Cationic contact lenses

Abstract

A cationic contact lens and a method for making the same are described. The cationic contact lens comprises a polymeric lens body, the polymeric lens body being the reaction product of a polymerizable composition, the polymerizable composition comprising at least one siloxane, at least one nonionic hydrophilic monomer, and at least one acyclic tertiary amine monomer. The cationic contact lens may be an unworn sterile silicone hydrogel contact lens. The contact lens is capable of substantially linearly releasing a releasable anionic agent and the at least one acyclic tertiary amine monomer facilitates the absorption and / or sustained release of the releasable anionic agent by the polymeric lens body. The contact lens may be present in a sealed contact lens package. The sealed contact lens package may comprise at least a) a base member having a cavity; b) a contact lens packaging solution in the cavity; c) an unworn sterile contact lens immersed in the contact lens packaging solution in the cavity in which a releasable anionic agent is present; and d) a cover, the cover forming a liquid-tight seal with the base member.

Description

Technical Field

[0001] This application claims the benefit of and / or otherwise claims priority under 35 USC §119(e) to prior U.S. Provisional Patent No. 63 / 125,418, filed on December 15, 2020, which is hereby incorporated by reference in its entirety.

[0002] The field of the invention relates to contact lenses and sealed contact lens packages, and in particular to contact lenses having cationic properties, and further to packages for containing the contact lenses, and methods for making the contact lenses. The contact lenses of the present invention having cationic properties can be considered cationic contact lenses. The contact lenses provide the ability to controllably release one or more comfort agents or other benefit agents in the form of releasable anionic agents. Background Art

[0003] One major approach to improving the comfort of contact lenses is to introduce one or more comfort agents into the lens material or packaging solution. When the lens is placed on the eye, the comfort agent is released to the eye surface. However, achieving controlled release of comfort agents during contact lens wear has been a challenge because the comfort agents are trapped inside the lens material and release is limited or presents a burst release instead of the desired controlled release or does not provide release for the desired time period (which can be 8 hours or more).

[0004] Therefore, there is a need in the industry to provide a controlled release of a comfort agent or an improved contact lens of a controlled release of a comfort agent. In addition, it would also be desirable to provide such a controlled release characteristic without significantly affecting other characteristics provided by a contact lens. Summary of the invention

[0005] It is a feature of the present invention to provide a contact lens that can release a comfort agent during lens wear and avoid burst release of the comfort agent.

[0006] Another feature of the present invention is to provide an unworn sterile contact lens that is a silicone hydrogel and has cationic properties.

[0007] Another feature of the present invention is to provide silicone hydrogel contact lenses comprising a comfort agent that is releasable when worn in the eye and has a controlled release over an extended period of time.

[0008] It is an additional feature of the present invention to provide a silicone hydrogel contact lens having a higher ability to absorb and release a comfort agent than conventional silicone hydrogel contact lenses.

[0009] An additional feature of the present invention is to provide a contact lens that can be loaded or replenished with a comfort agent by contacting the contact lens with an eye drop or multi-purpose contact lens care solution containing the comfort agent.

[0010] Other features and advantages of the present invention will be described in part in the following description, and in part will be known from the description, or can be learned by practicing the present invention. The objectives and other advantages of the present invention will be realized and obtained by means of the components and combinations particularly pointed out in this description and the appended claims.

[0011] To achieve these and other advantages, and in accordance with the purposes of the present invention, as embodied and broadly described herein, the present invention relates, in part, to silicone hydrogel contact lenses having (i) a polymeric lens body that is the reaction product of a polymerizable composition comprising 15 wt % to 65 wt % of at least one siloxane monomer, 25 wt % to 75 wt % of at least one nonionic hydrophilic monomer, and 0.1 wt % to 15 wt % of at least one acyclic tertiary amine monomer and (ii) at least one releasable anionic agent. The at least one acyclic tertiary amine monomer optionally promotes absorption and / or sustained release of the at least one releasable anionic agent by the polymeric lens body.

[0012] The present invention further relates to a silicone hydrogel contact lens, the silicone hydrogel contact lens comprising a polymeric lens body, the polymeric lens body being the reaction product of a polymerizable composition comprising 25 wt% to 55 wt% of a siloxane monomer, 30 wt% to 55 wt% of a vinyl monomer selected from N-vinyl pyrrolidone, N-vinyl-N-methylacetamide, or a combination thereof, 0.1 wt% to 10 wt% of 2-(dimethylamino)ethyl methacrylate, and optionally about 1 wt% to about 20 wt% of a hydrophilic monomer selected from N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA), or ethylene glycol methyl ether methacrylate (EGMA), or any combination thereof, and optionally about 1 wt% to about 20 wt% of a hydrophobic monomer selected from methyl methacrylate (MMA), isobornyl methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB), or any combination thereof.

[0013] In addition, the present invention relates to an unworn sterile silicone hydrogel contact lens, the contact lens comprising a polymeric lens body, the polymeric lens body being the reaction product of a polymerizable composition, the polymerizable composition comprising 15 wt % to 65 wt % of at least one siloxane monomer, 25 wt % to 75 wt % of at least one nonionic hydrophilic monomer, and 0.1 wt % to 15 wt % of at least one acyclic tertiary amine monomer. The unworn sterile silicone hydrogel contact lens is optionally capable of substantially linearly releasing a releasable anionic agent at a release rate of at least 6 μg / hour for at least 8 hours. The at least one acyclic tertiary amine monomer optionally promotes absorption and / or sustained release of the releasable anionic agent by the polymeric lens body.

[0014] In addition, the present invention is directed to a method of making the silicone hydrogel contact lens of the present invention. The method comprises the steps of: a) polymerizing a polymerizable composition (as described herein) in a contact lens mold to obtain a polymer lens body, b) removing the polymer lens body from the contact lens mold, c) extracting the polymer lens body in an organic solvent, d) hydrating the polymer lens body in a hydrating liquid to obtain a silicone hydrogel contact lens, e) sealing the hydrated silicone hydrogel contact lens with a packaging solution in a package, and f) autoclaving the package, wherein at least one of the organic solvent, hydrating liquid, or packaging solution contains at least one releasable anionic agent.

[0015] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are intended to provide further explanation of the invention as claimed.

[0016] The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate certain features of the invention and together with the description, serve to explain the principles of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1A The graph shows the amount of anionic agent released from a cationic silicone hydrogel contact lens compared to a control lens.

[0018] Figure 1B The percentage of anionic agent released from a cationic silicone hydrogel contact lens compared to a control lens is shown. DETAILED DESCRIPTION

[0019] Contact lenses with cationic properties and methods of making the same are described herein. Contact lenses with cationic properties may be cationic contact lenses herein. Sealed contact lens packages including the contact lenses are also described herein.

[0020] In the present invention, cationic contact lenses preferably provide controlled release during contact lens wear of one or more anionic agents (such as anionic comfort agents or other beneficial anionic agents) that can dissociate from the polymer lens material during wear under physiological conditions.

[0021] Regarding the contact lens in the present invention, the contact lens is an unworn sterile hydrogel contact lens. In other words, the contact lens is unused and new.

[0022] The hydrogel contact lenses are the reaction product of a polymerizable composition comprising an acyclic tertiary amine monomer.

[0023] As an example, a hydrogel contact lens is the reaction product of a non-silicone hydrogel polymerizable composition comprising at least one acyclic tertiary amine monomer. Non-silicone hydrogel contact lenses are typically formed by polymerization of one or more hydrophilic monomers such as 2-hydroxyethyl methacrylate (HEMA) or vinyl alcohol, optionally in combination with other monomers, and do not contain siloxanes (that is, molecules comprising at least one Si-O group).

[0024] As an example, a silicone hydrogel contact lens is the reaction product of a polymerizable composition comprising at least one siloxane monomer, at least one nonionic hydrophilic monomer, and at least one acyclic tertiary amine monomer.

[0025] As another example, a silicone hydrogel contact lens is the reaction product of a polymerizable composition comprising at least one siloxane monomer, at least one nonionic hydrophilic monomer, at least one acyclic tertiary amine monomer, and at least one hydrophobic monomer.

[0026] In general, "monomer" may include or refer to a molecule containing a polymerizable carbon-carbon double bond (that is, a polymerizable group) that is capable of reacting with the same or different other molecules containing polymerizable groups to form a polymer or copolymer. The term monomer encompasses polymerizable prepolymers and macromonomers, and unless otherwise indicated, there is no size limitation for the monomer. The monomer may contain a single polymerizable carbon-carbon double bond or more than one polymerizable group and, therefore, have crosslinking functionality.

