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 that is a reaction product of a polymerizable composition comprising at least one siloxane monomer, at least one non-ionic hydrophilic monomer, and at least one non-cyclic tertiary amine monomer. The cationic contact lens can be an unworn, sterile, silicone hydrogel contact lens. The contact lens is capable of a substantially linear release of a releasable anionic drug, and the at least one non-cyclic tertiary amine monomer facilitates the uptake and / or sustained release of the releasable anionic drug by the polymeric lens body. The contact lens can be present in a sealed contact lens package. The sealed contact lens package can include 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 with the releasable anionic drug present, and d) a cover forming a fluid-tight seal with the base member.

Description

[Technical field]

[0001] The field of the invention relates to contact lenses and sealed contact lens packaging, in particular to contact lenses having cationic properties, and further to packaging containing the contact lenses and methods of manufacturing the contact lenses. The contact lenses of the 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 beneficial agents in the form of releasable anionic agents. [Background technology]

[0002] One of the main approaches to improving the comfort of contact lenses is to incorporate one or more comfort agents into either the lens material or the packaging solution. When the lens is placed on the eye, the comfort agents are released to the surface of the eye. However, it has been difficult to achieve controlled release of comfort agents over the course of contact lens wear because the agents are either encapsulated within the lens material, limiting the release, or they exhibit a burst release rather than the desired controlled release, or they do not provide release over the required time period (which may be 8 hours or more). Thus, there is a need in the industry for contact lenses that provide a controlled release of comfort agents or improved controlled release of comfort agents. Furthermore, it would be desirable to provide such controlled release properties without significantly affecting other properties that the contact lenses provide. Summary of the Invention

[0003] It is a feature of the present invention to provide a contact lens that releases comfort agents during lens wear and that is capable of avoiding burst release of comfort agents. An additional feature of the present invention is to provide unworn, sterile contact lenses that are silicone hydrogels and have cationic properties. A further feature of the present invention is to provide a silicone hydrogel contact lens that contains a releasable comfort agent when worn on the eye and has a controlled release over an extended period of time. An additional feature of the present invention is to provide silicone hydrogel contact lenses that have a higher capacity for uptake and release of comfort agents than conventional silicone hydrogel contact lenses. An additional feature of the present invention is to provide contact lenses that can be loaded or reloaded with comfort agents by contacting the contact lenses with eye drops or a multi-purpose contact lens care solution containing the comfort agents. Additional features and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by the practice of the invention. The objectives and other advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the description and appended claims.

[0004] To achieve these and other advantages and in accordance with the purposes of the invention as embodied and broadly described herein, the present invention relates, in part, to a silicone hydrogel contact lens having (i) a polymeric lens body that is the reaction product of a polymerizable composition comprising 15% to 65% by weight of at least one siloxane monomer, 25% to 75% by weight of at least one non-ionic hydrophilic monomer, and 0.1% to 15% by weight of at least one acyclic tertiary amine monomer, and (ii) at least one releasable anionic agent. The at least one acyclic tertiary amine monomer advantageously facilitates the uptake and / or sustained release of the at least one releasable anionic agent by the polymeric lens body. Both 2-(dimethylamino)ethyl methacrylate (DMAEMA) and 3-(dimethylamino)propyl methacrylate (DMAPMA) have been found to be particularly suitable acyclic tertiary amine monomers.

[0005] The present invention further relates to a silicone hydrogel contact lens comprising a polymeric lens body that is the reaction product of a polymerizable composition comprising 25% to 55% by weight of a siloxane monomer; 30% to 55% by weight of a vinyl monomer selected from N-vinylpyrrolidone, N-vinyl-N-methylacetamide, or combinations thereof; 0.1% to 10% by weight of 2-(dimethylamino)ethyl methacrylate; and optionally, from about 1% to about 20% by weight 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, from about 1% to about 20% by weight of a hydrophobic monomer selected from methyl methacrylate (MMA), isobornyl methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB), or any combination thereof.

[0006] The present invention further relates to a silicone hydrogel contact lens comprising a polymeric lens body which is the reaction product of a polymerizable composition comprising 25% to 55% by weight of a siloxane monomer, 30% to 55% by weight of a vinyl monomer selected from N-vinylpyrrolidone, N-vinyl-N-methylacetamide, or combinations thereof, 0.5% to 3% by weight of 3-(dimethylamino)propyl methacrylate, optionally about 1% to about 20% by weight 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% to about 20% by weight of a hydrophobic monomer selected from methyl methacrylate (MMA), isobornyl methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB), or any combination thereof. Contact lenses which are the reaction product of such compositions have been found to have particularly good dimensional stability.

[0007] The present invention further relates to an unworn, sterile silicone hydrogel contact lens comprising a polymeric lens body that is the reaction product of a polymerizable composition comprising 15% to 65% by weight of at least one siloxane monomer, 25% to 75% by weight of at least one non-ionic hydrophilic monomer, and 0.1% to 15% by weight of at least one acyclic tertiary amine monomer. The unworn, sterile silicone hydrogel contact lens is advantageously capable of a substantially linear release of a releasable anionic drug at a release rate of at least 6 μg / hour over a period of at least 8 hours. The at least one acyclic tertiary amine monomer advantageously facilitates uptake and / or sustained release of the releasable anionic drug by the polymeric lens body.

