Examples 1-2 of US Pat. No. 9,127,099 B2. The MPC-containing copolymer used is an aqueous solution containing a solids content of about 10% by weight of the MPC-containing copolymer.</p><p>PAE solution (Kymene) is purchased from Ashland as an aqueous solution and is used as received.</p><p>IPC-1 saline is prepared as follows: about 74% by weight of MPC-containing copolymer solution, about 6% by weight of PAE solution, and about 20% by weight of phosphate buffer (about 0.22% by weight of NaH₂PO₄H₂O, 1.95% by weight Na₂HPO₄2H₂0, and about 4 wt% NaCl) (the concentration of MPC-containing copolymer and PAE is about 10 times that of the final saline solution). The pH is adjusted to about 7.3 with 1 N NaOH. The mixture in the water bath is reacted at a temperature of 70°C for 4 hours to form a water-soluble thermally crosslinkable polymeric material (i.e., "in-package crosslinker" or "IPC agent"). The mixture is removed from the water bath and cooled in a room temperature water bath. The mixture is diluted 10 times with PBS and the pH is adjusted to about 7.3. The mixture is filtered through a 0.22 μm PES sterile filter unit.</p><p>Cast Silicone Hydrogel (SiHy) Contact Lenses. SiHy contact lenses (uncoated) are cast according to the procedure described in Example 3 of US Patent Application Publication No. 2016/0326046A1.</p><p>Application of the crosslinked coating. Cast SiHy contact lenses are extracted and coated by dipping into a series of baths: baths 1-3 - three MEK baths (approximately 22 seconds, 138 seconds, and 224 seconds, respectively), bath 4 - DI water bath (approximately 56 seconds), baths 5-7 - as shown in Table 1, bath 8 - DI water (approximately 56 seconds unless otherwise indicated), bath 9 - DI water (approximately 56 seconds), bath 10 - DI water (approximately 168 seconds). Unless otherwise indicated, all baths are at room temperature (i.e., approximately 22-26 °C). After the tenth bath, the contact lenses are individually packaged in polypropylene lens packaging shells (blisters) with 0.6 mL of IPC-1 saline (half of the IPC-1 saline is added before inserting the lenses). The blisters are then sealed using foil and autoclaved at 121 °C for approximately 30 minutes to form a crosslinked coating on the lenses.</p><p><tables><img file="JP7635289B2_D0039.tif" /></tables></p><p>The lenses are then tested for the amount of carboxyl groups per lens according to the procedure described in Example 2 of US 2016/0326046 A1 and are also subjected to a finger rubbing test to evaluate lubricity (friction score) according to the procedure described in Example 1.</p><p>The control lenses (C3 and C4) and the test lenses (T8 and T9) have a lubricity rating of 4 as-is out of the package and without undergoing the cycling-lubricity test. These results may indicate that heating a lens with a PMAA coating thereon may result in significant loss of PMMA, such that an insufficient amount of PMAA remains on the lens to react with the thermally crosslinkable material to form a hydrogel top coating.</p><p>The test lenses (T2 and T3) have out-of-package lubricity ratings of 3 and 4, respectively. These results may indicate that at high pH (7 or 9), PMAA is loaded and PAE cannot penetrate into the PMAA coating, but forms a layer on top of the PMAA coating. The top layer of PAE prevents the PMAA underneath from reacting with the thermally crosslinkable polymeric material to form a hydrogel top coating. During autoclaving, the top layer of PAE crosslinks with the PMAA coating to form a less lubricious crosslinked coating.</p><p>The results in Table 2 indicate that the approach disclosed in U.S. Patent Application Publication No. 2016/0326046A1 may not be sufficient to produce water gradient contact lenses that have sufficient lubricity after cycling with Renu lens care solution and that do not have a significant decrease in the uptake rate of the positively charged antimicrobial agent.</p><p><tables><img file="JP7635289B2_D0040.tif" /></tables></p><p>Example 2 Preparation of Polymerizable Compositions Two lens formulations (polymerizable compositions) I and II are prepared having the compositions shown in Table 3 (part by part).</p><p><tables><img file="JP7635289B2_D0041.tif" /></tables></p><p>The formulation is prepared by adding the listed ingredients in their target amounts to a clean bottle and mixing with a stir bar at 600 rpm for 30 minutes at room temperature. After all solids are dissolved, the formulation is filtered by using a 2.7 μm glass microfiber filter (GMF).</p><p>Purge the cast molded silicone hydrogel contact lens formulation with nitrogen at room temperature for 30-35 minutes.₂The purged lens formulation is introduced into a polypropylene mold and heat cured under the following cure conditions: ramp from room temperature to 55°C at a ramp rate of about 7°C/min, hold at 55°C for about 30 minutes, ramp from 55°C to 80°C at a ramp rate of about 7°C/min, hold at 55°C for about 30 minutes, ramp from 80°C to 100°C at a ramp rate of about 7°C/min, hold at 100°C for about 30 minutes. The mold is opened and the molded lens is removed from the mold.</p><p>Formulations I and II are used in the coating studies in the examples below. Generally, Formulation II is used unless otherwise indicated.</p><p>The resulting silicone hydrogel (SiHy) contact lenses are subjected to the following post-molding process before the lenses are characterized: After demolding, the SiHy lenses prepared above are immersed in PBS at room temperature for about 60 minutes twice. After rinsing with PBS for 5 minutes, the lenses are placed into polypropylene lens packaging shells (or blisters) (one lens per shell) with 0.6 mL of PBS. The blisters are then sealed with foil and autoclaved at about 121° C. for about 45 minutes. The SiHy lenses have an oxygen permeability (measured by polarographic techniques) of about 91 barrer (for Formulation I) or about 83 barrer (for Formulation II), a bulk modulus of about 0.80 MPa (for Formulation I) or about 0.67 MPa (for Formulation II), a water content of about 49% by weight (for Formulation I) or about 50% by weight (for Formulation II), a relative ion permeability of about 12.5 (for Formulation I) or about 11.0 (for Formulation II) relative to Alsacon lenses, a WBUT of 0 seconds, and a friction rating of 4.</p><p>Example 3 Preparation of Polymerizable Compositions Lens formulations (polymerizable compositions) III-VI are prepared having the compositions shown in Table 4 (part by part).</p><p><tables><img file="JP7635289B2_D0042.tif" /></tables></p><p>The formulation is prepared by adding the listed ingredients in their target amounts to a clean bottle and mixing with a stir bar at 600 rpm for 30 minutes at room temperature. After all solids are dissolved, the formulation is filtered using a 2.7 μm glass microfiber filter.</p><p>Purge the cast molded silicone hydrogel contact lens formulation with nitrogen at room temperature for 30-35 minutes.₂The purged lens formulation is introduced into a polypropylene mold and heat cured in an oven under the following cure conditions: ramp from room temperature to a first temperature followed by holding at the first temperature for a first cure time; ramp from the first temperature to a second temperature and holding at the second temperature for a second cure time; optionally ramp from the second temperature to a third temperature and holding at the third temperature for a third cure time; optionally ramp from the third temperature to a fourth temperature and holding at the fourth temperature for a fourth cure time.</p><p>A mold releaser with a pressure pin is used to open the lens mold. The lens is pushed onto the base curve mold using the pressure pin, and the mold is subsequently separated into a base curve mold half and a front curve mold half. The base curve mold half with the lens thereon is placed in an ultrasonic device (e.g., a Dukane single horn ultrasonic device). A specific energy force is used to release the dry lens from the mold. The dry lens is loaded into a designed extraction tray. Alternatively, the lens can be removed from the base curve mold half by floating off (i.e., immersion in an organic solvent, e.g., IPA, without ultrasound).</p><p>The resulting silicone hydrogel (SiHy) contact lenses are subjected to the following post-molding processes before the lenses are characterized. After demolding, the SiHy lenses prepared above are extracted with 100% IPA for 15 minutes, immersed in a 50%/50% IPA/water mixture for 30 minutes, followed by DI water for 30 minutes, and finally rinsed with PBS saline at room temperature for about 60 minutes. After rinsing with PBS for 5 minutes, the lenses are placed in polypropylene lens packaging shells (or blisters) (one lens per shell) with 0.6 mL of PBS. The blisters are then sealed with foil and autoclaved at about 121° C. for about 45 minutes. The resulting SiHy contact lenses are characterized according to the procedure to have the following properties: Dkc: approximately 105 barrer to 118 barrer, EWC: approximately 54% to 57%, elastic modulus: approximately 0.45 MPa to 0.62 MPa, WBUT: approximately 23 seconds to 40 seconds, water contact angle due to trapped bubbles: approximately 47 degrees to 52 degrees, friction rating: approximately 2.0.</p><p>Example 4 Preparation of PAA Aqueous Solution An aqueous solution of polyacrylic acid (PAA) is prepared by adding an appropriate amount of PAA (Mn: about 450KD) to water (distilled water or deionized water). After the PAA is completely dissolved, the pH is adjusted to about 2 by adding about 1.85% formic acid to the PAA aqueous solution. The target concentration of PAA is about 0.1% by weight. The prepared PAA aqueous solution is filtered to remove any particulates or foreign matter.</p><p>Phosphate Buffered Saline (PBS) NaH₂PO₄H₂O, Na₂HPO₄2H₂Dissolve 2,5-dichlorophenyl ether (NaH2O) in a given amount of purified water (distilled or deionized) to obtain a solution of approximately 0.044 wt/w% NaH2O.₂PO₄H₂O, approximately 0.388% w/w Na₂HPO₄2H₂Phosphate buffered saline is prepared by making up approximately 0.79% w/w NaCl.</p><p>Phosphate buffered (PB) without NaCl (PB, No NaCl) Prepare PB using the same procedure as for preparing PBS but without the addition of NaCl.</p><p>IPC-2 saline: Mix appropriate amounts of poly(AAm-co-AA) (90/10), PAE, NaHPO, and PAE to have the following concentration: about 0.132 wt.% poly(AAm-co-AA), about 0.11 wt.% PAE, about 0.044 wt.% NaHPO.H2O, about 0.388 wt.% NaHPO.2H2O, and about 0.79 wt.% NaCl.₂PO4H₂O, Na₂HPO₄2H₂Prepare IPC-2 saline by dissolving/mixing 100% HO and NaCl in DI (deionized) water, followed by adjusting the pH to approximately 7.3. Poly(AAm-co-AA) (90/10) partial sodium salt, Poly(AAm-co-AA) 90/10, Mw 200,000) is purchased from Polysciences, Inc. and used as is. Pretreat the prepared solution at 65°C for approximately 6 hours. After heat pretreatment, cool the IPC saline back to room temperature. Up to 5 ppm hydrogen peroxide may be added to the final IPC saline to prevent growth of microbial contaminants, and filter the IPC saline using a 0.22 micrometer membrane filter.</p><p>After demolding of the SiHy lens containing the PAA base coating, the dry SiHy contact lens (prepared with Example 2, Formulation II) is placed in an appropriate tray. The tray containing the lens is then immersed in the PAA solution for a predetermined time, either in one PAA bath for 120 minutes, or in two sequential PAA baths, dipping in the first bath for 30 minutes and the second bath for 90 minutes. The PAA dip solution is heated above room temperature, for example to 40°C. Sufficient agitation (for example horizontal shaking or up-and-down motion) may be used to ensure proper flow of the PAA solution during the dipping process.</p><p>After PAA dipping, the lenses are transferred to a bath containing PB for up to about 1 hour, usually at room temperature. Sufficient agitation (e.g., horizontal shaking or up-and-down motion) may be used to ensure adequate flow of the PB during the dipping process.</p><p>The lenses are then transferred to a bath containing water for approximately 5-10 minutes, usually at room temperature, with sufficient agitation (e.g., horizontal shaking or up-and-down motion) to ensure adequate flow of water during the dipping process.