Weekly and monthly disposable water gradient contact lenses

Abstract

To provide contact lenses that not only comprise water gradient structural configurations, but also have a minimized uptakes of polycationic antimicrobials and a long-lasting surface hydrophilicity and wettability even after going through a 30-days lens care regime.SOLUTION: A contact lens can provide superior wearing comfort, because of a water gradient structural configuration and a relatively-thick, extremely-soft and water-rich hydrogel surface layer. Further, the contact lens is compatible with multipurpose lens care solutions present in the market and can endure harsh lens care handling conditions (e.g., digital rubbings, accidental inversion of contact lenses, etc.) encountered in a daily lens care regime. As such, they are suitable to be used as weekly- or monthly-disposable water gradient contact lenses.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates, in a broad sense, to disposable water gradient contact lenses for one week or one month, and specifically to silicone hydrogel contact lenses that are durable, highly hydrated, flexible, resistant to finger rubbing, and have a relatively thick hydrogel coating thereon, and also have relatively high durability against the incorporation of polycationic antibacterial agents.

Background Art

[0002] A new category of soft contact lenses, the water gradient silicone hydrogel contact lenses, has been developed and successfully introduced to the market as the daily disposable contact lens DAILIES (registered trademark) TOTAL1 (registered trademark) (Alcon). This new category of silicone hydrogel contact lenses is characterized by having a water gradient structure form with a water content improvement from 33% to over 80% from the core to the surface (see U.S. Patent No. 8,480,227). This unique design provides a highly lubricious and extremely flexible, highly hydrated lens surface, thereby enabling better wearing comfort to be provided to patients.

[0003] Such flexible contact lenses can be manufactured according to the cost-effective method described in U.S. Patent No. 8,529,057. The water gradient silicone hydrogel contact lenses can be manufactured by dipping the contact lenses in a coating solution of a polyanionic polymer and then covalently bonding a water-soluble highly branched hydrophilic polymer material directly to the adhesion layer in an autoclave within the lens package to form an adhesion layer on each contact lens. 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 the wetting agent and a reaction temperature over a given reaction time such that surface defects (such as surface cracks, etc.) are minimized or eliminated while achieving the desired lubricity of the surface gel.

[0004] Newly developed water gradient silicone hydrogel contact lenses can provide better wearing comfort to patients due to their extremely flexible, highly hydrated, and relatively thick hydrogel coatings, but they may not be compatible with all lens care solutions on the market. For example, these new contact lenses may incorporate (absorb) a large amount of polycationic antibacterial agents (e.g., polyhexamethylene biguanide, polyquaternium-1 (also known as Polyquad®), etc., which are commonly found in most multipurpose lens care solutions) due to the presence of a fixed layer of polyanionic material, and thus may not be compatible with some of the multipurpose lens care solutions existing in the market. These polycationic antibacterial agents adsorbed by the contact lenses may be released into the eye when the lenses are worn by the patient, and may cause undesirable clinical symptoms such as diffuse corneal staining and product intolerance in some people. Due to incompatibility with some multipurpose lens care solutions, newly developed water gradient silicone hydrogel contact lenses that need to be washed and disinfected almost daily with lens care solutions may not be suitable for use as one-week or one-month disposable contact lenses.

[0005] U.S. Patent Application Publication Nos. 2015 / 0166205A1 and 2016 / 0326046A1 disclose methods for reducing the ease of attachment and deposition of polycationic antibacterial agents in water gradient contact lenses by adding one step involving the use of polyamine amine-epichlorohydrin (PAE). However, these methods have several drawbacks. For example, by these methods, the ease of attachment and deposition of polycationic antibacterial agents in hydrogel coating-containing contact lenses can be reduced, but the resulting lubricity, wettability, and / or hydrophilicity of the contact lenses are also reduced at the same time. Also, the reduction in the attachment and deposition of polycationic antibacterial agents may not be sufficient to confer compatibility of the contact lenses with all multipurpose lens care solutions on the market. Furthermore, the contact lenses obtained by these methods may not be able to withstand finger rubbing required in a lens care regimen involving multipurpose lens care solutions, or accidental lens inversion during lens manufacture or handling. This is because finger rubbing and lens inversion of contact lenses may damage the hydrogel coating on the contact lenses such that crack lines that can be seen by the eye under dark field become apparent after the contact lens is inverted or rubbed between fingers.

[0006] Therefore, there remains a need for disposable water gradient contact lenses for one week or one month that have high resistance to finger rubbing and are compatible with all lens care solutions, including multipurpose lens care solutions. SUMMARY OF THE INVENTION MEANS FOR SOLVING THE PROBLEM

[0007] In some aspects, the present invention provides a contact lens having a long-lasting surface hydrophilicity and wettability, which not only has a highly desirable water gradient structure form, but also has a polyquaternium-1 uptake rate ( "PU") of about 0.4 micrograms / lens or less, and a water break-up time (WBUT) of at least 10 seconds after 30 cycles of finger rubbing treatment (i.e., simulating a 30-day lens care regimen) or after simulated polishing cycling treatment. The contact lens of the present invention can provide better wearing comfort because it has a desired water gradient structure form, and a relatively thick, extremely flexible and highly hydrated hydrogel surface layer. More importantly, the water gradient contact lens of the present invention is compatible with multi-purpose lens care solutions available in the market and can withstand the harsh lens care handling conditions (such as finger rubbing, accidental inversion of the contact lens, etc.) encountered in daily lens care regimens. Therefore, they are suitable for use as one-week or one-month disposable contact lenses.

[0008] In other aspects, the present invention provides a contact lens having a long-lasting surface hydrophilicity and wettability, which not only has an outer surface layer with desired flexibility, but also has a polyquaternium-1 uptake rate ( "PU") of about 0.4 micrograms / lens or less, and a water break-up time (WBUT) of at least 10 seconds after 30 cycles of finger rubbing treatment (i.e., simulating a 30-day lens care regimen). The contact lens of the present invention can provide better wearing comfort because it has a relatively thick and extremely flexible surface layer. More importantly, the contact lens of the present invention is compatible with multi-purpose lens care solutions available in the market and can withstand the harsh lens care handling conditions (such as finger rubbing, accidental inversion of the contact lens, etc.) encountered in daily lens care regimens. Therefore, they are suitable for use as one-week or one-month disposable contact lenses.

[0009] These and other aspects of the present invention will become apparent from the following description of the presently preferred embodiments. The embodiments for carrying out the invention are merely illustrative of the invention and do 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 present invention are possible without departing from the spirit and scope of the novel concepts of the present disclosure.

Brief Description of the Drawings

[0010]

Figure 1

Figure 2

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Figure 6

Embodiments for Carrying out the Invention

[0011] Unless otherwise specified, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the terms used in this specification, and the experimental procedures, are well known and commonly used in the art. These procedures are those of conventional methods such as those provided in the art and various general references. When a term is provided in the singular, the inventors also intend the plural form of that term. The terms used in this specification, and the experimental procedures described below, are well known and commonly used in the art.

[0012] As used in this application, "about" means that the number referred to as "about" includes a number that is the recited number plus or minus 1 to 10% of the recited number.

[0013] "Contact lens" refers to a structure that can be placed on or in the eye of a wearer. A contact lens can correct, improve, or modify the vision of a user, but it is not necessary to do so. A contact lens can be made of any suitable material known in the art or developed later, and can be a hard lens, a rigid gas permeable lens, a soft lens, or a hybrid lens.

[0014] "Hard contact lens" refers to a contact lens that includes a hard plastic (e.g., polymethyl methacrylate) as the bulk (core) material.

[0015] "Rigid gas permeable contact lens" refers to a contact lens that includes a gas permeable material (e.g., a material made from fluorosilicone acrylate) as the bulk (core) material.

[0016] The 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 containing a non-silicone hydrogel bulk (core) material. "Silicone hydrogel contact lens" refers to a contact lens containing a silicone hydrogel bulk (core) material. "Silicone contact lens" refers to a contact lens manufactured from a crosslinked silicone material as its bulk (or core or base) material, which has a three-dimensional polymer network (i.e., polymer matrix), is water-insoluble, and can hold 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.

[0017] The hybrid contact lens has a central optical zone made of a gas-permeable lens material, surrounded by an edge band made of a silicone hydrogel or standard hydrogel lens material.

[0018] "Hydrogel" or "hydrogel material" refers to a crosslinked polymer material that is water-insoluble but can hold at least 10% by weight of water within its three-dimensional polymer network (i.e., polymer matrix) when fully hydrated.

[0019] As used in this application, the term "non-silicone hydrogel" refers to a hydrogel that theoretically does not contain silicon.

[0020] As used in this application, the term "silicone hydrogel" refers to a hydrogel containing silicone. A silicone hydrogel is typically obtained by copolymerizing a polymerizable composition containing at least one silicone-containing vinyl monomer, or at least one silicone-containing vinyl macromer, or at least one silicone-containing prepolymer having an ethylenically unsaturated group.

[0021] As used herein, "hydrophilic" describes a material, or a portion thereof, that binds more readily to water than to lipids.

[0022] "Vinyl monomer" refers to a compound having one and only one ethylenically unsaturated group, being soluble in a solvent, and being polymerizable by actinic radiation or heat.

[0023] The term "soluble" in relation 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 give a solution having a concentration of at least about 0.05% by weight.

[0024] The term "insoluble" in relation 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.

[0025] As used in the present application, the term "ethylenically unsaturated group" is used in a broad sense herein and is intended to include any group containing at least one >C=C< group. Exemplary ethylenically unsaturated groups include (meth)acryloyl [Chemical formula] , allyl, vinyl, styrenyl, or other C=C-containing groups, but are not limited thereto.

[0026] The term "(meth)acrylamide" refers to methacrylamide and / or acrylamide.

[0027] The term "(meth)acrylate" refers to methacrylate and / or acrylate.

[0028] As used herein, "actinic" in relation to the 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 UV / visible light irradiation, ionizing radiation (e.g., γ-ray or X-ray irradiation), microwave irradiation, etc. Thermal curing or actinic curing methods are well known to those skilled in the art.

[0029] As used herein, "hydrophilic vinyl monomer" refers to a vinyl monomer from which a polymer that is water-soluble or can absorb at least 10 weight percent water is typically obtained as a homopolymer.

[0030] As used herein, "hydrophobic vinyl monomer" refers to a vinyl monomer from which a polymer that is water-insoluble and can absorb less than 10 weight percent water is typically obtained as a homopolymer.

[0031] "Blending vinylic monomer" refers to a vinyl monomer that can dissolve both the hydrophilic and hydrophobic polymerizable components of a polymerizable composition to form a solution.

[0032] "Acrylic monomer" refers to a vinyl monomer having only one (meth)acryloyl group.

[0033] "N-vinylamide monomer" refers to an amide compound having a vinyl group (-CH=CH 2 ) directly bonded to the nitrogen atom of the amide group.

[0034] "Macromer" or "prepolymer" refers to a compound or polymer containing ethylenically unsaturated groups and having a number average molecular weight exceeding 700 daltons.

[0035] As used herein, the term "vinylic crosslinker" refers to a compound having at least two ethylenically unsaturated groups. "Vinylic crosslinking agent" means a subclass of vinylic crosslinkers each having a number average molecular weight of 700 daltons or less.

[0036] As used herein, the term "polymer" means a material formed by polymerizing or crosslinking one or more monomers, macromers, prepolymers, and / or combinations thereof.

[0037] 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 otherwise indicated by the test conditions.

[0038] "Polysiloxane segment" means

Chemical formula

[0039] "Polysiloxane vinyl monomer" refers to a compound containing at least one polysiloxane segment and a single ethylenically unsaturated group.

[0040] "Polysiloxane vinyl crosslinker" refers to a compound containing at least one polysiloxane segment and at least two ethylenically unsaturated groups.

[0041] "Chain-extended polysiloxane vinyl crosslinker" refers to a compound containing at least two ethylenically unsaturated groups and at least two polysiloxane segments, with each pair being linked by a single divalent radical.

[0042] "Polycarbosiloxane" refers to

Chemical formula

[0043] The term “polycarbosiloxane vinyl monomer” refers to a compound containing at least one polycarbosiloxane segment and a single ethylenically unsaturated group.

[0044] The term “polycarbosiloxane vinyl crosslinker” refers to a compound containing at least one polycarbosiloxane segment and at least two ethylenically unsaturated groups.

[0045] As used herein, the term “fluid” indicates that the material can flow like a liquid.

[0046] As used in this application, the term “clear” in relation to a polymerizable composition means that the polymerizable composition is a transparent solution or liquid mixture (i.e., having a light transmittance of 85% or more in the range of 400 - 700 nm).

[0047] 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 another group in an organic compound.

[0048] The term “alkylene divalent group” or “alkylene diradical” or “alkyl diradical” interchangeably refers to a divalent radical obtained by removing one hydrogen atom from an alkyl. An alkylene divalent group forms two bonds with other groups in an organic compound.

[0049] The term "alkyltriradical" refers to a trivalent radical obtained by removing two hydrogen atoms from an alkyl group. An alkyltriradical forms three bonds with other groups in an organic compound.

[0050] The term "alkoxy" or "alkoxyl" refers to a monovalent radical obtained by removing a hydrogen atom from the hydroxyl group of a straight-chain or branched-chain alkyl alcohol. An alkoxy group (radical) forms one bond with another group in an organic compound.

[0051] As used in the present application, the term "amino group" refers to a primary or secondary amino group of the formula -NHR', where R' is hydrogen or an unsubstituted or substituted straight-chain or branched-chain alkyl group of C 1 ~C 20 to C

[0052] In the present application, the term "substituted" related to an alkyldiradical or an alkyl radical means that the alkyldiradical or alkyl radical replaces one hydrogen atom of the alkyldiradical or alkyl radical and contains at least one substituent selected from the group consisting of hydroxy (-OH), carboxy (-COOH), -NH 2 , sulfhydryl (-SH), C 1 ~C 4 alkyl, C 1 ~C 4 alkoxy, C 1 ~C 4 alkylthio (alkyl sulfide), C 1 ~C 4 acylamino, C 1 ~C 4 alkylamino, di-C 1 ~C 4 alkylamino, a halogen atom (Br or Cl), and combinations thereof.

[0053] In the present application, "oxazoline" refers to

Chemical formula

[0054] In the present application, the term "polyoxazoline" refers to [Chemical formula] a polymer or polymer segment of 1 wherein R 2 is hydrogen, methyl, ethyl, N - pyrrolidonylmethyl, N - pyrrolidonylethyl, N - pyrrolidonylpropyl, or - alk - (OC 4 ) m3 - OR ” (wherein alk is a C 1 ~ C 4 alkyl diradical, R” is a C 1 ~ C 4 alkyl (preferably methyl), m3 is an integer from 1 to 10 (preferably 1 to 5), and x is an integer from 5 to 500) is a monovalent radical.

[0055] In the present application, the term "poly(2 - oxazoline - co - ethyleneimine)" refers to [Chemical formula] a statistical copolymer having the formula of 1is hydrogen, methyl, ethyl, N - pyrrolidonylmethyl, N - pyrrolidonylethyl, N - pyrrolidonylpropyl, or - alk - (OC 2 H 4 ) m3 -OR ” (where alk is a C 1 ~C 4 alkyl diradical, R” is a C 1 ~C 4 alkyl (preferably methyl), m3 is an integer from 1 to 10 (preferably 1 to 5), x is an integer from 5 to 500, and z is an integer less than or equal to x) is a monovalent radical. Poly(2 - oxazoline - co - ethyleneimine) is obtained by hydrolyzing polyoxazoline.

[0056] In the present 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) into azetidinium groups. Examples of poly(2 - oxazoline - co - ethyleneimine) - epichlorohydrin are disclosed in co - pending U.S. Patent Application Publication No. 2016 / 0061995A1.

[0057] “Epichlorohydrin - functionalized polyamine” or “epichlorohydrin - functionalized polyamidoamine” refers to a polymer obtained by reacting a polyamine or polyamidoamine with epichlorohydrin to convert all or a substantial proportion of the secondary amine groups of the polyamine or polyamidoamine into azetidinium groups.

[0058] The term “polyamidoamine - epichlorohydrin” refers to an epichlorohydrin - functionalized adipic acid - diethylenetriamine copolymer.

[0059] In the present application, the term “azetidinium” or “3 - hydroxyazetidinium” is [Chemical formula] refers to a positively charged (i.e., cationic) divalent radical (or group or moiety).

[0060] The term "thermocrosslinkable" in relation to a polymer material or functional group means that the polymer material or functional group can undergo a crosslinking (or coupling) reaction with another material or functional group at a relatively high temperature (about 40 °C to about 140 °C), while on the other hand, the polymer material or functional group cannot undergo the same crosslinking reaction (or coupling reaction) with another material or functional group to a detectable extent at a temperature of about 5 °C to about 15 °C for a period of about 1 hour.

[0061] The term "azlactone" refers to a monovalent radical of the formula [Chemical formula] wherein p is 0 or 1 and R and 3 R, which are independent of each other, are C 4 R is C 1 ~C 8 alkyl (preferably methyl).

[0062] The term "aziridine group" refers to a monovalent radical of the formula [Chemical formula] wherein R1 is hydrogen, methyl, or ethyl.

[0063] As used herein, the term "phosphorylcholine" refers to a zwitterionic group of the formula [Chemical formula] wherein n is an integer from 1 to 5 and the mutually independent R 1 , R 2 , and R 3 are C 1 ~C 8 alkyl or C 1 ~C8 It is a hydroxyalkyl.

[0064] 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.

[0065] As used herein, the term "non-reactive vinyl monomer" refers to any vinyl monomer (either hydrophilic or hydrophobic) 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.

[0066] The free radical initiator may be either a photoinitiator or a thermal initiator. The "photoinitiator" refers to a chemical that initiates a free radical crosslinking / polymerization reaction by the use of light. The "thermal initiator" refers to a chemical that initiates a radical crosslinking / polymerization reaction by the use of thermal energy.

[0067] "Spatial confinement of actinic radiation" refers to the act or process in which actinic energy radiation, for example, is directed by a mask or a screen or a combination thereof and collides with a region having a distinct surrounding boundary in a spatially confined manner. Spatial confinement of UV radiation can be obtained by using a mask or a screen having a radiation (e.g., UV) transmissive region, a radiation (e.g., UV) non-transmissive region surrounding the radiation transmissive region, and a projection profile which is a boundary between the radiation non-transmissive region and the radiation transmissive region, as schematically shown in the drawings of U.S. Patent No. 6,800,225 (Figs. 1 - 11), as well as U.S. Patent No. 6,627,124 (Figs. 1 - 9), U.S. Patent No. 7,384,590 (Figs. 1 - 6), and U.S. Patent No. 7,387,759 (Figs. 1 - 6). The mask or screen enables spatially projecting a beam of radiation (e.g., UV radiation) having a cross-sectional profile defined by the projection profile of the mask or screen. The projected beam of radiation (e.g., UV radiation) limits the radiation (e.g., UV radiation) that collides with a lens combination located on the path of the projected beam from a first molding surface of a mold to a second molding surface. The resulting contact lens includes a front surface defined by the first molding surface, a rear surface on the opposite side defined by the second molding surface, and a lens edge defined by the cross-sectional profile of the projected UV beam (i.e., spatial confinement of actinic radiation). The radiation used for crosslinking is actinic energy, particularly UV radiation, gamma rays, electron beams, or heat rays, and in order to achieve good confinement of energy on the one hand and efficient use of energy on the other hand, the actinic energy is preferably in the form of a substantially parallel beam.

[0068] The intrinsic "oxygen permeability", Dk, of a material i is 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 a contact lens is a corrected oxygen permeability (Dk measured at about 34 - 35°C according to the procedure described in Example 1 of U.S. Patent Application Publication No. 2012 / 0026457A1 and corrected for the surface resistance to the oxygen flux caused by the boundary layer effect.c ) means. Oxygen permeability is conventionally expressed in units of barrer, where "barrer" is [(cm 3 oxygen)(mm) / (cm 2 )(seconds)(mmHg)]×10 -10 is defined as.

[0069] The "oxygen transmission rate", Dk / t, of a lens or material is the rate at which oxygen passes through a particular lens or material having an average thickness t [unit mm] over the region being measured. The oxygen transmission rate is conventionally expressed in units of barrer / mm, where "barrer / mm" is [(cm 3 oxygen) / (cm 2 )(seconds)(mmHg)]×10 -9 is defined as.

[0070] As used herein, "ophthalmic compatibility" refers to a material, or the surface of a material, that can be in close contact with the eye environment for an extended period of time without significantly damaging the eye environment and without significant user discomfort.

[0071] The term "ophthalmically safe" as related to a packaging solution for sterilizing and storing contact lenses means that a contact lens stored in the solution is safe to place directly on the eye without rinsing after autoclaving, and that the solution is safe and sufficiently comfortable for daily contact with the eye through the contact lens. An ophthalmically safe packaging solution after autoclaving has a tonicity and pH compatible with the eye and is substantially free of materials that are eye irritating or cytotoxic according to international ISO standards and U.S. FDA regulations.

[0072] As used herein, the term "water gradient" in relation to a contact lens means that an increase in water content is observed as it passes from the core to the surface of the contact lens, and reaches its maximum water content in the 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 stepwise, as long as the water content is maximum in the region near and including the surface of the contact lens.

[0073] As used herein, the term "cross-section" of a contact lens refers to the lens cross-section obtained by cutting the lens at an angle substantially perpendicular to either the front surface or the back surface of the lens using a knife or cutting tool. Those skilled in the art are well aware that to obtain a cross-section of a contact lens, the contact lens can be cut manually (i.e., by hand) or using a Cryosta Microtome or a razor. The obtained cross-section of the contact lens can be polished using ion etching or similar techniques.

[0074] The term "modulus" or "elastic modulus" in relation to a contact lens or material means the tensile modulus or Young's modulus, which is a measure of the stiffness of the contact lens or material. The modulus can be measured using a method in accordance with the ANSI Z80.20 standard. Those skilled in the art are well aware of the methods for determining the modulus of a silicone hydrogel material or a contact lens. For example, all commercially available contact lenses have reported values of modulus.

[0075] The terms "surface modulus", "surface softness", "surface elastic modulus", "surface Young's modulus" or "surface compression coefficient" are used interchangeably in the present application and, as known to those skilled in the art, mean the nanomechanical properties (elastic properties) measured by atomic force microscopy (AFM) on the surface of a material or the cross-section of a contact lens in a fully hydrated state (pH approximately 7.3 ± 0.2 in phosphate buffer solution) using the nanoindentation method. 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 can be carried out according to the experimental procedures described 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 Contact Lenses Using Nanoindentation with AFM”, pp554-559, 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), rather than the front or back surface of the contact lens, is analyzed using the AFM nanoindentation method.The nano-indentation method, Peakforce QNM method, and Harmonic Force method are described in the title "Nanomechanical properties of a-synuclein amyloid fibrils: a comparative study by nanoindentation, harmonic force microscopy, and Peakforce QNM" in the paper by Kim Sweers, et al. in Nanoscale Research Letters 2011, 6:270. Also, when measuring the surface elastic modulus using AFM from the front surface of the cross-section of a fully hydrated contact lens to the bulk or from the bulk to the back surface (and vice versa), it will be understood that the surface elastic modulus profile across the cross-section of the contact lens can be determined along the shortest line between the front and back surfaces of the surface of the cross-section of the contact lens. Further, as a good approximation, it will be further understood that any experimentally and directly measured quantity can be used to represent the surface elastic modulus as long as the measured quantity is proportional to the surface elastic modulus. Alternatively, when colloidal spheres of various sizes are used to measure the surface elastic modulus, the micro-indentation method or nano-indentation method may be used.

[0076] As used in this application, the terms "inner layer" or "bulk material" related to a contact lens mean, interchangeably, a layer having a three-dimensional shape of the contact lens, including a central curved surface (which divides the contact lens into two parts, one containing the front surface and the other containing the back surface), and having a variable thickness.

[0077] As used in this application, the term "outer surface hydrogel layer" related to a contact lens means the outermost hydrogel layer on the contact lens surface, which consists of a front surface outer hydrogel layer and a back surface outer hydrogel layer, and completely covers the inner layer (or lens bulk material).

[0078] As used herein, the term "front outer hydrogel layer" in connection with a contact lens means a hydrogel layer that includes the front surface of the contact lens, has a substantially uniform thickness (i.e., the thickness variation is about 20% or less from the average thickness of the layer), and has an average thickness of at least about 0.25 μm.

[0079] As used herein, the term "rear outer hydrogel layer" in connection with a contact lens means a hydrogel layer that includes the rear surface of the contact lens, has a substantially uniform thickness (i.e., the thickness variation is about 20% or less from the average thickness of the layer), and has an average thickness of at least about 0.25 μm.

[0080] As used herein, the term "transition layer" in connection with a contact lens means a layer polymeric material located between the inner layer (or lens bulk material) and one of the front outer hydrogel layer and the rear outer hydrogel layer. Each transition layer has a substantially uniform thickness (i.e., the thickness variation is about 20% or less from the average thickness of the layer).

[0081] As used herein, the "average thickness" of the front or outer hydrogel layer or the transition layer is simply referred to as the "thickness of the front outer hydrogel layer", the "thickness of the rear outer hydrogel layer", or the "thickness of the transition layer" measured using AFM on a cross-section of the contact lens in a specified state, e.g., in a fully hydrated state or when fully hydrated (i.e., in a phosphate buffer solution at pH about 7.3 ± 0.2), or in a dry state (e.g., completely oven-dried).

[0082] Figure 1 schematically shows 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 a front surface (or front curve or convex surface) 101 and a rear surface (or base curve or concave surface) 102 on the opposite side that is placed on the cornea of the eye when worn by the user. The contact lens 100 includes an inner (or intermediate) layer (or lens bulk material) 110 and front and rear outer hydrogel layers 120. The inner layer 110 is the bulk material of the contact lens 100 and has a three-dimensional shape similar to that of the contact lens 100. The front and rear outer hydrogel layers 120 are substantially uniform in thickness and are made of a silicone-free (preferably completely silicone-free) hydrogel material having a water content higher than that of the inner layer 110. The front and rear outer hydrogel layers 120 are integrated at the peripheral edge 103 of the contact lens 100 and completely cover the inner layer 110.