[0008] The present invention further relates to a method of making the silicone hydrogel contact lenses of the present invention, comprising the steps of a) polymerizing a polymerizable composition (as described herein) in a contact lens mold to obtain a polymeric lens body, b) removing the polymeric lens body from the contact lens mold, c) extracting the polymeric lens body in an organic solvent, d) hydrating the polymeric lens body in a hydration liquid to obtain a silicone hydrogel contact lens, e) sealing the hydrated silicone hydrogel contact lens in a package with a packaging solution, and f) autoclaving the package, wherein at least one of the organic solvent, hydration liquid, or packaging solution contains at least one releasable anionic drug. 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. The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate some of the features of the present invention and, together with the description, serve to explain the principles of the invention. [Brief description of the drawings]

[0009] [Figure 1A]1 is a graph plotting the amount of anionic drug released from cationic silicone hydrogel contact lenses compared to control lenses. [Figure 1B] 1 is a graph plotting the percentage of anionic drug released from cationic silicone hydrogel contact lenses compared to control lenses. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Contact lenses having cationic properties and methods for making the same are described herein. One or more contact lenses having one or more cationic properties can be referred to herein as cationic contact lenses. Also described herein is a sealed contact lens package that includes the contact lens. In the present invention, cationic contact lenses preferably provide controlled release of one or more anionic agents during the course of contact lens wear, such as anionic comfort agents or other beneficial anionic agents that may dissociate from the polymeric lens material during wear under physiological conditions. With respect to the contact lenses of the present invention, the contact lenses are virgin, sterile hydrogel contact lenses, in other words, the contact lenses have not been used and are new.

[0011] Hydrogel contact lenses are the reaction product of a polymerizable composition that includes one acyclic tertiary amine monomer. As an example, hydrogel contact lenses are the reaction product of a non-silicone hydrogel polymerizable composition that includes at least one acyclic tertiary amine monomer. Non-silicone hydrogel contact lenses are typically formed from the polymerization of one or more hydrophilic monomers, such as 2-hydroxyethyl methacrylate (HEMA) or vinyl alcohol, which may be in combination with other monomers, and do not contain siloxanes (i.e., molecules that include at least one Si-O group). As an example, silicone hydrogel contact lenses are the reaction product of a polymerizable composition that includes at least one siloxane monomer, at least one non-ionic hydrophilic monomer, and at least one acyclic tertiary amine monomer. As a further example, silicone hydrogel contact lenses are the reaction product of a polymerizable composition including at least one siloxane monomer, at least one non-ionic hydrophilic monomer, at least one acyclic tertiary amine monomer, and at least one hydrophobic monomer.

[0012] In general, a "monomer" may include or refer to a molecule that contains a polymerizable carbon-carbon double bond (i.e., a polymerizable group) that can react with other polymerizable group-containing molecules, either the same or different, to form a polymer or copolymer. The term monomer encompasses polymerizable prepolymers and macromers, and unless otherwise indicated, there is no restriction on the size of the monomer. A monomer may contain a single polymerizable carbon-carbon double bond or two or more polymerizable groups, and thus possess cross-linking functionality. With respect 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. As used herein, the term "siloxane monomer" refers to a molecule that contains 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, for example, U.S. Pat. Nos. 8,658,747 and 6,867,245). (All patents and publications mentioned herein and throughout are incorporated by reference in their entirety.)

[0013] In some examples, the polymerizable composition comprises a total amount of siloxane monomers of at least 10%, 15%, 20%, 25%, or 30% by weight up to about 40%, 45%, 50%, 55%, 60%, or 65% by weight. For example, the at least one siloxane monomer can be present in an amount of 15% to about 65% by weight, based on the weight of the polymerizable composition. Generally, unless otherwise specified, as used herein, a given weight percentage (wt %) of a component of a polymerizable composition is relative to the total weight of all polymerizable components (and any optional polymers or other components that may be present) in the polymerizable composition. The weight of the polymerizable composition contributed by components such as diluents that are not incorporated into the final contact lens product is not included in the weight % calculation. 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.

[0014] The nonionic hydrophilic monomer may be present in the reaction product of the polymerizable composition in an amount of at least 10%, 15%, 20%, 25%, or 30% by weight 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 may be present in an amount of 25% to about 70% by weight, based on the weight of the polymerizable composition. With respect to non-ionic hydrophilic monomers, as used herein, at least one non-ionic hydrophilic monomer can be understood to include a single hydrophilic monomer or to include a hydrophilic monomer component made up of two or more, e.g., two, three, or four or more, hydrophilic monomers.