</p><p>Water Gradient SiHy Contact Lenses SiHy lenses having a PAA-based coating thereon, prepared as described above, are placed into polypropylene lens packaging shells (one lens per shell) with 0.55 mL or 0.65 mL of IPC-2 saline (about half of the saline may be added prior to inserting the lens). The blisters are then sealed with foil and autoclaved at about 121° C. for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon.</p><p>Surface Properties of Water Gradient SiHy Contact Lenses The resulting water gradient SiHy contact lenses are lubricious (having a friction rating of 1) as-removed from the package, have a WBUT of greater than 10 seconds, and a sessile drop (static) water contact angle of approximately 30 degrees.</p><p>Example 5 This example uses water gradient contact lenses prepared in Example 4. They are determined to have a PU (polyquaternium-1 uptake) of approximately 9 μg/lens.</p><p>Preparation of Aqueous Polyaziridine Solutions A 1 wt % PZ-28 solution is prepared by simply adding PZ-28 to PBS and adjusting the pH to about 7.5, and a 1 wt % PZ-33 solution is prepared by simply adding PZ-33 to PBS and adjusting the pH to about 7.5.</p><p>PU Reduction with Water Gradient Contact Lenses Water gradient contact lenses prepared in Example 4 are individually repackaged in polypropylene lens packaging shells (one lens per shell) with 0.55 mL or 0.65 mL of 1% PZ-28 solution and autoclaved at about 121° C. for about 45 minutes. The resulting lenses are still lubricious (having a friction rating of 1) and have a PU of 0.56 μg/lens, i.e., a PU reduction of 93.8%.<math num="26"><img file="JP7635289B2_D0043.tif" /></math> 。</p><p>The water gradient contact lenses prepared in Example 4 are individually repackaged in polypropylene lens packaging shells (one lens per shell) with 0.55 mL or 0.65 mL of 1% PZ-33 solution and autoclaved for about 45 minutes at about 121° C. The resulting lenses are still lubricious (friction rating of 1) and have a PU of 1.95 μg/lens, i.e., a reduction in PU of 78.3%.</p><p>Example 6 Preparation of PMAA Solution A solution of polymethacrylic acid (PMAA) is prepared by adding an appropriate amount of PMAA (Mn: about 400-700 kDa (PolyMaterials, Inc.)) to an IPA/water (50/50 volume ratio) mixture to a concentration of about 0.12 wt%. After the PMAA is completely dissolved, the pH is adjusted to about 2 by adding formic acid to the PMAA solution. The prepared PMAA solution is filtered to remove any particulates or foreign matter.</p><p>Phosphate Buffered Saline (PBS) PBS is prepared according to the procedure described in Example 4.</p><p>Phosphate buffer solution (PB) without NaCl (PB, No NaCl) PB is prepared according to the procedure described in Example 4.</p><p>Preparation of Aqueous Polyaziridine Solutions A 1 wt % PZ-28 solution is prepared by simply adding PZ-28 to PBS and adjusting the pH to about 7.5, and a 1 wt % PZ-33 solution is prepared by simply adding PZ-33 to PBS and adjusting the pH to about 7.5.</p><p>IPC-3 saline solution containing approximately 90 mol% 2-methacryloyloxyethyl phosphorylcholine (MPC) and approximately 10 mol% <img file="JP7635289B2_D0044.tif" /> (Wherein, X is -CH₂CH(OH)CH₂SCH₂CH₂NH₂or -CH₂CH(CH₂OH)SCH₂CH₂NH₂The MPC-containing copolymer (Mw: 230-320 kD) containing is prepared according to a procedure similar to that described in Examples 1-2 of US Pat. No. 9,127,099 B2. The MPC-containing copolymer used is an aqueous solution containing a solids content of about 10% by weight of the MPC-containing copolymer.</p><p>PAE solution (Kymene) is purchased from Ashland as an aqueous solution and is used as received.</p><p>IPC-3 saline is prepared as follows: about 74.3 wt% MPC-containing copolymer solution, about 3.7 wt% PAE solution, and about 22 wt% phosphate buffer (about 0.22 wt% NaH₂PO₄H₂O, 1.95% by weight Na₂HPO₄2H₂0, and about 4 wt% NaCl) (the concentration of MPC-containing copolymer and PAE is about 10 times that of the final saline solution). The pH is adjusted to about 7.3 with 1 N NaOH. The mixture in the water bath is reacted at a temperature of 70°C for 4 hours to form a water-soluble thermally crosslinkable polymeric material (i.e., "in-package crosslinker" or "IPC agent"). The mixture is removed from the water bath and cooled in a room temperature water bath. The mixture is diluted 10 times with PBS and the pH is adjusted to about 7.3. The mixture is filtered through a 0.22 μm PES sterile filter unit.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with isopropanol (IPA) for 180 minutes for lens extraction, dip coated in the PMAA solution prepared above for about 1 hour, rinsed with PBS for about 60 minutes, and then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.6 mL of IPC-3 saline (half of the IPC-3 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test.</p><p>The resulting water gradient SiHy contact lenses are fairly lubricious (having a friction rating of 2), with a WBUT greater than 10 seconds and a PU (polyquaternium-1 uptake) of 1.2 μg/lens.</p><p>Reduction in PU Uptake with Water Gradient Contact Lenses The water gradient contact lenses prepared above are individually repackaged in polypropylene lens packaging shells (one lens per shell) with 0.55 mL or 0.65 mL of 1% PZ-28 solution and autoclaved at about 121° C. for about 45 minutes. The resulting lenses are still fairly lubricious (having a friction rating of about 1.7) and have a PU of 0.06 μg/lens, i.e., a reduction in PU of 95%.<math num="27"><img file="JP7635289B2_D0045.tif" /></math> 。</p><p>The water gradient contact lenses prepared above are individually repackaged in polypropylene lens packaging shells (one lens per shell) with 0.55 mL or 0.65 mL of 1% PZ-33 solution and autoclaved for about 45 minutes at about 121° C. The resulting lenses are still lubricious (friction rating of about 1.0) and have a PU of 0.32 μg/lens, i.e., a reduction in PU of 73.3%.</p><p>Example 7 This example uses a water gradient contact lens prepared according to the procedure described in Example 19 of US Patent No. 8,480,227. The water gradient SiHy contact lens has a water content of about 32% by weight, an oxygen permeability of about 146 barrer, a bulk modulus of about 0.76 MPa, a relative ion permeability of about 6 (compared to Alsacon lenses), a friction rating of 0, a WBUT of greater than 20 seconds, a water contact angle (by static drop) of about 34-47 degrees, and a PU of about 11 μg/lens.</p><p>Preparation of BTP Solution Prepare a Bis-Tris-Propane (BTP) solution by dissolving BTP in deionized (DI) or distilled water to a concentration of 0.03% and subsequently adjusting the pH to 7.5.</p><p>Preparation of Aqueous Polyaziridine Solutions PZ-28 BTP buffer solutions with PZ-28 concentrations of 0.1 wt%, 0.2 wt%, or 0.3 wt% are prepared by simply adding PZ-28 to the BTP solution and adjusting the pH to about 7.4.</p><p>A PZ-28 phosphate buffer solution with a PZ-28 concentration of 0.1% by weight is prepared by simply adding PZ-28 to PBS and adjusting the pH to about 7.5.</p><p>Reduction in PU Uptake with Water Gradient Contact Lenses The water gradient contact lenses prepared above are individually repackaged in polypropylene lens packaging shells (one lens per shell) with 0.55 mL of the 0.1% PZ-28BTP buffer solution prepared above and autoclaved at about 121° C. for about 45 minutes. The resulting lenses are still lubricious (have a friction rating of 0) and have 1.2 μg PU/lens, i.e., a reduction in PU of 89.1%.<math num="28"><img file="JP7635289B2_D0046.tif" /></math> 。</p><p>The water gradient contact lenses prepared above are individually repackaged in polypropylene lens packaging shells (one lens per shell) with 0.55 mL of 0.2% PZ-28BTP buffer solution and autoclaved for approximately 45 minutes at approximately 121° C. The resulting lenses are still lubricious (friction rating of 0) and have a PU of 0.4 μg/lens, i.e., a reduction in PU of 96.4%.</p><p>The water gradient contact lenses prepared above are individually repackaged in polypropylene lens packaging shells (one lens per shell) with 0.55 mL of 0.3% PZ-28BTP buffer solution and autoclaved for approximately 45 minutes at approximately 121° C. The resulting lenses are still lubricious (friction rating of 0) and have a PU of 0.3 μg/lens, i.e., a reduction in PU of 97.3%.</p><p>The water gradient contact lenses prepared above are individually repackaged in polypropylene lens packaging shells (one lens per shell) with 0.55 mL of the 0.1% PZ-28 phosphate buffer solution prepared above and autoclaved for about 45 minutes at about 121° C. The resulting lenses are still lubricious (have a friction rating of 0) and have a PU of 0.6 μg/lens, i.e., a reduction in PU of 94.5%.</p><p>Example 8 This example uses water gradient contact lenses as prepared in Example 4. They are determined to have a PU of about 9 μg/lens.</p><p>Preparation of BTP Solution A Bis-Tris-propane solution is prepared by dissolving BTP in DI (or distilled) water to a concentration of 0.03 wt % and then adjusting the pH to 7.5.</p><p>Preparation of Aqueous Polyaziridine Solutions PZ-28 solutions with concentrations of 0.1%, 0.2%, or 0.3% PZ-28 are prepared by simply adding PZ-28 to the BTP solution and adjusting the pH to about 7.5.</p><p>Reduction in PU Uptake by Water Gradient Contact Lenses Water gradient contact lenses prepared in Example 4 are individually repackaged in polypropylene lens packaging shells (one lens per shell) with 0.55 mL of the 0.1% PZ-28 solution prepared above and autoclaved at about 121° C. for about 45 minutes. The resulting lenses are still lubricious (having a friction rating of 0) and have a PU of 0.42 μg/lens, i.e., a reduction in PU of 95.3%.<math num="29"><img file="JP7635289B2_D0047.tif" /></math> 。</p><p>The water gradient contact lenses prepared in Example 4 are individually repackaged in polypropylene lens packaging shells (one lens per shell) with 0.55 mL of the 0.2% PZ-28 solution prepared above and autoclaved for about 45 minutes at about 121° C. The resulting lenses are still lubricious (friction rating of 0) and have a PU of 0.3 μg/lens, i.e., a reduction in PU of 96.7%.</p><p>The water gradient contact lenses prepared in Example 4 are individually repackaged in polypropylene lens packaging shells (one lens per shell) with 0.55 mL of the 0.3% PZ-28 solution prepared above and autoclaved for about 45 minutes at about 121° C. The resulting lenses are still lubricious (friction rating of 0) and have a PU of 0.05 μg/lens, i.e., a reduction in PU of 99.4%.</p><p>Example 9 Preparation of PAA Coating Solution The PAA coating solution is prepared by adding an appropriate amount of PAA (Mn: about 450KD) to a 50/50 water-IPA mixture. After the PAA is completely dissolved, the pH is adjusted to about 2 by adding about 1.85% formic acid to the PAA aqueous solution. The target concentration of PAA is about 0.1% by weight. The prepared PAA coating solution is filtered to remove any particulates or foreign matter.</p><p>Phosphate Buffered Saline (PBS) NaH₂PO₄H₂O, Na₂HPO₄2H₂Dissolve 2,5-dichlorophenyl ether (NaH2O) in a given amount of purified water (distilled or deionized) to obtain a solution of approximately 0.044 wt/w% NaH2O.₂PO₄H₂O, approximately 0.388% w/w Na₂HPO₄2H₂Phosphate buffered saline is prepared by making up approximately 0.79% w/w NaCl.</p><p>Phosphate buffer solution (PB) without NaCl (PB, No NaCl) Prepare PB using the same procedure as for preparing PBS but without adding NaCl.</p><p>Preparation of Aqueous Polyaziridine Solutions PZ-28 solutions with concentrations of 0.125%, 0.25%, or 0.5% PZ-28 are prepared by simply adding PZ-28 to DI water and adjusting the pH to about 7.4.</p><p>After the PZ-induced PU reduction release of the PAA-coated SiHy contact lens, the dried SiHy contact lens (prepared in Example 3) is extracted with isopropanol (IPA) for 180 minutes for lens extraction, dip-coated in the above-prepared PAA solution for about 30 minutes, rinsed twice with PB for about 15 minutes each, and then immersed in the above-prepared PZ-28 solution for about 2 hours at about 60° C. After the PZ-28 dipping step, the lens is again rinsed twice with PB (for 15 minutes each), and then subjected to various tests as shown in Table 5.