[0027] Referring to the reaction product of the polymerizable composition, the at least one siloxane monomer can be one siloxane monomer or two or three or more siloxane monomers.

[0028] As used herein, the term "siloxane monomer" is a molecule comprising at least one Si-O group and at least one polymerizable group. Siloxane monomers for use in contact lens compositions are well known in the art (see, e.g., U.S. Pat. No. 8,658,747 and U.S. Pat. No. 6,867,245). (All patents and publications mentioned herein and throughout are incorporated by reference in their entirety.)

[0029] In some examples, the polymerizable composition comprises a total amount of at least 10 wt%, 15 wt%, 20 wt%, 25 wt%, or 30 wt% up to about 40 wt%, 45 wt%, 50 wt%, 55 wt%, 60 wt%, or 65 wt% of siloxane monomers. For example, the at least one siloxane monomer can be present in an amount of 15 wt% to about 65 wt%, based on the weight of the polymerizable composition.

[0030] In general, unless otherwise indicated, as used herein, a given weight percentage (wt%) of a component of a polymerizable composition is relative to the total weight of all polymerizable ingredients (and any optional polymers or other components that may be present) in the polymerizable composition. The weight of the polymerizable composition contributed by components that are not incorporated into the final contact lens product (such as diluents) is not included in the wt% calculation.

[0031] Exemplary siloxane monomers are those used in the following FDA-approved silicone hydrogel materials: asmofilcon A, balafilcon A, comfilcon A, delefilcon A, enfilcon A, fanfilcon A, galyfilcon A, kalifilcon A, lotrafilcon A, lotrafilcon B, narafilcon A, narafilcon B, olifilcon A, riofilcon A, samfilcon A, senofilcon A, senofilcon B, senofilcon C, somofilcon A, and stenfilcon A.

[0032] The nonionic hydrophilic monomer can be present in the reaction product of the polymerizable composition in an amount of at least 10%, 15%, 20%, 25%, or 30% up to about 40%, 45%, 50%, 55%, 60%, 65%, 70%, or 75% by weight, based on the weight of the polymerizable composition. For example, the at least one nonionic hydrophilic monomer can be present in an amount of 25% to about 70% by weight, based on the weight of the polymerizable composition.

[0033] With respect to the nonionic hydrophilic monomer, as used herein, the at least one nonionic hydrophilic monomer may be understood to include a single hydrophilic monomer, or include a hydrophilic monomer component consisting of two or more hydrophilic monomers (eg, two, three, or four or more).

[0034] The hydrophilicity or hydrophobicity of a monomer can be determined using conventional techniques such as, for example, based on the water solubility of the monomer. For the purposes of this disclosure, a hydrophilic monomer is a monomer that is visibly soluble in an aqueous solution at room temperature (e.g., about 20 to 25° C.). For example, a hydrophilic monomer may be understood as any monomer in which 50 grams of the monomer is visibly completely soluble in 1 liter of water at 20° C. (that is, ≥5% soluble in water), as determined using a standard shaking flask method known to those of ordinary skill. A hydrophobic monomer, as used herein, is a monomer that is visibly insoluble in an aqueous solution at room temperature, such that a separate, visually identifiable phase is present in the aqueous solution, or such that the aqueous solution appears cloudy over time after standing at room temperature and separates into two distinct phases. For example, a hydrophobic monomer may be understood as any monomer in which 50 grams of the monomer is not visibly completely soluble in 1 liter of water at 20° C.

[0035] Non-silicon nonionic hydrophilic monomers useful as the hydrophilic monomer or hydrophilic monomer component in the polymerizable compositions disclosed herein include, for example, monomers containing acrylamide, or monomers containing acrylate, or monomers containing acrylic acid, or monomers containing methacrylate, or monomers containing methacrylic acid, or monomers containing vinyl, or any combination thereof. It should be understood that the hydrophilic monomer or hydrophilic monomer component is a non-silicon monomer.

[0036] Examples of nonionic hydrophilic monomers include, but are not limited to, N,N-dimethylacrylamide (DMA), or 2-hydroxyethyl acrylate, or 2-hydroxyethyl methacrylate (HEMA), or ethoxyethyl methacrylamide (EOEMA), or 2-hydroxypropyl methacrylate, or 2-hydroxybutyl methacrylate (HOB), or 2-hydroxybutyl acrylate, or 4-hydroxybutyl acrylate glycerol methacrylate, or 2-hydroxyethyl methacrylamide, or polyethylene glycol monomethacrylate, or methacrylic acid, or acrylic acid, ethylene glycol methyl ether methacrylate (EGMA), or any combination thereof.

[0037] The nonionic hydrophilic monomer may be at least one hydrophilic vinyl monomer. As used herein, a "hydrophilic vinyl monomer" is any siloxane-free (that is, Si-O-free) hydrophilic monomer having in its molecular structure a polymerizable carbon-carbon double bond (that is, a vinyl group) that is not part of an acrylic group, wherein the carbon-carbon double bond of the vinyl group is not as reactive under free radical polymerization as the carbon-carbon double bond present in a polymerizable methacrylate group. As used herein, the term "acrylic group" refers to a polymerizable group present in acrylates, methacrylates, acrylamides, and the like. Thus, although carbon-carbon double bonds are present in acrylate and methacrylate groups, such polymerizable groups are not considered vinyl groups as used herein.

[0038] Examples of hydrophilic vinyl-containing monomers that may be provided in the polymerizable composition include, but are not limited to, N-vinylformamide, or N-vinylacetamide, or N-vinyl-N-ethylacetamide, or N-vinylisopropylamide, or N-vinyl-N-methylacetamide (VMA), or N-vinylpyrrolidone (NVP), or N-vinylcaprolactam, or N-vinyl-N-ethylformamide, or N-vinylformamide, or N-2-hydroxyethylvinylcarbamate, or N-carboxy-β-alanine N-vinyl ester, 1,4-butanediol vinyl ether (BVE), or ethylene glycol vinyl ether (EGVE), or diethylene glycol vinyl ether (DEGVE), or any combination thereof. In one example, the hydrophilic monomer or hydrophilic monomer component comprises VMA, NVP, or both VMA and NVP.

[0039] In one embodiment, the polymerizable composition comprises at least 10%, 15%, 20%, or 25% up to about 45%, 50%, 55%, 60%, 65%, or 75% by weight of hydrophilic vinyl monomers. As used herein, a given weight percentage of a particular class of components (e.g., hydrophilic vinyl monomers, siloxane monomers, or the like) in a polymerizable composition is equal to the sum of the weight percentages of the ingredients in the composition that fall within that class. Thus, for example, a polymerizable composition comprising 5% by weight BVE and 25% by weight NVP and no other hydrophilic vinyl monomers is considered to comprise 30% by weight hydrophilic vinyl monomers.

[0040] In one example, the hydrophilic vinyl monomer is an N-vinyl amide monomer. Exemplary hydrophilic N-vinyl amide monomers are VMA and NVP. In one specific example, the polymerizable composition comprises at least 25 wt % (e.g., 25 wt % to 55 wt %) of at least one vinyl amide monomer. In another specific example, the polymerizable composition comprises from about 25 wt % up to about 75 wt % (e.g., 25 wt % to 55 wt %) of VMA or NVP or a combination thereof.

[0041] The acyclic tertiary amine monomer can be present in the reaction product of the polymerizable composition in an amount from 0.1 wt % to about 15 wt %, such as 1 wt % to 14 wt %, 1 wt % to 12 wt %, 1 wt % to 10 wt %, 1 wt % to 7 wt %, 1 wt % to 5 wt %, 5 wt % to 15 wt %, 6 wt % to 15 wt %, 8 wt % to 15 wt %, based on the total weight of the polymerizable composition.

[0042] Acyclic tertiary amine monomers can be considered as cationic monomers.

[0043] With respect to the acyclic tertiary amine monomer, as used herein, the at least one acyclic tertiary amine monomer may be understood to include a single acyclic tertiary amine monomer, or include an acyclic tertiary amine monomer component consisting of two or more acyclic tertiary amine monomers, such as two, three, or four or more.

[0044] Acyclic tertiary amine monomers are monomers in which the nitrogen of the tertiary amine group is not part of a ring structure, although the monomer may contain a ring structure (e.g., N-(2-aminoethyl)aminomethylstyrene). The term "tertiary amine group" is understood to mean a nitrogen atom directly bonded to three carbon atoms, provided that none of the carbon atoms is part of a carbonyl group.