[0083] Figure 2 schematically shows a contact lens of the present invention according to another preferred embodiment. The contact lens 100 includes an inner (or intermediate) layer (or lens bulk material) 110, front and rear 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.

[0084] As used herein, the term "equilibrium water content" in relation to a contact lens or polymer material means the amount of water (expressed as weight %) present in the contact lens or polymer material when fully hydrated (equilibrated) in saline (about 0.79 wt% NaCl) and measured at room temperature (as defined above).

[0085] As used herein, the terms "crosslinked coating", "hydrogel coating", or "hydrogel layer" on a contact lens are used interchangeably to refer to a crosslinked polymer material having a three-dimensional network capable of containing water when fully hydrated. The three-dimensional network of the crosslinked polymer material can be formed by crosslinking two or more linear or branched chain polymers via crosslinking linkages.

[0086] As used herein, the term "water swelling ratio" related to the front or rear outer hydrogel layer of the contact lens of the present invention

Number

[0087] The water swelling ratio of the outer surface hydrogel layer of the contact lens is considered to be proportional to the equilibrium water content of the outer surface hydrogel layer. The higher the water swelling ratio of the outer surface hydrogel layer, the higher the equilibrium water content of the outer surface hydrogel layer. Further, the water swelling ratio of the outer surface hydrogel layer is considered to be proportional to the mesh size of the outer surface hydrogel layer, and thus proportional 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 and proportional to the length of the crosslinked chains on the other hand. The higher the water swelling ratio of the outer surface hydrogel layer, the more flexible the outer surface hydrogel layer becomes. Therefore, the water swelling ratio can be a good indicator of both the equilibrium water content and the flexibility of the outer surface hydrogel layer.

[0088] 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 vertical force at the indentation depth along the load curve, measured in the micro-indentation or nano-indentation test described in Example 1.

[0089] As used herein, the terms "decrease in indentation force" or "Δ(IF) 400nm " related to a contact lens mean the difference between the indentation force (μN) at an indentation depth of 400 nm predicted 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 micro-indentation or nano-indentation test described in Example 1, which can be calculated by the following equation:

Equation

[0090] All contact lenses can have different mechanical properties on their surfaces. Specifically, when the contact lens has a soft hydrogel coating thereon. In the vicinity of the surface of the contact lens and in the region including the surface, the mechanical properties can be characterized by measuring the surface compression force or indentation force as a function of displacement in a micro-indentation or nano-indentation test.

[0091] In the case of a contact lens that does not contain any soft hydrogel coating thereon, the indentation force at a given displacement or indentation depth (e.g., 400 nm) is well related to the bulk (Young's) modulus (i.e., there is a linear bulk modulus-indentation force relationship between the bulk modulus at an indentation depth of 400 nm and the indentation force), while in the case of a contact lens that has a soft hydrogel coating thereon, the indentation force at an indentation depth of 400 nm has been found to be much smaller than that predicted based on the linear bulk modulus-indentation force relationship (i.e., a decrease in the indentation force at an indentation depth of 400 nm). The decrease in the indentation force at an indentation depth of 400 nm, i.e., Δ(IF) 400nm is considered to be usable for quantitatively characterizing contact lenses having a water gradient structure form. When the contact lens has a sufficiently thick (≧0.25 μm) outer surface hydrogel layer thereon, this results in a decrease in the indentation force at an indentation depth of 400 nm of about 40% or more (Δ(IF) 400nm ). The value of Δ(IF) for the water gradient contact lens 400nm is also considered to depend on both the flexibility and thickness of the outer surface hydrogel layer on the contact lens. The decrease in the indentation force at an indentation depth of 400 nm (Δ(IF) 400nm ) is proportional to the flexibility and / or thickness of the outer surface hydrogel layer (or outer surface layer) of the contact lens. The larger Δ(IF) 400nm , the more flexible and / or thicker the outer surface hydrogel layer (or outer surface layer) becomes, and the smaller the force induced on the corneal surface. Thus, Δ(IF) 400nmIt 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.

[0092] As used in this application, the term "normalized surface compressive force" or "NSCF" in relation to a contact lens means the ratio of the surface compressive force or indentation force at a 400 nm indentation depth of the contact lens (determined by a micro-indentation test using a 1 mm probe dimension as described in Example 1) to the elastic modulus of the contact lens, which has units of μN / MPa, i.e.,

Equation

[0093] When the contact lens does not have an outer surface hydrogel layer thereon, it has been found that, regardless of the bulk elastic modulus of the contact lens, it will have a normalized surface compressive force of about 14 μN / MPa or slightly higher as measured with a 1 mm colloidal probe. Thus, it is thought that the normalization of the surface compressive force across the elastic 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, when the contact lens has a sufficiently thick outer surface hydrogel layer thereon, it will have a normalized surface compressive force (at a 400 nm indentation depth) of less than about 14 μN / MPa. Δ(IF) 400nmSimilarly, it is considered that the contact lens having a water gradient structure can be qualitatively and quantitatively characterized using the normalized surface compressive force at a penetration depth of 400 nm. When the contact lens has a sufficiently thick (≧0.25 μm) outer surface hydrogel layer thereon, this will have a normalized surface compressive force (at a penetration depth of 400 nm) of about 12 μN / MPa or less. It will also be understood that the normalized surface compressive force (NSCF) at a penetration depth of 400 nm of the 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 a penetration depth of 400 nm, the more flexible the outer surface hydrogel layer (or outer surface layer) becomes, 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 a penetration depth of 400 nm. Therefore, the normalized surface compressive force at a penetration 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.

[0094] As used herein, the term "polyquaternium-1 uptake rate" or "PU" in relation to a contact lens means the amount of polyquaternium-1 absorbed by the contact lens, measured according to the procedure described in Example 1.

[0095] As used herein, the term "long-lasting surface hydrophilicity and wettability" in relation to a contact lens means that the contact lens has a water break-up time (WBUT) of at least 10 seconds after 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment. The determination of the WBUT of the contact lens, the cycles of finger rubbing treatment, and the simulated polishing cycling treatment are carried out according to the procedures described in Example 1.

[0096] As used herein, the term "long-lasting lubricity" as related to a contact lens means that after 30 cycles of finger rubbing or after simulated polishing cycling, the contact lens has a friction score of about 2.0 or less. The determination of the friction score of the contact lens, the cycles of finger rubbing, and the simulated polishing cycling are carried out according to the procedures described in Example 1.

[0097] As used herein, the term "30 cycles of finger rubbing" or "n cycles of finger rubbing" means that the contact lens is subjected to 30 or n repetitions of a finger rubbing procedure that consists essentially of finger rubbing the contact lens for 20 seconds using RENU® multipurpose lens care solution (or an equivalent, i.e., a multipurpose lens care solution disclosed in Table I of U.S. Patent No. 5,858,937) (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 cycles of finger rubbing can reasonably mimic daily cleaning and disinfection in a 30-day or n-day lens care regimen.

[0098] "UVA" refers to radiation occurring at wavelengths of 315 - 380 nanometers, "UVB" refers to radiation occurring at 280 - 315 nanometers, and "violet" refers to radiation occurring at wavelengths of 380 - 440 nanometers.

[0099] "UVA transmittance" (or "UVA %T"), "UVB transmittance" or "UVB %T", and "violet transmittance" or "violet %T" are calculated using the following formula:

Equation

[0100] The term "essentially wettable" related to silicone hydrogel contact lenses means that after a silicone hydrogel contact lens is formed by thermally or radiationally polymerizing (i.e., curing) a silicone hydrogel lens formulation, the silicone hydrogel contact lens has a water breakdown time (WBUT) of about 10 seconds or more and a water contact angle (WCA cb ) of about 80 degrees or less without being subjected to any surface treatment. According to the present invention, WBUT and WCA cb are measured according to the procedure described in Example 1.

[0101] As used herein, "surface modification" or "surface treatment" means that an article is treated in a surface treatment process (or surface modification process) of (1) applying a coating to the surface of the article, (2) adsorbing a chemical species to the surface of the article, (3) changing the chemical properties (e.g., electrostatic charge) of chemical groups on the surface of the article, or (4) modifying the surface characteristics of the article in other respects, either before or after the formation of the article. Exemplary surface treatment processes include surface treatment by 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, the mold-transfer coating process disclosed in U.S. Patent No. 6,719,929, the incorporation of wetting agents into lens formulations for manufacturing contact lenses proposed in U.S. Patent Nos. 6,367,929 and 6,822,016, the enhanced mold-transfer coating disclosed in U.S. Patent 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 contact lenses disclosed in U.S. Patent Nos. 8,147,897 and 8,409,599, and U.S. Patent Application Publications Nos. 2011 / 0134387, 2012 / 0026457, and 2013 / 0118127, but are not limited thereto.

[0102] "Post-curing surface treatment" in relation to a lens bulk material or a contact lens means a surface treatment process carried out after the formation of the lens bulk material or the contact lens formed by curing (i.e., thermal or radiation polymerization) of the lens formulation. "Lens formulation" refers to a polymerizable composition containing all the polymerizable components necessary for manufacturing a contact lens or a lens bulk material well-known to those skilled in the art.

[0103] "Organic-based solution" refers to a solution that is a homogeneous mixture composed of an organic-based solvent and one or more solutes dissolved in the organic-based solvent. An organic-based coating solution refers to an organic-based solution containing at least one polymer coating material as a solute in the solution.

[0104] "Organic-based solvent" is intended to mean a solvent system composed of one or more organic solvents and water of about 40% by weight or less, preferably about 30% by weight or less, more preferably about 20% by weight or less, still more preferably 10% by weight or less, and particularly about 5% by weight or less based on the weight of the solvent system.

[0105] Broadly speaking, the present invention relates to a one-week or one-month disposable water gradient contact lens that not only has a unique water gradient from the inside to the outside of the contact lens and a layered structure form providing relatively long-lasting wettability / hydrophilicity, but also has scratch resistance and is compatible with a lens care solution containing a multi-purpose lens care solution. The layered structure form includes an inner layer (i.e., the lens bulk material) having an equilibrium water content of about 70% by weight or less, and an outer surface hydrogel layer (composed of a front outer hydrogel layer and a rear outer hydrogel layer) that completely covers the inner layer (or the lens bulk material) and 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 the lens bulk material) and a sufficient thickness (about 0.25 μm to about 25 μm) when fully hydrated.

[0106] According to the present invention, in order to provide better wearing comfort, the outer surface hydrogel layer must not only have a relatively high water swelling ratio, but also have a sufficient thickness. Due to the relatively high water swelling ratio of the outer surface hydrogel layer, it can be guaranteed that the contact lens has a high equilibrium water content and an extremely flexible surface. However, if the outer surface hydrogel layer is too thin, the outer surface hydrogel layer is likely to be completely crushed against the lens bulk material by a slight compressive force, losing the advantages associated with the water gradient structure mechanism of the contact lens of the present invention. At a given high water swelling ratio, the wearing comfort provided by the contact lens of the present invention is considered to improve as the thickness of its outer surface hydrogel layer increases, and then level off after exceeding a specific thickness value.

[0107] The present invention solves the problems existing in the prior art related to the incompatibility of the water gradient contact lens with the multi-purpose lens care solution and the low scratch resistance. It has been found that in order to form a thick outer surface hydrogel layer, a relatively thick anchor layer (i.e., a reactive base coating) of a reactive polyanionic polymer (such as a carboxyl-containing polyanionic polymer) is required on the contact lens. 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 (such as carboxyl groups) in the anchor layer and a higher uptake rate of the polycationic antibacterial agent present in the lens care solution. Past attempts to reduce the uptake rate of the polycationic antibacterial agent by the water gradient contact lens mainly relied on reducing the thickness of the anchor layer and using polyanionic materials with higher pKa values. Such approaches overly thin the outer surface hydrogel layer, thus reducing the durability and / or lubricity of the outer surface hydrogel layer and impairing the wearing comfort provided by the resulting contact lens.

[0108] The anchor layer and the outer surface hydrogel layer of a water gradient contact lens during manufacture and / or a preformed water gradient contact lens are treated with a small, flexible hydrophilic charge neutralizer to convert most or the majority of the negatively charged groups in the water gradient contact lens to uncharged ester bonds, and simultaneously crosslink the anchor layer, without or with minimal effect on the wettability, hydrophilicity, and lubricity of the outer surface hydrogel layer on the contact lens, and it has been found that the durability of the outer surface hydrogel layer on the contact lens can be enhanced.

[0109] It has also been found that the durability of the hydrogel coating on the SiHy contact lens greatly depends on the processing conditions under which its underlying base coating made of a polyanionic polymer is formed. When the base coating is applied to the SiHy contact lens in a single coating step for a given coating period (e.g., 50 minutes) (i.e., by contacting it with the only coating solution of the polyanionic polymer (pH < 4.5)) and then one or more rinsing steps follow, the durability of the hydrogel coating formed on such a base coating may vary depending on the refractive power (i.e., the central thickness) of the SiHy contact lens during coating. For example, the durability of the hydrogel coating of a coated SiHy contact lens having a refractive power of -10.0 diopters is inferior to that of the hydrogel coating of a coated SiHy contact lens having a refractive power of -3.0 diopters. Even when the coating period was lengthened, the variation in the durability of the hydrogel coating due to the refractive power (central thickness) of the contact lens could not be improved. However, when the SiHy contact lens is contacted with one coating solution of the polyanionic polymer (having a low pH) even for a shorter coating period (e.g., 25 minutes), then rinsed with buffered saline having a neutral or slightly basic pH, and then contacted again with another coating solution of the polyanionic polymer (having a low pH) for a shorter period (e.g., 25 minutes) so that the base coating is applied on the SiHy contact lens, the durability of the hydrogel coating formed on such a base coating can be significantly improved and it has been found that it does not vary depending on the refractive power (i.e., the central thickness) of the SiHy contact lens during coating.

[0110] Furthermore, the PU of the coated SiHy contact lens having a hydrogel coating thereon depends significantly on the pH and / or salt concentration (i.e., ionic strength) of the buffered saline used to rinse the treated SiHy contact lens having a base coating (of a polyanionic polymer) thereon before forming the hydrogel coating on the base coating. By using a rinse solution having a higher pH and / or a higher ionic strength (higher salt concentration), a lower PU can be achieved. When combined with the above-described discovery regarding a method for significantly improving the durability of the hydrogel coating of the water gradient contact lens, this discovery may enable the production of a water gradient contact lens having a durable hydrogel coating and a minimized PU.

[0111] The present invention provides a water gradient contact lens that is compatible with a multi-purpose lens care solution and has rub resistance, and is thus suitable for use as a one-week or one-month disposable contact lens. The contact lens of the present invention can provide better wearing comfort because it has a desired water gradient structure form, and a relatively thick, extremely flexible, and high-moisture hydrogel surface layer.

[0112] In one aspect, the present invention provides a contact lens having 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), a 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 treatment or after simulated polishing cycling treatment, and / or a 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, even more preferably about 0.5 or less). The contact lens includes a front surface and an opposite rear surface, and has a layered structure including a front outer hydrogel layer, an inner layer of lens material, and a rear outer hydrogel layer in a direction from the front surface to the rear surface. The inner layer has a first equilibrium water content of about 70 wt% or less, where the front and rear outer hydrogel layers, which are independent of each other, have a thickness of about 0.25 μm to about 25 μm. The inner layer has a first equilibrium water content and a second equilibrium water content higher than the first equilibrium water content. The front and rear outer hydrogel layers, which are independent of each other, have a water swelling ratio 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, after rubbing the contact lens between the fingers 10 times, the contact lens substantially does not contain (i.e., less than 3) visible surface crack lines under dark field or preferably does not contain any visible surface crack lines at all.

[0113] In another aspect, the present invention provides a contact lens having 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), a 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 treatment or after simulated polishing cycling treatment, and / or a long-lasting lubricity characterized by having a friction score 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), a water content gradient from the inner side to the outer side of the contact lens, and the contact lens comprises a lens bulk material completely covered 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 back surface to the front surface of the contact lens in a fully hydrated state, the lens bulk material has a first equilibrium water content of about 70 wt% or less, and the outer surface hydrogel layer has a second equilibrium water content that is at least 1.2 times the first equilibrium water content and is at least 80 wt%. Preferably, the contact lens, after being rubbed 10 times between fingers, substantially does not contain (i.e., less than 3) or preferably does not contain any visible surface crack lines under dark field.

[0114] In a further aspect, the present invention provides a contact lens having a front surface and an opposite rear surface, 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), a 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 treatment or after simulated polishing cycling treatment, and / or a 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, even more preferably about 0.5 or less), and a cross-sectional surface-modulus profile comprising a front outer zone including the front surface and proximal thereto along the shortest line between the front and rear surfaces of the surface of the cross-section of the contact lens, an inner zone including the central portion of the shortest line and peripheral thereto, and a rear outer zone including the rear surface and proximal thereto, the front outer zone having an average front surface modulus (

Number

Number

Number

Number

[0115] In another further aspect, the present invention provides a contact lens having a normalized surface compressive force at an indentation depth of 400 nm 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) using a 1 mm micro-indentation probe, a polyquaternium-1 uptake rate ("PU") of about 0.4 or 0.30 μg / lens or less (preferably about 0.20 μg / lens or less, more preferably about 0.15 μg / lens or less, even more preferably about 0.10 μg / lens or less, and most preferably about 0.05 μg / lens or less), and having a 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 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment, and / or a long-lasting lubricity characterized by a friction score 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). The contact lens comprises a front surface and an opposite rear surface, and a layered structure form comprising a front external hydrogel layer, an inner layer of lens material, and a rear external hydrogel layer in a direction from the front surface to the rear surface. Preferably, after rubbing the contact lens between the fingers 10 times, the contact lens substantially does not contain (i.e., less than 3) or preferably does not contain any visible surface crack lines under dark field.

[0116] In a still further aspect, the present invention provides a contact lens having a normalized surface compressive force at an indentation depth of 400 nm of 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) using a 1 mm micro-indentation probe, a polyquaternium-1 uptake rate ("PU") of 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), 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 treatment or after simulated polishing cycling treatment, and / or a 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, even more preferably about 0.5 or less), and / or a long-lasting surface hydrophilicity and wettability. The contact lens comprises a lens bulk material which is a polymeric material.

[0117] In yet another further aspect, the present invention provides a contact lens having a long-lasting surface hydrophilicity and wettability characterized by a reduction in the indentation force at an indentation depth of about 400 nm of 50% or more (preferably 55% or more, more preferably 60% or more, even more preferably 65% or more, and most preferably 70% or more), i.e., Δ(IF)400nm, and a polyquaternium-1 uptake rate ("PU") of about 0.4 or less than 0.30 micrograms / lens (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 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 treatment or after simulated polishing cycling treatment, and / or a 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 comprises a front surface and an opposite rear surface, and a layered structure comprising a front external hydrogel layer, an internal layer of lens material, and a rear external hydrogel layer in a direction from the front surface to the rear surface. Preferably, the contact lens substantially does not contain (i.e., less than 3) or preferably does not contain any surface crack lines visible to the eye under dark field conditions after rubbing the contact lens between the fingers 10 times.

[0118] In yet another further aspect, the present invention provides a reduction in the indentation force at an indentation depth of about 400 nm of 40% or more (preferably 50% or more, more preferably 55% or more, even more preferably 60% or more, and most preferably 65% or more), i.e., Δ(IF) 400nmand a polyquaternium-1 uptake rate ("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 having a 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 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment, and / or a 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, even more preferably about 0.5 or less), and the contact lens comprises a lens bulk material which is a polymeric material.

[0119] When the decrease in the pushing force of the contact lens is determined by a nanoindentation test using an Optics11 Piuma and a Piuma probe having a tip radius of about 9.0 μm, the decrease in the pushing force at a pushing depth of 400 nm, i.e., Δ(IF) 400nm is [Number] calculated by wherein, (IF) t is the measured pushing force at a pushing depth of 400 nm of the contact lens, and E’ is the bulk elastic modulus (E’) of the contact lens.

[0120] When the decrease in the pushing force of the contact lens is determined by a microindentation test using a Bruker Hysitron (registered trademark) BioSoft (trademark) In-Situ Indenter and a 1 mm hemispherical borosilicate glass probe, the decrease in the pushing force at a pushing depth of 400 nm, i.e., Δ(IF) 400nm is

Number

[0121] 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 directly derived from a preformed contact lens. The 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, provided that it does not have a water gradient structure form. Those skilled in the art are familiar with the manufacturing methods of preformed contact lenses. Those skilled in the art are familiar with the manufacturing methods of preformed contact lenses. For example, the preformed contact lens can be manufactured in a conventional "spin casting mold" described in, for example, U.S. Patent No. 3,408,429, or by a static full casting molding process described in U.S. Patent Nos. 4,347,198, 5,508,317, 5,583,463, 5,789,464, and 5,849,810, or by turning and cutting a button of a polymer material used in manufacturing a customized contact lens. In casting molding, the lens formulation is typically dispensed into a mold and cured (i.e., polymerized and / or crosslinked) in the mold.

[0122] Lens molds for manufacturing contact lenses are well known to those skilled in the art and are used, for example, in injection molding or spin casting. For example, a mold (for injection 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 molding surface and the second molding surface. 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.

[0123] Methods for manufacturing mold sections for casting contact lenses are generally well known to those skilled in the art. The process of the present invention is not limited to any particular mold-forming method. In fact, any 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.

[0124] To manufacture a mold for contact lens production, substantially all materials known in the art regarding mold manufacturing can be used. For example, polymer materials such as polyethylene, polypropylene, polystyrene, PMMA, Topas® COC grade 8007-S10 (a transparent amorphous copolymer of ethylene and norbornene manufactured by Ticona GmbH (Frankfurt, Germany and Summit, New Jersey)) may be used. Other materials that allow ultraviolet transmission, such as quartz glass and sapphire, may also be used.

[0125] In a preferred embodiment, a reusable mold is used, and the lens-forming composition is cured by actinic radiation under spatial confinement of the 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 from fused silica, sapphire, CaF 2 , cyclic olefin copolymers (e.g., Topas® COC grade 8007-S10 (a transparent amorphous copolymer of ethylene and norbornene) manufactured by Ticona GmbH (Frankfurt, Germany and Summit, New Jersey), Zeonex® and Zeonor® manufactured by Zeon Chemicals LP (Louisville, KY)), polymethyl methacrylate (PMMA), polyoxymethylene manufactured by DuPont (Delrin), Ultem® (polyetherimide) manufactured by G.E. Plastics, PrimoSpire®, and the like.

[0126] According to the present invention, the polymerizable composition can be introduced (dispensed) into a cavity formed by a mold by any known method.

[0127] After the polymerizable composition has been dispensed into the mold, it is polymerized to produce a contact lens. Preferably, crosslinking may be initiated thermally or by actinic radiation by exposing the lens-forming composition in the mold to spatial confinement of the actinic radiation to crosslink the polymerizable components in the polymerizable composition.

[0128] Opening the mold so that the article molded from the mold can be removed may be done in a manner known per se.

[0129] The molded contact lens may be subjected to lens extraction to remove unpolymerized polymerizable components. The extraction solvent can be any solvent known to those skilled in the art. Examples of suitable extraction solvents are described below.

[0130] In a preferred embodiment, the preformed contact lens is a hard contact lens that includes a rigid plastic material as the lens bulk material. Preferably, the rigid plastic material is crosslinked polymethyl acrylate. Those skilled in the art are familiar with the manufacturing methods of rigid plastic materials including crosslinked polymethyl methacrylate.

[0131] In another preferred embodiment, the preformed contact lens is a rigid gas permeable contact lens. Those skilled in the art know the manufacturing methods of rigid gas permeable contact lenses.

[0132] In another preferred embodiment, the preformed contact lens is a hybrid contact lens having a central optical zone made from a rigid gas permeable lens material and surrounded by an edge zone made from a hydrogel material.

[0133] In another preferred embodiment, the preformed contact lens is a soft silicone contact lens that includes a crosslinked silicone material as the lens bulk material. Useful crosslinked silicone materials include, but are not limited to, crosslinked polysiloxanes, silicone elastomers, silicone rubbers, etc. obtained by crosslinking silicone compositions by any known method. The silicone contact lens can be prepared by any type of prior art well-known to those skilled in the art (e.g., lathe cutting manufacturing method, spin casting manufacturing method, cast molding manufacturing method, etc.).

[0134] In another preferred embodiment, the preformed contact lens is a non-silicone hydrogel contact lens (or so-called conventional hydrogel contact lens).

[0135] The preformed non-silicone hydrogel contact lens may be any commercially available non-silicone hydrogel contact lens or may be manufactured by any known method. For example, for the manufacture of preformed non-silicone hydrogel contact lenses, a non-silicone hydrogel lens formulation for cast molding or spin-cast molding or for manufacturing a rod used for lathe cutting of contact lenses typically comprises: (1)(a) at least one hydrophilic vinyl monomer (e.g., hydroxyethyl methacrylate, glycerol methacrylate, N-vinyl pyrrolidone, or a combination thereof), and (b) at least one component selected from the group consisting of a cross-linking agent, a hydrophobic vinyl monomer, a lubricant (or so-called internal wetting agent incorporated into the lens formulation), a free radical initiator (photoinitiator or thermal initiator), a UV-absorbing vinyl monomer, a high energy visible light (「HEVL」)-absorbing vinyl monomer, a visibility tinting agent (e.g., a reactive dye, a polymerizable dye, a pigment, or a mixture thereof), an antibacterial agent (e.g., preferably silver nanoparticles), a bioactive agent, and combinations thereof, or (2) any of an aqueous solution comprising one or more water-soluble prepolymers and at least one component selected from the group consisting of a hydrophilic vinyl monomer, a cross-linking agent, a hydrophobic vinyl monomer, a lubricant (or so-called internal wetting agent incorporated into the lens formulation), a free radical initiator (photoinitiator or thermal initiator), a UV-absorbing vinyl monomer, a HEVL-absorbing vinyl monomer, a visibility tinting agent (e.g., a reactive dye, a polymerizable dye, a pigment, or a mixture thereof), an antibacterial agent (e.g., preferably silver nanoparticles), a bioactive agent, and combinations thereof. The resulting preformed hydrogel contact lens can subsequently 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 understood that the lubricant present in the hydrogel lens formulation can improve the lubricity of the 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 the lubricant.