</p><p><tables><img file="JP7635289B2_D0048.tif" /></tables></p><p>The results in Table 5 show that after various PZ-dip treatments, the Polyquartenium-1 uptake rate by PAA-coated SiHy contact lenses can be significantly decreased by PZ-28 due to the reaction of the aziridine groups of PZ-28 with the -COOH groups in the PAA coating on the lens surface at about 60°C (relatively high temperature). Even at a concentration of about 0.125 wt%, PZ-28 can significantly decrease the Polyquartnium-1 uptake rate (PU) by PAA-coated SiHy lenses, while adversely affecting the lubricity.</p><p>Table 6 shows the results of treatment of PAA coated SiHy contact lenses with 0.25 wt % PZ-28 at room temperature and 45°C for about 1 hour to evaluate the effect of PZ-28 dipping temperature on the efficacy of PZ-28 in reducing PU. Table 6 shows that the efficacy of PZ-28 is significantly improved at 45°C compared to when the PZ dip is performed at room temperature (RT). The reduction in the percentage of polyquaternium-1 uptake is about 55% at room temperature compared to about 93% when the dip is performed at 45°C. This indicates that the efficacy of PZ-28 increases at elevated temperatures above RT.</p><p><tables><img file="JP7635289B2_D0049.tif" /></tables></p><p>Example 10 Preparation of PMAA Solution A polymethacrylic acid (PMAA) coating solution is prepared by dissolving a certain amount of PMAA (Mn: 400-700 kDa (PolyMaterials, Inc.)) in a given volume of 1-propanol/water (25/75 volume ratio) mixture to a concentration of about 0.06 wt%, and the pH is adjusted to about 2.0 using formic acid (typically about 1.8 wt% in the final solution).</p><p>Phosphate Buffered Saline (PBS) PBS is prepared according to the procedure described in Example 4.</p><p>Phosphate buffer solution (PB) without NaCl (PB, No NaCl) PB is prepared according to the procedure described in Example 4.</p><p>IPC Saline Solutions (IPC-4, IPC-5, IPC-6, and IPC-7) IPC-3 saline solution is prepared according to the procedure described in Example 6.</p><p>Four IPC saline solutions (IPC-4 to IPC-7) with PZ-28 concentrations of 0.05%, 0.1%, 0.5%, and 1% by weight, respectively, are prepared by adding the desired amount of PZ-28 to IPC-3 saline solution, followed by adjusting the pH to 7.5. Up to 5 ppm hydrogen peroxide may be added to each IPC saline solution to prevent growth of microbial contaminants, and each IPC saline solution is filtered using a 0.22 micrometer membrane filter.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with isopropanol (IPA) for 180 minutes for lens extraction, dip coated in the PMAA solution prepared above for about 1 hour, rinsed with PBS for about 60 minutes, and subsequently packaged/sealed in a polypropylene lens packaging shell (blister) with 0.6 mL of one of the IPC-3 to IPC-7 saline solutions prepared above (half of the IPC saline solution is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test.</p><p>The resulting water gradient SiHy contact lenses are fairly lubricious (having a friction rating of about 0), with a WBUT greater than 20 seconds and a static drop water contact angle of 40. They are determined to have a PU of 0.5, 0.19, 0.19, 0, and 0 for water gradient contact lenses prepared from IPC-3 saline (0 wt.% PZ-28), IPC-4 saline (0.05 wt.% PZ-28), IPC-5 saline (0.1 wt.% PZ-28), IPC-6 saline (0.5 wt.% mpPZ-28), and IPC-7 saline (1.0 wt.% PZ-28), respectively.</p><p>Example 11 Preparation of PAA Coating Solution PAA coating solution is prepared by adding an appropriate amount of PAA (Mn: about 450 KD) into a water-IPA mixture with the water content shown in Table 7 to obtain the desired PAA concentration as shown in Table 7. After the PAA is completely dissolved, the pH is adjusted to about 2 by adding about 1.85% formic acid to the PAA aqueous solution. The prepared PAA coating solution is filtered to remove any particulates or foreign matter.</p><p>Phosphate Buffered Saline (PBS) PBS is prepared according to the procedure described in Example 4.</p><p>Phosphate buffer solution (PB) without NaCl (PB, No NaCl) PB is prepared according to the procedure described in Example 4.</p><p>Preparation of Poly(MPC-co-AEM) (96/4 wt/wt) The copolymer poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethyl methacrylate) (96/4 wt/wt) (i.e., poly(MPC-co-AEM)) is prepared by thermally polymerizing a polymerizable composition comprising about 96 wt% MPC, about 4 wt% AEM, about 0.02 wt% Vazo56 [2,2'-azobis(2-methylpropionamidine) dihydrochloride], and about 0.1 wt% chain transfer agent (HS-CHCHOH) in water at about 60°C for about 2 hours and then at 20°C for about 2 hours. The resulting poly(MPC-co-AEM) (aqueous solution with a solids content of about 10%) is determined to have an amine functionality of about 0.22 meq/g and an Mn of about 160 kDa.</p><p>The resulting copolymer is used as a hydrophilic enhancer for reaction with polyamidoamine-epichlorohydrin (PAE) to prepare water-soluble thermally crosslinkable polymeric materials (i.e., "in-package crosslinkers" or "IPC agents"). PAE solution (Kymene) is purchased from Ashland as an aqueous solution and used as is.</p><p>IPC-8 Saline IPC-8 saline is prepared as follows: Mix the 77 wt/wt% poly(MPC-co-AEM) aqueous solution prepared above, 6.1 wt/wt% PAE, and 16.9 wt/wt% phosphate buffer (about 128 mM sodium phosphate salt and about 4 wt% NaCl) (the concentrations of poly(MPC-co-AEM) and PAE are about 10 times that of the final saline). Adjust the pH to about 7.3 with 1N NaOH. React the mixture in the water bath at a temperature of 70°C for 3 hours. Remove the mixture from the water bath and cool it in the water bath at room temperature. Dilute the mixture 10 times with phosphate buffer (about 33 mM sodium phosphate salt and 0.77 wt% NaCl) and adjust the pH to about 7.3. Filter the mixture through a 0.22 μm PES sterile filter unit.</p><p>IPC-9 Saline IPC-9 saline is prepared by adding PZ-28 to IPC-8 saline to achieve a PZ-28 concentration of 0.2% by weight. Up to 5 ppm hydrogen peroxide may be added to each IPC saline to prevent bioburden buildup, and each IPC saline is filtered using a 0.22 micrometer membrane filter.</p><p>After water gradient SiHy contact lens demolding, cast molded SiHy contact lenses (prepared in Example 3) are extracted with isopropanol (IPA) for 180 minutes for lens extraction, dip coated in the above prepared PAA solution for the time specified in Table 7, rinsed twice with PB for about 30 minutes each, and then packaged/sealed in polypropylene lens packaging shells (blisters) with 0.6 mL of either the above prepared IPC-8 saline or IPC-9 saline (half of the IPC saline is added before inserting the lens). The sealed lens packages are autoclaved at about 121°C for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test.</p><p>The resulting water gradient SiHy contact lenses are lubricious (having a friction rating of about 0), have a WBUT greater than 20 seconds, and a static drop water contact angle of about 40 degrees. They are determined to have the PU shown in Table 7.</p><p><tables><img file="JP7635289B2_D0050.tif" /></tables></p><p>Example 12 PMAA Coating Solution A polymethacrylic acid (PMAA) coating solution is prepared by dissolving a certain amount of PMAA (Mn: 400-700 kDa (PolyMaterials, Inc.)) in a given volume of 1-propanol/water (49%/51% wt/wt) mixture to a concentration of about 0.06 wt%, and the pH is adjusted to about 2.0 using formic acid (typically about 1.8 wt% in the final solution).</p><p>Phosphate Buffered Saline (PBS) PBS is prepared according to the procedure described in Example 4.</p><p>Phosphate buffer solution (PB) without NaCl (PB, No NaCl) PB is prepared according to the procedure described in Example 4.</p><p>Preparation of BTP Solution A Bis-Tris-propane solution is prepared by dissolving BTP in DI (or distilled) water to a concentration of 300 ppm and then adjusting the pH to 7.5.</p><p>Preparation of Aqueous Polyaziridine Solution A PZ-28 solution with a PZ-28 concentration of 0.15% is prepared by simply adding PZ-28 to the BTP solution prepared above and adjusting the pH to about 7.4.</p><p>Preparation of Poly(MPC-co-AEM) (96/4 wt/wt) Poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethyl methacrylate) (96/4 wt/wt) (i.e., poly(MPC-co-AEM)) is prepared according to the procedure described in Example 11.</p><p>IPC-10 Saline IPC-10 saline is prepared as follows: Mix the 77 wt/wt% poly(MPC-co-AEM) aqueous solution prepared above, 6.1 wt/wt% PAE, and 16.9 wt/wt% phosphate buffer (about 128 mM sodium phosphate salt and about 4 wt% NaCl) (the concentrations of poly(MPC-co-AEM) and PAE are about 10 times that of the final saline). Adjust the pH to about 7.3 with 1N NaOH. React the mixture in the water bath at a temperature of 70°C for 3 hours. Remove the mixture from the water bath and cool it in the water bath at room temperature. Dilute the mixture 5 times with phosphate buffer (about 33 mM sodium phosphate salt and 0.77 wt% NaCl) and adjust the pH to about 7.3. Filter the mixture through a 0.22 μm PES sterile filter unit.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with isopropanol (IPA) for 180 minutes for lens extraction, dip coated in PMAA solution prepared above for about 1 hour, rinsed twice with PB for about 30 minutes each, and then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.6 mL of a mixture of PZ-28 solution and IPC-10 saline prepared above (0.3 mL of PZ-28 solution is added before inserting the lens, followed by adding and mixing 0.3 mL of IPC-10). The sealed lens package is autoclaved at about 121° C. for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test.</p><p>The resulting water gradient SiHy contact lenses are lubricious (having a friction rating of about 0) either straight out of the package or after simulated abrasion cycling (i.e., equivalent to 30 cycles of finger rubbing), have a WBUT of about 17 seconds after simulated abrasion cycling (i.e., equivalent to 30 cycles of finger rubbing), and have no detectable incorporation of Polyquaternium-1. No surface cracks are observed.</p><p>Example 13 PAA Coating Solution A PAA coating solution is prepared by dissolving a certain amount of PAA (Mn: approximately 450 kDa (Polysciences, Inc.)) in a given volume of 1-propanol/water (10%/90% w/w) mixture to a concentration of approximately 250 ppm, and the pH is adjusted to approximately 2.0 using formic acid (typically approximately 1.87 wt % in the final solution).</p><p>Phosphate buffer solution (PB) without NaCl (PB, No NaCl) PB is prepared according to the procedure described in Example 4.</p><p>BTP+PG Dilution Buffer: Mix 1.95 grams BTP, 15.25 grams propylene glycol (PG), and 300 grams DI water until uniform. Add approximately 1.75 grams 5N HCl and allow to mix for approximately 30 minutes. Adjust pH to 7.4±0.1 using 5N HCl.</p><p>Preparation of BTP Solution: A Bis-Tris-propane solution is prepared by dissolving 0.14 grams of BTP in 100 grams of DI (or distilled) water. No pH adjustment is necessary.</p><p>Preparation of Aqueous Polyaziridine Solutions PZ-28 solutions with concentrations of 0.2 wt % or 0.3 wt % PZ-28 were prepared by simply adding PZ-28 to DI water, with no pH adjustment.</p><p>Preparation of Poly(MPC-co-AEM) (96/4 wt/wt) Poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethyl methacrylate) (96/4 wt/wt) (i.e., poly(MPC-co-AEM)) is prepared according to the procedure described in Example 11.</p><p>IPC-11 Saline IPC-11 saline is prepared as follows: Mix 74.3 wt/wt% of the above prepared poly(MPC-co-AEM) aqueous solution, 6.0 wt/wt% of PAE, and 19.7 wt/wt% of BTP solution. Adjust the pH to 8 ± 0.1 by 1N NaOH. React the mixture in the water bath at a temperature of 70 °C for 4 hours. Remove the mixture from the water bath and cool it in the water bath at room temperature. Dilute the mixture with BTP + PG dilution buffer in a 1 to 4 weight ratio (1 part reaction mixture and 4 parts BTP + PG dilution buffer) and adjust the pH to 7.4 ± 0.1. Filter the mixture into a sterile bottle by a 5 μm filter capsule (Satorius part number #: 5051342P5-00-B) and store in a refrigerator.