[0045] Exemplary acyclic tertiary amine monomers include, but are not limited to, 2-(dimethylamino)ethyl acrylate, or 2-(diethylamino)ethyl acrylate, or 3-(dimethylamino)propyl acrylate, or 3-(diethylamino)propyl acrylate, or 2-(dimethylamino)ethyl methacrylate, or 2-(diethylamino)ethyl methacrylate, or 3-(dimethylamino)propyl methacrylate, or 3-(diethylamino)propyl methacrylate, or N-(2-(dimethylamino)ethyl)acrylamide, or N-(2-(diethylamino)ethyl) )ethyl)acrylamide, or N-(3-(dimethylamino)propyl)acrylamide, or N-(3-(diethylamino)propyl)acrylamide, or N-(2-(dimethylamino)ethyl)methacrylamide, or N-(2-(diethylamino)ethyl)methacrylamide, or N-(3-(dimethylamino)propyl)methacrylamide, or N-(3-(diethylamino)propyl)methacrylamide, or 3-(diethylamino)propyl vinyl ether, or 3-(dimethylamino)propyl vinyl ether, or any combination thereof.

[0046] A more specific example of an acyclic tertiary amine monomer is 2-(diethylamino)ethyl methacrylate, which can be present in the polymerizable composition in an amount of 0.1 wt % to 15 wt % or 1 wt % to 10 wt % (based on the total weight of the polymerizable composition).

[0047] Generally, the acyclic tertiary amine monomer (and a portion of the polymer lens body) will form charged sites in lower pH and / or lower ionic strength solutions (e.g., pH below 8.0 or below 7) or in acidic conditions (e.g., pH 6 or lower (e.g., pH 4 to 6)). Under these conditions, the acyclic tertiary amine groups are protonated to form positively charged sites in the lens material. As further explained, these positively charged sites can form ionic complexes with negatively charged comfort agents or other releasable anionic agents.

[0048] Advantageously, one or more acyclic tertiary amine monomers are included in the polymerizable composition to provide a polymer body having a cationic content of about 1.0%, or 2.0%, or 3.0% up to about 5.0%, 7.0%, or 10.0%. As used herein, "cationic content" is the value determined by Formula I:

[0049] ∑(a n1 xb n1 / c n1 )x157=cation content% (I)

[0050] where a n1 is the weight percentage of the cationic monomer n1 as defined below used in the monomer mixture, b n1 is the number of tertiary amine groups on monomer n1, and c n1is the molecular weight of the tertiary amine-containing monomer n1. If more than one tertiary amine-containing monomer is used in the polymerizable composition, the tertiary amine content % of the resulting polymer mirror body is the sum of the ionic content % provided by each tertiary amine-containing monomer (that is, n1, n2, etc.). The weight percentage of the tertiary amine-containing monomer n1 in the polymerizable composition is relative to the weight of all components of the monomer mixture incorporated into the hydrogel. In other words, components of the monomer mixture that are not incorporated into the final hydrogel product (such as diluents removed from the hydrogel during processing) are not included in the weight percentage determination. Formula I adjusts for differences in molecular weight and charge relative to 2-(dimethylamino)ethyl methacrylate, which is an exemplary tertiary amine-containing monomer having a molecular weight of 157 and one tertiary amine group.

[0051] As an option, one or more hydrophobic monomers can be present as part of the polymerizable composition.

[0052] Examples of suitable hydrophobic monomers include, but are not limited to, one or more hydrophobic monomers that do not contain silicon. Examples of suitable hydrophobic monomers include methyl acrylate, or ethyl acrylate, or propyl acrylate, or isopropyl acrylate, or cyclohexyl acrylate, or 2-ethylhexyl acrylate, or methyl methacrylate (MMA), or ethyl methacrylate, or propyl methacrylate, or butyl acrylate, or 2-hydroxybutyl methacrylate, or vinyl acetate, or vinyl propionate, or vinyl butyrate, or vinyl valerate, styrene, or chloroprene, or vinyl chloride, or vinylidene chloride, or acrylonitrile, or 1-butene, or butadiene, or methacrylonitrile, or vinyl toluene, or vinyl ethyl ether, or perfluorohexylethylthiocarbonylaminoethyl methacrylate, or isoborneol methacrylate (IBM), or trifluoroethyl methacrylate, or hexafluoroisopropyl methacrylate, or tetrafluoropropyl methacrylate, or hexafluorobutyl methacrylate, or any combination thereof.

[0053] The hydrophobic monomer, if used, can be present in the reaction product of the polymerizable composition in an amount from 1 wt % to about 30 wt %, such as 1 wt % to 25 wt %, 1 wt % to 20 wt %, 1 wt % to 15 wt %, 2 wt % to 20 wt %, 3 wt % to 20 wt %, 5 wt % to 20 wt %, 5 wt % to 15 wt %, 1 wt % to 10 wt %, based on the total weight of the polymerizable composition.

[0054] In addition or as an alternative to hydrophilic monomers, the polymerizable composition may include a non-polymerizable hydrophilic polymer that produces a polymer lens body comprising an interpenetrating polymer network (IPN), wherein the non-polymerizable hydrophilic polymer interpenetrates the silicone hydrogel polymer matrix. In the present example, the non-polymerizable hydrophilic polymer is referred to as an IPN polymer, which is used as an internal lubricant in a contact lens. On the contrary, the polymer chains within the silicone hydrogel network formed by the polymerization of the monomers present in the polymerizable composition are not considered to be IPN polymers. The IPN polymer may be a high molecular weight hydrophilic polymer, such as about 50,000 to about 500,000 Daltons. In a specific example, the IPN polymer is polyvinyl pyrrolidone (PVP). In other examples, the polymerizable composition is substantially free of polyvinyl pyrrolidone or other IPN polymers.

[0055] The polymerizable composition may further comprise at least one crosslinking agent. As used herein, a "crosslinking agent" is a molecule having at least two polymerizable groups. Thus, a crosslinking agent can react with functional groups on two or more polymer chains in order to bridge one polymer to another. Various crosslinking agents suitable for use in silicone hydrogel polymerizable compositions are known in the art (see, e.g., U.S. Pat. No. 8,231,218, which is incorporated herein by reference). Examples of suitable crosslinking agents include, but are not limited to, lower alkylene glycol di(meth)acrylates, such as triethylene glycol dimethacrylate and diethylene glycol dimethacrylate; poly(lower alkylene) glycol di(meth)acrylates; lower alkylene di(meth)acrylates; allyl methacrylates, divinyl ethers, such as triethylene glycol divinyl ether, diethylene glycol divinyl ether, 1,4-butanediol divinyl ether, and 1,4-cyclohexanedimethanol divinyl ether; bisvinyl sulfone; di- and trivinylbenzene; trimethylolpropane tri(meth)acrylate; pentaerythritol tetra(meth)acrylate; bisphenol A di(meth)acrylate; methylenebis(meth)acrylamide; triallyl phthalate; 1,3-bis(3-methacryloxypropyl)tetramethyldisiloxane; diallyl phthalate; triallyl isocyanurate, and combinations thereof.

[0056] As is known to those skilled in the art, the polymerizable composition may include other polymerizable or non-polymerizable ingredients conventionally used in contact lens formulations, such as one or more of a polymerization initiator, an oxygen scavenger, a chain transfer agent, a diluent, or the like. In some examples, the polymerizable composition may include an organic diluent in an amount that can prevent or minimize the phase separation between the hydrophilic and hydrophobic components of the polymerizable composition, so as to obtain optically transparent lenses. The diluents commonly used in contact lens formulations include hexanol, ethanol, and / or other primary, secondary, or tertiary alcohols. In other examples, the polymerizable composition is free of or substantially free of (e.g., less than 500ppm) organic diluents. In such examples, the use of siloxane monomers containing hydrophilic moieties (such as polyethylene oxide groups, side hydroxyl groups, or other hydrophilic groups) may make it unnecessary to include diluents in the polymerizable composition. Non-limiting examples of these and other ingredients that may be included in the polymerizable composition are provided in U.S. Pat. No. 8,231,218.