[0136] Examples of water-soluble prepolymers include water-soluble crosslinkable poly(vinyl alcohol) prepolymers described in U.S. Patent Nos. 5,583,163 and 6,303,687, water-soluble vinyl group-terminated polyurethane prepolymers described in U.S. Patent No. 6,995,192, derivatives of polyvinyl alcohol, polyethyleneimine, or polyvinylamine disclosed in U.S. Patent No. 5,849,841, water-soluble crosslinkable polyurea prepolymers described in U.S. Patent Nos. 6,479,587 and 7,977,430, crosslinkable polyacrylamide, crosslinkable statistical copolymers of vinyl lactam, MMA, and comonomers disclosed in U.S. Patent No. 5,712,356, crosslinkable copolymers of vinyl lactam, vinyl acetate, and vinyl alcohol disclosed in U.S. Patent No. 5,665,840, polyether-polyester copolymers containing crosslinkable side chains disclosed in U.S. Patent No. 6,492,478, branched polyalkylene glycol-urethane prepolymers disclosed in U.S. Patent No. 6,165,408, polyalkylene glycol-tetra(meth)acrylate prepolymers disclosed in U.S. Patent No. 6,221,303, and crosslinkable polyallylamine gluconolactone prepolymers disclosed in U.S. Patent No. 6,472,489, but are not limited thereto.

[0137] A number of non-silicone hydrogel lens formulations have been described in a number of patents and patent applications published prior to the filing date of the present application and are also 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.

[0138] In a preferred embodiment, the inner layer is preferably composed of a non-silicone hydrogel material comprising at least 50 mol% of repeating units of at least one hydroxyl-containing vinyl monomer 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 molar percentage of the repeating units can be calculated based on the non-silicone hydrogel lens formulation for manufacturing the non-silicone hydrogel contact lens.

[0139] In another preferred embodiment, the preformed contact lens is a non-silicone hydrogel contact lens, preferably a silicone hydrogel contact lens with natural wettability.

[0140] 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, for the manufacture of preformed silicone hydrogel (SiHy) contact lenses, SiHy lens formulations for cast molding or spin-cast molding or for the production of SiHy rods used in lathe cutting of contact lenses generally include 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 can then be subjected to extraction with an extraction solvent to remove unreacted components from the resulting lens and to a hydration process, as is well known to those skilled in the art. Further, 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 is well known to those skilled in the art).

[0141] According to the present invention, the silicone-containing vinyl monomer may be any silicone-containing vinyl monomer known to those skilled in the art. Examples of preferred silicone-containing vinyl monomers include vinyl monomers each having a bis(trialkylsilyloxy)alkylsilyl group or a tris(trialkylsilyloxy)silyl group, polysiloxane vinyl monomers, polycarbosiloxane vinyl monomers, 3-methacryloxypropylpentamethyldisiloxane, t-butyldimethyl-siloxyethyl vinyl carbonate, trimethylsilylethyl vinyl carbonate, and trimethylsilylmethyl vinyl carbonate, and combinations thereof, but are not limited thereto.

[0142] 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(trimethylsiloxy)silyl)propyloxy)propyl)-2-methylacrylamide, N-(2-hydroxy-3-(3-(tris(trimethylsiloxy)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-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(trimethylsiloxy)silyl)propyloxy)propyl]-2-methyl(meth)acrylamide, N,N-N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl](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, 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. Patent Nos. 9,097,840, 9,103,965, and 9,475,827, and mixtures thereof, but not limited thereto. The above preferred silicone-containing vinyl monomers can also be obtained from commercial suppliers or prepared according to the procedures described in U.S. Patent Nos. 7,214,809, 8,475,529, 8,658,748, 9,097,840, 9,103,965, and 9,475,827.,

[0143] Examples of preferred polysiloxane vinyl monomers include, but are not limited to, mono-(meth)acryloyl-terminated. Examples of the monoalkyl-terminated polysiloxane 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-hydroxyl-methacryloxypropyloxypropyl)-ω-butyl-decamethylpentasiloxane, α-[3-(meth)acryloxyethoxy-2-hydroxypropyloxypropyl] -terminated ω-butyl (or ω-methyl) -terminated polydimethylsiloxane, α-[3-(meth)acryloxy-propyl-oxy-2-hydroxypropyloxypropyl] -terminated ω-butyl (or ω-methyl) -terminated polydimethylsiloxane, α-[3-(meth)acryloxyisopropyloxy-2-hydroxypropyloxypropyl] -terminated ω-butyl (or ω-methyl) -terminated polydimethylsiloxane, α-[3-(meth)acryloxybutyloxy-2-hydroxypropyloxypropyl] -terminated ω-butyl (or ω-methyl) -terminated polydimethylsiloxane, α-[3-(meth)acryloxyethylamino-2-hydroxypropyloxypropyl] -terminated ω-butyl (or ω-methyl) -terminated polydimethylsiloxane, α-[3-(meth)acryloxypropylamino-2-hydroxypropyloxypropyl] -terminated ω-butyl (or ω-methyl) -terminated polydimethylsiloxane, α-[3-(meth)acryloxy-butylamino-2-hydroxypropyloxypropyl] -terminated ω-butyl (or ω-methyl) -terminated polydimethylsiloxane, α-(meth)acryloxy(polyethyleneoxy)-2-hydroxypropyloxypropyl] -terminated ω-butyl (or ω-methyl) -terminated polydimethylsiloxane, α-[(meth)acryloxy-2-hydroxypropyloxy-ethoxypropyl] -terminated ω-butyl (or ω-methyl) -terminated polydimethylsiloxane, α-[(meth)acryloxy-2-hydroxypropyl-N-ethylaminopropyl] -terminated ω-butyl (or ω-methyl) -terminated polydimethylsiloxane,α-[(Meth)acryloxy-2-hydroxypropyl-aminopropyl]-terminated ω-butyl (or ω-methyl)-terminated polydimethylsiloxane, α-[(Meth)acryloxy-2-hydroxypropyloxy-(polyethyleneoxy)propyl]-terminated ω-butyl (or ω-methyl)-terminated polydimethylsiloxane, α-(Meth)acryloylamidopropyloxypropyl-terminated ω-butyl (or ω-methyl)-terminated polydimethylsiloxane, α-N-methyl-(Meth)acryloylamidopropyloxypropyl-terminated ω-butyl (or ω-methyl)-terminated polydimethylsiloxane, α-[3-(Meth)acrylamidoethoxy-2-hydroxypropyloxy-propyl]-terminated ω-butyl (or ω-methyl) polydimethylsiloxane, α-[3-(Meth)acrylamidopropyloxy-2-hydroxypropyloxypropyl]-terminated ω-butyl (or ω-methyl)-terminated polydimethylsiloxane, α-[3-(Meth)acrylamidoisopropyloxy-2-hydroxypropyloxypropyl]-terminated ω-butyl (or ω-methyl)-terminated polydimethylsiloxane, α-[3-(Meth)acrylamidobutyloxy-2-hydroxypropyloxypropyl]-terminated ω-butyl (or ω-methyl)-terminated polydimethylsiloxane, α-[3-(Meth)acryloylamido-2-hydroxypropyloxypropyl]-terminated ω-butyl (or ω-methyl) polydimethylsiloxane, α-[3-[N-methyl-(Meth)acryloylamido]-2-hydroxypropyloxypropyl]-terminated ω-butyl (or ω-methyl)-terminated polydimethylsiloxane, N-methyl-N'-(propyltetra(dimethylsiloxy)dimethylbutylsilane)(Meth)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. Patent Nos. 9,097,840 and 9,103,965, and mixtures thereof, but not limited thereto. The above preferred polysiloxane vinyl monomers areIt can also be obtained from commercial suppliers (such as Shin-Etsu Chemical Co., Ltd., Gelest, etc.), or by following the procedures described in patents such as U.S. Patent 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 monoepoxypropyl-terminated polydimethylsiloxane, or 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.

[0144] 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.

[0145] 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.

[0146] 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, polysiloxane-containing macromers selected from the group consisting of macromer A, macromer B, macromer C, and macromer D described in U.S. Patent No. 5,760,100, polysiloxane-containing macromers disclosed in U.S. Patent Nos. 4,136,250, 4,153,641, 4,182,822, 4,189,546, 4,343,927, 4,254,248, 4,355,147, 4,276,402, 4,327,203, 4,341,889, 4,486,577, 4,543,398, 4,605,712, 4,661,575, 4,684,538, 4,703,097, 4,833,218, 4,837,289, 4,954,586, 4,954,587, 5,010,141, 5,034,461, 5,070,170, 5,079,319, 5,039,761, 5,346,946, 5,358,995, 5,387,632, 5,416,132, 5,451,617, 5,486,579, 5,962,548, 5,981,675, 6,039,913, 6,762,264, and polysiloxane-containing macromers disclosed in U.S. Patent Nos. 4,259,467, 4,260,725, and 4,261,875.

[0147] Examples of preferred di-(meth)acryloyloxy-terminated polysiloxane vinyl crosslinkers include the reaction product of glycidyl methacrylate and di-amino-terminated polydimethylsiloxane, the reaction product of glycidyl methacrylate and di-hydroxy-terminated polydimethylsiloxane, the reaction product of isocyantoethyl (meth)acrylate and di-hydroxy-terminated polydimethylsiloxane, and those disclosed in U.S. Patent No. 10081697, each having one methyl substituent and one monovalent C having 2 to 6 hydroxyl groups 4 ~C 40Di-(meth)acryloyloxy-terminated polysiloxane vinyl crosslinkers each having a hydrophilic siloxane unit having an organic radical substituent, the chain-extension polysiloxabe vinyl crosslinkers disclosed in U.S. Patent Application Publication Nos. 201008843A1 and 20120088844A1, the chain-extension polysiloxane vinyl crosslinkers described in U.S. Patent Nos. 5034461, 5416132, 5449729, 5760100, 7423074, and 8529057, the chain-extension polysiloxane vinyl crosslinkers described in U.S. Patent Application Publication No. 2018-0100053, the chain-extension polysiloxane vinyl crosslinkers described in U.S. Patent Application Publication No. 2018-0100038, the chain-extension polysiloxane vinyl crosslinkers described in U.S. Patent No. 8993651, α,ω-bis[3-(meth)acrylamidepropyl] -terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxypropyl] -terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxy-2-hydroxypropyl-oxypropyl] -terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxyethoxy-2-hydroxypropyl-oxypropyl] -terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxypropyl-oxy-2-hydroxypropyl-oxypropyl] -terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxy-isopropyl-oxy-2-hydroxypropyl-oxypropyl] -terminated polydimethylsiloxane, α,ω-bis[3-(meth)acryloxybutyl-oxy-2-hydroxypropyl-oxypropyl] -terminated polydimethylsiloxane, α,ω-bis[3-(meth)acrylamideethoxy-2-hydroxypropyl-oxypropyl] -terminated polydimethylsiloxane, α,ω-bis[3-(meth)acrylamidepropyl-oxy-2-hydroxypropyl-oxypropyl] -terminated polydimethylsiloxane, α,ω-bis[3-(meth)acrylamideisopropyl-oxy-2-hydroxypropyl-oxypropyl] -terminated polydimethylsiloxane, α,ω-Bis[3-(meth)acrylamidobutyloxy-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)acryloxybutylamino-2-hydroxypropyloxypropyl] terminated polydimethylsiloxane, α,ω-bis[(meth)acrylamidoethylamino-2-hydroxypropyl-oxy-propyl] terminated polydimethylsiloxane, α,ω-bis[3-(meth)acrylamidopropylamino-2-hydroxypropyloxypropyl] terminated polydimethylsiloxane, α,ω-bis[3-(meth)acrylamido-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-amino-propyl] polydimethylsiloxane, α,ω-bis[(meth)acryloxy-2-hydroxypropyloxy-(polyethyleneoxy)propyl] terminated polydimethylsiloxane, α,ω-bis[(meth)acryloxyethylamino-carbonyl-oxy-ethoxypropyl] terminated polydimethylsiloxane, α,ω-bis[(meth)acryloxyethylamino-carbonyl-oxy-(polyethyleneoxy)propyl] terminated polydimethylsiloxane are exemplified but not limited thereto.,

[0148] 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.,

[0149] 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 bonded to the pyrrolidone ring at the 3- or 5-position, respectively) (described below), C 1 ~C 4 acrylic monomers having an alkoxyethoxy group (described below), vinyl ether monomers (described below), allyl ether monomers (described below), vinyl monomers containing phosphorylcholine (described below), N-2-hydroxyethyl vinyl carbamate, N-carboxyvinyl-β-alanine (VINAL), N-carboxyvinyl-α-alanine, and combinations thereof.

[0150] 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.

[0151] Examples of hydroxyl-containing acrylic monomers include, but are not limited to, N-2-hydroxyethyl (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.

[0152] 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.

[0153] Examples of carboxyl-containing acrylic monomers include, but are not limited to, 2-(meth)acrylamidoglycolic acid, (meth)acrylic acid, ethylacrylic acid, and combinations thereof.

[0154] Examples of preferred N-vinylamide monomers include, but are not limited to, 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-3,5-dimethyl-2-piperidone, N-vinyl-4,4-dimethyl-2-piperidone, N-vinylcaprolactam (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-vinylamide monomer is N-vinylpyrrolidone, N-vinyl-N-methylacetamide, or a combination thereof.

[0155] Preferred methylene-containing (=CH 2)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.

[0156] C 1 ~C 4 Examples 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 having a weight average molecular weight of up to 1500 1 ~C 4 alkoxypoly(ethylene glycol) (meth)acrylate, methoxy-poly(ethylene glycol) ethyl (meth)acrylamide having a number average molecular weight of up to 1500, and combinations thereof, but are not limited thereto.

[0157] 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.

[0158] 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.

[0159] 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, but not limited thereto.

[0160] According to the present invention, any hydrophobic vinyl monomer may be present in the present invention. Examples of preferred hydrophobic vinyl monomers 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, vinyltoluene, vinyl ethyl ether, perfluorohexylethyl-thio-carbonyl-aminoethyl-methacrylate, isobornyl (meth)acrylate, trifluoroethyl (meth)acrylate, hexafluoro-isopropyl (meth)acrylate, hexafluorobutyl (meth)acrylate, and combinations thereof.

[0161] According to the present invention, any non-silicone vinyl crosslinker may be present in the present invention. Examples of preferred non-silicone vinyl crosslinking agents 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, 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'-methylenebis(meth)acrylamide, N,N'-ethylenebis(meth)acrylamide, N,N'-dihydroxyethylenebis(meth)acrylamide, N,N'-propylenebis(meth)acrylamide, N,N'-2-hydroxypropylenebis(meth)acrylamide, N,N'-2,3-dihydroxybutylenebis(meth)acrylamide, 1,3-bis(meth)acrylamidepropane-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, but are not limited thereto.Preferred non-silicone vinyl crosslinking agents 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.

[0162] 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 nitrile), persulfates, percarbonates, or mixtures thereof.Examples of preferred thermal polymerization initiators include, but are not limited to, 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(methyl isobutyrate), 4,4'-azobis(4-cyanovaleric acid), and combinations thereof.Preferably, the thermal initiator is 2,2'-azobis(isobutyronitrile) (AIBN or VAZO 64).

[0163] Suitable photoinitiators include benzoin methyl ether, diethoxyacetophenone, benzoylphosphine oxide, 1-hydroxycyclohexyl phenyl ketone, and Darocur and Irgacur types, preferably Darocur 1173 (registered trademark) and Darocur 2959 (registered trademark), germanium-based Norrish type I photoinitiators (such as those described in U.S. Patent No. 7,605,190). Examples of benzoylphosphine initiators include 2,4,6-trimethylbenzoyldiphenylphosphine oxide, bis-(2,6-dichlorobenzoyl)-4-N-propylphenylphosphine oxide, and bis-(2,6-dichlorobenzoyl)-4-N-butylphenylphosphine oxide. Reactive photoinitiators that can be incorporated into macromers or used as special monomers are also suitable. Examples of reactive photoinitiators are disclosed in European Patent No. 632,329.

[0164] Any silicon-containing prepolymer containing a hydrophilic segment and a hydrophobic segment can be used in the present invention. Examples of such silicone-containing prepolymers include those described in U.S. Patent Nos. 6,039,913, 7,091,283, 7,268,189, 7,238,750, 7,521,519, 8,383,744, and 8,642,712, and U.S. Patent Application Publication Nos. 2008 / 0015315A1, 2008 / 0143958A1, 2008 / 0143003A1, 2008 / 0234457A1, and 2008 / 0231798A1.

[0165] The SiHy contact lens formulation may further contain other essential components 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, polymerizable dyes, pigments, or mixtures thereof well-known to those skilled in the art), antibacterial agents (e.g., preferably silver nanoparticles), bioactive agents, leachable lubricants, leachable tear stabilizers, and mixtures thereof.

[0166] According to a preferred embodiment of the present invention, the preformed silicone hydrogel contact lens of the present invention may further contain repeating units of one or more UV-absorbing vinyl monomers and optionally (but preferably) one or more UV / HEVL-absorbing vinyl monomers (however, it is preferred to include these). The term "UV / HEVL-absorbing vinyl monomer" refers to a vinyl monomer capable of absorbing UV light and high-energy visible light (i.e., light having a wavelength of 380 nm to 440 nm).

[0167] Any suitable UV-absorbing vinyl monomer and UV / HEVL-absorbing vinyl monomer may be used in the polymerizable composition to prepare the preformed SiHy contact lens 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-tert octylphenyl)benzotriazole, 2-(2'-hydroxy-5'-methacrylamidophenyl)-5-chlorobenzotriazole, 2-(2'-hydroxy-5'-methacrylamidophenyl)-5-methoxybenzotriazole, 2-(2'-hydroxy-5'-methacryloxypropyl-3'-t-butyl-phenyl)-5-chlorobenzotriazole, 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-methoxybenzotriazole (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), 3-[3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl]-propyl 2-methylacrylate (16-100, CAS#96478-15-8), 2-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2H-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-benzotriazol, phenol, 2-(5-ethenyl-2H-benzotriazol-2-yl)-4-methyl-, homopolymer (9CI) (CAS#83063-87-0), among others, are included but not limited to these. According to the present invention, the polymerizable composition contains one or more UV-absorbing vinyl monomers in an amount of about 0.1% by weight to about 3.0% by weight, preferably about 0.2% by weight to about 2.5% by weight, more preferably about 0.3% by weight to about 2.0% by weight, in relation to the amount of all polymerizable components in the polymerizable composition.,

[0168] When vinyl monomers capable of absorbing ultraviolet and high-energy visible light (HEVL) are used in the present invention, germanium-based Norrish type I photoinitiators and a light source containing light in the region 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 free radical polymerization can be initiated under irradiation using a light source containing light in the region of about 400 to about 550 nm. Examples of germanium-based Norrish type I photoinitiators are acylgermanium compounds described in U.S. Patent No. 7605190.

[0169] 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.).

[0170] 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. n is preferably 5,000 to 1,000,000.

[0171] Examples of leachable 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 a mixture thereof.

[0172] The polymerizable composition (SiHy lens formulation) may be a solventless transparent liquid prepared by mixing all the polymerizable components and other essential components, or all the desired components may be dissolved in any suitable solvent such as a mixture of water and one or more water-miscible organic solvents, an organic solvent, or a mixture of one or more organic solvents, which are known to those skilled in the art. The term "solvent" refers to a chemical substance that cannot participate in a free radical polymerization reaction.

[0173] The solventless lens SiHy lens formulation typically includes at least one blend vinyl monomer as a reactive solvent to dissolve all the other polymerizable components of the solventless SiHy lens formulation. Examples of preferred blend vinyl monomers include C 1 ~C 10Alkyl (meth)acrylate (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 a combination thereof. Preferably, methyl methacrylate is used as the blend vinyl monomer in the preparation of the solvent-free SiHy lens formulation.

[0174] 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, propylene 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 exo-norborneol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, tert-butanol, tert-amyl alcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol, 2,2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol, 1-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, including but not limited to these.,

[0175] A number of SiHy lens formulations have been described in a number of patents and patent applications published prior to the filing date of this application and are used in the manufacture of 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.

[0176] SiHy lens formulations (i.e., polymerizable compositions) can preferably be cured (polymerized) thermally or by actinic radiation in a mold for cast molding of contact lenses, as is well known to those skilled in the art.

[0177] 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 a wide range, but conveniently is, for example, 1 to 24 hours, or preferably 2 to 12 hours. It is advantageous to degas the components and solvents used in the polymerization reaction in advance and to carry out the copolymerization reaction under an inert atmosphere, for example, a nitrogen or argon atmosphere.

[0178] Subsequently, actinic polymerization may be triggered by actinic radiation, such as light, especially UV light or visible light of a suitable wavelength. The spectral requirements can be controlled, if appropriate, by the addition of a suitable sensitizer.

[0179] In a preferred embodiment, the inner layer or lens bulk material consists of a silicone hydrogel material comprising repeating units of at least one polysiloxane vinyl monomer (preferably selected from those described above) and repeating units of at least one hydrophilic vinyl monomer (preferably selected from those described above).

[0180] In a preferred embodiment, the inner layer or lens bulk material is made of a silicone hydrogel material comprising repeating units of at least one polysiloxane vinyl crosslinker (preferably selected from those described above) and repeating units of at least one hydrophilic vinyl monomer (preferably selected from those described above).

[0181] In a preferred embodiment, the inner layer or lens bulk material is made of a silicone hydrogel material comprising repeating units of at least one polysiloxane vinyl monomer (preferably selected from those described above) and repeating units of at least one hydrophilic N-vinylamide monomer (preferably selected from those described above).

[0182] In a preferred embodiment, the inner layer or lens bulk material is made of a silicone hydrogel material comprising repeating units of at least one polysiloxane vinyl crosslinker (preferably selected from those described above) and repeating units of at least one hydrophilic N-vinylamide monomer (preferably selected from those described above).

[0183] In a preferred embodiment, the inner layer or lens bulk material is made of a silicone hydrogel material comprising repeating units of at least one polycarbosiloxane vinyl monomer (preferably selected from those described above) and repeating units of at least one hydrophilic vinyl monomer (preferably selected from those described above).

[0184] In a preferred embodiment, the inner layer or lens bulk material is made of a silicone hydrogel material comprising repeating units of at least one polycarbosiloxane vinyl crosslinker (preferably selected from those described above) and repeating units of at least one hydrophilic vinyl monomer (preferably selected from those described above).

[0185] In a preferred embodiment, the inner layer or the lens bulk material is made of a silicone hydrogel material comprising repeating units of at least one polycarbosiloxane vinyl monomer (preferably selected from those described above) and repeating units of at least one hydrophilic N-vinylamide monomer (preferably selected from those described above).

[0186] In a preferred embodiment, the inner layer or the lens bulk material is made of a silicone hydrogel material comprising repeating units of at least one polycarbosiloxane vinyl crosslinker (preferably selected from those described above) and repeating units of at least one hydrophilic N-vinylamide monomer (preferably selected from those described above).

[0187] In a preferred embodiment, the inner layer or the lens bulk material is made of a silicone hydrogel material comprising repeating 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 repeating units of at least one hydrophilic vinyl monomer (preferably selected from those described above).

[0188] In a preferred embodiment, the inner layer or the lens bulk material is made of a silicone hydrogel material comprising repeating units of at least one polycarbosiloxane vinyl crosslinker (preferably selected from those described above), repeating 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 repeating units of at least one hydrophilic vinyl monomer (preferably selected from those described above).

[0189] In a preferred embodiment, the inner layer or the lens bulk material is composed of a silicone hydrogel material comprising repeating 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 repeating units of at least one hydrophilic N-vinylamide monomer (preferably selected from those described above).

[0190] In a preferred embodiment, the inner layer or the lens bulk material is composed of a silicone hydrogel material comprising repeating units of at least one polycarbosiloxane vinyl crosslinker (preferably selected from those described above), repeating 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 repeating units of at least one hydrophilic N-vinylamide monomer (preferably selected from those described above).

[0191] According to any one of the preferred embodiments of the present invention, the inner layer or the lens bulk material is composed of a silicone hydrogel material further comprising repeating units of one or more blend vinyl monomers in an amount preferably 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 the silicone hydrogel material. The amount of the repeating units of the blend vinyl monomers can be calculated based on the amount of the blend vinyl monomers in the polymerizable composition used for the preparation of the preformed silicone hydrogel contact lens (i.e., the inner layer) relative to the total amount of all polymerizable components in the polymerizable composition.

[0192] According to any one of the preferred embodiments of the present invention, the inner layer or lens bulk material is preferably in an amount of about 1.0% by weight or less (preferably about 0.8% by weight or less, more preferably about 0.05% to about 0.6% by weight) based on the dry weight of the inner layer, and is composed of a silicone hydrogel material further containing repeating units of one or more non-silicone vinyl crosslinking agents (preferably selected from those described above). The amount of the repeating units of the non-silicone vinyl crosslinking agent can be calculated based on the amount of the non-silicone vinyl crosslinking agent in the polymerizable composition used for the preparation of the preformed silicone hydrogel contact lens (i.e., the inner layer) with respect to the total amount of all polymerizable components of the polymerizable composition.

[0193] According to any one of the preferred embodiments of the present invention, the inner layer or the 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 any post-curing surface treatment). Naturally wettable preformed SiHy contact lenses are disclosed in U.S. Pat. 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; 7,750,079; 7,934,830; 8,231,218; 8,367,746; 8,445,614; 8,481,662; 8,487,058; 8,513,325; 8,703,891; 8,820,928; 8,865,789; 8,937,110; 8,937,111; 9,057,821; 9,057,822; 9,121,998; 9,125,808; 9,140,825; 9,140,908; 9,156,934; 9,164,298; 9,170,349; 9,188,702; 9,217,813; 9,296,159; 9,322,959; 9,322,960; 9,360,594; and 9,529,119, as well as U.S. Provisional Patent Application Nos. 16 / 000,930 and 16 / 000,933.