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted twice with IPA for lens extraction (first for 30 minutes and second for 150 minutes), dipped in a 50/50 volume ratio IPA/water mixture for about 30 minutes, dip coated in the PAA coating solution prepared above for about 20 minutes, rinsed twice with PB for about 30 minutes each, and then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.6 mL of a mixture of PZ-28 solution and IPC-11 saline prepared above (0.3 mL of IPC-11 is added before inserting the lens, followed by 0.3 mL of PZ-28 solution and mixed after sealing). The sealed lens package is staged (i.e., left in an oven) at a temperature below 120° C. for the time specified in Table 8. After staging, the sealed lens package is autoclaved at about 121° C. for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passes the Sudan Black dye test.</p><p>Table 8 reports some properties of the resulting water gradient SiHy contact lenses.</p><p><tables><img file="JP7635289B2_D0051.tif" /></tables></p><p>Example 14 PMAA Coating Solution A PMAA coating solution is prepared by dissolving a certain amount of PMAA (Mn: approximately 644 kDa (PolyMaterials, Inc.)) in a water/isopropanol (IPA) mixture (48.1 wt % IPA/50 wt % water) to a concentration of approximately 600 ppm, and the pH is adjusted to approximately 2.0 using formic acid (typically approximately 1.87 wt % in the final solution).</p><p>Phosphate Buffered Saline (PBS) PBS is prepared according to the procedure described in Example 4.</p><p>Phosphate buffer solution (PB) without NaCl (PB, No NaCl) PB is prepared according to the procedure described in Example 4.</p><p>Preparation of Poly(MPC-co-AEM) (96/4 wt/wt) Poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethyl methacrylate) (96/4 wt/wt) (i.e., poly(MPC-co-AEM)) is prepared according to the procedure described in Example 11.</p><p>IPC-12 Saline The reaction mixture of IPC-12 saline is prepared in the same manner as described in Example 11 for IPC-8. The mixture is diluted 5-fold with phosphate buffer (about 33 mM sodium phosphate salt and 0.77% by weight NaCl) (i.e., 1 part by weight reaction mixture and 4 parts by weight phosphate buffer) and 0.15% by weight sodium citrate dihydrate is added. Finally, the pH is adjusted to about 7.3. The mixture is filtered through a 0.22 μm PES sterile filter unit.</p><p>IPC-13 Saline Prepare the same reaction mixture as described in IPC-12, except replace PBS with PB, and the reaction time is 5 hours, the same amount of sodium citrate dihydrate, pH adjustment, and sterile filtration.</p><p>IPC-14 The same reaction mixture as described in IPC-3, except that the saline MPC-containing copolymer is replaced with poly(MPC-co-AEM) prepared in Example 11. Dilution, addition of sodium citrate dihydrate, pH adjustment, and sterile filtration are the same as those shown in IPC-12.</p><p>Same reaction mixture as described in IPC-14 except substitute PB for PBS for the IPC-15 saline reaction. Dilution, addition of sodium citrate dihydrate, pH adjustment, and sterile filtration are the same as those indicated in IPC-14.</p><p>Preparation of Aqueous Polyaziridine Solutions PZ-28 solutions with concentrations of 0.3 wt % or 0.4 wt % PZ-28 were prepared by simply adding PZ-28 to DI water, with no pH adjustment.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted twice with IPA for lens extraction (first time for 35 minutes and second time for 145 minutes), dip coated in the PMAA coating solution prepared above for about 50 minutes, rinsed twice with PB for about 25 minutes each, and then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.6 mL of a mixture of PZ-28 solution and various IPC saline solutions prepared above (e.g., add 0.3 mL of one of IPC-12 to IPC-15 before inserting the lens, followed by 0.3 mL of PZ-28 solution (or water without PZ) and mix after sealing). The sealed lens package is staged (i.e., placed in an oven) at room temperature for about 4 hours. After staging, the sealed lens package is autoclaved at about 121° C. for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (ie, a hydrogel coating) thereon.</p><p>Table 9 reports some properties of the resulting water gradient SiHy contact lenses.</p><p><tables><img file="JP7635289B2_D0052.tif" /></tables></p><p>Example 15 Preparation of PAA Coating Solution The PAA coating solution is prepared by adding an appropriate amount of PAA into a water-IPA mixture (e.g., 50/50 or 90/10 wt/wt). After the PAA is completely dissolved, adjust the pH to about 2 by adding about 1.8% formic acid into the PAA aqueous solution. The target concentration of PAA is about 0.025 wt%. The prepared PAA coating solution is filtered to remove any particulates or foreign matter.</p><p>Phosphate Buffered Saline (PBS) NaH₂PO₄H₂O, Na₂HPO₄2H₂Dissolve 2.25% NaH2O in a given amount of purified water (distilled or deionized) to obtain a solution of approximately 0.22% w/w NaH2O.₂PO₄H₂O, about 1.95% w/w Na₂HPO₄2H₂Phosphate buffered saline is prepared by making up approximately 3.97% w/w of NaCl, and approximately 3.05% W/W of NaCl.</p><p>IPC Saline IPC-8 and IPC-9 saline prepared in Example 11 are used in this example.</p><p>IPC-16 saline is prepared as follows: 77.0 wt/wt% poly(MPC-co-AEM) aqueous solution prepared in Example 11, 6.7 wt/wt% PAE, and 16.3 wt/wt% phosphate buffer (about 128 mM sodium phosphate salt and about 4 wt% NaCl) are mixed (the concentration of poly(MPC-co-AEM) and PAE is about 10 times that of the final saline). The pH is adjusted to about 7.3 with 1N NaOH. The mixture in the water bath is reacted at a temperature of about 70°C for 3 hours. The mixture is removed from the water bath and cooled in the water bath at room temperature. The mixture is diluted 10 times (i.e., 1 part reaction mixture and 9 parts phosphate buffer) with phosphate buffer (about 33 mM sodium phosphate salt and 0.77 wt% NaCl) and the pH is adjusted to about 7.3. The mixture is filtered through a 0.22 μm PES sterile filter unit.</p><p>IPC-17 saline is prepared by adding 0.2 wt % PZ-28 to the IPC-16 prepared above.</p><p>IPC-18 saline is prepared by adding 0.2 wt % PZ-28 to IPC-11 prepared in Example 13.</p><p>After the PZ-induced PU reduction release of the PAA-coated SiHy contact lens, the dried SiHy contact lens (prepared in Example 3) is extracted with isopropanol (IPA) for 180 minutes for lens extraction, dip-coated with the PAA solution prepared above for about 5 and 10 minutes, and rinsed with PB twice for about 30 minutes each.The lens is then packaged with one of the IPC saline solutions prepared above (either with 0.2 wt% PZ-28 or without PZ-28).The results of polyquaternium-1 uptake rate and surface cracks are summarized in the following table.</p><p><tables><img file="JP7635289B2_D0053.tif" /></tables></p><p>Example 16 IPC-19 Saline The following ingredients are mixed in a container at room temperature in the following concentrations: 7.5 wt% poly(MPC-co-AEM) (96/4 wt/wt) prepared in Example 11, 1.58 wt% PAE, and 0.03 wt% BTP, with the balance being DI water. The final pH is adjusted to 8±0.1 using 5N HCl. The mixture is placed in a 70°C bath for 4 hours. After pre-reaction, they are cooled to room temperature and then diluted 5 times (pH adjusted to 7.4) with a dilution buffer consisting of 0.61 wt% BTP, 4.8 wt% propylene glycol, and the balance being DI water. The saline is filtered using a 5 μm capsule filter from Sartorius and then immediately stored in a refrigerator until further use in packaging lenses. This prepared saline solution has a charge density of 3050±200 uEq/L as measured using the Cary 60 technique for residual charge.</p><p>Example 17 PMAA Coating Solution The PMAA coating solution prepared in Example 14 is used in this example.</p><p>BTP+PG Dilution Buffer: Mix 0.846 grams of BTP, 6.6 grams of propylene glycol (PG), and 300 grams of Di water until uniform. Add approximately 1.75 grams of 5N HCl and allow to mix for approximately 30 minutes. Adjust the pH to 7.4±0.1 using 5N HCl.</p><p>BTP+Glycerol Dilution Buffer: Mix 0.846 grams BTP, 7.8 grams glycerol, and 300 grams Di water until uniform. Add approximately 1.75 grams 5N HCl and allow to mix for approximately 30 minutes. Adjust pH to 7.4±0.1 using 5N HCl.</p><p>BTP+NaCl Dilution Buffer: Mix 0.846 grams of BTP, 2.55 grams of sodium chloride (NaCl), and 300 grams of Di water until uniform. Add approximately 1.75 grams of 5N HCl and allow to mix for approximately 30 minutes. Adjust the pH to 7.4±0.1 using 5N HCl.</p><p>Preparation of BTP Solution The Bis-Tris-propane solution prepared in Example 13 is used in this example.</p><p>Preparation of Aqueous Polyaziridine Solutions PZ solution I, with a PZ-28 concentration of 0.24 wt %, is prepared by simply adding PZ-28 to the BTP+PG dilution buffer.</p><p>PZ solution II, with a PZ-28 concentration of 0.24 wt %, is prepared by simply adding PZ-28 to the BTP+glycerol dilution buffer.</p><p>PZ solution III, with a PZ-28 concentration of 0.24 wt %, is prepared by simply adding PZ-28 to the BTP+NaCl dilution buffer.</p><p>IPC Saline IPC-8 prepared in Example 11 is used in this example.</p><p>IPC-20 saline is prepared by mixing IPC-11, as prepared in Example 13, with DI water in a 1:1 ratio.</p><p>IPC-21 saline is prepared by mixing IPC-11 as prepared in Example 13 (BTP+glycerol is also used to dilute the reaction mixture for IPC-11 after pre-reaction) with BTP+glycerol dilution buffer in a 1:1 ratio.</p><p>IPC-22 saline is prepared by mixing IPC-11 prepared in Example 13 (also using the BTP+PG dilution buffer prepared earlier in this example to dilute the reaction mixture for IPC-11 after pre-reaction) with PZ solution I prepared above in a 1:1 ratio.</p><p>IPC-23 saline is prepared by mixing IPC-11 prepared in Example 13 (also using BTP+glycerol to dilute the reaction mixture for IPC-11 after pre-reaction) with PZ solution II prepared above in a 1:1 ratio.</p><p>IPC-24 saline is prepared by mixing IPC-11 prepared in Example 13 (also using BTP+NaCl to dilute the reaction mixture for IPC-11 after pre-reaction) with PZ solution III prepared above in a 1:1 ratio.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with IPA twice for lens extraction (first time for 30 minutes and second time for 150 minutes), dipped in a 50/50 volume ratio IPA/water mixture for about 30 minutes, dip coated in the above prepared PMAA coating solution for about 20 minutes, rinsed twice with PB for about 30 minutes each, and then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.6 mL of a mixture of PZ solution and IPC saline prepared above (0.3 mL of IPC saline is added before inserting the lens, followed by 0.3 mL of PZ solution and mixed after sealing). The sealed lens packages are autoclaved at 121°C for 1 autoclave cycle (45 min), 5 autoclave cycles (225 min), 10 autoclave cycles (450 min), and 15 autoclave cycles (675 min), respectively. The multiple autoclave cycles are intended to determine the thermal stability (or shelf life of SiHy lenses) in an accelerated shelf life test. The lens dimensions of the resulting lenses are measured and reported in Table 11.</p><p>Table 11 shows that when the packaging solution is phosphate-based, the diameter and BCE (base curvature equivalent) increase as the number of autoclave cycles increases, and when the packaging solution is BTP-based, the diameter or BCE decreases with little or minimal change as the number of autoclave cycles increases, indicating that BTP buffer can stabilize the dimension/metro over the shelf life of silicone hydrogel contact lenses.</p><p><tables><img file="JP7635289B2_D0054.tif" /></tables></p><p>Example 18 PMAA Coating Solution A PMAA coating solution is prepared by dissolving a certain amount of PMAA (Mn: approximately 644 kDa (PolyMaterials, Inc.)) in a water/isopropanol (IPA) mixture (48.1 wt % IPA/50 wt % water) to a concentration of approximately 600 ppm, and the pH is adjusted to approximately 2.0 using formic acid (typically approximately 1.87 wt % in the final solution).</p><p>Another PMAA coating solution is prepared by dissolving a certain amount of PMAA (Mn: approx. 644 kDa (PolyMaterials, Inc.)) in a water/n-propanol (PrOH) mixture (48.1 wt % PrOH/50 wt % water) to a concentration of approx. 600 ppm, and the pH is adjusted to approx. 