[0057] A specific example of the silicone hydrogel contact lens of the present invention is a contact lens based on a polymerizable composition comprising 25 wt% to 55 wt% of a siloxane monomer, 30 wt% to 55 wt% of a vinyl monomer selected from NVP, VMA or a combination thereof, and optionally about 1 wt% to about 20 wt% of a hydrophilic monomer selected from N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA) or ethylene glycol methyl ether methacrylate (EGMA) or any combination thereof, and optionally about 1 wt% to about 20 wt% of a hydrophobic monomer selected from methyl methacrylate (MMA), isobornyl methacrylate (IBM) or 2-hydroxybutyl methacrylate (HOB) or any combination thereof. Silicone hydrogel materials made from this specific embodiment of the polymerizable composition include Stanfecon A, Canfecon A, Shamofecon A, Vanfecon A and Enfecon A. The above base polymerizable composition is further modified to additionally include 0.1 to 15 wt % of at least one acyclic tertiary amine, such as, for example, 1 to 10 wt % of 2-(dimethylamino)ethyl methacrylate and cured to provide a cationic polymer mirror body.

[0058] As part of the present invention, the contact lens is a silicone hydrogel contact lens comprising a polymer lens body and at least one releasable anionic agent attached to the polymer lens body. The anionic agent can be attached to the polymer lens body through cationic and / or hydrophobic interactions, and / or can be physically embedded by the polymer network of the polymer lens body. The releasable anionic agent can be one or more releasable anionic agents (e.g., one, two, or more).

[0059] As an option, the releasable anion agent is capable of blocking the TRPV1 receptor and / or is capable of interacting with the PPARa receptor, for example, on the cornea.

[0060] Examples of releasable anionic agents include, but are not limited to, at least one acid. In a specific example, the anionic agent comprises a single carboxylic acid group. In another example, the anionic agent comprises two or more carboxylic acid groups. In one example, the anionic agent is a small molecule (that is, having a molecular weight of less than about 900 Daltons). In some examples, as an option, the releasable anionic agent is not a polymer. As an option, the releasable anionic agent is not a polymer of a disaccharide.

[0061] Examples of releasable anionic agents include, but are not limited to, at least one fatty acid. A more specific example of a releasable anionic agent is oleic acid.

[0062] When the releasable anionic agent is complexed by ionic interaction with the polymer lens body (e.g., due to low pH conditions and / or low ionic strength conditions, such as below about 7 pH or below about 6 pH), in such a state, the releasable anionic agent itself is an anionic agent or material complexed by ionic interaction with a cationic moiety or molecule that forms part of the polymer lens material. As an example, the releasable anionic agent, once deprotonated, can form a complex with at least some of the protonated moieties or molecules in the polymer lens body (e.g., protonated tertiary amine groups present in the polymer lens body). The releasable anionic agent complexed by ionic interaction with the polymer lens body is released from the polymer lens body, such as by dissociating under physiological conditions by interacting with anti-ionic ions in tears. The anionic agent released at this time generally becomes a salt or ester (e.g., a salt of at least one acid (e.g., oleic acid or oleate)).

[0063] The amount of the releasable anionic agent attached to the polymer mirror body can be at least 25 μg, such as about 25 μg to 1000 μg or more, or 25 μg to 700 μg, or 25 μg to 650 μg, or 25 μg to 600 μg, or 25 μg to 550 μg, or 25 μg to 500 μg, or 25 μg to 450 μg, or 25 μg to 400 μg. , or 25 μg to 350 μg, or 25 μg to 300 μg, or 25 μg to 250 μg, or 50 μg to 750 μg, or 75 μg to 750 μg, or 100 μg to 750 μg, or 125 μg to 700 μg, or 150 μg to 700 μg, or 175 μg to 700 μg, or 200 μg to 700 μg, etc. In one example, the releasable anionic agent is oleic acid, which is attached to the polymer lens body in an amount of about 25 μg to about 500 μg, or about 100 μg to about 300 μg. As used herein, the phrase "the amount of the releasable anionic agent attached to the polymer lens body" refers to the total amount of the releasable anionic agent that can be extracted from the contact lens by a suitable extraction method (such as the isopropyl alcohol (IPA) extraction method described in Example 1 below).

[0064] As an option, the releasable anionic agent can be uniformly distributed throughout the polymer lens body through the ionic interactions described herein. As an option, the releasable anionic agent can be non-uniformly distributed. For example, the releasable anionic agent can be present in a higher amount on one side of the contact lens or on both sides of the contact lens (that is, the back side and the front side) than in the inner portion of the contact lens (the area located between the back side and the front side).

[0065] The releasable anionic agents present within the silicone hydrogel contact lenses are not covalently attached to the polymer lens body.

[0066] Instead of or in addition to the ionic interactions between the polymer lens body and the releasable anionic agent described herein, as an option, the releasable anionic agent can be considered to be embedded, trapped, dispersed, absorbed and / or localized within the contact lens. As mentioned, the releasable anionic agent is preferably present in and / or on the surface of the contact lens due to the releasable anionic agent forming a complex with the lens material or a portion of the lens material, which complex would be considered an ionic interaction.

[0067] Another example of a contact lens of the present invention is an unworn sterile silicone hydrogel contact lens comprising a polymeric lens body, the polymeric lens body being the reaction product of a polymerizable composition comprising 15 wt % to 65 wt % of at least one siloxane monomer, 25 wt % to 75 wt % of at least one nonionic hydrophilic monomer, and 0.1 wt % to 15 wt % of at least one acyclic tertiary amine monomer. The unworn sterile silicone hydrogel contact lens is capable of releasing a releasable anionic agent at a release rate of at least 6 μg / hour for at least 8 hours. When tested in the in vitro release assay described in Example 2, the amount or duration of release of an anionic agent from the contact lens herein is intended to mean the amount and / or duration of release from the contact lens. The at least one acyclic tertiary amine monomer promotes the absorption and / or sustained release of the releasable anionic agent by the polymeric lens body.

[0068] With respect to at least one acyclic tertiary amine monomer that promotes absorption and / or sustained release of at least one releasable anionic agent from a polymeric lens body, this means that if we compare a "control lens" that is a silicone hydrogel contact lens comprising a polymeric lens body formed from a polymerizable composition in which an acyclic tertiary amine monomer is absent (but otherwise the same polymerizable composition, but in place of the amount of acyclic tertiary amine monomer, the amount is replaced by a hydrophobic monomer (such as MMA)), the absorption amount of the polymeric lens body containing the acyclic tertiary amine monomer will be higher than that of the control lens using the same concentration of a releasable anionic agent contained in the loading solution, and a "cationic lens" that is a silicone hydrogel contact lens comprising a polymeric lens body formed from a polymerizable composition in which an acyclic tertiary amine monomer is present. Similarly, in promoting sustained release, the polymeric lens body containing the acyclic tertiary amine monomer in the polymerizable composition will have a longer release period, such as 8 hours or 9 hours, compared to the control lens, and / or will have a more linear release profile over a period of 8 hours or 9 hours compared to the control lens. As used herein, the term "release curve" refers to the shape of the line when plotting the amount of anionic agent released from the lens at 1 hour, 3 hours, 6 hours and 9 hours time points using the release media and release assay method described in Example 2 below, as shown in Figure 1A middle.

[0069] In one example, the cationic contact lens exhibits a substantially linear release of the anionic agent for at least 8 hours. As used herein, if the linear regression of the anionic agent release curve has an R square value of at least 0.90, and the release amount is measured at 1 hour, 3 hours, 6 hours and 9 hours (at each time point, n = 3), then at least 8 hours of substantially linear release is demonstrated. In one example, the cationic contact lens exhibits a substantially linear release of the anionic agent for at least 8 hours and has an R square value of at least 0.90. In some examples, the cationic contact lens exhibits a substantially linear release of the anionic agent for at least 8 hours and has an R square value of at least 0.90, and the control lens exhibits a burst release of 50% by weight or more of the anionic agent that can be released from the contact lens is released within a time of 3 hours or less.

[0070] In some examples, the cationic contact lenses of the present invention can have an anionic agent release of 2 μg to 50 μg (e.g., 5 μg to 50 μg, or 10 μg to 40 μg, or 10 μg to 30 μg) of anionic agent per hour for a period of at least 8 hours, at least 9 hours, or at least 10 hours, such as 8 hours to 16 hours, or 10 hours to 16 hours, or 12 hours to 16 hours.

[0071] Using the present invention, preferably, burst release of anionic agents is avoided.An example of a burst release (or burst effect) is when 50% by weight or more of the anionic agent releasable from the contact lens is released in 3 hours or less.