[0194] According to the present invention, the silicone hydrogel material of the inner layer (or 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 barrer, and most preferably at least about 110 barrer. The silicone hydrogel material can also have an equilibrium water content of about 10 wt% to about 70 wt%, preferably about 10 wt% to about 65 wt%, more preferably about 10 wt% to about 60 wt%, even more preferably about 15 wt% to about 55 wt%, and most preferably about 15 wt% to about 50 wt%. The silicone hydrogel material can 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, more preferably about 0.5 MPa to about 1.2 MPa (hereinafter, the terms "flexibility", "modulus", and "Young's modulus" are used interchangeably in this application to mean the bulk modulus when the term is not modified by the word "surface"). The oxygen permeability, 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, modulus, and water content of the preformed SiHy lens from which the inner layer is derived. Since the outer hydrogel layer is much thinner, it should be understood that, as a reasonable approximation, the modulus of the SiHy contact lens of the present invention can be regarded as the modulus of the silicone hydrogel material of the inner layer. Those skilled in the art are familiar with the methods for determining the modulus and water content of silicone hydrogel materials or SiHy contact lenses. For example, all commercially available SiHy contact lenses have reported values of oxygen permeability, modulus, and water content.

[0195] According to various aspects of the present invention, in order to ensure the biocompatibility of the contact lens, to provide sufficient wearing comfort, and to prevent the underlying lens bulk material from being exposed to the eye, the thicknesses of the outer surface hydrogel layer, the front outer surface hydrogel layer, and the rear outer surface hydrogel layer vary according to the inner layer or the lens bulk material of the contact lens of the present invention.

[0196] When the inner layer or lens bulk material is a rigid plastic material (preformed hard contact lens) or a rigid gas permeable lens material (i.e., preformed rigid gas permeable 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 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.

[0197] When the inner layer or lens bulk material is a crosslinked silicone material (i.e., 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.

[0198] When the inner layer or lens bulk material is a crosslinked non-silicone hydrogel material (i.e., preformed non-silicone hydrogel 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 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.

[0199] When the inner layer or lens bulk material is a silicone hydrogel material that is not naturally wettable (i.e., preformed silicone hydrogel 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 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.

[0200] When the inner layer or the 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 front outer surface hydrogel layer, and the rear 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.

[0201] The front and rear external hydrogel layers of the contact lens of the present invention are preferably substantially identical to each other (i.e., become the outer surface hydrogel layer), and are crosslinked coating applied on the preformed contact lens.

[0202] In a preferred embodiment, the front and rear external hydrogel layers independent of each other, and the outer surface hydrogel layer, contain at least 25 mol% (preferably at least 35 mol%, more preferably at least 45 mol%, even more preferably at least 55 mol%) of 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., a pyrrolidone derivative having a methylene group bonded to the pyrrolidone ring at the 3- or 5-position respectively) (any one of the above), C 1 ~C 4(Meth)acrylate monomer having an alkoxyethoxy group (any one of the above), vinyl ether monomer (any one of the above), allyl ether monomer (any one of the above), and a combination thereof selected from the group consisting of (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)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 1500 1 ~C 4-Alkoxypolyethylene 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(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, 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, even more preferably, (meth)acrylamide, dimethyl(meth)acrylamide, N-2-hydroxyethyl(meth)acrylamide, N,N-bis(hydroxyethyl)(meth)acrylamide, N-2,A crosslinked polymer material comprising repeating monomer units of at least one hydrophilic vinyl monomer selected from the group consisting of 3-dihydroxypropyl (meth)acrylamide, 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.,

[0203] In a preferred embodiment, the front and rear external hydrogel layers independent of each other, and the outer surface hydrogel layer are crosslinked polymer materials, and at least 25 mol% (preferably at least 35 mol%, more preferably at least 45 mol%, even more preferably at least 55 mol%) of, 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, and combinations thereof, and are provided with repeating monomer units of at least one phosphrylcholine-containing vinyl monomer selected from the group consisting of.,

[0204] In a preferred embodiment, the front and rear external hydrogel layers independent of each other, and the outer surface hydrogel layer are crosslinked polymer materials containing poly(ethylene glycol) chains. The poly(ethylene glycol) chains preferably have (1)-NH 2Pol(ethylene glycol) having a single unique functional group of -SH or -COOH, (2) -NH 2 Pol(ethylene glycol) having two terminal functional groups selected from the group consisting of -COOH, -SH, and combinations thereof, (3) -NH 2 Multi-arm poly(ethylene glycol) having one or more functional groups selected from the group consisting of -COOH, -SH, and combinations thereof, and (4) is directly derived from combinations thereof.

[0205] According to a preferred embodiment, the front and rear outer hydrogel layers of the contact lens of the present invention are identical to each other, have a substantially uniform thickness, integrate at the edge of the contact lens to completely cover the inner layer, 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.

[0206] According to a preferred embodiment, the outer surface hydrogel layer of the contact lens of the present invention has 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.

[0207] According to the present invention, each of the front and rear outer hydrogel layers is substantially free of silicone, preferably free of silicone altogether. However, when demonstrating the presence or absence of silicon in the outer hydrogel layer using X-ray photoelectron spectroscopy (XPS) (generally a probing depth of 1.5 to 6 nm), for example, a polyethylene sheet from Goodfellow (1.3 ± 0.2%), DAILIES® AquaComfortPlus™ contact lenses from Alcon (1.7 ± 0.9%), or ACUVUE® Moist from Johnson & Johnson (2.8 ± 0.9%), it is well known that samples are inevitably contaminated by silicon in the environment, as shown by silicon being detected by XPS on the surface of samples that theoretically contain no silicon atoms at all. Therefore, the term "substantially free of silicone" is used in the present application to mean that the silicon atom concentration on the surface of the SiHy contact lens measured by XPS is less than about 200%, preferably less than about 175%, more preferably less than about 150%, still more preferably less than about 125% of the silicon atom concentration of a control sample known to be inherently (theoretically) free of silicon (e.g., a polyethylene sheet, DAILIES® AquaComfortPlus™ contact lenses from Alcon, or ACUVUE® Moist from Johnson & Johnson). Alternatively, each outer hydrogel layer of the SiHy contact lens of the present invention is characterized as being substantially free of silicone by having a silicon atom concentration of about 5% or less, preferably about 4% or less, still more preferably about 3% or less of the total elemental percentage as measured by XPS analysis of the dry contact lens. Optionally (although not preferred), it will be understood that a small proportion of silicone may be incorporated into the polymer network of the outer hydrogel layer as long as it does not significantly degrade the surface properties (hydrophilicity, wettability, and / or lubricity) of the contact lens.

[0208] In a preferred embodiment, each of the front and rear external hydrogel layers (crosslinked coatings) is characterized by having no surface crack lines visible to the eye under dark field after rubbing the contact lens between the fingers, so as to have high finger-rub resistance. Surface cracks caused by finger rubbing may reduce surface lubricity and / or may not be able to prevent silicone from moving (exposing) on the surface. Surface cracks also indicate the presence of excessive crosslinking density in the surface layer, which can affect the surface elastic modulus. Preferably, the non-silicone hydrogel material in the external hydrogel layer (crosslinked coating) contains crosslinks derived from azetidinium groups during the thermally induced coupling reaction.

[0209] In another preferred embodiment, the contact lens of the present invention further includes two transition layers made of a polymer material in its layered structure form. Each of the two transition layers is located between the inner layer and one of the front and rear external hydrogel layers. Each transition layer has a substantially uniform thickness. The thickness of each transition layer is at least about 0.05 μm, preferably about 0.05 μm to about 10 μm, more preferably about 0.1 μm to about 7.5 μm, and even more preferably about 0.15 μm to about 5 μm. The transition layers are integrated at the peripheral edge of the contact lens and completely surround the inner layer of the lens material.

[0210] As is well known to those skilled in the art, the layered structure form of the contact lens of the present invention can be verified by analyzing the cross-section of the contact lens in a fully hydrated state (i.e., directly in water or buffered physiological saline) by atomic force microscopy (AFM). As is well known to those skilled in the art, the average thickness of each external hydrogel layer can be determined from the AFM image.

[0211] The two transition layers of the contact lens of the present invention are essentially a base (or primer or anchor) coating (or layer) that is 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 fix / adhere the outer hydrogel layer. Preferably, the transition layer comprises a carboxyl (COOH)-containing polymer crosslinked by polyaziridine, preferably acrylic acid or methacrylic acid or C 2 ~C 12 a homo- or copolymer of alkylacrylic acid. It will be understood that the carboxyl-containing polymer can penetrate into the bulk material and extend into the outer hydrogel layer. When such penetration occurs in the inner layer of the lens material, each transition layer will comprise an intertwined carboxyl-containing polymer and the lens material.

[0212] In another preferred embodiment, each of the front and rear outer hydrogel layers, independent of each other, has a reduced surface elastic modulus of at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, and most preferably at least about 40% with respect to the inner layer.

[0213] To visualize any change in the surface elastic modulus from the rear surface side to the front surface side across the entire cross-section, the surface elastic modulus of the cross-section can be characterized (imaged) by AFM (for example, according to the nanoindentation method). A significant change (for example, about 30% or more) observed in the surface elastic modulus over a thickness of about 0.02 μm, preferably about 0.01 μm, along the shortest line between the front surface and the rear surface across the cross-section of the fully hydrated contact lens (by examining the AFM image) indicates a transition from one layer to another.

[0214] In any one of the preferred embodiments described above for various aspects of the present invention, the contact lens of the present invention has a friction score 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 test.

[0215] In any one of the preferred embodiments described above for various aspects of the present invention, the contact lens of the present invention has 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) at 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) at 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% at 380 nm to 440 nm.

[0216] The contact lens of the present invention can be obtained or developed by any method known to those skilled in the art.

[0217] For example, the contact lens of the present invention can be obtained by neutralizing a preformed hydrogel 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.

[0218] The preformed hydrogradient contact lens can be obtained by heating a contact lens precursor comprising an anchor layer (or base coating) of a polyanionic polymer having reactive functional groups (such as carboxyl groups) in an aqueous solution containing a thermally crosslinkable hydrophilic polymer material, in the same manner as the procedures described in U.S. Patent Nos. 8,480,227, 8,529,057, and 9,505,184, and U.S. Patent Application Publication Nos. 2017 / 0068018A1, 2017 / 0068019A1, 2017 / 0165932A1, 2018 / 0079157A1, 2018 / 0079158A1, 2018 / 0081197A1, 2018 / 0113236A1, and 2018 / 0120590A1.

[0219] The contact lens precursor having an anchor layer thereon can be obtained by contacting the 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.

[0220] Contacting the preformed contact lens with the polymer coating solution can be accomplished by dipping it into the coating solution or by spraying the coating solution onto it. One contacting process simply involves dipping the contact lens into a bath of the coating solution for a certain period of time, or, alternatively, involves dipping the contact lens sequentially into a series of baths of the coating solution, each bath for a predetermined shorter period of time. Another contacting process simply involves spraying the coating solution. However, numerous alternative methods can involve various combinations of spraying and dipping steps that can be devised by those skilled in the art.

[0221] Any polyanionic polymer can be used to form an anchor layer on a preformed contact lens as long as it contains at least 60 mol% of repeating units of one or more carboxyl-containing acrylic monomers (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 a combination thereof.

[0222] 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 n is at least about 25,000 Daltons, preferably at least about 50,000 Daltons, more preferably from about 100,000 Daltons to about 5,000,000 Daltons.

[0223] A solution of a polyanionic polymer for forming an anchor layer (or base coating) on a preformed contact lens with or without a plasma coating can be prepared by dissolving one or more polyanionic polymers in water, a mixture of water and one or more water-miscible organic solvents, an organic solvent, or a mixture of one or more organic solvents. Preferably, the 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. A solvent system containing at least one organic solvent can swell the preformed contact lens, and as a result, a portion of the polyanionic polymer can penetrate into the preformed contact lens, which is considered to be able to increase the durability and thickness of the anchor layer (base coating). Any of the above organic solvents can be used in the preparation of the polyanionic polymer solution as long as it can dissolve the polyanionic polymer.

[0224] The concentration of the polyanionic polymer is about 0.001 wt% to about 2.5 wt%, preferably about 0.002 wt% to about 1.5 wt%, more preferably 0.003 wt% to about 0.75 wt% based on the total weight of the organic-based solution.

[0225] As is 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 between the preformed contact lens and the polyanionic polymer solution, the solvent system (e.g., the amount of one or more organic solvents), or a combination thereof.

[0226] Alternatively, a 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 a 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 (RAFT) initiator) and a functional group co-reactive with the functional groups 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 a free radical initiator moiety thereon is immersed in a solution of one or more carboxyl-containing vinyl monomers (preferably the above carboxyl-containing acrylic monomers) and subjected to conditions for initiating the free radical polymerization of these carboxyl-containing vinyl monomers to form a layer of a graft-from polyanionic polymer of the carboxyl-containing vinyl monomers.

[0227] According to the present invention, the thermally crosslinkable hydrophilic polymer material for forming an outer surface hydrogel layer or front and rear external hydrogel layers (i.e., a crosslinked hydrophilic coating) contains crosslinkable groups, preferably thermally crosslinkable groups (e.g., epoxy groups, azetidinium groups, or combinations thereof), more preferably azetidinium groups. Preferably, the water-soluble and crosslinkable hydrophilic polymer material is a partially crosslinked polymer material containing a three-dimensional network and thermally crosslinkable groups, preferably azetidinium groups, within or bonded to the network. The term "partially crosslinked" related to the polymer material means that the crosslinkable groups of the starting material for manufacturing the polymer material during the crosslinking reaction are not completely consumed. For example, such a thermally crosslinkable hydrophilic polymer material contains azetidinium groups and is a partial reaction product of at least one azetidinium-containing polymer based on the crosslinking reaction shown in Scheme I and at least one hydrophilic enhancer (i.e., wetting agent) having at least one carboxyl, primary amine, secondary amine, or thiol group, [Chemical formula] wherein X 1 is -S-*, -OC(=O)-*, or -NR'-*, wherein R' is hydrogen or an unsubstituted or substituted alkyl group of C 1 ~C 20 and * represents an organic radical.

[0228] 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 and one or more vinyl monomers.

[0229] 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 react with epichlorohydrin to form an epichlorohydrin-functionalized polymer. A homopolymer or copolymer of mono-alkylaminoalkyl (meth)acrylate or mono-alkylaminoalkyl (meth)acrylamide can also react with epichlorohydrin to form an epichlorohydrin-functionalized polyamine. A poly(2-oxazoline-co-ethyleneimine copolymer) can react with epichlorohydrin to form an epichlorohydrin-functionalized polyamine (i.e., poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin). The reaction conditions for the epichlorohydrin functionalization of polyamine or polyamidoamine polymers are taught in European Patent No. 1465931. Preferred epichlorohydrin-functionalized polyamines are polyamidoamine-epichlorohydrin (PAE) or poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin.

[0230] Polyamidoamine-epichlorohydrin is commercially available, for example, as Kymene® or Polycup® resin from Hercules (epichlorohydrin-functionalized adipic acid-diethylenetriamine copolymer).

[0231] Poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin can be prepared according to the procedure described in U.S. Patent Application Publication No. 2016 / 0061995A1.

[0232] Homopolymers and copolymers of azetidinium-containing vinyl monomers can be obtained according to the procedures described in U.S. Patent Application Publication No. 2013 / 0337160A1.

[0233] Any suitable hydrophilic enhancer can be used in the present invention as 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.

[0234] Preferred classifications of hydrophilic 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, glucosaminic acid, mannosamine, sugar acid 1,4-lactone, saccharic acid, ketodeoxynonulosonic acid, N-methyl-D-glucamine, 1-amino-1-deoxy-β-D-galactose, 1-amino-1-deoxysorbitol, 1-methylamino-1-deoxysorbitol, N-aminoethylgluconamide), 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, but are not limited thereto.

[0235] Another preferred classification of the hydrophilic enhancer is a hydrophilic polymer 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 the 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.

[0236] One preferred class of hydrophilic polymers as hydrophilic enhancers is, for example, carboxymethyl cellulose (repeating unit -[C 6 H 10-m O 5 (CH 2 CO 2 H) m - (having a carboxyl content of about 40% or less estimated based on a composition of (where m is from 1 to 3)), carboxyethyl cellulose (repeating unit -[C 6 H 10-m O 5 (C 2 H 4 CO 2 H) m - (having a carboxyl content of about 36% or less estimated based on a composition of (where m is from 1 to 3)), carboxypropyl cellulose (repeating unit -[C 6 H 10-m O 5 (C 3 H 6 CO 2 H) m - (having a carboxyl content of about 32% or less estimated based on a composition of (where m is from 1 to 3)), hyaluronic acid (repeating unit -(C 13 H 20 O 9 NCO 2 H)-) having a carboxyl content of about 11% estimated based on a composition of), chondroitin sulfate (repeating unit -(C 12 H 18 O 13 NS CO 2)(having a carboxyl content of about 9.8% estimated based on the composition of H)-), or (primary or secondary) aminos such as combinations thereof, or carboxyl-containing polysaccharides).

[0237] Another preferred classification of hydrophilic polymers as hydrophilic enhancers includes poly(ethylene glycol) (PEG) having a mono-amino (primary or secondary amino), carboxyl, or thiol group (e.g., PEG-NH 2 , PEG-SH, PEG-COOH), H 2 N-PEG-NH 2 , HOOC-PEG-COOH, HS-PEG-SH, H 2 N-PEG-COOH, HOOC-PEG-SH, H 2 N-PEG-SH, multi-arm PEG having one or more amino (primary or secondary), carboxyl, or thiol groups, PEG dendrimer having one or more amino (primary or secondary), carboxyl, or thiol groups, diamino (primary or secondary) or dicarboxyl terminal homo- or copolymers of non-reactive hydrophilic vinyl monomers, monoamino (primary or secondary) or monocarboxyl terminal homo- or copolymers of non-reactive hydrophilic vinyl monomers, (1) one or more reactive vinyl monomers of about 60% by weight or less, preferably about 0.1% to about 30% by weight, more preferably about 0.5% to about 20% by weight, even more preferably about 1% to about 15% by weight, and (2) a copolymer which is a polymerization product of a composition containing at least one non-reactive hydrophilic vinyl monomer, and combinations thereof are included but not limited thereto.

[0238] 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.

[0239] 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.

[0240] 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.

[0241] According to the present invention, the non-reactive vinyl monomer is a vinyl monomer that does not contain any carboxyl groups, primary amino groups, secondary amino groups, epoxide groups, isocyanate groups, azlactone groups, or aziridine groups. 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 those described above can be used herein), a phosphorylcholine-containing vinyl monomer (any of those described above can be used herein), or a combination thereof.

[0242] More preferably, the hydrophilic polymer as a hydrophilic enhancer is -NH 2 , -SH, or poly(ethylene glycol) having only one functional group of -COOH, -NH 2Poly(ethylene glycol) having two terminal functional groups selected from the group consisting of -COOH, -SH, and combinations thereof, -NH 2 Multi-arm poly(ethylene glycol) having one or more functional groups selected from the group consisting of -COOH, -SH, and combinations thereof, Monoamide, monocarboxyl, diamino, or dicarboxyl terminal homo- or copolymers of non-reactive hydrophilic vinyl monomers, (1) About 0.1 wt% to about 30 wt%, preferably about 0.5 wt% to about 20 wt%, more preferably about 1 wt% to about 15 wt% of 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-methylaminopropyl (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 combinations thereof, and (2) acrylamide, 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 ~C 4 -alkoxypolyethylene glycol (meth)acrylate, vinyl alcohol, and a copolymer that is a polymerization product of a composition containing at least one non-reactive hydrophilic vinyl monomer selected from the group consisting thereof, Here, the non-reactive hydrophilic vinyl monomer is 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., a pyrrolidone derivative having a methylene group bonded to the pyrrolidone ring at the 3- or 5-position) (any one of the above), C 1 ~C 4An 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 1500 1 ~C 4Selected from the group consisting of -alkoxypolyethylene 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)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), 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, 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 more preferably, (meth)acryloyloxyethyl phosphorylcholine, (meth)acryloyloxypropyl phosphorylcholine, 2-[(meth)acryloylamino]ethyl-2'-(trimethylammonio)ethyl phosphate, 3-[(meth)acryloylamino]propyl-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, 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.,

[0243] PEGs with functional groups and multi-arm PEGs with functional groups can be obtained from various commercial suppliers, such as Creative PEGWorks, Polyscience, and Shearwater Polymers.

[0244] Monoamino-, monocarboxy-, diamino-, or dicarboxy-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. Patent No. 6,218,508. For example, to prepare a diamino- or dicarboxy-terminated homo- or copolymer of a non-reactive hydrophilic vinyl monomer, a non-reactive vinyl monomer, a chain transfer agent having an amino group or a carboxyl group (e.g., 2-aminoethanethiol, mercaptopropinic acid, thioglycolic acid, thiolactic acid, or other hydroxymercaptans, aminomercaptans, or carboxyl-containing mercaptans) and optionally other vinyl monomers are copolymerized (thermally or by radiation) with a reactive vinyl monomer (having an amino or carboxyl group) in the presence of a free radical initiator. Generally, the molar ratio of the chain transfer agent to all vinyl monomers other than the reactive vinyl monomer is about 1:5 to about 1:100, 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 an amino or carboxyl group is used to control the molecular weight of the resulting hydrophilic polymer and to form the terminal portions of the resulting hydrophilic polymer, such that one terminal amino or carboxyl group is imparted 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 a monoamino- or monocarboxy-terminated homo- or copolymer of a non-reactive hydrophilic vinyl monomer, a non-reactive vinyl monomer, a chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid, or other hydroxymercaptans, aminomercaptans, or carboxyl-containing mercaptans) and optionally other vinyl monomers are copolymerized (thermally or by radiation) in the absence of any reactive vinyl monomer.

[0245] Copolymers containing a non-reactive hydrophilic vinyl monomer and a reactive vinyl monomer (e.g., a carboxyl-containing vinyl monomer, a primary amino group-containing vinyl monomer, or a secondary amino group-containing vinyl monomer) can also be prepared according to any well-known radical polymerization method or obtained from commercial suppliers. Copolymers containing methacryloyloxyethyl phosphorylcholine and a carboxyl-containing vinyl monomer (or an amino-containing vinyl monomer) can also be obtained from NOF Corporation (e.g., LIPIDURE®-A and -AF) or prepared according to the procedures described in U.S. Patent No. 9,127,099.

[0246] The weight average molecular weight M of the hydrophilic polymer (as a hydrophilic enhancer) having at least one amino, carboxyl, or thiol group w is preferably from about 500 to about 5,000,000, more preferably from about 1,000 to about 2,000,000, and even more preferably from about 5,000 to about 1,000,000 daltons.

[0247] Water-soluble and thermally crosslinkable hydrophilic polymer materials can be prepared according to the processes disclosed in U.S. Patent Application Publication Nos. 2016 / 0061995A1 and 2013 / 0337160A1, and U.S. Patent No. 8,529,057.

[0248] In a preferred embodiment, a water-soluble thermally crosslinkable polymer material is obtained by heating a reactive aqueous solution containing at least one azetidinium-containing polymer and at least one hydrophilic 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 (about 8 hours or less, preferably about 5 hours, more preferably about 2 hours to about 4 hours). The reactive aqueous solution preferably contains one or more ionic compounds at about 70 mM to about 170 mM (preferably about 90 mM to about 150 mM, more preferably about 100 mM to about 130 mM) 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). The reaction time should be long enough to covalently bond the hydrophilic enhancer onto the polymer chain of the azetidinium-containing polymer, but not so long as to consume all of the azetidinium groups of the azetidinium-containing polymer or so much crosslinking is formed between the azetidinium-containing polymer and the hydrophilic enhancer that a gel is formed (i.e., it is not water-soluble). The resulting polymer material is a lightly crosslinked polymer material having a highly branched structure and still containing thermally crosslinkable azetidinium groups.

[0249] Those skilled in the art are familiar with methods for adjusting the pH of the reactive mixture, for example, by adding a base (e.g., NaOH, KOH, NH 4 OH, or a mixture thereof) or an acid (e.g., HCl, H 2 SO 4 , H 3 PO 4 , citric acid, acetic acid, boric acid, or a mixture thereof).

[0250] According to the present invention, any ionic compound can be used in the reactive mixture. Preferably, the ionic compound is one used as an ionic tonicity regulator and an ionic buffer in ophthalmic solutions. Examples of preferred ionic tonicity regulators include, but are not limited to, sodium chloride, potassium chloride, and combinations thereof. Examples of preferred ionic buffers include salts of various phosphoric acids (e.g., NaH 2 PO 4 、Na 2 HPO 4 、Na 3 PO 4 、KH 2 PO 4 、K 2 HPO 4 、K 3 PO 4 、or mixtures thereof), salts of various boric acids (e.g., sodium borate, potassium borate, or mixtures thereof), salts of various citric acids (e.g., sodium citrate monohydrate, disodium citrate, trisodium citrate, potassium citrate monohydrate, dipotassium citrate, tripotassium citrate, or mixtures thereof), salts of various carbonic acids (e.g., Na 2 CO 3 、NaHCO 3 、K 2 CO 3 、KHCO 3 or mixtures thereof).

[0251] The reactive aqueous solution for preparing the water-soluble thermally crosslinkable polymer material can be prepared by dissolving a desired amount of the azetidinium-containing polymer, a desired amount of the hydrophilic enhancer having at least one reactive functional group, and a desired amount of other components (e.g., ionic buffer, ionic tonicity regulator, etc.) in water (or a mixture of water and a small amount of water-soluble organic solvent) to form an aqueous solution, and then adjusting the pH of the aqueous solution as necessary.

[0252] According to the present invention, the concentration ratio of the hydrophilic enhancer to the azetidinium-containing polymer in the reactive aqueous solution should be selected such that the obtained water-soluble thermally crosslinkable polymer material is not rendered water-insoluble (i.e., having a solubility of less than 0.005 g per 100 mL of water at room temperature), and does not 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.