2.0 with formic acid (typically approx. 1.87 wt % in the final solution).</p><p>Phosphate Buffered Saline (PBS) PBS is prepared according to the procedure described in Example 4.</p><p>Phosphate buffer solution (PB) without NaCl (PB, No NaCl) PB is prepared according to the procedure described in Example 4.</p><p>IPC-15 Saline IPC-15 saline as prepared in Example 14 is used in this example.</p><p>Preparation of Aqueous Polyaziridine Solutions A PZ-28 solution with a PZ-28 concentration of 0.3 wt % was prepared by simply adding PZ-28 to DI water, with no pH adjustment.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with IPA three times for lens extraction (first time for 40 minutes, second time for 115 minutes, and third time for 25 minutes), dip coated in the PMAA coating solution prepared above for about 55 minutes, rinsed with PB twice for about 25 minutes each, and then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.6 mL of a mixture of PZ-28 solution and IPC-15 saline prepared above (e.g., add 0.3 mL of IPC-15 before inserting the lens, followed by 0.3 mL of PZ-28 solution and mix after sealing). The sealed lens package is staged at room temperature for about 4 hours. After staging, the sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The same coating solution is reused two more times using fresh IPA to coat and prepare lenses following the procedure described above for the fresh IPA coating solution.</p><p>Another set of lenses was treated using n-propanol (PrOH) as the extraction solvent and a PMAA coating solution prepared using PrOH, and the coating solution was reused twice as described above and lenses were prepared according to the procedure above.</p><p>Some of the key properties of the resulting water-gradient SiHy contact lenses are summarized below. Results indicate at least three reuses of the coating solution when done from IPA or PrOH as the extraction and coating solution solvent. All lenses show excellent long-lasting lubricity after 14 cycles in a heavy cycler using renu as the lens care solution. WBUT measurements after simulated abrasive cycling (corresponding to 30 finger rubbing cycles) and even Sudan Black staining of lenses after simulated abrasive cycling (corresponding to 30 finger rubbing cycles) (results not shown) further support this finding.</p><p><tables><img file="JP7635289B2_D0055.tif" /></tables></p><p>Example 19 Preparation of Water Gradient SiHy Contact Lenses This example uses SiHy contact lenses with a PAA-based coating thereon prepared according to the procedure described in Example 19 of US Patent No. 8,480,227. The resulting PAA-coated SiHy contact lenses have a water content of about 32% by weight, an oxygen permeability of about 146 barrers, a bulk modulus of about 0.76 MPa, and a relative ion permeability of about 6 (compared to Alsacon lenses). The PAA-coated SiHy contact lenses are individually packaged/sealed in polypropylene lens packaging shells (blisters) with about 0.55 mL of IPC-9 saline solution prepared in Example 11. The sealed lens packages are autoclaved at about 121°C for about 45 minutes to form SiHy contact lenses with a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passes the Sudan Black dye test. The resulting water gradient SiHy contact lenses have a friction rating of 0, a WBUT of about 28 seconds measured on the lenses as-removed from the package and about 20 seconds measured on the lenses after simulated abrasion cycling (i.e., equivalent to 30 cycles of finger rubbing), and an average PU of about 0.06 μg/lens.</p><p>Sample preparation: AFM testing was performed on the above prepared water gradient SiHy contact lenses in hydrated and dry states. The lenses were removed from the blister packs (sealed and autoclaved) and two cross sections were obtained by cutting one water gradient contact lens into two equal halves with a razor blade (i.e., cutting through the center of the contact lens). Each lens cross section was mounted vertically in a metal clamp as shown in FIG. 7 of US Pat. No. 8,480,227, with the lens edge of the lens cross section protruding 1-2 mm above the clamp edge from the metal clamp to allow the AFM tip (above the lens cross section in FIG. 7) to scan it. The mounted cross section assembly was immersed in PBS to ensure that it was fully hydrated. To perform AFM on the lenses in the dry state, the lenses were dried overnight (at least 18 hours) in a 50° C. oven.</p><p>AFM Experiments: All AFM measurements are performed using a Bruker Inc. Dimension Icon® instrument. Samples are imaged using PeakForce QNM tapping imaging mode and a ScanAsyst-Fluid probe. A freshly calibrated probe is used to image the samples. Each cross section is first inspected under an optical microscope to identify good locations for AFM imaging of the cross section containing the outer surface hydrogel layer. At least three 20 μm×20 μm AFM images are collected from three random locations on the sample for each cross section. To determine the thickness of the outer surface hydrogel layer, additional AFM images with higher resolution (5 μm×5 μm or 10 μm×10 μm) will eventually be collected on areas that clearly show the outer surface hydrogel layer. For each group of water gradient contact lenses to be tested, data from three different cross sections (three replicates) will be collected.</p><p>Data analysis is performed using NanoScope Analysis Software ver.1.4 by Bruker, Inc. All high-resolution AFM images are uniformly flattened to remove the curvature of the sample. Approximately 20 random thickness measurements are performed on the high-resolution images by measuring the distance between the leading edge of the outer surface hydrogel layer and the edge of the lens cross section. The individual measurements from all replicates of the same group of samples are pooled and averaged to obtain the final thickness of the outer surface hydrogel layer for this group of water gradient contact lenses.</p><p>Based on the analysis of the high-resolution AFM images, the outer surface hydrogel layer of the water gradient contact lens (excluding the transition layer neutralized with PZ) is found to have a thickness of 2.6 micrometers in the fully hydrated state and a thickness of 0.7 micrometers in the dry state. Water Swelling Ratio (WSR) of the outer surface hydrogel layer on the water gradient contact lens under test<math num="30"><img file="JP7635289B2_D0056.tif" /></math>, where L_Wetis the average thickness of the outer surface hydrogel layer of a fully hydrated SiHy contact lens, and L_Dryis the average thickness of the outer surface hydrogel layer of a SiHy contact lens in a dry state) is calculated to be 376%.</p><p>Example 20 Following the procedure described in Example 1, microindentation tests were performed for several different contact lenses: ACUVUE2® (available from Johnson &amp; Johnson), ACUVUE® Oasys (uncoated SiHy lens available from Johns &amp; Johnson), Biofinity® (uncoated SiHy lens available from CooperVision), MyDay® (uncoated SiHy lens available from CooperVision), AIROPTIX® Night &amp; Day® (plasma coated SiHy lens available from Alcon), the naturally wettable SiHy lens without coating of Example 3, the water gradient SiHy lens of Example 13 (IPC-11 + 0.1 wt% PZ-28 as packaging solution), and the water gradient SiHy contact lens of Example 15 (IPC-18 as packaging solution). The bulk modulus (E') of the commercially available contact lenses is data generated by the manufacturer (Contact Lens &amp; Anterior Eye 33(2010),210-214, Table 1 of the article by G. Young, CooperVision Biofinity Is Fastest Growing Contact Lens Brand In The US, CooperVision's press release dated June 17, 2013, entitled "CooperVision Biofinity Is Fastest Growing Contact Lens Brand In The US", CooperVision's press release dated June 25, 2015, entitled "CooperVision Introduces MyDay® Lenses in the US". The bulk modulus of the SiHy lens of Example 3 is determined according to the procedure described in Example 1. The surface compressive force (SCF) at an indentation depth of 400 nm and the normalized surface compressive force (NSCF) at an indentation depth of 400 nm are reported in Table 13.</p><p><tables><img file="JP7635289B2_D0057.tif" /></tables></p><p>5 shows the indentation force at an indentation depth of 400 nm (i.e., the surface compressive force at an indentation depth of 400 nm) as a function of the bulk (Young's) elastic modulus of the contact lenses. The indentation force at an indentation depth of 400 nm shows a good linear fit with the bulk elastic modulus for those contact lenses (including Acuvue2, Biofinity, MyDay, Night&amp;Day, Oasys, and the lens of Example 3) that do not have a hydrogel coating thereon. This means that these materials all have similar Poisson's ratios. The best linear fit is y=13.98x+0.62, R²=0.99.</p><p>However, the water gradient contact lenses of Examples 13 and 15 (each having a hydrogel coating thereon) do not follow the same trend and have indentation force values much smaller than would be predicted from the trend of the linear fit. The water gradient contact lenses of Examples 13 and 15 have a reduction in indentation force at an indentation depth of 400 nm of about 66% and about 69%, respectively, as calculated based on the formula:<math num="31"><img file="JP7635289B2_D0058.tif" /></math>In the formula, (IF)_tis the measured indentation force of the water gradient contact lens at an indentation depth of 400 nm, and E' is the bulk modulus of the water gradient contact lens.</p><p>Example 21 Solution PMAA-1 Solution PMAA-1 is a solution of polymethacrylic acid (PMAA), which is prepared by adding an appropriate amount of PMAA (Mn: about 400-600 kDa (ProChem)) to a PrOH/water (50 wt% water) mixture to a concentration of about 0.04 wt%. After PMAA is completely dissolved, the pH is adjusted to about 2 by adding formic acid to the PMAA solution. The prepared PMAA solution is filtered to remove any particulates or foreign matter.</p><p>Phosphate buffered saline solution (PBS-1) for preparing IPC saline solution NaH₂PO₄H₂O, Na₂HPO₄2H₂Dissolve 2,5-dichlorophenyl ether (NaH2O) in a given amount of purified water (distilled or deionized) to obtain a solution of approximately 0.174 wt/w% NaH2O.₂PO₄H₂O, approximately 0.711% w/w Na₂HPO₄2H₂PBS-1 is prepared by making up approximately 1.920% w/w of NaCl and 0.5% water.</p><p>Poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethyl methacrylate) of IPC saline (IPC-25) copolymer (96/4 wt/wt) (i.e., poly(MPC-co-AEM)) is prepared by thermally polymerizing a polymerizable composition comprising about 96 wt% MPC, about 4 wt% AEM, about 0.02 wt% Vazo56 [2,2'-azobis(2-methylpropionamidine) dihydrochloride], and about 0.1 wt% chain transfer agent (HS-CH2CH2OH) in water at about 60°C for about 2 hours and then at 20°C for about 2 hours. The resulting poly(MPC-co-AEM) (aqueous solution having a solids content of about 10%) is determined to have an amine functionality of about 0.22 meq/g.</p><p>About 75 wt. % of the poly(MPC-co-AEM) solution prepared above, about 4.6 wt. % of a PAE solution (purchased as an aqueous solution from Ashland and used as is), about 20 wt. % of a phosphate solution (about 0.22 wt. NaH₂PO₄H₂O, 0.9% by weight Na₂HPO₄2H₂Mix the PBS-1 and PBS-2 (O) and adjust the pH to about 7.3 with 1N NaOH. Allow the mixture in the water bath to react at 60°C for 4 hours to form a water-soluble thermally crosslinkable polymeric material (i.e., "in-package crosslinker" or "IPC agent"). Remove the mixture from the water bath and cool in a room temperature water bath. Dilute the mixture about 10-fold with PBS-1 and water and adjust the pH to about 7.3 if necessary. The final IPC saline may also contain low concentrations of peroxide (e.g., 5 ppm) and sodium citrate dihydrate (e.g., 0.07%). Filter the mixture through a 0.22 μm PES sterile filter unit.</p><p>Phosphate buffer solution (PB: about 15 mM, pH: about 7.8) PB is prepared by dissolving NaH2PO4·H2O and Na2HPO4·2H2O in a given volume of purified water (distilled or deionized) to obtain a solution of about 0.028 wt/vol% NaH₂PO₄H₂O, and about 0.231% by weight/volume of Na₂HPO₄2H₂The solution is adjusted to a composition of 0 and the final solution pH is approximately 7.8.