[0072] Thus, using the present invention, the contact lenses of the present invention are able to provide at least one or more of the following properties: a) a substantially linear release profile of the anionic agent, b) the ability to load large amounts of the anionic agent (at least 50 μg, or at least 100 μg, or at least 150 μg, or at least 200 μg into the lens), c) release of the anionic agent over a prolonged period of time (at least 8 hours, such as 8 hours to 16 hours, or 9 hours to 16 hours, or 10 hours to 16 hours, or 8 hours to 12 hours), and / or d) avoidance of any burst release.

[0073] The absorption or loading of the silicone hydrogel contact lens with a releasable anionic agent can occur during the extraction step and / or during the hydration step and / or during the packaging step. For example, the absorption of the releasable anionic agent can occur during a solvent extraction step after the contact lens material has been cured and / or during one or more hydration steps, wherein the at least one releasable anionic agent is present in the extraction solvent and / or the hydration solution. Generally, if the anionic agent is insoluble in water, it is added to an organic extraction solvent, such as ethanol, or a mixture of ethanol and water. After curing, the polymer lens body is swollen in the extraction solvent containing the anionic agent. When the extracted polymer lens body is placed in a hydration solution (such as deionized water), the extraction solvent is removed and the anionic agent remains in the hydrated polymer lens body.

[0074] Generally, if the anionic agent is hydrophilic, the anionic agent is included in the hydration solution or in the final packaging solution from which the polymeric lens body absorbs the anionic agent.

[0075] For example, the extraction and hydration liquid used in the extraction and hydration process may consist of denatured ethanol, a 50 / 50 (by volume) mixture of denatured ethanol and deionized water, and deionized water. As an example, the extraction and hydration process may involve at least one extraction step in denatured ethanol followed by a 50:50 mixture of ethanol and water followed by at least one hydration step in deionized water, and wherein each extraction and hydration step may last for about 15 minutes to about 3 hours at a temperature of about 20° C. to about 30° C. For the purposes of the present invention, any one or more or all of the liquids used for extraction and / or hydration may further contain one or more releasable anionic agents to achieve uploading of the releasable anionic agents to the polymeric lens body. To achieve uploading more effectively, the liquid may be adjusted to have a pH of 7 or less (e.g., about 4 to about 6).

[0076] In one example, the cationic silicone hydrogel contact lens contains at least 25% more (by weight) releasable anionic agent than a control lens, such as at least 50% more or at least 75% more.

[0077] As further described below, the unworn contact lens after the extraction and hydration steps is generally placed in a base member containing a packaging solution and the base member with the contact lens and the packaging solution is then sealed and subjected to a sterilization process (e.g., autoclave sterilization). As an option, the packaging solution may contain an amount of a releasable anionic agent so that the agent is loaded onto the contact lens after packaging. Preferably, the sterilization step does not affect the loading or stability of the agent in the contact lens or the packaging solution.

[0078] As an option, the eye drops and / or multi-purpose contact lens care solution (MPS) may contain a releasable anionic agent. This option is particularly effective in replenishing contact lenses with other releasable anionic agents. Therefore, another aspect of the present invention is the ability to replenish contact lenses with a loading solution containing a releasable anionic agent.

[0079] Any liquid used as a loading solution for a releasable anionic agent may contain a releasable anionic agent concentration of at least 50 ppm of the releasable anionic agent. This concentration may be at least 100 ppm, at least 250 ppm, at least 500 ppm, at least 750 ppm, at least 1000 ppm, at least 1250 ppm, at least 1500 ppm, at least 1750 ppm, or at least 2000 ppm of the anionic agent. For example, a concentration of 50 ppm to 2000 ppm or more of the anionic agent may be contained in the loading solution (or solution for loading anionic agents onto contact lenses).

[0080] In some examples, the releasable anionic agent is stable when attached to the polymeric lens body and is not substantially released or degraded from the polymeric lens body during autoclave sterilization of a sealed contact lens package containing an unworn silicone hydrogel contact lens contained in a packaging solution or during storage of its packaging solution, but does release during lens wear. Thus, the packaging solution in which the contact lens is immersed releases less than 10 ppm of the releasable anionic agent from the contact lens into the packaging solution before autoclave sterilization or just after autoclave sterilization or after 1 day thereafter or after 30 days thereafter or after 60 days thereafter or after 120 days thereafter, or releases less than 5 ppm or less than 1 ppm or 0 ppm from the contact lens into the packaging solution. Whether the releasable anionic agent is released from the contact lens during autoclave sterilization or storage can be determined by testing the packaging solution for the presence of the releasable anionic agent using HPLC, LCMS or other suitable analytical methods.

[0081] Using the present invention, one feature that can be achieved is improved comfort of soft contact lenses, which includes reducing corneal sensitivity by releasing agents that block TRPV1 receptors or interact with PPARa receptors on the cornea.

[0082] In addition, the present invention relates to a method of making a sealed contact lens package of the present invention or an unworn sterile silicone hydrogel contact lens comprising a polymeric lens body. The method comprises the steps of: a) polymerizing a polymerizable composition (as described herein) in a contact lens mold to obtain a hydrogel contact lens, b) removing the hydrogel contact lens from the contact lens mold, c) extracting the removed hydrogel contact lens one or more times and hydrating it, d) sealing the hydrated silicone hydrogel contact lens with a packaging solution in a package, and e) autoclaving the package.

[0083] Silicone hydrogel materials molded into the shape of a contact lens can generally be formed by curing a polymerizable composition (that is, a monomer mixture) comprising at least one siloxane monomer, at least one hydrophilic monomer, and at least one tertiary amine monomer, and optionally at least one hydrophobic monomer.

[0084] The contact lenses of the present invention can be manufactured using conventional methods. As an example, a polymerizable silicone hydrogel composition is dispensed into a female mold member having a concave surface defining the front surface of the contact lens. A male mold member having a convex surface defining the back surface (that is, the corneal contact surface) of the contact lens is combined with the female mold member to form a contact lens mold assembly, which is subjected to curing conditions (such as UV or thermal curing conditions) under which the curable composition is formed into a polymer lens body. The female mold and male mold members can be non-polar molds or polar molds. The mold assembly is disassembled (that is, demolded) and the polymer lens body is removed from the mold and contacted with a solvent (e.g., an organic solvent, such as ethanol) to extract unreacted components from the lens body. After extraction, the lens body is hydrated in a hydrating liquid (e.g., water or an aqueous solution). As shown, the releasable anionic agent can be included in one or more extraction solvents used in the extraction step, in one or more hydrating liquids used in the hydration step, or in both the extraction solvent and the hydrating liquid.

[0085] If the releasable anionic agent is included in the extraction solvent, the hydration step will displace the solvent with the hydration liquid, thereby hydrating the polymer lens body to form a silicone hydrogel, and the releasable anionic agent (or a portion thereof) can be retained within the resulting silicone hydrogel by ionic interactions. An exemplary method for making silicone hydrogel contact lenses is described in U.S. Pat. No. 8,865,789.

[0086] The contact lenses in the present invention can be regarded as soft contact lenses, and in particular soft silicone hydrogel contact lenses. The contact lenses sealed in the contact lens packaging of the present invention can be any glasses wearing mode. The glasses wearing mode refers to how many consecutive days and nights the glasses can be worn without removal. In one example, the contact lenses sealed in the contact lens packaging of the present invention are daily disposable glasses. Indication that daily disposable glasses are suitable for single use, up to about 12 or 16 hours of continuous wear and should be discarded after a single use. In another example, the contact lenses sealed in the contact lens packaging of the present invention are daily wear glasses. Daily wear glasses are worn during waking hours (usually up to 12 to 16 hours) and removed before going to bed. Daily wear glasses are usually stored in a contact lens box, which contains a contact lens care solution for cleaning and disinfecting glasses during non-use time. Daily wear glasses are usually discarded after wearing for up to 30 days. In another example, the contact lenses are long-wear glasses. Extended wear glasses are usually worn continuously for up to 6, 14, or 30 consecutive days and nights.

[0087] The packaging solution sealed in the contact lens package of the present disclosure can be any conventional contact lens compatibility solution. In one example, the packaging solution comprises, consists of, or consists essentially of an aqueous solution of a buffer and / or a tonicity agent. In another example, the packaging solution contains additional agents, such as one or more additional antimicrobial agents, and / or comfort agents, and / or hydrophilic polymers, and / or surfactants and / or other additives that prevent glasses from adhering to the package. The packaging solution can have a pH in the range of about 6.8 or 7.0 up to about 7.8 or 8.0. In one example, the packaging solution comprises a phosphate buffer or a borate buffer. In another example, the packaging solution comprises a tonicity agent selected from sodium chloride or sorbitol, in an amount to maintain an osmotic pressure of about 200 to 400 mOsm / kg, and typically about 270 mOsm / kg up to about 310 mOsm / kg. In some examples, the packaging solution may include a polysaccharide (e.g., hyaluronic acid, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, etc.) or other high molecular weight polymers, such as polyvinylpyrrolidone, which is commonly used as a comfort polymer or thickener in ophthalmic solutions and contact lens packaging solutions.