[0253] In a preferred embodiment, the reactive aqueous solution contains from 0.01 wt% to about 10 wt% (preferably from 0.05 wt% to about 5 wt%, more preferably from 0.08 wt% to about 1 wt%, and even more preferably from 0.1 wt% to about 0.4 wt%) of the azetidinium-containing polymer and from about 0.01 wt% to about 10 wt% (preferably from 0.02 wt% to about 5 wt%, more preferably from 0.05 wt% to about 2 wt%, and even more preferably from 0.08 wt% to about 1.0 wt%) of a hydrophilic enhancer having at least one reactive functional group (carboxyl, primary amino, secondary amino group). The concentration ratio of the azetidinium-containing polymer to the hydrophilic enhancer is from about 1000:1 to 1:1000 (preferably from about 500:1 to about 1:500, more preferably from about 250:1 to about 1:250, and even more preferably from about 100:1 to about 1:100).

[0254] In a preferred embodiment, the water-soluble thermally crosslinkable polymer material comprises: (i) a first polymer chain derived from about 20 wt% to about 95 wt% of polyamidoamine-epichlorohydrin or poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin; and (ii) a hydrophilic moiety or a second polymer chain derived from at least one hydrophilic enhancer having at least one reactive functional group selected from the group consisting of amino groups, carboxyl groups, thiol groups, and combinations thereof (preferably a carboxyl or thiol group), wherein the hydrophilic moiety or the second polymer chain is covalently bonded to the first polymer chain via one or more covalent bonds formed between one azetidinium group of polyamidoamine-epichlorohydrin or poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin and one amino, carboxyl, or thiol group of the hydrophilic enhancer; and (iii) an azetidinium group that is part of the first polymer chain or a pendant or terminal group covalently bonded 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 the reactants) used for such polymers according to the crosslinking reaction shown in Scheme I above. For example, if the reaction mixture comprises about 75 wt% of polyamidoamine-epichlorohydrin and about 25 wt% of at least one hydrophilic enhancer based on the total weight of the reactants, the resulting chemically modified polyamidoamine-epichlorohydrin comprises about 75 wt% of a first polymer chain derived from polyamioamine-epichlorohydrin and about 25 wt% of a hydrophilic moiety or a second polymer chain derived from the at least one hydrophilic enhancer described above.

[0255] According to the present invention, a preformed contact lens having an anchor layer thereon is heated in an aqueous solution containing a thermally crosslinkable hydrophilic polymer material having an azetidinium group and optionally (but preferably) an amino group, a thiol group, a carboxyl group, or a combination thereof, at a temperature of about 60°C to about 140°C for a period sufficient to crosslink the thermally crosslinkable hydrophilic polymer material and simultaneously covalently bond the crosslinked thermally crosslinkable hydrophilic polymer material onto the anchor layer to form a water gradient contact lens.

[0256] Preferably, the heating step is carried out by autoclaving a preformed contact lens having an anchor layer thereon, immersed in an aqueous coating solution which is a packaging solution (i.e., a buffered aqueous solution having a pH of 6.7 to 7.6) within a sealed lens package, at a temperature of about 115°C to about 125°C for about 20 to 90 minutes. During autoclaving, these azetidinium groups not involved in the crosslinking reaction can be hydrolyzed to 2,3-dihydroxypropyl (HO-CH 2 -CH(OH)-CH 2 -) groups, and the azetidinium-containing polymer material present in the lens packaging solution can, where applicable, be converted to a non-reactive polymer wetting agent capable of improving the insertion comfort of the lens. As a result, the second coating aqueous solution is ophthalmically safe after autoclaving.

[0257] 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 sterilized packaging solution and the contact lens.

[0258] Before being dispensed to the user, the lenses are packaged, sealed, and sterilized (e.g., by autoclaving at about 120° C. or higher for at least 30 minutes under pressure) within individual packages. Those skilled in the art will be well aware of methods for sealing and sterilizing lens packages.

[0259] According to the present invention, the packaging solution contains at least one buffering agent and one or more other ingredients known to those skilled in the art. Examples of other ingredients include, but are not limited to, tonicity agents, surfactants, antibacterial agents, preservatives, and lubricants (e.g., cellulose derivatives, polyvinyl alcohol, polyvinyl pyrrolidone).

[0260] The packaging solution contains a buffer in an amount sufficient to maintain the pH of the packaging solution within a desired range, for example, preferably within a physiologically acceptable range of about 6.5 to about 7.5. Any known physiologically compatible buffer can be used. Buffers suitable as components of the contact lens care composition of the present invention are known to those skilled in the art. Examples are boric acid, borates such as sodium borate, citric acid, citrates such as potassium citrate, carbonates such as 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-aminopolyol, triethanolamine, ACES [i.e., N-(2-hydroxyethyl)-2-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 buffers such as Na 2 HPO 4 、NaH 2 PO 4 、and KH 2 PO 4 、or mixtures thereof. The amount of each buffer in the packaging solution is preferably from 0.001% to 2% by weight, preferably from 0.01% to 1% by weight, most preferably from about 0.05% to about 0.30% by weight.

[0261] 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 isotonic agents tolerated by suitable eyes include, but are not limited to, sodium chloride, potassium chloride, glycerol, propylene glycol, polyols, mannitol, sorbitol, xylitol, and mixtures thereof.

[0262] The packaging solution of the present invention has a viscosity of about 1 centipoise to about 5 centipoises at 25°C.

[0263] In a preferred embodiment, the packaging solution preferably contains a water-soluble and thermally crosslinkable hydrophilic polymer material having an azetidinium group of about 0.01 wt% to about 2 wt%, more preferably about 0.05 wt% to about 1.5 wt%, even more preferably about 0.1 wt% to about 1 wt%, and most preferably about 0.2 wt% to about 0.5 wt%.

[0264] The resulting water gradient contact lens can then be heated at a temperature of 40°C to 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 required polyaziridine in addition to all the necessary components described above for the lens packaging solution.

[0265] Any polyaziridine can be used in the present invention to neutralize the negative charges present in the water-gradient contact lens. Examples of preferred polyaziridines include 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), the Michael reaction product of a vinyl crosslinker having at least two (meth)acryloyl groups and 2-methylaziridine (or aziridine), and combinations thereof, but are not limited thereto. Preferably, a polyaziridine containing at least a methyl-aziridinyl group is used in the present invention.

[0266] In an alternative manufacturing process of the contact lens of the present invention, in the process of preparing a water-gradient contact lens, in the presence of a polyaziridine having a number average molecular weight of about 2000 daltons or less and at least two aziridine groups, a contact lens precursor having an anchor layer thereon is heated in an aqueous solution containing a thermally crosslinkable hydrophilic polymer material (any one of those described above). For example, a preformed contact lens having an anchor layer thereon is first contacted with a solution containing such a polyaziridine at room temperature or below to add the polyaziridine to the preformed contact lens, and then the polyaziridine-added contact lens having an anchor layer thereon is heated in an aqueous solution containing a thermally crosslinkable hydrophilic polymer 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 polymer material (any one of those described above) and a polyaziridine at a temperature of about 60°C to about 140°C to form the contact lens of the present invention.

[0267] Some alternative processes for manufacturing the contact lens of the present invention are illustrated in the Examples section.

[0268] Although various embodiments of the present invention have been described using specific terms, devices, and methods, such descriptions are for illustrative purposes only. The words used are explanatory rather than limiting. 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 aspects of various embodiments of the present invention may be, in whole or in part, interchangeable, or may be combined and / or used together in any manner, as shown below.

[0269] Embodiment 1 A polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms / lens or less (or about 0.30 micrograms / lens or less), and A contact lens having a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment, wherein The contact lens Comprises a front surface and an opposite rear surface, and a layered structure comprising a front external hydrogel layer, an internal layer of lens material, and a rear external hydrogel layer in a direction from the front surface to the rear surface, The internal layer has a first equilibrium water content of about 70% by weight or less, wherein the front and rear external hydrogel layers, independent of each other, have a thickness of about 0.25 μm to about 25 μm when fully hydrated, a first equilibrium water content, and a second equilibrium water content higher than the first equilibrium water content, and the front and rear external hydrogel layers, independent of each other, have a water swelling ratio of at least 140%.

[0270] Embodiment 2 A polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms / lens or less (or about 0.30 micrograms / lens or less), and A contact lens having a friction rating of about 2.0 or less after 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment, wherein The contact lens A front surface and an opposite rear surface, and a layered structure including a front external hydrogel layer, an internal layer of lens material, and a rear external hydrogel layer in a direction from the front surface to the rear surface. The internal layer has a first equilibrium water content of about 70% by weight or less, and the front and rear external hydrogel layers, which are independent of each other, have a thickness of about 0.25 μm to about 25 μm when fully hydrated. The contact lens has a first equilibrium water content and a second equilibrium water content higher than the first equilibrium water content, and the front and rear external hydrogel layers, which are independent of each other, have a water swelling ratio of at least 140%.

[0271] Embodiment 3 The contact lens according to Embodiment 1 or 2, wherein the front and rear external hydrogel layers, which are independent of each other, have a water swelling ratio of at least 170%.

[0272] Embodiment 4 The contact lens according to Embodiment 1 or 2, wherein the front and rear external hydrogel layers, which are independent of each other, have a water swelling ratio of at least 200%.

[0273] Embodiment 5 The contact lens according to Embodiment 1 or 2, wherein the front and rear external hydrogel layers, which are independent of each other, have a water swelling ratio of at least 250%.

[0274] Embodiment 6 The contact lens according to Embodiment 1 or 2, wherein the front and rear external hydrogel layers, which are independent of each other, have a water swelling ratio of at least 300%.

[0275] Embodiment 7 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 treatment or after simulated polishing cycling treatment, A contact lens having a water content gradient increasing from the inside to one of the front or rear surfaces of the contact lens, The contact lens comprises a lens bulk material completely covered by a front external hydrogel layer and a rear external hydrogel layer. The front and rear external hydrogel layers independent of each other have a thickness of about 0.25 μm to about 25 μm when fully hydrated. The lens bulk material has a first equilibrium water content of about 70 wt% or less, and the front and rear external hydrogel layers independent of each other have a second equilibrium water content that is at least 1.2 times the first equilibrium water content and is at least 80 wt%.

[0276] Embodiment 8 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 treatment or after simulated polishing cycling treatment, And a water content gradient that increases from the inside to the outside of the contact lens. The contact lens comprises a lens bulk material completely covered by a front external hydrogel layer and a rear external hydrogel layer. The front and rear external hydrogel layers independent of each other have a thickness of about 0.25 μm to about 25 μm when fully hydrated. The lens bulk material has a first equilibrium water content of about 70 wt% or less, and the front and rear external hydrogel layers independent of each other have a second equilibrium water content that is at least 1.2 times the first equilibrium water content and is at least 80 wt%.

[0277] Embodiment 9 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 treatment or after simulated polishing cycling treatment. The contact lens A front surface and an opposite rear surface, and a layered structure including a front external hydrogel layer, an internal layer of lens material, and a rear external hydrogel layer in a direction from the front surface to the rear surface. A contact lens in which each of the front and rear external hydrogel layers, which are independent of each other, has a reduced surface elastic modulus of at least about 20% compared to the internal layer.

[0278] Embodiment 10 A polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms / lens or less (or about 0.30 micrograms / lens or less), and A contact lens having a friction score of about 2.0 or less after 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment. The contact lens A front surface and an opposite rear surface, and a layered structure including a front external hydrogel layer, an internal layer of lens material, and a rear external hydrogel layer in a direction from the front surface to the rear surface. A contact lens in which each of the front and rear external hydrogel layers, which are independent of each other, has a reduced surface elastic modulus of at least about 20% compared to the internal layer.

[0279] Embodiment 11 The contact lens according to Embodiment 9 or 10, wherein each of the front and rear external hydrogel layers, which are independent of each other, has a reduced surface elastic modulus of at least 25% compared to the internal layer.

[0280] Embodiment 12 The contact lens according to Embodiment 9 or 10, wherein each of the front and rear external hydrogel layers, which are independent of each other, has a reduced surface elastic modulus of at least 30% compared to the internal layer.

[0281] Embodiment 13 The contact lens according to Embodiment 9 or 10, wherein each of the front and rear external hydrogel layers, which are independent of each other, has a reduced surface elastic modulus of at least about 35% compared to the internal layer.

[0282] Embodiment 14 The contact lens according to Embodiment 9 or 10, wherein each of the front and rear external hydrogel layers independent of each other has a reduced surface elastic modulus of at least 40% compared to the internal layer.

[0283] Embodiment 15 The normalized surface compressive force at an indentation depth of 400 nm measured by a micro-indentation test using a 1 mm micro-indentation probe and The polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms / lens or less (or about 0.30 micrograms / lens or less), and A contact lens having a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment, The contact lens includes a front surface, a rear surface on the opposite side, and a layered structure form, and the layered structure form includes a front external hydrogel layer, an internal layer of lens material, and a rear external hydrogel layer in the direction from the front surface to the rear surface.

[0284] Embodiment 16 The normalized surface compressive force at an indentation depth of 400 nm measured by a micro-indentation test using a 1 mm micro-indentation probe and The polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms / lens or less (or about 0.30 micrograms / lens or less), and A contact lens having a friction score of about 2.0 or less after 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment, The contact lens includes a front surface, a rear surface on the opposite side, and a layered structure form, and the layered structure form includes a front external hydrogel layer, an internal layer of lens material, and a rear external hydrogel layer in the direction from the front surface to the rear surface.

[0285] Embodiment 17 The normalized surface compressive force at a penetration depth of 400 nm, measured by a micro-indentation test using a 1 mm micro-indentation probe, and which is about 12 μN / MPa or less, and 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 treatment or after simulated polishing cycling treatment, a contact lens having wherein the contact lens comprises a lens bulk material that is a polymer material, the contact lens.

[0286] Embodiment 18 The normalized surface compressive force at a penetration depth of 400 nm, measured by a micro-indentation test using a 1 mm micro-indentation probe, and which is about 12 μN / MPa or less, and 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 treatment or after simulated polishing cycling treatment, a contact lens having wherein the contact lens comprises a lens bulk material that is a polymer material, the contact lens.

[0287] Embodiment 19 The contact lens has a normalized surface compressive force at a penetration depth of 400 nm of about 10 μN / MPa or less, the contact lens according to any one of Embodiments 15 to 18.

[0288] Embodiment 20 The contact lens has a normalized surface compressive force at a penetration depth of 400 nm of about 8 μN / MPa or less, the contact lens according to any one of Embodiments 15 to 18.

[0289] Embodiment 21 The contact lens has a normalized surface compressive force at an indentation depth of 400 nm of about 6 μN / MPa or less, and is the contact lens according to any one of Embodiments 15 to 18.

[0290] Embodiment 22 The contact lens has a normalized surface compressive force at an indentation depth of 400 nm of about 4 μN / MPa or less, and is the contact lens according to any one of Embodiments 15 to 18.

[0291] Embodiment 23 A reduction in the indentation force at an indentation depth of 400 nm 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), i.e., Δ(IF) 400nm and A polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms / lens or less (or about 0.30 micrograms / lens or less), and After 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment, a water disintegration time of at least 10 seconds, and is a contact lens having The contact lens includes a front surface, a rear surface opposite thereto, and a layered structure form. The layered structure form includes a front external hydrogel layer, an internal layer of the lens material, and a rear external hydrogel layer in the direction from the front surface to the rear surface.

[0292] Embodiment 24 A reduction in the indentation force at an indentation depth of 400 nm 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), i.e., Δ(IF) 400nm and A polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms / lens or less (or about 0.30 micrograms / lens or less), and After 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment, a friction rating of about 2.0 or less, and is a contact lens having The contact lens comprises a front surface, an opposite rear surface, and a layered structure form, and the layered structure form comprises a front external hydrogel layer, an internal layer of lens material, and a rear external hydrogel layer in a direction from the front surface to the rear surface.

[0293] Embodiment 25 A reduction in the indentation force at an indentation depth of 400 nm 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), i.e., Δ(IF) 400nm and A polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms / lens or less (or about 0.30 micrograms / lens or less), A contact lens having a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment, The contact lens comprises a lens bulk material which is a polymer material.

[0294] Embodiment 26 A reduction in the indentation force at an indentation depth of 400 nm 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), i.e., Δ(IF) 400nm and A polyquaternium-1 uptake rate ("PU") of about 0.40 micrograms / lens or less (or about 0.30 micrograms / lens or less), A contact lens having a friction score of about 2.0 or less after 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment, The contact lens comprises a lens bulk material which is a polymer material.

[0295] Embodiment 27 Δ(IF) 400nm is determined by a nanoindentation test using a probe having a tip radius of about 9.0 ± 0.9 μm,

Number

[0296] Embodiment 28 Δ(IF) 400nm is determined by a micro-indentation test by using a 1 mm hemispherical borosilicate glass probe.

Number

[0297] Embodiment 29 Δ(IF) 400nm is about 55% or more. The contact lens according to any one of Embodiments 23 to 28.

[0298] Embodiment 30 Δ(IF) 400nm is about 60% or more. The contact lens according to any one of Embodiments 23 to 28.

[0299] Embodiment 31 Δ(IF) 400nm is about 65% or more. The contact lens according to any one of Embodiments 23 to 28.

[0300] Embodiment 32 Δ(IF) 400nm is about 70% or more. The contact lens according to any one of Embodiments 23 to 28.

[0301] Embodiment 33 The contact lens according to any one of Embodiments 1 to 32, having a polyquaternium-1 uptake rate ("PU") of about 0.20 micrograms / lens or less.

[0302] Embodiment 34 The contact lens according to any one of Embodiments 1 to 32, having a polyquaternium-1 uptake rate ("PU") of about 0.15 micrograms / lens or less.

[0303] Embodiment 35 The contact lens according to any one of Embodiments 1 to 32, having a polyquaternium-1 uptake rate ("PU") of about 0.10 micrograms / lens or less.

[0304] Embodiment 36 The contact lens according to any one of Embodiments 1 to 32, having a polyquaternium-1 uptake rate ("PU") of about 0.075 micrograms / lens or less.

[0305] Embodiment 37 The contact lens according to any one of Embodiments 1 to 32, having a polyquaternium-1 uptake rate ("PU") of about 0.050 micrograms / lens or less.

[0306] Embodiment 38 The contact lens according to any one of Embodiments 1 to 37, having a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing treatment.

[0307] Embodiment 39 The contact lens according to any one of Embodiments 1 to 37, having a water disintegration time of at least 12.5 seconds after 30 cycles of finger rubbing treatment.

[0308] Embodiment 40 The contact lens according to any one of Embodiments 1 to 37, having a water disintegration time of at least 15 seconds after 30 cycles of finger rubbing treatment.

[0309] Embodiment 41 The contact lens according to any one of Embodiments 1 to 37, having a water disintegration time of at least 17.5 seconds after 30 cycles of finger rubbing treatment.

[0310] Embodiment 42 The contact lens according to any one of Embodiments 1 to 37, having a water disintegration time of at least 20 seconds after 30 cycles of finger rubbing treatment.

[0311] Embodiment 43 The contact lens according to any one of Embodiments 1 to 37, having a water disintegration time of at least 10 seconds after simulated polishing cycling treatment.

[0312] Embodiment 44 The contact lens according to any one of Embodiments 1 to 37, having a water disintegration time of at least 12.5 seconds after simulated polishing cycling treatment.

[0313] Embodiment 45 The contact lens according to any one of Embodiments 1 to 37, having a water disintegration time of at least 15 seconds after simulated polishing cycling treatment.

[0314] Embodiment 46 The contact lens according to any one of Embodiments 1 to 37, having a water disintegration time of at least 17.5 seconds after simulated polishing cycling treatment.

[0315] Embodiment 47 The contact lens according to any one of Embodiments 1 to 37, having a water disintegration time of at least 20 seconds after simulated polishing cycling treatment.

[0316] Embodiment 48 The 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.

[0317] Embodiment 49 The contact lens according to Embodiment 48, wherein the hard plastic material is crosslinked polymethacrylate.

[0318] Embodiment 50 The 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.

[0319] Embodiment 51 The contact lens according to any one of Embodiments 48 to 50, wherein the front and rear outer hydrogel layers independent of each other have a thickness of about 1.0 μm to about 20 μm when fully hydrated.

[0320] Embodiment 52 The contact lens according to any one of Embodiments 48 to 50, wherein the front and rear outer hydrogel layers independent of each other have a thickness of about 2.0 μm to about 15 μm when fully hydrated.

[0321] Embodiment 53 The contact lens according to any one of Embodiments 48 to 50, wherein the front and rear outer hydrogel layers independent of each other have a thickness of about 2.0 μm to about 10 μm when fully hydrated.

[0322] Embodiment 54 The contact lens according to any one of embodiments 48 to 50, wherein the front and rear external hydrogel layers independent of each other have a thickness of about 2.5 μm to about 8 μm when fully hydrated.

[0323] Embodiment 55 The 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 essentially made of a crosslinked silicone material.

[0324] Embodiment 56 The contact lens according to embodiment 55, wherein the front and rear external hydrogel layers independent of each other have a thickness of about 2.0 μm to about 25 μm when fully hydrated.

[0325] Embodiment 57 The contact lens according to embodiment 55, wherein the front and rear external hydrogel layers independent of each other have a thickness of about 3.0 μm to about 25 μm when fully hydrated.

[0326] Embodiment 58 The contact lens according to embodiment 55, wherein the front and rear external hydrogel layers independent of each other have a thickness of about 4.0 μm to about 20 μm when fully hydrated.

[0327] Embodiment 59 The contact lens according to embodiment 55, wherein the front and rear external hydrogel layers independent of each other have a thickness of about 5.0 μm to about 20 μm when fully hydrated.

[0328] Embodiment 60 The 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 essentially made of a hard gas permeable lens material and surrounded by an edge zone essentially made of a non-silicone hydrogel material.

[0329] Embodiment 61 The inner layer or lens bulk material is the contact lens according to any one of Embodiments 1 to 47, which is a preformed non-silicone hydrogel contact lens essentially made of a non-silicone hydrogel material.

[0330] Embodiment 62 The non-silicone hydrogel material is the contact lens according to Embodiment 60 or 61, which comprises at least 50 mol% of repeating units of at least one hydroxyl-containing vinyl monomer.

[0331] Embodiment 63 The above 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. The contact lens according to Embodiment 62.

[0332] Embodiment 64 The above at least one hydroxyl-containing vinyl monomer is selected from the group consisting of hydroxyethyl (meth)acrylate, glycerol (meth)acrylate, and vinyl alcohol. The contact lens according to Embodiment 62.

[0333] Embodiment 65 The front and rear outer hydrogel layers, which are independent of each other, have a thickness of about 0.25 μm to about 20 μm when fully hydrated. The contact lens according to any one of Embodiments 60 to 64.

[0334] Embodiment 66 The contact lens according to any one of Embodiments 60 to 64, wherein the front and rear outer hydrogel layers independent of each other have a thickness of about 0.50 μm to about 15 μm when fully hydrated.

[0335] Embodiment 67 The contact lens according to any one of Embodiments 60 to 64, wherein the front and rear outer hydrogel layers independent of each other have a thickness of about 0.5 μm to about 10 μm when fully hydrated.

[0336] Embodiment 68 The contact lens according to any one of Embodiments 60 to 64, wherein the front and rear outer hydrogel layers independent of each other have a thickness of about 0.5 μm to about 6 μm when fully hydrated.

[0337] Embodiment 69 The contact lens according to any one of Embodiments 1 to 47, wherein the inner layer and the lens bulk material independent of each other are a preformed contact lens essentially made of a silicone hydrogel material.

[0338] Embodiment 70 The contact lens according to Embodiment 69, wherein the silicone hydrogel material comprises repeating units of at least one polysiloxane vinyl monomer.

[0339] Embodiment 71 The contact lens according to Embodiment 69 or 70, wherein the silicone hydrogel material comprises repeating units of at least one polysiloxane vinyl crosslinker.

[0340] Embodiment 72 The contact lens according to any one of Embodiments 69 to 71, wherein the silicone hydrogel material comprises repeating units of at least one hydrophilic vinyl monomer.

[0341] Embodiment 73 The silicone hydrogel material is a contact lens according to any one of Embodiments 69 to 72, comprising repeating units of at least one hydrophilic N-vinylamide monomer.

[0342] Embodiment 74 The silicone hydrogel material is a contact lens according to any one of Embodiments 69 to 73, comprising repeating units of at least one polycarbosiloxane vinyl monomer.

[0343] Embodiment 75 The silicone hydrogel material is a contact lens according to any one of Embodiments 69 to 74, comprising repeating units of at least one polycarbosiloxane vinyl crosslinker.

[0344] Embodiment 76 The silicone hydrogel material is a contact lens according to any one of Embodiments 69 to 75, comprising repeating units of at least one silicone-containing vinyl monomer having a bis(trialkylsilyloxy)alkylsilyl or tris(trialkylsilyloxy)silyl group.

[0345] Embodiment 77 The silicone hydrogel material is a contact lens according to any one of Embodiments 69 to 76, comprising repeating units of one or more blend vinyl monomers.

[0346] Embodiment 78 The silicone hydrogel material is a contact lens according to any one of Embodiments 69 to 76, comprising repeating units of one or more blend 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.

[0347] Embodiment 79 The silicone hydrogel material is a contact lens according to any one of Embodiments 69 to 76, comprising repeating units of one or more blend 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.

[0348] Embodiment 80 The silicone hydrogel material contains repeating units of one or more blend vinyl monomers in an amount of about 15 wt% or less based on the dry weight of the inner layer of the silicone hydrogel material, and the contact lens according to any one of Embodiments 69 to 76.

[0349] Embodiment 81 The silicone hydrogel material comprises repeating units of one or more non-silicone vinyl crosslinking agents, and the contact lens according to any one of Embodiments 69 to 80.

[0350] Embodiment 82 The silicone hydrogel material contains repeating units of one or more non-silicone vinyl crosslinking agents in an amount of about 1.0 wt% or less based on the dry weight of the inner layer, and the contact lens according to any one of Embodiments 69 to 80.