</p><p>Preparation of Water Gradient SiHy Contact Lens (Lens 21-1) (Control) Water gradient SiHy contact lens (Lens 21-1) is prepared according to a method including only a dip coating step to form a base coating as follows.</p><p>After demolding, the cast molded SiHy contact lenses (prepared in Example 3) are extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-1 prepared above for about 50 minutes or 1 hour, rinsed in PrOH/water (55/45) for about 25 minutes, rinsed in PB for about 50-60 minutes, and then packaged/sealed in polypropylene lens packaging shells (blisters) with 0.65 mL of IPC-25 saline (half of the IPC-25 saline is added before inserting the lens). The sealed lens packages are autoclaved at about 121° C. for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon.</p><p>Preparation of Water-Gradient SiHy Contact Lens (Lens 21-2) The water-gradient SiHy contact lens (Lens 21-2) is prepared according to a method including at least two dip-coating steps to form a base coating, and one buffered saline rinse step between each pair of dip-coating steps, as follows.</p><p>After demolding, the cast SiHy contact lenses (prepared in Example 3) were extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-1 prepared above for about 25 minutes, rinsed in PB for about 10 minutes, and then washed with deionized (DI) H2O.₂The lenses are then rinsed in O for about 10 minutes, followed by dip coating again in PMAA-1 for about 25 minutes and rinsing twice in PB for 25 minutes each, then packaged/sealed in polypropylene lens packaging shells (blisters) with 0.65 mL of IPC-25 saline (half of the IPC-25 saline is added prior to inserting the lenses). The sealed lens packages are autoclaved at about 121° C. for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon.</p><p>Characterization of the Obtained Water Gradient SiHy Contact Lenses The obtained water gradient SiHy contact lenses are tested for the properties of lubricity by friction rating, PU, and coating integrity by Sudan Black (SB) staining test according to the procedure described in Example 1. WBUT is measured according to the procedure described in the Examples with the following modifications: The lens is removed from the test tube and placed on a pedestal submerged in PBS, then the pedestal is raised out of the PBS solution (t=0) and a video camera monitors the fluid flowing down from the lens surface, and this WBUT time is recorded when the fluid on the lens surface breaks down. Optionally, a stopwatch may be used to measure the time between when the pedestal is raised out of the PBS solution and when the fluid on the lens surface breaks down. As the pedestal is raised, the lens is pulled under the surface of the PBS. At least three points are measured per lens, and at least three lenses are measured to obtain an average WBUT measurement for each lens group.</p><p>The lenses are tested either as-is (DOOP), or after being subjected to 30 cycles of finger rubbing (30 DRT), or after being subjected to a simulated abrasion cycle treatment (SACT) according to the procedure described in Example 1. The results are reported in Table 14.</p><p><tables><img file="JP7635289B2_D0059.tif" /></tables></p><p>The results in Table 14 show that both methods can produce water gradient SiHy contact lenses with good lubricity (friction rating of about 0). However, the method of the present invention can be used to produce a water gradient contact lens (Lens 21-2) having a more durable hydrogel coating thereon compared to lenses produced by the control method, as shown by passing the Sudan Black staining test (no SB staining) after 30 cycles of finger rubbing and by having a longer WBUT after simulated polishing cycling.</p><p>Example 22 SBC Solution: 0.1% Sodium Bicarbonate Rinse Solution The SBC rinse solution is about 0.1% w/w NaHCO₃It is prepared by dissolving sodium bicarbonate in a given volume of purified water (distilled or deionized) to have a composition of:</p><p>Preparation of Water Gradient SiHy Contact Lens (Lens 22-1) (Control) Water gradient SiHy contact lens (Lens 22-1) is prepared according to a method including only a dip coating step to form a base coating as follows.</p><p>After demolding, the cast molded SiHy contact lenses (prepared in Example 3) are extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-1 prepared in Example 21 for about 50 minutes or 1 hour, rinsed in SBC for about 50-60 minutes, and then packaged/sealed in polypropylene lens packaging shells (blisters) with 0.65 mL of IPC-25 saline prepared in Example 21 (half of the IPC-25 saline is added prior to inserting the lens). The sealed lens packages are autoclaved at about 121° C. for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon.</p><p>Preparation of Water-Gradient SiHy Contact Lens (Lens 22-2) The water-gradient SiHy contact lens (Lens 22-2) is prepared according to a method including at least two dip-coating steps and one saline rinse step between each pair of dip-coating steps to form a base coating, as follows.</p><p>After demolding, the cast SiHy contact lenses (prepared in Example 3) were extracted with n-propanol (nPA) for 180 minutes for lens extraction, dip coated in PMAA-1 prepared in Example 21 for about 25 minutes, rinsed in SBC for about 10 minutes, and then dried in DI H₂The lenses are then rinsed in O for about 10 minutes, followed by dip coating again in PMAA-1 for about 25 minutes and rinsing twice in SBC for 25 minutes each, then packaged/sealed in polypropylene lens packaging shells (blisters) with 0.65 mL of IPC-25 saline (half of the IPC-25 saline is added prior to inserting the lenses). The sealed lens packages are autoclaved at about 121° C. for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon.</p><p>Characterization of the Obtained Water Gradient SiHy Contact Lenses The obtained water gradient SiHy contact lenses are tested for properties of lubricity by friction rating, PU, and coating integrity by Sudan Black (SB) staining test according to the procedure described in Example 1. WBUT is measured according to the procedure described in Example 21.</p><p>The lenses are tested either as-removed from the package (DOOP) or after being subjected to 30 cycles of finger rubbing treatment (30 DRT) according to the procedure described in Example 1. The results are reported in Table 15.</p><p><tables><img file="JP7635289B2_D0060.tif" /></tables></p><p>The results in Table 15 show that both methods are capable of producing water gradient SiHy contact lenses with good lubricity (friction rating of about 0). However, the method of the present invention can be used to produce a water gradient contact lens (Lens 22-2) having a more durable hydrogel coating thereon compared to lenses produced by the control method, as shown by passing the Sudan Black staining test after 30 cycles of finger rubbing (no SB staining).</p><p>Example 23 PMAA solution (PMAA-2): A solution of polymethacrylic acid (PMAA) is prepared by adding an appropriate amount of PMAA (Mn: about 400-600 kDa (ProChem)) to a PrOH/water (50 wt% water) mixture to a concentration of about 0.04 wt%. After PMAA is completely dissolved, the pH is adjusted to about 2 by adding sulfuric acid to the PMAA solution. The prepared PMAA solution is filtered to remove any particulates or foreign matter.</p><p>SBC Solution: 0.1% Sodium Bicarbonate Rinse Solution The SBC rinse solution is approximately 0.1% w/w NaHCO₃It is prepared by dissolving sodium bicarbonate in a given volume of purified water (distilled or deionized) to have a composition of:</p><p>Preparation of Water Gradient SiHy Contact Lens (Lens 23-1) (Control) Water gradient SiHy contact lens (Lens 23-1) is prepared according to a method including only a dip coating step to form a base coating as follows.</p><p>After demolding, the cast molded SiHy contact lenses (prepared in Example 3) are extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-2 prepared above for about 50 minutes or 1 hour, rinsed in SBC for about 50-60 minutes, and then packaged/sealed in polypropylene lens packaging shells (blisters) with 0.65 mL of IPC-25 saline (half of the IPC-25 saline is added prior to inserting the lens). The sealed lens packages are autoclaved at about 121° C. for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon.</p><p>Preparation of Water Gradient SiHy Contact Lens (Lens 23-2) The water gradient SiHy contact lens (Lens 23-2) is prepared according to a method including at least two dip coating steps and one saline rinse step between each pair of dip coating steps to form a base coating, as follows.</p><p>After demolding, the cast SiHy contact lenses (prepared in Example 3) were extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-2 prepared above for about 25 minutes, rinsed in SBC for about 10 minutes, and then washed with DI H.₂The lenses are then rinsed in O for about 10 minutes, followed by dip coating again in PMAA-2 for about 25 minutes and rinsing twice in SBC for 25 minutes each, then packaged/sealed in polypropylene lens packaging shells (blisters) with 0.65 mL of IPC-25 saline (half of the IPC-25 saline is added prior to inserting the lenses). The sealed lens packages are autoclaved at about 121° C. for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon.</p><p>Characterization of the Obtained Water Gradient SiHy Contact Lenses The obtained water gradient SiHy contact lenses are tested for properties of lubricity by friction rating, PU, and coating integrity by Sudan Black (SB) staining test according to the procedure described in Example 1. WBUT is measured according to the procedure described in Example 21.</p><p>The lenses are tested either as-is (DOOP), or after being subjected to 30 cycles of finger rubbing (30 DRT), or after being subjected to a simulated abrasion cycle treatment (SACT) according to the procedure described in Example 1. The results are reported in Table 16.</p><p><tables><img file="JP7635289B2_D0061.tif" /></tables></p><p>The results in Table 16 show that both methods can produce water gradient SiHy contact lenses with good lubricity (friction rating of about 0). However, the method of the present invention can be used to produce a water gradient contact lens (Lens 23-2) having a more durable hydrogel coating thereon compared to lenses produced by the control method, as shown by passing the Sudan Black staining test (no SB staining) after 30 cycles of finger rubbing and by having a longer WBUT after simulated polishing cycling.</p><p>Example 24 PMAA solution (PMAA-2): A solution of polymethacrylic acid (PMAA) is prepared by adding an appropriate amount of PMAA (Mn: about 400-600 kDa (ProChem)) to a mixture of nPA/water (50% water by weight) to a concentration of about 0.04% by weight. After the PMAA is completely dissolved, the pH is adjusted to about 2 by adding sulfuric acid to the PMAA solution. The prepared PMAA solution is filtered to remove any particulates or foreign matter.</p><p>SBC Solution: 0.1% Sodium Bicarbonate Rinse Solution The SBC rinse solution is approximately 0.1% w/w NaHCO₃It is prepared by dissolving sodium bicarbonate in a given volume of purified water (distilled or deionized) to have a composition of:</p><p>Preparation of Water-Gradient SiHy Contact Lens (Lens 24-1) The water-gradient SiHy contact lens (Lens 24-1) is prepared according to a method including at least two dip-coating steps and one saline rinse step between each pair of dip-coating steps to form a base coating, as follows.</p><p>After demolding, the cast SiHy contact lenses (prepared in Example 3) were extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-2 prepared above for about 25 minutes, rinsed in SBC for about 10 minutes, and then washed with DI H.₂The lenses are then rinsed in O for about 10 minutes, followed by dip coating again in PMAA-2 for about 25 minutes, and rinsed twice in SBC for 25 minutes each. They are then packaged/sealed in polypropylene lens packaging shells (blisters) with 0.65 mL of IPC-25 saline prepared in Example 21 (half of the IPC-25 saline is added before inserting the lenses). The sealed lens packages are autoclaved at about 121° C. for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The coating uniformity or intactness is tested by Sudan Black dye test, and the coating passes the Sudan Black dye test.