[0088] Regarding contact lens packaging, this packaging may include or comprise a base member (e.g., a plastic base member) comprising a cavity designed to hold a contact lens and a packaging solution and a flange area extending outwardly around the cavity. A removable foil or seal is attached to the flange area to provide a sealed contact lens package. Such contact lens packaging is well known in the art and is commonly referred to as a "blister pack" (see, e.g., U.S. Pat. No. 7,426,993).

[0089] It should be understood that conventional manufacturing methods can be used to manufacture sealed contact lens packaging. Therefore, in one aspect of the present disclosure, a method for manufacturing contact lens packaging, the method comprising the following steps: unworn contact lenses and contact lens packaging solution are placed in a container, a cover is placed on the container, and a cover on a sealed container. In general, the container is designed to receive a single contact lens and an amount of packaging solution sufficient to completely cover the contact lens, typically about 0.5 to 1.5 ml. The container can be made of any suitable material (such as glass or plastic). In one example, the container includes a plastic base component, the plastic base component includes a cavity designed to keep contact lenses and packaging solution and a flange area extending outward around the cavity, and the cover includes a removable foil attached to the flange area to provide a sealed contact lens package. Removable foil can be sealed by any conventional means (such as heat sealing or gluing). In another example, the container is in the form of a plastic base component comprising a plurality of threads and the cover includes a plastic cap component, and the plastic cap component includes a group of compatible threads for providing a resealable cover with the thread engagement of the base component. It should be appreciated that other types of packaging may also be used to provide a resealable package. For example, a contact lens package may include a plastic cover that includes a feature that engages with a compatible feature of a container to form an interference fit.

[0090] The method of making a sealed contact lens package can further include sterilizing an unworn contact lens by autoclaving the sealed contact lens package. Autoclave sterilization generally involves subjecting the sealed contact lens package to a temperature of at least 121° C. for at least 20 minutes. The final product is a sterile, packaged silicone hydrogel contact lens having an ophthalmologically acceptable surface wettability. In a specific example, the present invention provides a contact lens package comprising: a base member having a cavity for accommodating a packaging solution and a contact lens; an unworn silicone hydrogel contact lens in the cavity of the base member; and a packaging solution in the cavity of the base member.

[0091] The following examples illustrate certain aspects and advantages of the present invention, which should not be construed as being limiting thereof.

[0092] Example 1. Oleic acid absorption from cationic silicone hydrogel lenses

[0093] Silicone hydrogel contact lenses were prepared using polymerizable compositions for: Stanfecon A (control lenses) or Stanfecon A modified to include about 4.5 wt% 2-(dimethylamino)ethyl methacrylate (cationic lenses). The polymerizable compositions were cured in polypropylene contact lens molds. The polymer lens bodies were removed from the molds and extracted by immersing them in ethanol (EtOH) containing oleic acid (Sigma) at the concentrations shown in Table 1 for 215 minutes. The lenses were removed from the EtOH and washed in a 50 / 50 (by volume) mixture of EtOH / water for about 30 minutes followed by three exchanges of DI water for about 6 minutes, 30 minutes, and 30 minutes, respectively.

[0094] The amount of oleic acid (OA) in each lens (n=3) was determined by extracting the lens with isopropyl alcohol (IPA) and measuring the oleic acid in the extract by liquid chromatography-mass spectrometry (LCMS). Briefly, each lens was removed from its container, lightly dotted to remove excess packaging solution, and placed in a 20 mL glass vial containing 10 mL of 100% isopropyl alcohol (IPA). The vial was placed on a bench top shaker at 300 rpm overnight (approximately 16 hours) at room temperature. For Stanfecon A, a single overnight extraction step was sufficient to extract substantially all of the oleic acid from the lens. More hydrophobic silicone hydrogel lens materials may require a second overnight extraction in order to extract all of the oleic acid, in which case the IPA from the first extraction step was removed and replaced with 3 mL of fresh IPA, then shaken overnight at 300 rpm at room temperature. The amount of oleic acid in the IPA extract from each lens was determined by liquid chromatography-mass spectrometry (LCMS). The oleic acid loading concentration and the average oleic acid uptake per lens are shown in Table 1.

[0095] Table 1.

[0096] Glasses OA loading concentration Average amount of OA / glasses Comparison 750ppm 59μg test 750ppm 106μg Comparison 1500ppm 124 μg test 1500ppm 218μg

[0097] Example 2. Oleic acid release from cationic silicone hydrogel lenses.

[0098] Artificial tear film (ATF) having the composition shown in Table 2 was used as the in vivo release medium.

[0099] Table 2.

[0100] Components Concentration (mg / L) Sodium chloride 5259.8 Potassium chloride 1192.8 Sodium Citrate 441.09 glucose 36.032 Urea 72.072 Calcium chloride 55.49 Sodium carbonate 1271.88 Potassium bicarbonate 300.33 Disodium hydrogen phosphate 3407.04 Bovine serum albumin (fatty acid free) 2000 Lysozyme from hen egg white 1900 Mucin from bovine axillary gland 150 DI water 1L Hydrochloric acid (10 mol, 37%) pH 7.1 to 7.2

[0101] Each lens was removed from its container and shaken to remove excess packaging solution. Each lens (n=3) was transferred to a 6 mL glass vial and 5 mL of ATS pre-heated to 35°C was added to each vial. The vials were placed in a 35°C incubator and shaken at 125 rpm. The release medium was exchanged with 4.5 mL of fresh ATS at 1, 3, and 7 hours. The IPA extraction method described in Example 1 was used to determine the amount of oleic acid in the lens at each time point. The results are shown in Table 3 and graphically in Figure 1A and Figure 1B middle.

[0102] Table 3.

[0103]

[0104] The linear regression equation and R-squared value of the release curve are provided in Table 4.

[0105] Table 4.

[0106]

[0107] The present invention includes the following aspects / embodiments / features in any order and / or in any combination:

[0108] 1. An unworn sterile silicone hydrogel contact lens, optionally immersed in a packaging solution and sealed in a package, the contact lens comprising:

[0109] a. a polymeric lens body which is the reaction product of a polymerizable composition comprising from 15 wt % to 65 wt % of at least one siloxane monomer, from 25 wt % to 75 wt % of at least one nonionic hydrophilic monomer, and from 0.1 wt % to 15 wt % of at least one acyclic tertiary amine monomer; and

[0110] b. at least one releasable anionic agent attached to said polymer mirror body,

[0111] wherein the at least one acyclic tertiary amine monomer optionally promotes absorption and / or sustained release of the at least one releasable anionic agent by the polymer body.

[0112] 2. The contact lens of any preceding or following embodiment / feature / aspect, wherein the acyclic tertiary amine monomer is 2-(dimethylamino)ethyl methacrylate.

[0113] 3. The contact lens of any preceding or following embodiment / feature / aspect, wherein the polymerizable composition comprises 0.1 wt% to 10 wt% 2-(dimethylamino)ethyl methacrylate.

[0114] 4. The contact lens of any preceding or following embodiment / feature / aspect, wherein the at least one releasable anionic agent is a fatty acid.

[0115] 5. The contact lens of any preceding or following embodiment / feature / aspect, wherein the at least one releasable anionic agent is a small molecule, optionally oleic acid.

[0116] 6. The contact lens of any preceding or following embodiment / feature / aspect, wherein when placed in an artificial tear film solution, the polymer lens body continuously releases the at least one releasable anionic agent substantially linearly for at least 8 hours.

[0117] 7. The contact lens of any preceding or following embodiment / feature / aspect, wherein when placed in an artificial tear film solution, the polymeric lens body continuously releases the at least one releasable anionic agent substantially linearly for at least 8 hours, and wherein the linear regression of the release curve has an R-squared value of at least 0.90.

[0118] 8. The contact lens of any preceding or following embodiment / feature / aspect, wherein when placed in an artificial tear film solution, the polymeric lens body releases the at least one releasable anionic agent substantially linearly for at least 8 hours, wherein a linear regression of the release curve has an R-squared value of at least 0.90, and wherein the release curve of the control lens exhibits a burst release in which 50% by weight or more of the anionic agent releasable from the control lens is released within a period of 3 hours or less.