[0351] Embodiment 83 The silicone hydrogel material contains repeating units of one or more non-silicone vinyl crosslinking agents in an amount of about 0.8 wt% or less based on the dry weight of the inner layer, and the contact lens according to any one of Embodiments 69 to 80.

[0352] Embodiment 84 The silicone hydrogel material contains repeating units of one or more non-silicone vinyl crosslinking agents in an amount of about 0.05 wt% to about 0.6 wt% based on the dry weight of the inner layer, and the contact lens according to any one of Embodiments 69 to 80.

[0353] Embodiment 85 The silicone hydrogel material has an oxygen permeability of at least about 50 barrer, and the contact lens according to any one of Embodiments 69 to 84.

[0354] Embodiment 86 The silicone hydrogel material has an oxygen permeability of at least about 60 barrer, and the contact lens according to any one of Embodiments 69 to 84.

[0355] Embodiment 87 The 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.

[0356] Embodiment 88 The 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.

[0357] Embodiment 89 The 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.

[0358] Embodiment 90 The contact lens according to any one of Embodiments 69 to 89, wherein the silicone hydrogel material has an equilibrium water content of about 10 wt% to about 70 wt%.

[0359] Embodiment 91 The contact lens according to any one of Embodiments 69 to 89, wherein the silicone hydrogel material has an equilibrium water content of about 10 wt% to about 65 wt%.

[0360] Embodiment 92 The contact lens according to any one of Embodiments 69 to 89, wherein the silicone hydrogel material has an equilibrium water content of about 10 wt% to about 60 wt%.

[0361] Embodiment 93 The contact lens according to any one of Embodiments 69 to 89, wherein the silicone hydrogel material has an equilibrium water content of about 15 wt% to about 55 wt%.

[0362] Embodiment 94 The contact lens according to any one of Embodiments 69 to 89, wherein the silicone hydrogel material has an equilibrium water content of about 15 wt% to about 50 wt%.

[0363] Embodiment 95 The silicone hydrogel material is not naturally wettable, and the front and rear outer hydrogel layers that are independent of each other have a thickness of about 0.5 μm to about 25 μm when fully hydrated, and the contact lens according to any one of Embodiments 69 to 94.

[0364] Embodiment 96 The silicone hydrogel material is not naturally wettable, and the front and rear outer hydrogel layers that are independent of each other have a thickness of about 1.0 μm to about 20 μm when fully hydrated, and the contact lens according to any one of Embodiments 69 to 94.

[0365] Embodiment 97 The silicone hydrogel material is not naturally wettable, and the front and rear outer hydrogel layers that are independent of each other have a thickness of about 1.0 μm to about 15 μm when fully hydrated, and the contact lens according to any one of Embodiments 69 to 94.

[0366] Embodiment 98 The silicone hydrogel material is not naturally wettable, and the front and rear outer hydrogel layers that are independent of each other have a thickness of about 1.5 μm to about 10 μm when fully hydrated, and the contact lens according to any one of Embodiments 69 to 94.

[0367] Embodiment 99 The silicone hydrogel material is naturally wettable, and the front and rear outer hydrogel layers that are independent of each other have a thickness of about 0.25 μm to about 20 μm when fully hydrated, and the contact lens according to any one of Embodiments 69 to 98.

[0368] Embodiment 100 The silicone hydrogel material is naturally wettable, and the front and rear outer hydrogel layers that are independent of each other have a thickness of about 0.5 μm to about 20 μm when fully hydrated, and the contact lens according to any one of Embodiments 69 to 98.

[0369] Embodiment 101 The silicone hydrogel material is naturally wettable, and the front and rear external hydrogel layers independent of each other have a thickness of about 0.5 μm to about 15 μm when fully hydrated, and the contact lens according to any one of Embodiments 69 to 98.

[0370] Embodiment 102 The silicone hydrogel material is naturally wettable, and the front and rear external hydrogel layers independent of each other have a thickness of about 1.0 μm to about 10 μm when fully hydrated, and the contact lens according to any one of Embodiments 69 to 98.

[0371] Embodiment 103 The front and rear external hydrogel layers independent of each other are alkyl (meth) acrylamide, N-2-dimethylaminoethyl (meth) acrylamide, dimethylaminoethyl (meth) acrylate, hydroxyl-containing acrylic monomer, N-vinylamide monomer, methylene-containing pyrrolidone monomer, C 1 ~C 4 A crosslinked hydrophilic polymer 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 an alkoxyethoxy group, vinyl ether monomers, allyl ether monomers, and combinations thereof, and the contact lens according to any one of Embodiments 1 to 102.

[0372] Embodiment 104 The front and rear external hydrogel layers independent of each other are alkyl (meth) acrylamide, N-2-dimethylaminoethyl (meth) acrylamide, dimethylaminoethyl (meth) acrylate, hydroxyl-containing acrylic monomer, N-vinylamide monomer, methylene-containing pyrrolidone monomer, C 1 ~C 4A contact lens according to any one of Embodiments 1 to 102, which is a crosslinked hydrophilic polymer 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 an alkoxyethoxy group, vinyl ether monomers, allyl ether monomers, and combinations thereof.

[0373] Embodiment 105 The front and rear outer hydrogel layers, which are independent of each other, are alkyl (meth)acrylamide, N-2-dimethylaminoethyl (meth)acrylamide, dimethylaminoethyl (meth)acrylate, hydroxyl-containing acrylic monomers, N-vinylamide monomers, methylene-containing pyrrolidone monomers, C 1 ~C 4 A contact lens according to any one of Embodiments 1 to 102, which is a crosslinked hydrophilic polymer 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 an alkoxyethoxy group, vinyl ether monomers, allyl ether monomers, and combinations thereof.

[0374] Embodiment 106 The front and rear outer hydrogel layers, which are independent of each other, are alkyl (meth)acrylamide, N-2-dimethylaminoethyl (meth)acrylamide, dimethylaminoethyl (meth)acrylate, hydroxyl-containing acrylic monomers, N-vinylamide monomers, methylene-containing pyrrolidone monomers, C 1 ~C 4 A contact lens according to any one of Embodiments 1 to 102, which is a crosslinked hydrophilic polymer 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 an alkoxyethoxy group, vinyl ether monomers, allyl ether monomers, and combinations thereof.

[0375] Embodiment 107 The front and rear outer hydrogel layers, which are independent of each other, are contact lenses according to any one of Embodiments 1 to 102, which are crosslinked hydrophilic polymer materials comprising at least 25 mol% of repeating monomer units of at least one phosphrylcholine-containing vinyl monomer.

[0376] Embodiment 108 The front and rear outer hydrogel layers, which are independent of each other, are contact lenses according to any one of Embodiments 1 to 102, which are crosslinked hydrophilic polymer materials comprising at least 35 mol% of repeating monomer units of at least one phosphrylcholine-containing vinyl monomer.

[0377] Embodiment 109 The front and rear outer hydrogel layers, which are independent of each other, are contact lenses according to any one of Embodiments 1 to 102, which are crosslinked hydrophilic polymer materials comprising at least 45 mol% of repeating monomer units of at least one phosphrylcholine-containing vinyl monomer.

[0378] Embodiment 110 The front and rear outer hydrogel layers, which are independent of each other, are contact lenses according to any one of Embodiments 1 to 102, which are crosslinked hydrophilic polymer materials comprising at least 55 mol% of repeating monomer units of at least one phosphrylcholine-containing vinyl monomer.

[0379] Embodiment 111 The front and rear outer hydrogel layers, which are independent of each other, are contact lenses according to any one of Embodiments 1 to 102, which are crosslinked hydrophilic polymer materials comprising poly(ethylene glycol) chains.

[0380] Embodiment 112 The front and rear outer hydrogel layers, which are independent of each other, are (1) pol(ethylene glycol) having only one functional group of -NH 2 , -SH, or -COOH, (2) -NH 2, poly(ethylene glycol) having two terminal functional groups selected from the group consisting of -COOH, -SH, and combinations thereof, (3) -NH 2 , multi-arm poly(ethylene glycol) having one or more functional groups selected from the group consisting of -COOH, -SH, and combinations thereof, or (4) a crosslinked hydrophilic polymer material comprising a poly(ethylene glycol) chain directly derived from a combination thereof, the contact lens according to any one of Embodiments 1 to 102.

[0381] Embodiment 113 The front and rear outer hydrogel layers are identical to each other, have a substantially uniform thickness, and integrate at the edge of the contact lens to completely cover the inner layer, the contact lens according to any one of Embodiments 1 to 112.

[0382] Embodiment 114 The front and rear outer hydrogel layers independent of each other have an equilibrium water content of at least 80% by weight, the contact lens according to any one of Embodiments 1 to 113.

[0383] Embodiment 115 The front and rear outer hydrogel layers independent of each other have an equilibrium water content of at least 85% by weight, the contact lens according to any one of Embodiments 1 to 113.

[0384] Embodiment 116 The front and rear outer hydrogel layers independent of each other have an equilibrium water content of at least about 90% by weight, the contact lens according to any one of Embodiments 1 to 113.

[0385] Embodiment 117 The front and rear outer hydrogel layers independent of each other have an equilibrium water content of at least 95% by weight, the contact lens according to any one of Embodiments 1 to 113.

[0386] Embodiment 118 The front and rear outer hydrogel layers that are independent of each other are the contact lenses according to any one of Embodiments 1 to 117, which substantially do not contain silicone.

[0387] Embodiment 119 The front and rear outer hydrogel layers that are independent of each other are the contact lenses according to any one of Embodiments 1 to 117, which do not contain any silicone.

[0388] Embodiment 120 The contact lens further includes two transition layers of polymer material, and each of the two transition layers is located between the inner layer or the lens bulk material and one of the front and rear outer hydrogel layers, which is the contact lens according to any one of Embodiments 1 to 119.

[0389] Embodiment 121 The two transition layers are integrated at the peripheral edge of the contact lens and completely surround the inner layer or the lens bulk material of the lens material, which is the contact lens according to Embodiment 120.

[0390] Embodiment 122 The two transition layers have a thickness of at least about 0.05 μm when fully hydrated, which is the contact lens according to Embodiment 120 or 121.

[0391] Embodiment 123 The two transition layers have a thickness of about 0.05 μm to about 10 μm when fully hydrated, which is the contact lens according to Embodiment 120 or 121.

[0392] Embodiment 124 The two transition layers have a thickness of about 0.1 μm to about 7.5 μm when fully hydrated, which is the contact lens according to Embodiment 120 or 121.

[0393] Embodiment 125 The two transition layers have a thickness of about 0.1 μm to about 5 μm when fully hydrated, which is the contact lens according to Embodiment 120 or 121.

[0394] Embodiment 126 The contact lens according to any one of Embodiments 120 to 125, wherein each of the two transition layers is a layer of a polyanionic polymer neutralized and crosslinked by a polyaziridine having at least two aziridine groups and a number average molecular weight of 2000 daltons or less.

[0395] Embodiment 127 The contact lens according to Embodiment 126, wherein the polyanionic polymer is a carboxyl-containing polymer containing at least 60 mol% of repeating units of one or more carboxyl-containing acrylic monomers.

[0396] Embodiment 128 The contact lens according to 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.

[0397] Embodiment 129 The contact lens according to Embodiment 126, wherein the polyanionic polymer is a graft polymer grafted onto an inner layer or a lens bulk material, and the graft polymer comprises repeating units of at least one carboxyl-containing vinyl monomer.

[0398] Embodiment 130 The polyanionic polymer is a graft polymer grafted onto an inner layer or a lens bulk material, and the graft polymer comprises repeating units of at least one carboxyl-containing acrylic monomer, the contact lens according to Embodiment 127.

[0399] Embodiment 131 The polyaziridine is trimethylolpropane tris(2-methyl-1-aziridinepropionate), pentaerythritol tris[3-(1-aziridinyl)propionate], trimethylolpropane tris(3-azirinopropionate), a Michael reaction product of a vinyl crosslinker having at least two (meth)acryloyl groups and 2-methylaziridine or aziridine, or a combination thereof, the contact lens according to any one of Embodiments 126 to 130.

[0400] Embodiment 132 The front and rear outer hydrogel layers, which are independent of each other, have a reduced surface elastic modulus of at least about 25% compared to the inner layer, the contact lens according to any one of Embodiments 1 to 131.

[0401] Embodiment 133 The front and rear outer hydrogel layers, which are independent of each other, have a reduced surface elastic modulus of at least about 30% compared to the inner layer, the contact lens according to any one of Embodiments 1 to 131.

[0402] Embodiment 134 The front and rear outer hydrogel layers, which are independent of each other, have a reduced surface elastic modulus of at least about 35% compared to the inner layer, the contact lens according to any one of Embodiments 1 to 131.

[0403] Embodiment 135 The front and rear outer hydrogel layers, which are independent of each other, have a reduced surface elastic modulus of at least about 40% compared to the inner layer, the contact lens according to any one of Embodiments 1 to 131.

[0404] Embodiment 136 The contact lens according to any one of Embodiments 1 to 135, having a friction score of about 1.5 or less after 30 cycles of finger rubbing treatment.

[0405] Embodiment 137 The contact lens according to any one of Embodiments 1 to 135, having a friction score of about 1.0 or less after 30 cycles of finger rubbing treatment.

[0406] Embodiment 138 The contact lens according to any one of Embodiments 1 to 135, having a friction score of about 0.5 or less after 30 cycles of finger rubbing treatment.

[0407] Embodiment 139 The front surface and the opposite rear surface, A polyquaternium-1 uptake rate (「PU」) of about 0.40 micrograms / lens or less (or about 0.30 micrograms / lens or less), After 30 cycles of finger rubbing treatment, or at least 10 seconds of water disintegration time after simulated polishing cycling treatment, Along the shortest line between the front surface and the rear surface of the surface of the cross-section of the contact lens, including the front surface and the front outer band proximal thereto, including the central part of the shortest line and the inner band peripheral thereto, and including the rear surface and the rear outer band proximal thereto, having a cross-sectional surface-modulus profile, and having a structural form, a contact lens, The front outer band has an average front surface modulus

Number

Number

[0408] Embodiment 140 The contact lens according to Embodiment 139, wherein the contact lens has a water disintegration time of at least 10 seconds after 30 cycles of finger rubbing treatment.

[0409] Embodiment 141 The contact lens according to Embodiment 139, wherein the contact lens has a water disintegration time of at least 12.5 seconds after 30 cycles of finger rubbing treatment.

[0410] Embodiment 142 The contact lens according to Embodiment 139, wherein the contact lens has a water disintegration time of at least 15 seconds after 30 cycles of finger rubbing treatment.

[0411] Embodiment 143 The contact lens according to Embodiment 139, wherein the contact lens has a water disintegration time of at least 17.5 seconds after 30 cycles of finger rubbing treatment.

[0412] Embodiment 144 The contact lens according to Embodiment 139, wherein the contact lens has a water disintegration time of at least 20 seconds after 30 cycles of finger rubbing treatment.

[0413] Embodiment 145 The contact lens according to Embodiment 139, wherein the contact lens has a water disintegration time of at least 10 seconds after simulated polishing cycling treatment.

[0414] Embodiment 146 The contact lens according to Embodiment 139, having a water disintegration time of at least 12.5 seconds after simulated polishing cycling treatment.

[0415] Embodiment 147 The contact lens according to Embodiment 139, having a water disintegration time of at least 15 seconds after simulated polishing cycling treatment.

[0416] Embodiment 148 The contact lens according to Embodiment 139, having a water disintegration time of at least 17.5 seconds after simulated polishing cycling treatment.

[0417] Embodiment 149 The contact lens according to Embodiment 139, having a water disintegration time of at least 20 seconds after simulated polishing cycling treatment.

[0418] Embodiment 150 The front surface and the opposite rear 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 score of about 2.0 or less after 30 cycles of finger rubbing treatment or after simulated polishing cycling treatment, A cross-sectional surface-modulus profile including a front outer zone including the front surface and proximal thereto along the shortest line between the front surface and the rear surface of the surface of the cross-section of the contact lens, an inner zone including the central portion of the shortest line and peripheral thereto, and a rear outer zone including the rear surface and proximal thereto. A contact lens having a structural form characterized by having, The front outer zone has an average front surface modulus

Number

[0419] Embodiment 151 The contact lens has a friction score of about 2.0 or less after 30 cycles of finger rubbing treatment, the contact lens according to Embodiment 150.

[0420] Embodiment 152 The contact lens has a friction score of about 1.5 or less after 30 cycles of finger rubbing treatment, the contact lens according to Embodiment 150.

[0421] Embodiment 153 The contact lens has a friction score of about 1.0 or less after 30 cycles of finger rubbing treatment, the contact lens according to Embodiment 150.

[0422] Embodiment 154 The contact lens has a friction score of about 0.5 or less after 30 cycles of finger rubbing treatment, the contact lens according to Embodiment 150.

[0423] Embodiment 155 The contact lens has a friction score of about 2.0 or less after simulated polishing cycling treatment, the contact lens according to Embodiment 150.

[0424] Embodiment 156 The contact lens according to Embodiment 150, which has a friction score of about 1.5 or less after simulated polishing cycling treatment.

[0425] Embodiment 157 The contact lens according to Embodiment 150, which has a friction score of about 1.0 or less after simulated polishing cycling treatment.

[0426] Embodiment 158 The contact lens according to Embodiment 150, which has a friction score of about 0.5 or less after simulated polishing cycling treatment.

[0427] Embodiment 159

Number

[0428] Embodiment 160

Number

[0429] Embodiment 161

Number

[0430] Embodiment 162

Number

[0431] Embodiment 163 The 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.

[0432] Embodiment 164 The 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.

[0433] Embodiment 165 The 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.

[0434] Embodiment 166 The 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.

[0435] Embodiment 167 The 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.

[0436] Embodiment 168 The contact lens according to any one of Embodiments 1 to 167, having a UVB transmittance of about 10% or less at 280 to 315 nanometers, a UVA transmittance of about 30% or less at 315 to 380 nanometers, and a violet transmittance of 0% to about 70% at 380 nm to 440 nm.

[0437] Embodiment 169 The contact lens is the contact lens according to Embodiment 168, having a UVB transmittance of about 5% or less at 280 to 315 nanometers.

[0438] Embodiment 170 The contact lens is the contact lens according to Embodiment 168, having a UVB transmittance of about 2.5% or less at 280 to 315 nanometers.

[0439] Embodiment 171 The contact lens is the contact lens according to Embodiment 168, having a UVB transmittance of about 1% or less at 280 to 315 nanometers.

[0440] Embodiment 172 The contact lens is the contact lens according to any one of Embodiments 168 to 171, having a UVA transmittance of about 20% or less at 315 to 380 nanometers.

[0441] Embodiment 173 The contact lens is the contact lens according to any one of Embodiments 168 to 171, having a UVA transmittance of about 10% or less at 315 to 380 nanometers.

[0442] Embodiment 174 The contact lens is the contact lens according to any one of Embodiments 168 to 171, having a UVA transmittance of about 5% or less at 315 to 380 nanometers.

[0443] Embodiment 175 The contact lens is the contact lens according to any one of Embodiments 168 to 174, having a violet transmittance of 5% to about 60% at 380 to 440 nanometers.

[0444] Embodiment 176 The contact lens is the contact lens according to any one of Embodiments 168 to 174, having a violet transmittance of 5% to about 50% at 380 to 440 nanometers.

[0445] Embodiment 177 The contact lens is the contact lens according to any one of Embodiments 168 to 174, having a violet transmittance of about 5% to about 40% at 380 to 440 nanometers.

[0446] Embodiment 178 The contact lens is the contact lens according to any one of Embodiments 1 to 177, which substantially does not contain (i.e., less than 3) surface crack lines visible to the eye under dark field after rubbing the contact lens 10 times between fingers.

[0447] Embodiment 179 The contact lens is the contact lens according to any one of Embodiments 1 to 177, which does not contain any surface crack lines visible to the eye under dark field after rubbing the contact lens 10 times between fingers.

[0448] 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. References to the following examples are proposed to enable the reader to better understand a particular embodiment and its advantages. The specification and examples are intended to be regarded as exemplary.

Examples

[0449] Example 1 Chemical substance In the following examples, the following abbreviations are used. AMA represents allyl methacrylate, NVP represents N-vinylpyrrolidone, DMA represents N,N-dimethylacrylamide, VMA represents N-vinyl-N-methylacetamide, MMA represents methyl methacrylate, TEGDMA represents triethylene glycol dimethacrylate, TEGDVE represents triethylene glycol divinyl ether, EGMA represents ethylene glycol methyl ether methacrylate, VAZO64 represents 2,2-dimethyl-2,2-azodipropionitrile, Nobloc is 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate from Aldrich, UV28 represents 2-{2’-hydroxy-3’-tert-butyl-5’-[3’-methacryloyloxypropoxy]phenyl}-5-chloro-2H-benzotriazole, RB246 is Reactive Blue246, RB247 is Reactive Blue247, TAA represents tert-amyl alcohol, PrOH represents 1-propanol, IPA represents isopropanol, PAA represents polyacrylic acid, PMAA represents polymethacrylic acid, PAE represents polyamideamine-epichlorohydrin (also known as polyamine-epichlorohydrin), MPC represents 2-methacryloyloxyethyl phosphorylcholine, poly(AAm-co-AA) represents poly(acrylamide-co-acrylic acid), PZ-28 represents trimethylolpropane tris(2-methyl-1-aziridinepropionate), PZ-33 represents pentaerythritol tris[3-(1-aziridinyl)propionate], BTP or bis-tris-propane represents bis[tris(hydroxymethyl)methylamino]propane, tris-HCl represents tris(hydroxymethyl)aminomethane hydrochloride, EDTA represents ethylenediaminetetraacetic acid, PBS has a pH of 7.2 ± 0.2 at 25°C and contains approximately 0.044 wt% Na 2 PO 4 ·H 2 O, approximately 0.388 wt% Na 2 HPO 4 2H 2Phosphate buffered saline containing O 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.), LM-CEPDMS represents dimethacrylate-terminated chain-extended polydimethylsiloxane (Mn: about 6000 g / mol) having three polydimethylsiloxane (PDMS) segments bonded by a diurethane bond between two PDMS segments and two urethane bonds, each located between one terminal methacrylate group and one PDMS segment, and prepared according to a method similar to that described in Example 2 of U.S. Patent No. 8,529,057, the "GA" macromer represents dimethacryloyloxypropyl-terminated polysiloxane of formula (A) (Mn: about 6,800 g / mol, OH content: about 1.2 meq / g), and the "G4" macromer represents dimethacryloyloxypropyl-terminated polysiloxane of formula (A) (Mn: about 13,500 g / mol, OH content: about 1.8 meq / g).

Chemical formula

[0450] Measurement of oxygen permeability The apparent oxygen permeability (Dk app ) and apparent oxygen transmission rate (Dk / t) of a lens or lens material, and the intrinsic (or edge-corrected) oxygen permeability (Dk c ) are determined according to the procedure described in Example 1 of U.S. Patent Application Publication No. 2012 / 0026457A1.

[0451] Finger rubbing treatment Rub the lens for 20 seconds using RENU (registered trademark) multi-purpose lens care solution (or another multi-purpose lens care solution) (while wearing disposable powder-free latex gloves), followed by rinsing with saline. Repeat the above procedure i times (i.e., i cycles of rubbing) to mimic the daily cleaning in an i-day lens care regimen, e.g., 7 times (i.e., 7 cycles of rubbing) to mimic the daily cleaning and disinfection in a 7-day lens care regimen, or 30 times (i.e., 30 cycles of rubbing) to mimic the daily cleaning and disinfection in a 30-day lens care regimen.

[0452] Simulated polishing cycling process To simulate the worst-case scenario of manual cycling, use a simulated polishing technique to ensure certain pressure and shear conditions. To do this, manufacture a customized lens holder that clamps the lens and simultaneously shears the lens. As shown in Figure 3, place the lens (Part 1) on top of a rubber insert (Part 2) into which a central shaft (Part 3) with a diameter of 7.7 mm is axially inserted. Clip the upper clip (Part 4) onto the bottom clip (Part 5), thereby firmly holding the lens against the silicone gasket. Subsequently, extend the central shaft so that the lens protrudes above the external body surface, exposing the circumferential region of the lens around the central part 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 the visualization of the polishing.

[0453] Place the entire lens holder on the mounting end of a Taber linear polishing system (Taber Industries, model 5750, http: / / www.taberindustries.com / linear-abraser). Without attaching additional weights, the total weight of the support arm and the lens holder (230 g vertical force) is 47 mm 2Apply it to the contact lens area and apply 49 kPa to the counter surface. On the counter surface, place a silicone rubber sheet (10A, 1 / 4 inch thick) under the support arm and clip the reservoir channel to the silicone rubber. Subsequently, fill the reservoir with PBS at room temperature.

[0454] During the experiment, slowly lower the lens holder onto the counter surface and polish the lens 20 times at a cycle rate of 75 cycles per minute (total movement of 3 inches per stroke and 6 inches per cycle). The lens surface can be analyzed using the water disintegration time method, lubricity evaluation, and / or Sudan black staining test.

[0455] This technique applies shear forces that greatly exceed what typical contact lenses experience, but this controlled shear technique (i.e., simulated polishing cycling process) has been found to be a reasonable equivalent of 30 cycles of finger rubbing, ensuring that these contact lenses can handle even the most severe mechanical cycling.

[0456] Lubricity evaluation The lubricity of the contact lens is evaluated by using a finger - felt lubricity test that qualitatively characterizes the slipperiness of the lens surface on a friction rating scale of 0 - 4. The higher the friction rating, the lower the slipperiness (or lubricity).

[0457] Assign friction ratings of 0, 1, 2, 3, and 4 (hereinafter referred to as "FR") to the commercially available lenses DAILIES® TOTAL1®, ACUVUE® OASYS®, ACUVUE® ADVANCE PLUS®, DAILIES® Aqua Comfort Plus®, and AIR OPTIX®, respectively. These are used as standard lenses to determine the friction ratings of the lenses under test.