</p><p>Water Gradient SiHy Contact Lens (Lens 24-2) The water gradient SiHy contact lens (Lens 24-2) is prepared according to a method including at least two dip coating steps and one saline rinse step between each pair of dip coating steps to form a base coating, as follows:</p><p>After demolding, the cast SiHy contact lenses (prepared in Example 3) were extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-2 prepared above for about 25 minutes, rinsed in SBC for about 20 minutes, and then washed with DI H.₂The lenses are then rinsed in O for about 10 minutes, followed by dip coating again in PMAA-2 for 25 minutes and rinsing twice in SBC for 25 minutes each. They are then packaged/sealed in polypropylene lens packaging shells (blisters) with 0.65 mL of IPC-25 saline (half of the IPC-25 saline is added before inserting the lenses). The sealed lens packages are autoclaved at about 121° C. for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test.</p><p>Characterization of the Obtained Water Gradient SiHy Contact Lenses The obtained water gradient SiHy contact lenses are tested for properties of lubricity by friction rating, PU, and coating integrity by Sudan Black (SB) staining test according to the procedure described in Example 1. WBUT is measured according to the procedure described in Example 21.</p><p>The lenses are tested either as-is (DOOP), or after being subjected to 30 cycles of finger rubbing (30 DRT), or after being subjected to a simulated abrasion cycle treatment (SACT) according to the procedure described in Example 1. The results are reported in Table 17.</p><p><tables><img file="JP7635289B2_D0062.tif" /></tables></p><p>The results in Table 17 show that the duration of the saline rinse step can have some effect on durability, as shown by the longer WBUT after simulated polishing cycling testing for lens 24-2, which is produced according to a process that includes a longer saline rinse step between the two dip coating steps.</p><p>Example 25 Preparation of Polymerizable Composition A lens formulation (polymerizable composition) is prepared with the following composition (unit parts): MSil (34), GA (6), NVP (40), MMA (9), EGMA (10.2), TEGDMA (0.4), AMA (0.1), Norbloc (1.8), Vazo 64 (0.5), RB 247 (0.01), and TAA (1). The formulation is prepared by adding the listed components in their target amounts to a clean bottle and mixing with a stir bar at 600 rpm for 30 minutes at room temperature. After all solids are dissolved, the formulation is filtered by using a 2.7 μm glass microfiber filter (GMF).</p><p>Cast Molded SiHy Contact Lenses SiHy contact lenses are cast molded as described in Example 4.</p><p>Characterization of Uncoated SiHy Contact Lenses The resulting SiHy contact lenses are subjected to post-molding processes described in Example 4 prior to lens characterization. The SiHy lenses have an oxygen permeability of about 93 barrer, a bulk modulus of about 0.69 MPa, a water content of about 52% by weight, a WBUT of 0 seconds, and a friction rating of 4.</p><p>SiHy Lenses Containing a PAA-Based Coating SiHy contact lenses each having a PAA-based coating thereon are prepared as described in Example 4.</p><p>Water Gradient SiHy Contact Lenses SiHy contact lenses having a PAA-based coating thereon, prepared as described above, are placed into polypropylene lens packaging shells (one lens per shell) with 0.55 mL or 0.65 mL of IPC-2 saline as prepared in Example 4 (approximately half of the saline may be added prior to inserting the lens). The blisters are then sealed with foil and autoclaved at about 121° C. for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon.</p><p>Surface Properties of Water Gradient SiHy Contact Lenses The resulting water gradient SiHy contact lenses are lubricious (having a friction rating of 1) as-removed from the package, have a WBUT of greater than 10 seconds, a sessile drop (static) water contact angle of about 30 degrees, and a PU (polyquaternium-1 uptake) of about 9 μg/lens.</p><p>Example 26 PMAA Solution (PMAA-1) A solution of polymethacrylic acid (PMAA) is prepared by adding an appropriate amount of PMAA (Mn: about 400-600 kDa (ProChem)) to a PrOH/water (50 wt% water) mixture to a concentration of about 0.04 wt%. After PMAA is completely dissolved, the pH is adjusted to about 2 by adding formic acid to the PMAA solution. The prepared PMAA solution is filtered to remove any particulates or foreign matter.</p><p>Phosphate buffer solutions PB-1a, -1b, and -1c. PB-1a has a pH of about 7.1 and about 23 mM phosphate.₂HPO₄2H₂0, and 0.134% NaH₂PO₄H₂PB-1b, which has a pH of about 7.1 and about 11.5 mM phosphate, is prepared by dissolving about 0.118% NaO in water.₂HPO₄2H₂O, and 0.067% NaH₂PO₄H₂PB-1c, which has a pH of about 7.1 and about 5.8 mM phosphate, is prepared by dissolving about 0.059% NaO in water.₂HPO₄2H₂0, and 0.034% NaH₂PO₄H₂It is prepared by dissolving O in water.</p><p>Phosphate buffered saline solution (PBS-1) for preparing IPC saline solution NaH₂PO₄H₂O, Na₂HPO₄2H₂Dissolve 2,5-dichlorophenyl ether (NaH2O) in a given amount of purified water (distilled or deionized) to obtain a solution of approximately 0.174 wt/w% NaH2O.₂PO₄H₂O, approximately 0.711% w/w Na₂HPO₄2H₂PBS-1 is prepared by making up approximately 1.920% w/w of NaCl and 0.5% water.</p><p>IPC Saline (IPC-25) IPC-25 saline, prepared in Example 21, is used in this example.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-1 prepared above for about 50 minutes or 1 hour, rinsed in nPA/water (55/45) for about 25 minutes, rinsed in PB-1a, or PB-1b, or PB-1c prepared above for about 50-60 minutes, and subsequently packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test.</p><p>The resulting water-gradient SiHy contact lenses were fairly smooth (having a friction rating of 0) with PU (Polyquaternium-1 Uptake) of 0.35±0.03, 0.43±0.04, 0.52±0.07 μg/lens for lenses with diopter 3.00, and 0.21±0.02, 0.26±0.00, 0.52±0.07 μg/lens for lenses with diopter 12.00 when rinsed with PB-1a, PB-1b, and PB-1c, respectively.</p><p>Example 27 Phosphate Buffer Solutions PB-2a, -2b, and -2c PB-2a, having a pH of about 7.5 and about 23 mM phosphate, contains about 0.312% Na₂HPO₄2H₂O, and 0.076% NaH₂PO₄H₂PB-2b, which has a pH of about 7.5 and about 11.5 mM phosphate, is prepared by dissolving about 0.156% NaO in water.₂HPO₄2H₂O, and 0.038% NaH₂PO₄H₂PB-2c, which has a pH of about 7.5 and about 5.8 mM phosphate, is prepared by dissolving about 0.078% NaO in water.₂HPO₄2H₂O, and 0.019% NaH₂PO₄H₂It is prepared by dissolving O in water.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-1 prepared in Example 26 for about 50 minutes or 1 hour, rinsed in PrOH/water (55/45) for about 25 minutes, rinsed in PB-2a, PB-2b, PB-2c prepared above for about 50-60 minutes, and subsequently packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121° C. for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating was tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water-gradient SiHy contact lenses were fairly smooth (having a friction rating of 0) and had PU (Polyquaternium-1 uptake) of 0.24±0.13, 0.32±0.05, 0.38±0.05 μg/lens for lenses with diopter -3.00, and 0.11±0.03, 0.16±0.04, 0.18±0.01 μg/lens for lenses with diopter -12.00 when rinsed with PB-2a, PB-2b, and PB-2c, respectively.</p><p>Example 28 Phosphate Buffer Solution (PB-3) Approximately 0.077% w/w NaH in Di water₂PO₄H₂O, approximately 0.48% w/w Na₂HPO₄2H₂Prepare PB-3 (approximately 23 mM, pH approximately 7.4) with HO.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-1 solution prepared in Example 26 for about 50 minutes or 1 hour, rinsed in PrOH/water (55% by volume/45% by volume) for about 25 minutes, rinsed in PB-3 prepared above for about 50-60 minutes, and subsequently packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water-gradient SiHy contact lenses were fairly smooth (having a friction rating of 0) and had a PU (polyquaternium-1 uptake) of 0.19±0.06 μg/lens (n=6).</p><p>Example 29 PMAA Solution (PMAA-2) A solution of polymethacrylic acid (PMAA) is prepared by adding an appropriate amount of PMAA-2 (Mn: about 400-600 kDa (ProChem)) to a PrOH/water (60% water by weight) mixture to a concentration of about 0.04% by weight. After the PMAA is completely dissolved, the pH is adjusted to about 2 by adding formic acid to the PMAA solution. The prepared PMAA solution is filtered to remove any particulates or foreign matter.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-2 solution prepared above for about 50 minutes or 1 hour, rinsed in PrOH/water (60% by volume/40% by volume) for about 25 minutes, rinsed in PB-3 prepared in Example 28 for about 50-60 minutes, and subsequently packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water-gradient SiHy contact lenses were fairly smooth (having a friction rating of 0) and had a PU (polyquaternium-1 uptake) of 0.20±0.04 μg/lens (n=6).</p><p>Example 30 Phosphate buffer solution (PB-4: about 15 mM, pH: about 8.2) NaH₂PO₄H₂O and Na₂HPO₄2H₂Dissolve 2,5-dichlorophenyl ether (NaH2O) in a given amount of purified water (distilled or deionized) to obtain a solution of approximately 0.044 wt/w% NaH2O.₂PO₄H₂O, and about 0.388% w/w Na₂HPO₄2H₂Prepare PB-4 by making up to 0. After complete dissolution, adjust the pH to 8.2 by addition of 0.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-1 solution prepared in Example 26 for about 50 minutes or 1 hour, rinsed with PB-4 prepared above for about 50-60 minutes, and subsequently packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline solution prepared in Example 26 (half of the IPC-25 saline solution is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water-gradient SiHy contact lenses were fairly smooth (having a friction rating of 0) and had a PU (polyquaternium-1 uptake) of 0.13±0.05 μg/lens (n=12).</p><p>Example 31 Water Gradient SiHy Contact Lens After demolding, cast molded SiHy contact lenses (prepared in Example 3) are extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-1 solution prepared in Example 26 for about 50 minutes or 1 hour, rinsed with PB-3 prepared in Example 28 for about 50-60 minutes, and subsequently packaged/sealed in polypropylene lens packaging shells (blisters) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens packages are autoclaved at about 121°C for about 45 minutes to form SiHy contact lenses having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passes the Sudan Black dye test. The resulting water-gradient SiHy contact lenses were fairly smooth (having a friction rating of 0) and had a PU (polyquaternium-1 uptake) of 0.38±0.04 μg/lens (n=12).</p><p>Example 32 Preparation of PMAA solution (PMAA-3) The same preparation procedure as shown in Example 26, except that a different PMAA raw material (Mw: about 800 kDa (GEO Specialty Chemicals, Inc.)) was used.</p><p>Phosphate buffered saline (PBS) for preparing IPC saline is prepared using the same procedure as in Example 26.</p><p>Phosphate buffer solution (PB-5: 15 mM, pH: 7.8) NaH₂PO₄H₂O and Na₂HPO₄2H₂Dissolve 100 in a given amount of purified water (distilled or deionized) to obtain a solution of approximately 0.028% by weight/volume of NaH₂PO₄H₂O, and about 0.231% by weight/volume of Na₂HPO₄2H₂Prepare PB-5 by making up to 100% PBS and adjusting the final solution pH to approximately 7.8.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-3 solution prepared above for about 50 minutes or 1 hour, rinsed in PrOH/water (55% by volume/45% by volume) for about 25 minutes, rinsed in PB-5 prepared above for about 50-60 minutes, and then packaged and sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water-gradient SiHy contact lenses were fairly smooth (having a friction rating of 0) and had a PU (polyquaternium-1 uptake) of 0.17±0.04 μg/lens (n=18).</p><p>Example 33 Water Gradient SiHy Contact Lens After demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 210 minutes for lens extraction, dip coated in PMAA-3 solution prepared in Example 32 for about 70-80 minutes, rinsed in PrOH/water (50% by volume/50% by volume) for about 25 minutes, and rinsed with PB-5 prepared in Example 32 for about 50-60 minutes, all of the above solutions being at 21-23°C. The lens is then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The resulting water-gradient SiHy contact lenses had a PU (polyquaternium-1 uptake) of 0.40±0.05 μg/lens (n=6).