[0119] 9. The contact lens of any preceding or following embodiment / feature / aspect, wherein when placed in an artificial tear film solution, the polymeric lens body releases the at least one releasable anionic agent substantially linearly for at least 8 hours, wherein a linear regression of the release curve has an R-squared value of at least 0.90, wherein the release curve of the control lens exhibits a burst release of 50% by weight or more of the anionic agent releasable from the contact lens is released within a time period of 3 hours or less, and wherein the releasable anionic agent is optionally oleic acid.

[0120] 10. The contact lens of any preceding or following embodiment / feature / aspect, wherein the unworn sterile silicone hydrogel contact lens is immersed in a packaging solution and sealed in a package, and wherein the packaging solution comprises another releasable anionic agent that is the same as or different from the at least one releasable anionic agent.

[0121] 11. The contact lens of any preceding or following embodiment / feature / aspect, wherein about 25 μg to about 1000 μg of the releasable anionic agent is attached to the polymeric lens body.

[0122] 12. The contact lens of any preceding or following embodiment / feature / aspect, wherein about 100 μg to about 300 μg of a releasable anionic agent is attached to said polymeric lens body, and wherein said releasable anionic agent is optionally oleic acid.

[0123] 13. The contact lens of any preceding or following embodiment / feature / aspect, wherein the unworn sterile silicone hydrogel contact lens is immersed in a packaging solution and sealed in a package, and wherein the package comprises:

[0124] c. a base member having a cavity for holding a packaging solution; and

[0125] d. A cover that forms a fluid-tight seal with the base component.

[0126] 14 A silicone hydrogel contact lens comprising a polymeric lens body, the polymeric lens body being the reaction product of a polymerizable composition comprising 25 wt% to 55 wt% of a siloxane monomer, 30 wt% to 55 wt% of a vinyl monomer selected from N-vinyl pyrrolidone, N-vinyl-N-methylacetamide, or a combination thereof, 0.1 wt% to 10 wt% of 2-(dimethylamino)ethyl methacrylate, and optionally about 1 wt% to about 20 wt% of a hydrophilic monomer selected from N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA), or ethylene glycol methyl ether methacrylate (EGMA), or any combination thereof, and optionally about 1 wt% to about 20 wt% of a hydrophobic monomer selected from methyl methacrylate (MMA), isobornyl methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB), or any combination thereof.

[0127] 15. A method of making a silicone hydrogel contact lens as in any preceding or following embodiment / feature / aspect (when the unworn sterile silicone hydrogel contact lens is immersed in a packaging solution and sealed in a package, especially the silicone hydrogel contact lens of embodiments / features / aspects 1 to 13, 17, 18 and 19), the method comprising a) polymerizing the polymerizable composition in a contact lens mold to obtain a polymer lens body, b) removing the polymer lens body from the contact lens mold, c) extracting the polymer lens body in an extraction solvent, d) hydrating the polymer lens body in a hydrating liquid to obtain a silicone hydrogel contact lens, e) sealing the silicone hydrogel contact lens with a packaging solution in a package, and e) autoclaving the package, wherein at least one of the extraction solvent, or the hydrating liquid, or the packaging solution comprises at least one releasable anionic agent.

[0128] 16. The method of any preceding or following embodiment / feature / aspect, wherein said extraction solvent comprises said at least one releasable anionic agent.

[0129] 17. An unworn, sterile silicone hydrogel contact lens comprising a polymeric lens body, the polymeric lens body being the reaction product of a polymerizable composition comprising 15 wt % to 65 wt % of at least one siloxane monomer, 25 wt % to 75 wt % of at least one nonionic hydrophilic monomer, and 0.1 wt % to 15 wt % of at least one acyclic tertiary amine monomer, and when tested in an in vitro release assay, the unworn, sterile silicone hydrogel contact lens is capable of substantially linear release of a releasable anionic agent at a release rate of at least 6 μg / hour for at least 8 hours, wherein the at least one acyclic tertiary amine monomer promotes absorption and / or sustained release of the releasable anionic agent from the polymeric lens body.

[0130] 18. The contact lens of any preceding or following embodiment / feature / aspect, wherein the acyclic tertiary amine monomer is 2-(dimethylamino)ethyl acrylate, or 2-(diethylamino)ethyl acrylate, or 3-(dimethylamino)propyl acrylate, or 3-(diethylamino)propyl acrylate, or 2-(dimethylamino)ethyl methacrylate, or 2-(diethylamino)ethyl methacrylate, or 3-(dimethylamino)propyl methacrylate, or 3-(diethylamino)propyl methacrylate, or N-(2-(dimethylamino)ethyl)acrylamide, or N-(2-(diethylamino)ethyl)acrylamide, or N-(3-(dimethylamino)propyl)acrylamide, or N-(3-(diethylamino)propyl)acrylamide, or N-(2-(dimethylamino)ethyl)methacrylamide, or N-(2-(diethylamino)ethyl)methacrylamide, or N-(3-(dimethylamino)propyl)methacrylamide, or N-(3-(diethylamino)propyl)methacrylamide, or 3-(diethylamino)propyl vinyl ether, or 3-(dimethylamino)propyl vinyl ether, or any combination thereof.

[0131] 19. An unworn sterile silicone hydrogel contact lens of any preceding or following embodiment / feature / aspect, wherein the acyclic tertiary amine monomer is 2-(dimethylamino)ethyl acrylate, or 2-(diethylamino)ethyl acrylate, or 3-(dimethylamino)propyl acrylate, or 3-(diethylamino)propyl acrylate, or 2-(dimethylamino)ethyl methacrylate, or 2-(diethylamino)ethyl methacrylate, or 3-(dimethylamino)propyl methacrylate, or 3-(diethylamino)propyl methacrylate, or N-(2-(dimethylamino)ethyl) acrylamide, or N-(2-(diethylamino)ethyl)acrylamide, or N-(3-(dimethylamino)propyl)acrylamide, or N-(3-(diethylamino)propyl)acrylamide, or N-(2-(dimethylamino)ethyl)methacrylamide, or N-(2-(diethylamino)ethyl)methacrylamide, or N-(3-(dimethylamino)propyl)methacrylamide, or N-(3-(diethylamino)propyl)methacrylamide, or 3-(diethylamino)propyl vinyl ether, or 3-(dimethylamino)propyl vinyl ether, or any combination thereof.

[0132] The present invention may include any combination of these various features or embodiments described above and / or below as stated in a sentence and / or paragraph.Any combination of features disclosed herein is considered part of the present invention and no limitation is intended to be placed on the features that can be combined.

[0133] Disclosure herein refers to certain illustrative examples, it should be understood that these examples are presented by way of example and not by way of limitation. Although exemplary examples are discussed, the foregoing detailed description is intended to be interpreted as covering all modifications, substitutions and equivalents of the examples, which modifications, substitutions and equivalents may fall within the spirit and scope of the present invention as defined by the additional disclosure.

[0134] Reference herein to "one example" or "one specific example" or "one aspect" or "one embodiment" or similar phrases is intended to introduce one or more features of a cationic silicone hydrogel contact lens or components thereof, a sealed contact lens package or components thereof, or a method of making a cationic silicone hydrogel contact lens (depending on the context) that can be combined with any combination of previously described or subsequently described examples, aspects, embodiments (that is, features), unless the specific combination of features is mutually exclusive or if the context indicates otherwise. In addition, as used in this specification, the singular forms "a", "an", and "the" include plural referents (e.g., at least one or more) unless the context clearly indicates otherwise. Thus, for example, reference to "a contact lens" includes a single lens and two or more of the same or different lenses.

[0135] All references cited in this disclosure are hereby incorporated by reference in their entirety to the extent they are not inconsistent with this disclosure.

[0136] Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered exemplary only, with a true scope and spirit of the invention being indicated by the following claims and their equivalents.

Claims

1. An unworn sterile silicone hydrogel contact lens immersed in a packaging solution and sealed in a package, the contact lens comprising: (a) a polymeric lens entity which is the reaction product of a polymerizable composition comprising from 15 wt% to 65 wt% of at least one siloxane monomer, from 25 wt% to 75 wt% of at least one nonionic hydrophilic monomer, and from 0.1 wt% to 15 wt% of at least one acyclic tertiary amine monomer; and (b) at least one releasable anionic agent attached to the polymeric lens body, wherein the at least one releasable anionic agent is at least one acid having a single carboxylic acid group and having a molecular weight of less than 900 Daltons; and The at least one acyclic tertiary amine monomer facilitates the absorption and / or sustained release of the at least one releasable anionic agent by the polymer body.