[0458] Place the samples in PBS for at least two rinses of 30 minutes each, and then transfer them to fresh PBS before evaluation. Before evaluation, wash your hands with soap solution, rinse thoroughly with DI water, and then wipe with a KimWipe® towel. Handle the samples between your fingers and assign a numerical value to each sample in relation to the above-described standard lens. For example, a numerical value of 3 is assigned if the lens is determined to be slightly better than the AIR OPTIX® lens. The value of the friction score is obtained by averaging the results of at least two friction scores of the contact lens by two or more persons and / or by averaging the friction scores of two or more contact lenses (from the same batch of lens production) by one person.

[0459] The finger lubricity (i.e., friction score) of the contact lens can be determined either out-of-pack (OOP) (but after being immersed in PBS for more than 30 minutes), or after finger rubbing treatment for i cycles (e.g., 7, 14, 21, or 30 cycles) according to the above procedure, or after simulated polishing cycling treatment.

[0460] Surface Wettability Test The water contact angle (WCA) on a contact lens is a general measure of the surface wettability of the contact lens. Specifically, a low water contact angle corresponds to a surface with higher wettability. The dynamic captive bubble contact angle of the contact lens is measured using an FDS measuring device manufactured by FDS Future Digital Scientific Corp. The FDS instrument can measure the advancing and receding contact angles. The measurement is carried out at room temperature on a hydrated contact lens. The contact lens is taken out of the vial and immersed in about 40 mL of fresh PBS and shaken for at least 30 minutes, then replaced with fresh PBS, immersed, and shaken for an additional 30 minutes unless otherwise specified. Subsequently, the contact lens is placed on lens paper, gently tapped to remove the water on the surface, then placed on a lens holder with an upward front curve, and then the upper part of the lens holder is screwed on. The fixed lens holder is placed in a glass cell cuvette filled with filtered PBS. The glass cell cuvette is placed on the stage of the FDS measuring instrument. The height of the stage and the injection needle is adjusted to distribute the bubbles onto the lens surface. The dispensing / withdrawal is repeated 3 cycles for all lenses to obtain the advancing and receding contact angles. The receding contact angle is reported in the following examples.

[0461] Water break-up time (WBUT) test The surface hydrophilicity of the lens (after autoclaving) is evaluated by determining the time required for the water film to begin to break down on the lens surface. Lenses showing a WBUT of 10 seconds or more are considered to have a hydrophilic surface and are expected to show sufficient wettability (ability to support the tear film) on the eye.

[0462] The lens is removed from its blister using soft plastic tweezers (e.g., those made by Menicon), and the lens is placed in a test tube containing phosphate buffered saline to prepare the lens for the water break-up measurement. This test tube contains 10 mL of phosphate buffered saline per lens and 1 lens per test tube. The lens is immersed overnight (at least 16 hours) before the test.

[0463] Measure the WBUT at room temperature as follows. Remove the lens from the test tube and place it on a pedestal submerged in PBS. Subsequently, lift the pedestal out of the PBS solution (t = 0), and a video camera monitors the fluid flowing down from the lens surface. Record this WBUT time when the fluid on the lens surface collapses. Optionally, a stopwatch can be used to measure the time between when the pedestal is lifted out of the PBS solution and when the fluid on the lens surface collapses. When the pedestal is lifted, the lens under the surface of the PBS is pulled. Measure at least three points per lens and at least three lenses to obtain the average WBUT measurement value for each lens group.

[0464] Equilibrium moisture content The equilibrium water content (EWC) of the contact lens is determined as follows.

[0465] Determine the amount of water (expressed as weight %) present in the hydrated hydrogel contact lens that is completely equilibrated in saline at room temperature. After blotting the lens with a cloth, quickly stack the lenses and transfer the lens stack to an aluminum dish on a chemical balance. The number of lenses in each sample dish is typically five. Record the hydrated weight of the dish and the lenses. Cover the dish with aluminum foil. Place the dish in a laboratory oven at 100 ± 2 °C and dry for 16 - 18 hours. Remove the dish and the 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 dish and the dry lens sample on a chemical balance. Repeat for all remaining ones. The wet and dry weights of the lens sample can be calculated by subtracting the weight of the empty weighing dish.

[0466] Elastic modulus The elastic modulus of the contact lens is determined using an MTS insight measuring instrument. First, the contact lens is cut into strips with a width of 3.12 mm using a Precision Concept 2-stage cutter. Five thickness values within a 6.5 mm gauge length are measured. The strip is placed on the grip of the measuring instrument and submerged in PBS with the temperature controlled at 21 ± 2°C. Typically, a 5 N load cell is used for the test. A constant force and speed are applied to the sample until the sample disintegrates. Force and displacement data are collected using TestWorks software. The elastic modulus value, which is the stress gradient in the elastic displacement region or the tangent to the strain curve near zero elongation, is calculated by TestWorks software.

[0467] Mechanical properties of the contact lens surface All contact lenses can have different mechanical properties on their surfaces. Specifically, in the case where the contact lens has a soft hydrogel coating on it. The mechanical properties of the region near and including the surface of the contact lens can be characterized by measuring the surface compressive force or indentation force as a function of displacement in a micro-indentation or nano-indentation test.

[0468] In the case of a contact lens that does not contain any soft hydrogel coating on it, the indentation force at a given displacement or indentation depth (e.g., 400 nm) is well related to the bulk (Young's) elastic modulus (i.e., there is a linear bulk elastic modulus-indentation force relationship between the bulk elastic modulus and the indentation force at a given displacement). On the other hand, in the case of a contact lens that has a soft hydrogel coating on it, it has been found that the indentation force at a given displacement is much smaller than that predicted based on the linear bulk elastic modulus-indentation force relationship. Such deviation can be used as a good indicator of the soft hydrogel coating on the contact lens.

[0469] Micro-indentation test The surface compressive force of the contact lens at a penetration depth of 400 nm is measured by the following micro-indentation test. The contact lens to be tested is rinsed and placed in PBS overnight. Subsequently, the lens is placed on a hemispherical stage submerged in PBS, and pushed in using a pressure-driven quasi-static transducer indenting system (Hysitron® BioSoft® In-Situ Indenter manufactured by Bruker) equipped with a 1 mm hemispherical borosilicate glass probe. Between each experiment, the probe is cleaned using a plasma cleaner (e.g., an oxygen, air, or argon plasma cleaner) and coated with F-127 Pluronic (by dipping it in an aqueous solution of F-127 with a concentration exceeding the CMC of F-127, e.g., about 0.1 wt%). The probe is attached to the indenting system and pulled down at a constant penetration rate of 1 μm / second along a typical loading curve and unloading curve (i.e., vertical force vs. penetration depth). The vertical force and displacement position (or penetration depth) are simultaneously measured by the quasi-static transducer at a rate of 125 Hz. The above procedure is repeated 20 times per lens (i.e., 20 penetrations). The surface compressive force (in units of micronewtons (μN)) at a penetration depth of 400 nm is obtained by averaging all the vertical forces at a penetration depth of 400 nm along each of the 20 penetration loading curves. The normalized surface compressive force (NSCF) is obtained by dividing the obtained surface compressive force at a penetration depth of 400 nm by the elastic modulus of the contact lens under test.

[0470] Nano-indentation test The indentation force of the contact lens at a penetration depth of 400 nm is measured by the following micro-indentation test.

[0471] Using the Optics11 Piuma device, the indentation force is determined as a function of displacement. Before performing the indentation, the Piuma probe is calibrated in PuriLens (trademark) Plus, a sterile and preservative-free saline solution manufactured by LifeStyle Company, Inc. (Freehold, NJ). This calibration consists first of submerging the probe into PuriLens (trademark) Plus without engaging the surface of the substrate, thereby calibrating the optical sensor. Next, a second cantilever calibration is performed by forming a test indentation on a glass slide. The lens is rinsed with PuriLens (trademark) Plus to wash away excess lens package solution and then blot dried. Next, the lens is placed in a 3D printed lens holder with the front curve facing down (Figure 4). Subsequently, to position the lens at a predetermined location, PuriLens (trademark) Plus is partially filled in the base curve, provided that the amount of PuriLens (trademark) Plus added should not be so much that the base curve overflows during the test. Finally, the Piuma probe is moved just above the lens surface and the nano-indentation routine is executed according to the manufacturer's typical procedure. The indentation routine consists of a 10 μm indentation at a speed of 1 μm / second, and the sampling speed is at a speed of 100 Hz. The probe moves to the surface where the contact point is determined by the first deflection detected by the cantilever.

[0472] Two different Piuma probes are used to collect data. The first is a Piuma probe with a stiffness of 0.500 N / m and a tip radius of 9.500 μm, and the other is a Piuma probe with a stiffness of 4.710 N / m and a tip radius of 9.000 μm. Since both probes are pushed to the same depth (400 nm), the contact area is slightly different. The contact area (S cap ) of these spherical caps can be calculated by the following formula: S cap =2πRh where "R" is the tip radius and h is the indentation depth. Thus, the two probe tips are 23.9 μm at an indentation depth of 400 nm2 and 22.6 μm 2 of the contact surface area, or only a 5% difference. The pressure of the resulting 9-μm tip should be only 5% higher than that of the 9.5-μm tip. This small pressure difference should have little effect on the measured forces compared between these tips.

[0473] It should be understood that it is more desirable to use a single type of Piuma probe for all nano-indentation experiments. However, if multiple Piuma probes are required to optimize contact lens measurements with a wide range of bulk elastic moduli (e.g., 0.2 MPa to 1.5 MPa), Piuma probes with a tip radius difference of about 10% or less can be used.

[0474] When indentation is performed, both the depth of indentation and the indentation force are recorded. Five lenses per lens type are tested, and three measurements are made per lens. This results in a total of 15 data points per lens group.

[0475] All raw data are processed using MATLAB and analyzed using Excel. The indentation force value at an indentation depth of 400 nm is determined by interpolating between the two closest force values. For each lens group, all indentation forces at an indentation depth of 400 nm are averaged, and the contact lens of that lens group is characterized using the averaged indentation force at an indentation depth of 400 nm.

[0476] Transmittance The contact lens is manually placed into a special sample holder or the like that can hold the shape of the lens as it is when placed on the eye. This holder is then submerged in a quartz cell with a path length of 1 cm containing PBS as a standard. A UV / visible spectrophotometer such as a Varian Cary 3E UV-visible spectrophotometer equipped with a LabSphere DRA-CA-302 beam splitter or the like can be used for this measurement. The percent of the transmission spectrum is collected in the wavelength range of 250 - 800 nm, and the T value is collected at 0.5 nm intervals. This data is transferred onto an Excel spreadsheet and used to determine whether the lens conforms to Class 1 UV absorbance. The transmittance is calculated using the following equation, [Number] wherein the emitted %T is the average % transmittance of 380 - 780.

[0477] Determination of the polyquaternium-1 uptake rate (PU). The polyquaternium-1 uptake rate by the contact lens is determined according to the DNA intercalation method based on the PicoGreen dsDNA assay kit (i.e., Quanti-iT PicoGreen dsDNA kit (ThermoFisher)). The polyquaternium-1 uptake rate by the contact lens is determined as follows.

[0478] A reference solution is prepared by dissolving the components of 5 ppm myristamidopropyl dimethylamine, 1000 ppm sodium decanoyl ethylenediamine triacetate, 83 ppm sodium citrate dehydrate, 1000 ppm NaCl, 1000 ppm Tetronic 1304, 1150 ppm sodium borate decahydrate, and 10000 ppm propylene glycol in purified water and then adjusting the pH to approximately 7.8.

[0479] A polyquaternium-1 (PQ) test solution is prepared by dissolving a desired amount in the reference solution prepared above to have 5 ppm of PQ, and then adjusting the pH to about 7.8 as necessary. A series of PQ standard solutions with concentrations within the respective ranges are prepared to establish a calibration curve between 0 and 6 ppm (or more) of PQ.

[0480] Remove the contact lenses from the individual lens packages and shake them in 25 mL of PBS per lens for 30 minutes. Blot the lenses immersed in PBS with a paper towel of a constant weight (i.e., 0.6 kg), preferably a W4 polypropylene towel made by Kimberly Clark, and then incubate overnight.

[0481] In the overnight incubation experiment, a 24-well plate is used. The wells are divided into the following categories: negative control wells each containing 0.5 mL of the reference solution and two blotted contact lenses completely immersed therein, positive control wells containing 0.5 mL of the polyquaternium-1 test solution, sample wells each containing 0.5 mL of the polyquaternium-1 test solution and two blotted contact lenses completely immersed therein, and standard wells each containing 0.5 mL of one of the standard solutions. Subsequently, the 24-well plate is shaken on an orbital shaker for 20 minutes and then placed on a bench top at room temperature overnight (16 - 20 hours).

[0482] Add 25 μL aliquots from each well of the 24-well plate incubated overnight to the cell wells of a 96-well plate (e.g., DNA LoBind (Eppendorf)) containing 450 μL of a lambda DNA solution (1 μg / mL lambda DNA, 10 mM Tris-HCl, 1 mM EDTA, pH 7.5). Mix the solutions and incubate on an orbital shaker at 700 - 800 rpm for 60 minutes.

[0483] A 100 μL aliquot from each cell well incubated with DNA is transferred to a 96-well plate (e.g., black opaque, medium binding (Grenier)). Subsequently, 100 μL of PicoGreen solution (diluted with Tris-EDTA buffer [10 mM Tris-HCl, 1 mM EDTA, pH 7.5] according to the kit instructions from ThermoFisher) is added to and mixed with each of these wells. Subsequently, the cell wells are incubated on an orbital shaker at 250 rpm for 5 minutes. Each plate is read using a fluorescence plate reader (e.g., Victor X5 Plate Reader (Perkin Elmer)) that uses standard fluorescence excitation and emission wavelengths for PicoGreen. Each sample is compared to the 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 the incubation volume and dividing by the number of lenses incubated. The PQ uptake rate by the lens is calculated by multiplying the difference in [polyquaternium-1] between the positive control incubated with DNA and the sample solution by the incubation volume (0.5 mL) and dividing by 2.

[0484] Surface Crack (SC) Test A test for evaluating surface cracks is carried out as follows. Take the lens out of the package. Gently invert the lens (i.e., put the lens in an inverted form) by holding the edge of the lens between the thumb and index finger of one hand. The concave side of the lens should face the experimenter's body. With the thumb and / or index finger of the other hand, gently bend the top of the lens on the index finger holding the lens until the lens confirmation inverts. Subsequently, gently fold the lens in half and apply slight pressure to the folded lens. Then, return the lens to its original form before inversion and repeat the above steps. Place the lens on a Petri dish and examine the lens using a dark-field stereomicroscope. First, examine the surface cracks of the lens at a low magnification (i.e., 10 - 20 times) with the focus on the center of the lens. If the crack lines are not distinguishable, further examine the lens at a high magnification (e.g., 35 - 45 times). If no cracks are observed at a magnification of 45 times, the lens obtains a surface crack score of zero (0). If cracks are observed, a crack score is obtained by counting the number of dividing lines. Score 1 is 2 - 4 lines in the field of view, score 2 is 5 - 8 lines, and score 3 is 8 or more lines.

[0485] Coating Intactness Test The integrity of the coating on the surface of the contact lens can be tested according to the Sudan black staining test as follows. A contact lens having 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). The Sudan black dye is hydrophobic and has a high tendency to be adsorbed by hydrophobic materials or on hydrophobic spots on the hydrophobic lens surface or on the partially coated surface of a hydrophobic lens (such as a silicone hydrogel contact lens). If the coating on the hydrophobic lens is intact, no stained spots should be observed on or in the lens. All lenses under test are fully hydrated. Fine visible lines on the lens surface may indicate the presence of cracks in the crosslinked coating.

[0486] Comparative Example To reduce the uptake rate of the positively charged antibacterial agent by the water gradient contact lens, the method disclosed in U.S. Patent Application Publication No. 2016 / 0326046A1 is used in this example.

[0487] PMAA coating solution. The polymethacrylic acid (PMAA) coating solution is prepared by dissolving a certain amount of PMAA (Mn: 300 - 600 kDa (manufactured by Polysciences, Inc.)) in a predetermined volume of 1-propanol / water (90% / 10% wt / wt) mixture to a concentration of about 0.011 wt%, and adjusting the pH to about 2.0 using formic acid.

[0488] PAE solution - 1. The PAE solution is prepared by dissolving a certain amount of polyamine amine epichlorohydrin (Kymene) in a predetermined volume of water to a concentration of about 0.5 wt%, and adjusting the pH to the desired pH (e.g., 2.0, 3.5, 7, or 9).

[0489] PAE solution - 2. The PAE solution is prepared by dissolving a certain amount of polyamideamine epichlorohydrin (Kymene) in a mixture of a predetermined volume of water (68% by weight) and 1 - propanol (32% by weight) to a concentration of about 0.5% by weight, and the pH is adjusted to pH 2.0.

[0490] Preparation of the in - package coating (IPC) physiological saline (IPC - 1) About 90 mol% of 2 - methacryloyloxyethyl phosphorylcholine (MPC) and about 10 mol% of [Chemical formula] (wherein X is - CH 2 CH(OH)CH 2 SCH 2 CH 2 NH 2 or - CH 2 CH(CH 2 OH)SCH 2 CH 2 NH 2 (which is a monovalent radical of) and, the MPC - containing copolymer (Mw: 230 - 320 kD) is prepared according to a procedure similar to that described in Examples 1 - 2 of U.S. Patent No. 9127099B2. The MPC - containing copolymer used is an aqueous solution containing about 10% by weight of the solid content of the MPC - containing copolymer.

[0491] The PAE solution (Kymene) is purchased from Ashland as an aqueous solution and used as it is.

[0492] IPC - 1 physiological saline is prepared as follows. About 74% by weight of the MPC - containing copolymer solution, about 6% by weight of the PAE solution, and about 20% by weight of a phosphate buffer (about 0.22% by weight of NaH 2 PO 4 ·H 2 O, 1.95% by weight of Na 2 HPO 4 ·2H 2Mix (O, and about 4 wt% NaCl), where the concentrations of the MPC-containing copolymer and PAE are about 10 times that of the final physiological saline. Adjust the pH to about 7.3 with 1N NaOH. React the mixture in a water bath at 70 °C for 4 hours to form a water-soluble thermally crosslinkable polymer material (i.e., "in-package crosslinking agent" or "IPC agent"). Remove the mixture from the water bath and cool it in a water bath at room temperature. Dilute the mixture 10-fold with PBS and adjust the pH to about 7.3. Filter the mixture through a 0.22 μm PES sterile filter unit.

[0493] Cast-molded silicone hydrogel (SiHy) contact lens. The SiHy contact lens (uncoated) is cast-molded according to the procedure described in Example 3 of US Patent Application Publication No. 2016 / 0326046A1.

[0494] Application of the crosslinked coating. Extract the cast-molded SiHy contact lens and coat it by dipping it into a series of baths. Baths 1 - 3 - three MEK baths (about 22 seconds, about 138 seconds, and about 224 seconds respectively), Bath 4 - DI water bath (about 56 seconds), Baths 5 - 7 - as shown in Table 1, Bath 8 - DI water (about 56 seconds unless otherwise indicated), Bath 9 - DI water (about 56 seconds), Bath 10 - DI water (about 168 seconds). Unless otherwise indicated, the temperature of all baths is room temperature (i.e., about 22 - 26 °C). After Bath 10, individually package the contact lens in a polypropylene lens packaging shell (blister) with 0.6 mL of IPC-1 physiological saline (half of the IPC-1 physiological saline is added before inserting the lens). Subsequently, seal the blister with foil and autoclave at 121 °C for about 30 minutes to form a crosslinked coating on the lens.

[0495]

Table 1

[0496] Subsequently, the lenses were tested for the amount of carboxyl groups per lens according to the procedure described in Example 2 of US Patent No. 2016 / 0326046A1, and also subjected to a finger rubbing test according to the procedure described in Example 1 to evaluate lubricity (friction rating).

[0497] The control lenses (C3 and C4) and the test lenses (T8 and T9) have a lubricity degree of 4 in the as-taken-out state from the package and without undergoing a cycling-lubricity test. Such results may indicate that when heating lenses containing a PMAA coating thereon, a significant amount of PMMA is lost, so that only an insufficient amount of PMAA remains on the lens to react with the thermally crosslinkable material to form a hydrogel top coating.

[0498] The test lenses (T2 and T3) have a lubricity degree of 3 and 4, respectively, in the as-taken-out state from the package. Such results may indicate that at high pH (7 or 9), PMAA is filled and PAE cannot penetrate into the PMAA coating but forms a layer on top of the PMAA coating. The upper layer of PAE prevents the underlying PMAA from reacting with the thermally crosslinkable polymer material to form a hydrogel top coating. In the autoclave, the upper layer of PAE crosslinks with the PMAA coating to form a crosslinked coating with poor lubricity.

[0499] The results in Table 2 indicate that the approach disclosed in US Patent Application Publication No. 2016 / 0326046A1 may not be sufficient to produce a water gradient contact lens that has sufficient lubricity after cycling with a Renu lens care solution and has no significant decrease in the uptake rate of the positively charged antibacterial agent.

[0500]

Table 2

[0501] Example 2 Preparation of the polymerizable composition Two lens formulations (polymerizable compositions) I and II are prepared to have the compositions shown in Table 3 (in parts as units).

[0502]

Table 3

[0503] The listed components are added to a clean bottle in their target amounts and the formulation is prepared by mixing at 600 rpm for 30 minutes using a stir bar at room temperature. After all solids have dissolved, the formulation is filtered using a 2.7 μm glass microfiber filter (GMF).

[0504] Cast silicone hydrogel contact lens The lens formulation is purged with nitrogen at room temperature for 30 - 35 minutes. N 2 The lens formulation purged with N is introduced into a polypropylene mold and thermally cured under the following curing conditions: ramping from room temperature to 55 °C at a ramp rate of about 7 °C / min, holding at 55 °C for about 30 minutes, ramping from 55 °C to 80 °C at a ramp rate of about 7 °C / min, holding at 55 °C for about 30 minutes, ramping from 80 °C to 100 °C at a ramp rate of about 7 °C / min, holding at 100 °C for about 30 minutes. The mold is opened and the molded lens is removed from the mold.

[0505] Formulations I and II are used in the coating studies of the following examples. Generally, formulation II is used unless otherwise instructed.

[0506] The resulting silicone hydrogel (SiHy) contact lenses are subjected to the following post - molding processes before lens characterization. After demolding, the SiHy lenses prepared above are immersed in PBS twice at room temperature for about 60 minutes. After rinsing with PBS for 5 minutes, the lenses are placed in a polypropylene lens packaging shell (or blister) (1 lens per shell) with 0.6 mL of PBS. Subsequently, the blisters are sealed with foil and autoclaved at about 121 °C for about 45 minutes. The SiHy lenses have an oxygen permeability of about 91 barrer (for formulation I) or about 83 barrer (for formulation II) (measured by polarography), a bulk modulus of about 0.80 MPa (for formulation I) or 0.67 MPa (for formulation II), a water content of about 49 wt% (for formulation I) or about 50 wt% (for formulation II), a relative ion permeability of about 12.5 with respect to the Alsacon lens (for formulation I) or about 11.0 with respect to the Alsacon lens (for formulation II), a WBUT of 0 seconds, and a friction rating of 4.

[0507] Example 3 Preparation of the Polymerizable Composition Lens formulations (polymerizable compositions) III - VI are prepared to have the compositions (in parts as units) shown in Table 4.

[0508]

Table 4

[0509] The listed components are added to a clean bottle in their target amounts and the formulation is prepared by mixing at 600 rpm for 30 minutes using a stir bar at room temperature. After all solids are dissolved, the formulation is filtered using a 2.7 μm glass microfiber filter.

[0510] Cast - Molded Silicone Hydrogel Contact Lenses The lens formulation is purged with nitrogen at room temperature for 30 - 35 minutes. N 2The purged lens formulation is introduced into a polypropylene mold and thermally cured in an oven under the following curing conditions: ramping from room temperature to a first temperature and then holding at the first temperature for a first curing time, ramping from the first temperature to a second temperature and holding at the second temperature for a second curing time, optionally ramping from the second temperature to a third temperature and holding at the third temperature for a third curing time, and optionally ramping from the third temperature to a fourth temperature and holding at the fourth temperature for a fourth curing time.

[0511] Open the lens mold using a mold release machine equipped with a pressing pin. Push the lens out onto the base curve mold using the pressing pin and then separate the mold into a base curve mold half and a front curve mold half. Place the base curve mold half with the lens on it into an ultrasonic device (e.g., a Dukane single horn ultrasonic device). Release the dry lens from the mold using a specific energy force. Load the dry lens into a designed extraction tray. Alternatively, the lens can be removed from the base curve mold half by floating off (i.e., immersing in an organic solvent such as IPA without ultrasonic).

[0512] The obtained silicone hydrogel (SiHy) contact lenses are subjected to the following post-molding processes before the lens characteristics are evaluated. After demolding, the SiHy lens prepared above is extracted with 100% IPA for 15 minutes, immersed in a 50% / 50% IPA / water mixture for 30 minutes, followed by immersion in 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 lens is placed in a polypropylene lens packaging shell (or blister) (1 lens per shell) together with 0.6 mL of PBS. Subsequently, the blister is sealed with foil and autoclaved at about 121 °C for about 45 minutes. The obtained SiHy contact lenses are evaluated for characteristics according to the procedure for having the following properties: Dkc: about 105 barrer - 118 barrer, EWC: about 54% - 57%, elastic modulus: about 0.45 MPa - 0.62 MPa, WBUT: about 23 seconds - 40 seconds, water contact angle by trapped bubbles: about 47 degrees - 52 degrees, friction score: about 2.0.

[0513] Example 4 Preparation of Aqueous PAA Solution An aqueous solution of polyacrylic acid (PAA) is prepared by adding an appropriate amount of PAA (Mn: about 450 KD) 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 wt%. The prepared PAA aqueous solution is filtered to remove any fine particles or foreign matter.