</p><p>Example 34 Water Gradient SiHy Contact Lens After demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 210 minutes for lens extraction, dip coated in PMAA-3 solution prepared in Example 32 for about 70-80 minutes, rinsed in PrOH/water (50% by volume/50% by volume) for about 25 minutes, and rinsed with PB-5 prepared in Example 32 for about 50-60 minutes, all of the above solutions being at 24-26°C. The lens is then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The resulting water-gradient SiHy contact lenses had a PU (polyquaternium-1 uptake) of 0.37±0.07 μg/lens (n=6).</p><p>Example 35 Water Gradient SiHy Contact Lens After demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 210 minutes for lens extraction, dip coated in PMAA-3 solution prepared in Example 32 for about 70-80 minutes, rinsed in PrOH/water (50/50) for about 25 minutes, and rinsed with PB-5 prepared in Example 32 for about 50-60 minutes, all of the above solutions being at 18-20°C. The lens is then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating was tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water gradient SiHy contact lenses have a PU (polyquaternium-1 uptake rate) of 0.33±0.07 μg/lens (n=6).</p><p>Example 36 Phosphate Buffer (PB-6) NaH₂PO₄H₂O and Na₂HPO₄2H₂Dissolve 2,5-dichlorophenyl ether (NaH2O) in a given amount of purified water (distilled or deionized) to obtain a solution of approximately 0.041% by weight/volume of NaH2O.₂PO₄H₂O, and about 0.214% weight/volume Na₂HPO₄2H₂PB-6 is prepared by adjusting the composition to O.</p><p>After water gradient SiHy contact lens release, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 210 minutes for lens extraction, dip coated in PMAA-3 solution prepared in Example 32 for about 70-80 minutes, the temperature of PrOH and PMAA solution is 24-26°C, followed by rinsing in PrOH/water (50% by volume/50% by volume) for about 25 minutes, and rinsing in PB-6 prepared above for about 50-60 minutes, the temperature of rinse and PB solution is 21-23°C. The lens is then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating was tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water-gradient SiHy contact lens was fairly smooth (having a friction rating of 0) and had a PU (polyquaternium-1 uptake) of 0.46±0.09 μg/lens (n=6).</p><p>Example 37 IPC Saline (IPC-26) A mixture of 75 wt. % of the MPC-containing copolymer solution prepared in Example 26, about 4 wt. % of a PAE solution, and about 15 wt. % of a phosphate solution (about 0.31 wt. % of NaH₂PO₄H₂O, 1.24% by weight Na₂HPO₄2H₂0) and adjust the pH to about 7.3 with 1N NaOH. Allow the mixture in the water bath to react at 62°C-63°C for 4 hours and 15 minutes to form a water-soluble thermally crosslinkable polymeric material (i.e., "in-package crosslinker" or "IPC agent"). Remove the mixture from the water bath and cool in a room temperature water bath. Dilute the mixture about 10-fold with PBS-1 and water prepared in Example 26 and adjust the pH to about 7.3 if necessary. The final IPC saline may also contain low concentrations of peroxide (e.g., 5 ppm) and sodium citrate dihydrate (e.g., 0.07%). Filter the mixture through a 0.22 μm PES sterile filter unit.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 210 minutes for lens extraction, dip coated in PMAA-3 solution prepared in Example 32 for about 70-80 minutes, the temperature of PrOH and PMAA solution is 24-26°C, followed by rinsing in PrOH/water (50/50) for about 25 minutes, and rinsing in PB-6 prepared in Example 36 for about 50-60 minutes, the temperature of rinse and PB solution is 21-23°C. The lens is then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-26 saline (half of the IPC-26 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating was tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water gradient SiHy contact lenses were fairly smooth (having a friction rating of 0) and had a PU (polyquaternium-1 uptake rate) of 0.43±0.06 μg/lens (n=6).</p><p>Example 38 Water Gradient SiHy Contact Lens After demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 180 minutes for lens extraction, and dip coated in PMAA-3 solution prepared in Example 32 for about 50-60 minutes. It is rinsed in PrOH/water (55%/45% by volume) for about 25 minutes, followed by rinsing in PB-5 prepared in Example 32 for about 50-60 minutes. The temperature of PrOH, PMAA, and rinsing solutions is about 21-23°C, and the temperature of the PB solution is about 24-26°C. The lens is then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating was tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water-gradient SiHy contact lens was fairly smooth (having a friction rating of 0) and had a PU (polyquaternium-1 uptake) of 0.27±0.03 μg/lens (n=6).</p><p>Example 39 Water Gradient SiHy Contact Lens After demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-3 solution prepared in Example 32 for about 50-60 minutes, rinsed in PrOH/water (55/45) for about 25 minutes, followed by rinsing in PB-5 prepared in Example 32 for about 50-60 minutes. The temperature of PrOH, PMAA, and rinse solutions is about 21-23°C, and the temperature of the PB solution is about 17-19°C. The lens is then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121°C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating was tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water-gradient SiHy contact lens was fairly smooth (having a friction rating of 0) and had a PU (polyquaternium-1 uptake) of 0.16±0.01 μg/lens (n=6).</p><p>Example 40 SBC Solution: 0.1% Sodium Bicarbonate Rinse Solution The SBC rinse solution is about 0.1% w/w NaHCO₃It is prepared by dissolving sodium bicarbonate in a given volume of purified water (distilled or deionized) to have a composition of: The final pH is adjusted to 8.6 with 5N NaOH.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-1 solution prepared in Example 26 for about 50 minutes, rinsed with SBC for about 50 minutes, and then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline solution prepared in Example 26 (half of the IPC-25 saline solution is added before inserting the lens). The sealed lens package is autoclaved at about 121° C. for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water-gradient SiHy contact lenses were fairly smooth (having a friction rating of 0) and had a PU (polyquaternium-1 uptake) of 0.25±0.04 μg/lens (n=6).</p><p>Example 41 Preparation of PMAA solution (PMAA-4) The same preparation procedure as shown in Example 26, except that the PMAA used is 0.02%.</p><p>SBC-1 solution: 0.1% sodium bicarbonate rinse solution The SBC-1 rinse solution is approximately 0.1% w/w NaHCO₃It is prepared by dissolving sodium bicarbonate in a given volume of purified water (distilled or deionized) to have a composition of: The final pH is adjusted to about 9 with 5N NaOH.</p><p>After water gradient SiHy contact lens demolding, the cast molded SiHy contact lens (prepared in Example 3) is extracted with PrOH for 180 minutes for lens extraction, dip coated in PMAA-4 solution prepared above for about 50 minutes, rinsed with SBC-1 prepared above for about 50 minutes, and then packaged/sealed in a polypropylene lens packaging shell (blister) with 0.65 mL of IPC-25 saline prepared in Example 26 (half of the IPC-25 saline is added before inserting the lens). The sealed lens package is autoclaved at about 121° C. for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., hydrogel coating) thereon. The uniformity or intactness of the coating is tested by Sudan Black dye test, and the coating passed the Sudan Black dye test. The resulting water-gradient SiHy contact lenses were fairly smooth (having a friction rating of 0) and had a PU (polyquaternium-1 uptake) of 0.13±0.04 μg/lens (n=3).</p><p>Example 42 Nanoindentation testing was performed according to the procedure described in Example 1 on eight different contact lenses that did not contain any hydrogel coating thereon, and on four water gradient SiHy contact lenses: ACUVUE2® (an uncoated, non-silicone hydrogel contact lens available from Johnson &amp; Johnson), ACUVUE® Oasys (an uncoated SiHy contact lens available from Johns &amp; Johnson), Biofinity® (an uncoated SiHy contact lens available from CooperVision), MyDay® (an uncoated SiHy contact lens available from CooperVision), and delefilcon®, which had no surface treatment. The tests were carried out using A lens (DAILIES® TOTAL1® SiHy lens body manufactured by Alcon), AIROPTIX® Night &amp; Day® (plasma coated SiHy contact lens commercially available from Alcon), naturally wettable SiHy contact lens without any surface treatment of Example 3, uncoated SiHy contact lens of Example 25, DAILIES® TOTAL1® (water gradient SiHy contact lens commercially available from Alcon), water gradient SiHy contact lens of Example 25, water gradient SiHy lens of Example 28, and water gradient SiHy contact lens of Example 29. All of the contact lenses tested have a refractive power of -3.00 diopters. The bulk modulus (E') of commercially available SiHy contact lenses is data generated by the manufacturer (Table 1 in the article by G. Young, "CooperVision Biofinity Is Fastest Vision in Contact Lens &amp; Anterior Eye 33 (2010), 210-214, all of which are incorporated herein by reference in their entirety). (See CooperVision's press release dated June 17, 2013, entitled "Growing Contact Lens Brand In The US," and CooperVision's press release dated June 25, 2015, entitled "CooperVision Introduces MyDay® Lenses in the US.") The bulk moduli of the delefilcon A and uncoated SiHy lenses of Examples 3 and 25, and the water-gradient SiHy contact lenses of Examples 25, 28, and 29 are determined according to the procedure described in Example 1.</p><p>Nanoindentation testing of Biofinity®, the uncoated SiHy contact lens of Example 3, delefilcon A lenses, DAILIES® TOTAL 1®, and the water gradient SiHy contact lenses of Examples 25, 28, and 29 is performed using a Piuma probe with a tip radius of 9.5 μm and a stiffness of 0.500 N/m, and nanoindentation testing of ACUVUE2®, MyDay®, AIROPTIX® Night &amp; Day®, ACUVUE® Oasys, and the uncoated SiHy contact lens of Example 25 is performed using a Piuma probe with a tip radius of 9.0 μm and a stiffness of 4.710 N/m.</p><p>Average indentation force (IF) at an indentation depth of 400 nm_tare reported in Table 18.</p><p><tables><img file="JP7635289B2_D0063.tif" /></tables></p><p>FIG. 6 shows the indentation force at an indentation depth of 400 nm (i.e., the surface compressive force at an indentation depth of 400 nm) as a function of the bulk (Young's) elastic modulus of the contact lens. The indentation force at an indentation depth of 400 nm shows a good linear fit with the bulk elastic modulus for a contact lens that does not have a hydrogel coating thereon. This means that these materials all have similar Poisson's ratios. The best linear fit is Y=2.12X-0.38, R²=0.92.</p><p>However, the water gradient contact lenses (each having a hydrogel coating thereon) do not follow the same trend and have indentation force values that are much lower than would be predicted from the linear fit trend. Table 19 shows the indentation force reduction values at an indentation depth of 400 nm for the water gradient contact lenses, calculated based on the following formula:<math num="32"><img file="JP7635289B2_D0064.tif" /></math>In the formula, (IF)_tis the measured indentation force of the water gradient contact lens at an indentation depth of 400 nm, and E' is the bulk modulus of the water gradient contact lens.</p><p><tables><img file="JP7635289B2_D0065.tif" /></tables></p><p>These results indicate that the hydrogel coating forms a softer surface on the lens compared to other contact lenses that do not have any hydrogel coating thereon, while the lens bulk maintains a high elastic modulus.</p><p>All publications, patents, and published patent applications cited herein above are hereby incorporated by reference in their entirety.</p>