2. The contact lens of claim 1, wherein the acyclic tertiary amine monomer is 2-(dimethylamino)ethyl methacrylate.

3. The contact lens of claim 1, wherein the polymerizable composition comprises 0.1 wt% to 10 wt% 2-(dimethylamino)ethyl methacrylate.

4. The contact lens of claim 1, wherein the at least one releasable anionic agent is a fatty acid.

5. The contact lens of claim 1, wherein the sustained release of the at least one releasable anionic agent from the polymeric lens body is substantially linear for at least 8 hours when placed in an artificial tear film solution.

6. The contact lens of claim 1, wherein the sustained release of the at least one releasable anionic agent from the polymeric lens body when placed in an artificial tear film solution is substantially linear for at least 8 hours, and wherein a linear regression of the release curve has an R-squared value of at least 0.

90.

7. The contact lens of claim 1, wherein the sustained release of the at least one releasable anionic agent from the polymeric lens body when placed in an artificial tear film solution is substantially linear for at least 8 hours, wherein a linear regression of the release curve has an R-squared value of at least 0.90, and wherein the release curve of a control lens exhibits a burst release of 50% by weight or more of the anionic agent releasable from the control lens is released within a period of 3 hours or less, wherein the control lens is a silicone hydrogel contact lens comprising a polymeric lens body formed from a polymerizable composition in the absence of an acyclic tertiary amine monomer.

8. The contact lens of claim 1, wherein the sustained release of the at least one releasable anionic agent from the polymeric lens body when placed in an artificial tear film solution is substantially linear for at least 8 hours, wherein a linear regression of the release curve has an R-squared value of at least 0.90, wherein the release curve of a control lens exhibits a burst release in which 50% by weight or more of the anionic agent releasable from the control lens is released within a time period of 3 hours or less, and wherein the releasable anionic agent is oleic acid, wherein the control lens is a silicone hydrogel contact lens comprising a polymeric lens body formed from a polymerizable composition in the absence of an acyclic tertiary amine monomer.

9. The contact lens of claim 1, wherein the packaging solution comprises another releasable anionic agent that is the same as or different from the at least one releasable anionic agent.

10. The contact lens of claim 1, wherein 25 μg to 1000 μg of the releasable anionic agent is attached to the polymeric lens body.

11. The contact lens of claim 1, wherein 100 μg to 300 μg of the releasable anionic agent is attached to the polymeric lens body, and wherein the releasable anionic agent is oleic acid.

12. The contact lens of claim 1, wherein the packaging comprises: (a) a base member having a cavity for containing the packaging solution; and (b) A cover that forms a fluid-tight seal with the base member.

13. A silicone hydrogel contact lens comprising a polymeric lens body, the polymeric lens body being the reaction product of a polymerizable composition comprising: (a) 25 wt % to 55 wt % of a siloxane monomer, (b) 30 wt % to 55 wt % of a vinyl monomer selected from N-vinyl pyrrolidone, N-vinyl-N-methylacetamide or a combination thereof, (c) 0.1 to 10% by weight of 2-(dimethylamino)ethyl methacrylate or 0.1 to 15% by weight of 3-(dimethylamino)propyl methacrylate, and (d) 1 to 20 wt% of a hydrophobic monomer selected from methyl methacrylate (MMA), isobornyl methacrylate (IBM) or 2-hydroxybutyl methacrylate (HOB), or any combination thereof.

14. A method of making the silicone hydrogel contact lens of claim 1, the method comprising a) polymerizing the polymerizable composition in a contact lens mold to obtain a polymer lens body, b) removing the polymer lens body from the contact lens mold, c) extracting the polymer lens body in an extraction solvent, d) hydrating the polymer lens body in a hydration liquid to obtain the silicone hydrogel contact lens, e) sealing the silicone hydrogel contact lens with a packaging solution in a package, and e) autoclaving the package, wherein at least one of the extraction solvent or the hydration liquid or the packaging solution comprises at least one releasable anionic agent.

15. The method of claim 14, wherein the extraction solvent comprises the at least one releasable anionic agent.

16. An unworn sterile silicone hydrogel contact lens comprising a polymeric lens body, the polymeric lens body being the reaction product of a polymerizable composition comprising 15 wt% to 65 wt% of at least one siloxane monomer, 25 wt% to 75 wt% of at least one nonionic hydrophilic monomer, and 0.1 wt% to 15 wt% of at least one acyclic tertiary amine monomer, and wherein the unworn sterile silicone hydrogel contact lens is capable of substantially linearly releasing a releasable anionic agent at a release rate of at least 6 μg / hour for at least 8 hours when tested in an in vitro release assay, wherein the at least one releasable anionic agent is at least one acid having a single carboxylic acid group and having a molecular weight of less than 900 Daltons; and wherein the at least one acyclic tertiary amine monomer facilitates uptake and / or sustained release of the releasable anionic agent by the polymeric lens body.

17. The contact lens of claim 1, wherein the acyclic tertiary amine monomer is 2-(dimethylamino)ethyl acrylate, or 2-(diethylamino)ethyl acrylate, or 3-(dimethylamino)propyl acrylate, or 3-(diethylamino)propyl acrylate, or 2-(diethylamino)ethyl methacrylate, or 3-(dimethylamino)propyl methacrylate, or 3-(diethylamino)propyl methacrylate, or N-(2-(dimethylamino)ethyl)acrylamide, or N-(2-(diethylamino)ethyl)acrylamide, or N-(3-(dimethylamino)propyl)acrylamide, or N-(3-(diethylamino)propyl)acrylamide, or N-(2-(dimethylamino)ethyl)methacrylamide, or N-(2-(diethylamino)ethyl)methacrylamide, or N-(3-(dimethylamino)propyl)methacrylamide, or N-(3-(diethylamino)propyl)methacrylamide, or 3-(diethylamino)propyl vinyl ether, or 3-(dimethylamino)propyl vinyl ether; or The acyclic tertiary amine monomer is any combination of the following substances: 2-(dimethylamino)ethyl acrylate, or 2-(diethylamino)ethyl acrylate, or 3-(dimethylamino)propyl acrylate, or 3-(diethylamino)propyl acrylate, or 2-(dimethylamino)ethyl methacrylate, or 2-(diethylamino)ethyl methacrylate, or 3-(dimethylamino)propyl methacrylate, or 3-(diethylamino)propyl methacrylate, or N-(2-(dimethylamino)ethyl)acrylamide, or N-(2- N-(3-(dimethylamino)propyl)acrylamide, or N-(2-(dimethylamino)ethyl)methacrylamide, or N-(2-(diethylamino)ethyl)methacrylamide, or N-(3-(dimethylamino)propyl)methacrylamide, or N-(3-(diethylamino)propyl)methacrylamide, or N-(3-(diethylamino)propyl)methacrylamide, or 3-(diethylamino)propyl vinyl ether, or 3-(dimethylamino)propyl vinyl ether.

18. The unworn sterile silicone hydrogel contact lens of claim 16, wherein the acyclic tertiary amine monomer is 2-(dimethylamino)ethyl acrylate, or 2-(diethylamino)ethyl acrylate, or 3-(dimethylamino)propyl acrylate, or 3-(diethylamino)propyl acrylate, or 2-(dimethylamino)ethyl methacrylate, or 2-(diethylamino)ethyl methacrylate, or 3-(dimethylamino)propyl methacrylate, or 3-(diethylamino)propyl methacrylate, or N-(2-(dimethylamino)ethyl)acrylamide , or N-(2-(diethylamino)ethyl)acrylamide, or N-(3-(dimethylamino)propyl)acrylamide, or N-(3-(diethylamino)propyl)acrylamide, or N-(2-(dimethylamino)ethyl)methacrylamide, or N-(2-(diethylamino)ethyl)methacrylamide, or N-(3-(dimethylamino)propyl)methacrylamide, or N-(3-(diethylamino)propyl)methacrylamide, or 3-(diethylamino)propyl vinyl ether, or 3-(dimethylamino)propyl vinyl ether, or any combination thereof.

19. The silicone hydrogel contact lens of claim 13, further comprising (e) 1 to 20 weight percent of a hydrophilic monomer selected from N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA) or ethylene glycol methyl ether methacrylate (EGMA), or any combination thereof.

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