[0514] Phosphate Buffered Saline (PBS) NaH 2 PO 4 ·H 2 O, Na 2 HPO 4 ·2H 2 O is dissolved in a predetermined amount of purified water (distilled or deionized) to obtain about 0.044 wt / wt% NaH 2 PO 4 ·H 2 O, about 0.388 wt / wt% Na 2 HPO 4 ·2H 2Prepare phosphate buffered saline by making the composition about 0.01 M phosphate buffer, about 0.0027 M KCl, about 0.137 M NaCl, and about 0.79 wt / wt% NaCl.

[0515] Phosphate buffered (PB) without NaCl (PB, No NaCl) Prepare PB using the same procedure as for the preparation of PBS but without adding NaCl.

[0516] IPC-2 saline Prepare IPC-2 saline by dissolving / mixing appropriate amounts of poly(AAm-co-AA) (90 / 10), PAE, NaH 2 PO4·H 2 O, Na 2 HPO 4 ·2H 2 O, and NaCl in DI (deionized) water and then adjusting the pH to about 7.3. Poly(AAm-co-AA) (90 / 10) partial sodium salt (Mw 200,000) is purchased from Polysciences, Inc. and used as received. Pretreat the prepared solution at 65 °C for about 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 an increase in the number of contaminating microorganisms, and filter the IPC saline using a 0.22 micrometer membrane filter.

[0517] SiHy lens with PAA-based coating It should be noted that there may be some inaccuracies in the original Japanese text, especially in the chemical formula parts. The translation is based on the best understanding and translation of the provided content.After release, the dried SiHy contact lens (Example 2, prepared with Formulation II) is placed in a suitable tray. Subsequently, the tray containing the lens is immersed in a PAA solution for a predetermined time, either for 120 minutes in one PAA bath or in two sequential PAA baths, dipping in the first bath for 30 minutes and in the second bath for 90 minutes. Heat the PAA dip solution above room temperature, for example, to 40 °C. Sufficient agitation (e.g., horizontal oscillation or up-and-down movement) may be used to ensure an appropriate flow of the PAA solution during the dipping process.

[0518] After dipping in PAA, transfer the lens to a bath containing PB for up to about 1 hour, usually at room temperature. Sufficient agitation (e.g., horizontal oscillation or up-and-down movement) may be used to ensure an appropriate flow of the PB during the dipping process.

[0519] Subsequently, transfer the lens to a bath containing water for about 5 - 10 minutes, usually at room temperature. Sufficient agitation (e.g., horizontal oscillation or up-and-down movement) may be used to ensure an appropriate flow of the water during the dipping process.

[0520] Water gradient SiHy contact lens Place the SiHy lens having a PAA-based coating prepared as described above into a polypropylene lens packaging shell together with 0.55 mL or 0.65 mL of IPC-2 saline (one lens per shell) (about half of the saline may be added before inserting the lens). Subsequently, seal the blister with foil and autoclave at about 121 °C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., a hydrogel coating) thereon.

[0521] Surface properties of the water gradient SiHy contact lens The resulting water gradient SiHy contact lens is lubricious (has a friction rating of 1) as removed from the package, has a WBUT exceeding 10 seconds, and a water contact angle with a droplet (static) of about 30 degrees.

[0522] Example 5 In this example, the water-gradient contact lenses prepared in Example 4 are used. These are determined to have a PU (polyquaternium-1 uptake rate) of about 9 μg / lens.

[0523] Preparation of polyaziridine aqueous solution 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.

[0524] Reduction of PU by water-gradient contact lenses The water-gradient contact lenses prepared in Example 4 are individually repackaged in polypropylene lens packaging shells together with 0.55 mL or 0.65 mL of 1% PZ-28 solution (1 lens per shell) and autoclaved at about 121 °C for about 45 minutes. The resulting lenses are still lubricious (having a friction score of 1), with a PU of 0.56 μg / lens, that is, a 93.8% reduction in PU.

Number

[0525] The water-gradient contact lenses prepared in Example 4 are individually repackaged in polypropylene lens packaging shells together with 0.55 mL or 0.65 mL of 1% PZ-33 solution (1 lens per shell) and autoclaved at about 121 °C for about 45 minutes. The resulting lenses are still lubricious (friction score of 1), with a PU of 1.95 μg / lens, that is, a 78.3% reduction in PU.

[0526] Example 6 Preparation of PMAA solution The solution of polymethacrylic acid (PMAA) is prepared by adding an appropriate amount of PMAA (Mn: about 400 - 700 kDa (manufactured by 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 fine particles or foreign matter.

[0527] Phosphate Buffered Saline (PBS) PBS is prepared according to the procedure described in Example 4.

[0528] Phosphate Buffer without NaCl (PB) (PB, No NaCl) PB is prepared according to the procedure described in Example 4.

[0529] Preparation of Aqueous Polyaziridine Solution 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.

[0530] IPC - 3 Physiological Saline About 90 mol% of 2 - Methacryloyloxyethyl Phosphorylcholine (MPC) and about 10 mol% of

Chemical Formula

[0531] The PAE solution (Kymene) is purchased from Ashland as an aqueous solution and used as it is.

[0532] IPC-3 physiological saline is prepared as follows. Mix about 74.3% by weight of the MPC-containing copolymer solution, about 3.7% by weight of the PAE solution, and about 22% by weight of a phosphate buffer (about 0.22% by weight of NaH 2 PO 4 ·H 2 O, 1.95% by weight of Na 2 HPO 4 ·2H 2 O, and about 4% by weight of NaCl) (the concentrations of the MPC-containing copolymer and PAE are about 10 times that of the final physiological saline). Adjust the pH to about 7.3 with 1N NaOH. React the mixture in a water bath at 70°C for 4 hours to form a water-soluble thermally crosslinkable polymer material (i.e., the "in-package crosslinking agent" or "IPC agent"). Remove the mixture from the water bath and cool it in a water bath at room temperature. Dilute the mixture 10-fold with PBS and adjust the pH to about 7.3. Filter the mixture through a 0.22 μm PES sterile filter unit.

[0533] Water gradient SiHy contact lens After release, the cast SiHy contact lens (prepared in Example 3) was 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) together with 0.6 mL of IPC-3 saline (half of the IPC-3 saline is added before inserting the lens). The sealed lens package was autoclaved at about 121 °C for about 45 minutes to form a SiHy contact lens having a crosslinked hydrophilic coating (i.e., a hydrogel coating) thereon. The uniformity or integrity of the coating was tested by a Sudan black dye test, and the coating passed the Sudan black dye test.

[0534] The resulting water gradient SiHy contact lens is quite lubricious (having a friction score of 2), WBUT is more than 10 seconds, and PU (polyquaternium-1 uptake rate) is 1.2 μg / lens.

[0535] Reduction of PU uptake rate by water gradient contact lens The water gradient contact lens prepared above was repackaged individually (one lens per shell) in a polypropylene lens packaging shell together 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 lens is still quite lubricious (having a friction score of about 1.7), the PU is 0.06 μg / lens, that is, the reduction of PU is 95%.

Number

[0536] The water gradient contact lenses prepared above were individually repackaged (one lens per shell) in polypropylene lens packaging shells together with 0.55 mL or 0.65 mL of 1% PZ-33 solution and autoclaved at about 121 °C for about 45 minutes. The resulting lenses were still lubricious (friction score of about 1.0), with PU being 0.32 μg / lens, i.e., a 73.3% reduction in PU.

[0537] Example 7 In this example, water gradient contact lenses prepared according to the procedure described in Example 19 of U.S. Patent No. 8,480,227 are used. The water gradient SiHy contact lenses have a water content of about 32 wt%, an oxygen permeability of about 146 barrer, a bulk modulus of elasticity of about 0.76 MPa, a relative ion permeability of about 6 (compared to the Alsacon lens), a friction score of 0, a WBUT of more than 20 seconds, a water contact angle of about 34 - 47 degrees (by static droplet), and about 11 μg / lens of PU, respectively.

[0538] Preparation of BTP solution A bis-tris-propane (BTP) solution is prepared by dissolving BTP in deionized (DI) or distilled water to a concentration of 0.03% and then adjusting the pH to 7.5.

[0539] Preparation of polyaziridine aqueous solution PZ-28BTP 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.

[0540] A PZ-28 phosphate buffer solution with a PZ-28 concentration of 0.1 wt% is prepared by simply adding PZ-28 to PBS and adjusting the pH to about 7.5.

[0541] Reduction of PU uptake rate by water gradient contact lenses The water-gradient contact lenses prepared above are individually repackaged (one lens per shell) into polypropylene lens packaging shells together 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 (having a friction score of 0), the PU is 1.2 μg / lens, that is, the reduction of PU is 89.1%.

Number

[0542] The water-gradient contact lenses prepared above are individually repackaged (one lens per shell) into polypropylene lens packaging shells together with 0.55 mL of 0.2% PZ-28BTP buffer solution, and autoclaved at about 121 °C for about 45 minutes. The resulting lenses are still lubricious (friction score of 0), the PU is 0.4 μg / lens, that is, the reduction of PU is 96.4%.

[0543] The water-gradient contact lenses prepared above are individually repackaged (one lens per shell) into polypropylene lens packaging shells together with 0.55 mL of 0.3% PZ-28BTP buffer solution, and autoclaved at about 121 °C for about 45 minutes. The resulting lenses are still lubricious (friction score of 0), the PU is 0.3 μg / lens, that is, the reduction of PU is 97.3%.

[0544] The water-gradient contact lenses prepared above are individually repackaged (one lens per shell) into polypropylene lens packaging shells together with 0.55 mL of the 0.1% PZ-28 phosphate buffer solution prepared above, and autoclaved at about 121 °C for about 45 minutes. The resulting lenses are still lubricious (having a friction score of 0), the PU is 0.6 μg / lens, that is, the reduction of PU is 94.5%.

[0545] Example 8 In this example, the water-gradient contact lenses prepared in Example 4 are used. These are determined to have about 9 μg / lens of PU.

[0546] 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.

[0547] Preparation of Aqueous Polyaziridine Solution PZ-28 solutions with PZ-28 concentrations of 0.1%, 0.2%, or 0.3% are prepared by simply adding PZ-28 to the BTP solution and adjusting the pH to about 7.5.

[0548] Reduction of PU Uptake Rate by Water-Gradient Contact Lenses The water-gradient contact lenses prepared in Example 4 are individually repackaged (1 lens per shell) in polypropylene lens packaging shells together 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 score of 0), with 0.42 μg / lens of PU, i.e., a 95.3% reduction in PU.

Number

[0549] The water-gradient contact lenses prepared in Example 4 are individually repackaged (1 lens per shell) in polypropylene lens packaging shells together with 0.55 mL of the 0.2% PZ-28 solution prepared above and autoclaved at about 121 °C for about 45 minutes. The resulting lenses are still lubricious (with a friction score of 0), with 0.3 μg / lens of PU, i.e., a 96.7% reduction in PU.

[0550] The water-gradient contact lenses prepared in Example 4 are individually repackaged (one lens per shell) in polypropylene lens packaging shells together with the 0.55 mL of 0.3% PZ-28 solution prepared above, and autoclaved at about 121 °C for about 45 minutes. The resulting lenses are still lubricious (friction score of 0), the PU is 0.05 μg / lens, i.e., the reduction of PU is 99.4%.

[0551] Example 9 Preparation of PAA coating solution The PAA coating solution is prepared by adding an appropriate amount of PAA (Mn: about 450 KD) 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 wt%. The prepared PAA coating solution is filtered to remove any particulates or foreign matter.

[0552] Phosphate Buffered Saline (PBS) NaH 2 PO 4 ·H 2 O, Na 2 HPO 4 ·2H 2 O is dissolved in a predetermined amount of purified water (distilled or deionized) to prepare phosphate buffered saline with a composition of about 0.044 wt / wt% NaH 2 PO 4 ·H 2 O, about 0.388 wt / wt% Na 2 HPO 4 ·2H 2 O, and about 0.79 wt / wt% NaCl.

[0553] Phosphate Buffer without NaCl (PB) (PB, No NaCl) PB is prepared using the same procedure as for the preparation of PBS but without adding NaCl.

[0554] Preparation of polyaziridine aqueous solution PZ-28 solutions with concentrations of 0.125%, 0.25%, or 0.5% are prepared by simply adding PZ-28 to DI water and adjusting the pH to about 7.4.

[0555] Reduction of PU by PZ in PAA-coated SiHy contact lenses After release, the dried SiHy contact lenses (prepared in Example 3) are extracted with isopropanol (IPA) for 180 minutes for lens extraction, dip-coated in the PAA solution prepared above for about 30 minutes, rinsed twice with PB for about 15 minutes each, and then immersed in the PZ-28 solution prepared above at about 60 °C for about 2 hours. After the dipping step of PZ-28, the lenses are rinsed twice again with PB (15 minutes each) and then subjected to various tests shown in Table 5.

[0556]

Table 5

[0557] The results in Table 5 show that after various PZ dip treatments, the uptake rate of Polyquartenium-1 by PAA-coated SiHy contact lenses can be significantly reduced by PZ-28 due to the reaction between the aziridine groups of PZ-28 and 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 reduce the uptake rate of Polyquartnium-1 (PU) by PAA-coated SiHy lenses, but on the other hand, it has an adverse effect on lubricity.

[0558] Table 6 shows the results of treating PAA-coated SiHy contact lenses with 0.25 wt% of PZ-28 at room temperature and 45 °C for about 1 hour to evaluate the effect of the 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 dip of PZ was carried out at room temperature (RT). The decrease in the polyquaternium-1 uptake rate is about 55% at room temperature compared to about 93% when the dip was carried out at 45 °C. This indicates that the efficacy of PZ-28 increases at elevated temperatures above RT.

[0559]

Table 6

[0560] Example 10 Preparation of PMAA Solution The polymethacrylic acid (PMAA) coating solution is prepared by dissolving a certain amount of PMAA (Mn: 400 - 700 kDa (manufactured by PolyMaterials, Inc.)) in a predetermined 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 (typic...

Claims

1. 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 or a friction rating of about 2.0 or less after 30 cycles of finger rubbing (or after simulated abrasion cycling), The contact lens comprises: a layered structural configuration 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; 1. A contact lens, comprising: said inner layer having a first equilibrium water content of about 70% by weight or less, wherein said anterior and posterior outer hydrogel layers, independent of one another, have a thickness of about 0.25 μm to about 25 μm when fully hydrated; and a second equilibrium water content greater than said first equilibrium water content, wherein said anterior and posterior outer hydrogel layers, independent of one another, have a water swelling ratio 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%).

2. 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 or a friction rating of about 2.0 or less after 30 cycles of finger rubbing (or after simulated abrasion cycling); a water content gradient that increases from an interior side to one of an anterior or posterior surface of the contact lens, 1. The contact lens, comprising: a lens bulk material completely coated with a front outer hydrogel layer and a rear outer hydrogel layer, the front and rear outer hydrogel layers being independent of each other and 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% or less by weight, and the front and rear outer hydrogel layers being independent of each other and 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.

3. 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 or a friction rating of about 2.0 or less after 30 cycles of finger rubbing (or after simulated abrasion cycling), The contact lens comprises: a layered structural configuration 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, wherein each of said front and rear outer hydrogel layers, independent of one another, has a reduced surface modulus of at least about 20% (preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, and most preferably at least about 40%) compared to said inner layer.

4. a normalized surface compressive force at an indentation depth of 400 nm 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) 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); a water disintegration time of at least 10 seconds or a friction rating of about 2.0 or less after 30 cycles of finger rubbing (or after simulated abrasion cycling), The contact lens comprises an anterior surface, an opposing posterior surface, and a layered configuration 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.

5. a normalized surface compressive force at an indentation depth of 400 nm 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) 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); a water disintegration time of at least 10 seconds or a friction rating of about 2.0 or less after 30 cycles of finger rubbing (or after simulated abrasion cycling), The contact lens comprises a lens bulk material that is a polymeric material.

6. 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). ４００ｎｍ and, 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 or a friction rating of about 2.0 or less after 30 cycles of finger rubbing (or after simulated abrasion cycling), The contact lens comprises an anterior surface, an opposing posterior surface, and a layered configuration 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.

7. 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). ４００ｎｍ and, 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 or a friction rating of about 2.0 or less after 30 cycles of finger rubbing (or after simulated abrasion cycling), The contact lens comprises a lens bulk material that is a polymeric material.

8. Δ(IF) ４００ｎｍ is determined by nanoindentation testing using a probe with a tip radius of about 9.0±0.9 μm, [0010] 、 In the formula, (IF) ｔ 8. A contact lens according to claim 6 or 7, wherein E is the measured indentation force at an indentation depth of 400 nm of the contact lens and E' is the bulk modulus of the contact lens.

9. Δ(IF) ４００ｎｍ is determined by microindentation testing using a 1 mm hemispherical borosilicate glass probe, [0025] In the formula, (IF) ｔ 8. A contact lens according to claim 6 or 7, wherein E is the measured indentation force at an indentation depth of 400 nm of the contact lens and E' is the bulk modulus of the contact lens.

10. 10. The contact lens of any one of claims 1 to 9, wherein the contact lens has a Polyquaternium-1 Uptake ("PU") of about 0.20 micrograms / lens or less, about 0.15 micrograms / lens or less, about 0.10 micrograms / lens or less, about 0.075 micrograms / lens or less, or about 0.050 micrograms / lens or less.

11. 11. The contact lens of any one of claims 1 to 10, wherein the contact lens has a water disintegration time of at least 10 seconds, at least 12.5 seconds, at least 15 seconds, at least 17.5 seconds, or at least 20 seconds after 30 cycles of finger rubbing.

12. 12. The contact lens of any one of claims 1 to 11, wherein the contact lens has a friction rating of about 1.5 or less (preferably about 1.0 or less, more preferably about 0.5 or less) after 30 cycles of finger rubbing.

13. The contact lens of any one of claims 1 to 12, wherein the inner layer and the lens bulk material, which are separate from one another, are a preformed contact lens made essentially from a silicone hydrogel material.

14. 14. The contact lens of claim 13, wherein the silicone hydrogel material comprises repeating units of at least one polysiloxane vinyl monomer and / or at least one polysiloxane vinyl crosslinker and at least one repeating unit of at least one hydrophilic vinyl monomer.

15. The contact lens of claim 13 or 14, wherein the silicone hydrogel material comprises repeat units of at least one hydrophilic N-vinyl amide monomer.

16. The contact lens of any one of claims 13 to 15, wherein the silicone hydrogel material comprises repeat units of at least one silicone-containing vinylic monomer having a bis(trialkylsilyloxy)alkylsilyl or tris(trialkylsilyloxy)silyl group.

17. 17. The contact lens of any one of claims 13 to 16, wherein the silicone hydrogel material comprises repeat units of one or more blended vinyl monomers (preferably in an amount of about 25% by weight or less, about 20% by weight or less, or about 15% by weight or less, based on the dry weight of the inner layer of silicone hydrogel material).

18. 18. The contact lens of any one of claims 13 to 17, wherein the silicone hydrogel material comprises one or more repeating units of a non-silicone vinyl crosslinker (preferably in an amount of about 1.0 wt.% or less, about 0.8 wt.% or less, or about 0.05 wt.% to about 0.6 wt.%, based on the dry weight of the inner layer).

19. 19. The contact lens of any one of claims 13-18, wherein the silicone hydrogel material has an oxygen permeability of at least about 50 barrers, at least about 60 barrers, at least about 70 barrers, at least about 90 barrers, or at least about 60 barrers, and / or an equilibrium water content of about 10% to about 70%, about 10% to about 65%, about 10% to about 60%, about 15% to about 55%, or about 15% to about 50% by weight.

20. 20. The contact lens of any one of claims 13 to 19, wherein the silicone hydrogel material is not naturally wettable and the anterior and posterior outer hydrogel layers, independent of one another, have a thickness of from about 0.5 μm to about 25 μm, from about 1.0 μm to about 20 μm, from about 1.0 μm to about 15 μm, or from about 1.5 μm to about 10 μm when fully hydrated.

21. 21. The contact lens of any one of claims 13 to 20, wherein the silicone hydrogel material is naturally wettable and the anterior and posterior outer hydrogel layers, independent of one another, have a thickness of from about 0.25 μm to about 20 μm, from about 0.5 μm to about 20 μm, from about 0.5 μm to about 15 μm, or from about 1.0 μm to about 10 μm when fully hydrated.

22. 13. The contact lens of any one of claims 1 to 12, wherein the inner layer or the lens bulk material is a preformed hard contact lens made essentially of a hard plastic material (preferably cross-linked polymethacrylate) and the anterior and posterior outer hydrogel layers, independent of each other, have a thickness when fully hydrated of about 1.0 μm to about 20 μm, about 2.0 μm to about 15 μm, about 2.0 μm to about 10 μm, or about 2.5 μm to about 8 μm.

23. 13. The contact lens of any one of claims 1 to 12, wherein the inner layer or the lens bulk material is a preformed rigid gas permeable contact lens made essentially of a rigid gas permeable lens material, and the anterior and posterior outer hydrogel layers, independent of one another, have a thickness when fully hydrated of from about 1.0 μm to about 20 μm, from about 2.0 μm to about 15 μm, from about 2.0 μm to about 10 μm, or from about 2.5 μm to about 8 μm.

24. 13. The contact lens of any one of claims 1 to 12, wherein the inner layer or the lens bulk material is a preformed soft silicone contact lens made essentially of crosslinked silicone material, and the anterior and posterior outer hydrogel layers, independent of one another, have a thickness when fully hydrated of about 2.0 μm to about 25 μm, about 3.0 μm to about 25 μm, about 4.0 μm to about 20 μm, or about 5.0 μm to about 20 μm.

25. 13. The contact lens of any one of claims 1 to 12, wherein the inner layer or the lens bulk material is a preformed hybrid contact lens having a central optic zone made essentially of a rigid gas permeable lens material surrounded by a peripheral zone made essentially of a non-silicone hydrogel material, and the anterior and posterior outer hydrogel layers, independent of one another, have a thickness when fully hydrated of about 0.25 μm to about 20 μm, about 0.50 μm to about 15 μm, about 0.5 μm to about 10 μm, or about 0.5 μm to about 6 μm.

26. 13. The contact lens of any one of claims 1 to 12, wherein the inner layer or the lens bulk material is a preformed non-silicone hydrogel contact lens made essentially of non-silicone hydrogel material, and the anterior and posterior outer hydrogel layers, independent of one another, have a thickness when fully hydrated of about 0.25 μm to about 20 μm, about 0.50 μm to about 15 μm, about 0.5 μm to about 10 μm, or about 0.5 μm to about 6 μm.

27. 27. The contact lens of claim 25 or 26, wherein the non-silicone hydrogel material comprises at least 50 mol % 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.

28. 28. The contact lens of any one of claims 1 to 27, wherein the anterior and posterior outer hydrogel layers, which are independent of one another, are crosslinked hydrophilic polymeric materials comprising at least 25 mol % (preferably at least 35 mol %, more preferably at least 45 mol %, and even more preferably at least 55 mol %) of repeating monomer units of at least one hydrophilic vinyl monomer selected from the group consisting of alkyl (meth)acrylamides, N-2-dimethylaminoethyl (meth)acrylamide, dimethylaminoethyl (meth)acrylate, hydroxyl-containing acrylic monomers, N-vinyl amide monomers, methylene-containing pyrrolidone monomers, (meth)acrylate monomers having C1 to C4 alkoxyethoxy groups, vinyl ether monomers, allyl ether monomers, and combinations thereof.

29. 28. A contact lens according to any one of claims 1 to 27, wherein the anterior and posterior outer hydrogel layers, which are independent of each other, are crosslinked hydrophilic 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 phosphyrylcholine-containing vinyl monomer.

30. The front and rear outer hydrogel layers, which are independent of each other, are formed of poly(ethylene glycol) chains (preferably (1)-NH ２ (2) poly(ethylene glycol) having one unique functional group, -NH ２ (3) poly(ethylene glycol) having two terminal functional groups selected from the group consisting of -NH ２ 28. The contact lens of any one of claims 1 to 27, wherein the polymer is a crosslinked hydrophilic polymeric material comprising (i) a multi-arm poly(ethylene glycol) having one or more functional groups selected from the group consisting of -COOH, -SH, and combinations thereof, or (3) a mixture thereof.

31. 31. The contact lens of any one of claims 1 to 30, wherein the anterior and posterior outer hydrogel layers are identical to one another, are substantially uniform in thickness, and merge at the edge of the contact lens to completely cover the inner layer.

32. 32. The contact lens of any one of claims 1 to 31, wherein the anterior and posterior outer hydrogel layers, independent of one another, 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, even more preferably at least 95% by weight).

33. A contact lens according to any one of claims 1 to 32, wherein the separate anterior and posterior outer hydrogel layers are substantially free of silicone (preferably completely free of silicone).

34. 34. The contact lens of any one of claims 1 to 33, further comprising two transitional layers of polymeric material, each of the two transitional layers being located between the inner layer or the lens bulk material and one of the anterior and posterior outer hydrogel layers.

35. 35. The contact lens of claim 34, wherein the two transitional layers merge at the peripheral edge of the contact lens and completely surround the inner layer of lens material or the lens bulk material.

36. 36. The contact lens of claim 34 or 35, wherein the two transitional layers have a thickness when fully hydrated of at least about 0.05 μm (preferably from about 0.05 μm to about 10 μm, more preferably from about 0.1 μm to about 7.5 μm, and even more preferably from about 0.1 μm to about 5 μm).

37. 37. The contact lens of any one of claims 34 to 36, 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.

38. 38. The contact lens of claim 37, wherein the polyanionic polymer is a carboxyl-containing polymer comprising at least 60 mole percent repeat units of one or more carboxyl-containing acrylic monomers.

39. 38. The contact lens of claim 37, 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 combinations thereof.

40. 38. The contact lens of claim 37, wherein the polyanionic polymer is a graft polymer grafted onto the inner layer or the lens bulk material, the graft polymer comprising repeat units of at least one carboxyl-containing vinyl monomer.

41. 41. The contact lens of claim 40, wherein the polyanionic polymer is a grafted polymer grafted onto the inner layer or the lens bulk material, the grafted polymer comprising repeat units of at least one carboxyl-containing acrylic monomer.

42. The contact lens of any one of claims 37 to 41, 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.

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