[0015] The hydrophilicity or hydrophobicity of a monomer can be determined using conventional techniques, for example, based on the water solubility of the monomer. For purposes of this disclosure, a hydrophilic monomer is one that is visually soluble in an aqueous solution at room temperature (e.g., about 20-25°C). For example, a hydrophilic monomer can be understood to be any monomer in which 50 grams of the monomer is visually completely soluble in 1 liter of water at 20°C (i.e., ≥ 5% soluble in water), as determined using standard shake flask techniques known to those of skill in the art. A hydrophobic monomer, as used herein, is one that is visually insoluble in an aqueous solution at room temperature, separates, and has a visually discernable phase in the aqueous solution, or the aqueous solution appears cloudy and separates into two distinct phases over time after standing at room temperature. For example, a hydrophobic monomer can be understood to be any monomer in which 50 grams of the monomer is visually insoluble in 1 liter of water at 20°C.

[0016] Non-silicon non-ionic hydrophilic monomers that may be used as hydrophilic monomers or hydrophilic monomer components in the polymerizable compositions disclosed herein include, for example, acrylamide-containing monomers, or acrylate-containing monomers, or acrylic acid-containing monomers, or methacrylate-containing monomers, or methacrylic acid-containing monomers, or vinyl-containing monomers, or any combination thereof. A hydrophilic monomer or hydrophilic monomer component is understood to be a non-silicon monomer.

[0017] Examples of non-ionic 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.

[0018] The nonionic hydrophilic monomer may be at least one hydrophilic vinyl monomer. As used herein, a "hydrophilic vinyl monomer" is any siloxane-free (i.e., does not contain Si-O groups) hydrophilic monomer that has a polymerizable carbon-carbon double bond (i.e., vinyl group) present in its molecular structure that is not part of an acrylic group, and the carbon-carbon double bond of the vinyl group is less reactive under free radical polymerization than 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 acrylate, methacrylate, acrylamide, etc. Thus, carbon-carbon double bonds are present in acrylate and methacrylate groups, and as used herein, such polymerizable groups are considered not to be vinyl groups.

[0019] Examples of hydrophilic vinyl-containing monomers that may be provided in the polymerizable composition include, without limitation, 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 includes VMA, NVP, or both VMA and NVP.

[0020] In one example, the polymerizable composition comprises at least 10%, 15%, 20%, or 25% by weight up to about 45%, 50%, 55%, 60%, 65%, or 75% by weight of hydrophilic vinyl monomer. As used herein, a given weight percentage of a particular class of component (e.g., hydrophilic vinyl monomer or siloxane monomer, etc.) in the polymerizable composition is equal to the sum of the weight percentages of each component in that class in the composition. Thus, for example, a polymerizable composition comprising 5% by weight BVE and 25% by weight NVP, but no other hydrophilic vinyl monomers, is said to comprise 30% by weight hydrophilic vinyl monomer. In one example, the hydrophilic vinyl monomer is an N-vinyl amide monomer. Exemplary hydrophilic N-vinyl amide monomers are VMA and NVP. In a specific example, the polymerizable composition comprises at least 25% by weight (e.g., 25% to 55% by weight) of at least one vinyl amide monomer. In further specific examples, the polymerizable composition includes from about 25% up to about 75% (eg, 25% to 55%) by weight VMA or NVP, or a combination thereof.

[0021] The acyclic tertiary amine monomer may be present in the reaction product of the polymerizable composition in an amount of 0.1% by mass to about 15% by mass, for example, 1% by mass to 14% by mass, 1% by mass to 12% by mass, 1% by mass to 10% by mass, 1% by mass to 7% by mass, 1% by mass to 5% by mass, 5% by mass to 15% by mass, 6% by mass to 15% by mass, or 8% by mass to 15% by mass, relative to the total mass of the polymerizable composition. The acyclic tertiary amine monomers can be considered cationic monomers. With respect to acyclic tertiary amine monomers, as used herein, at least one acyclic tertiary amine monomer can be understood to include a single acyclic tertiary amine monomer or to include an acyclic tertiary amine monomer component made up of two or more, e.g., two, three, or four or more, acyclic tertiary amine monomers. Acyclic tertiary amine monomers are those 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 refer to a nitrogen atom directly attached to three carbon atoms, provided that none of the carbon atoms are part of a carbonyl group.

[0022] 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-(diethyl ...

[0043] Examples of suitable vinyl ethers include N-(3-(dimethylamino)propyl)acrylamide, N-(2-(dimethylamino)ethyl)acrylamide, N-(3-(dimethylamino)propyl)acrylamide, N-(3-(diethylamino)propyl)acrylamide, N-(2-(dimethylamino)ethyl)methacrylamide, N-(2-(diethylamino)ethyl)methacrylamide, N-(3-(dimethylamino)propyl)methacrylamide, N-(3-(diethylamino)propyl)methacrylamide, 3-(diethylamino)propyl vinyl ether, or 3-(dimethylamino)propyl vinyl ether, or any combination thereof.

[0023] A more specific example of a non-cyclic tertiary amine monomer is 2-(diethylamino)ethyl methacrylate, which may be present in the polymerizable composition in an amount of 0.1% to 15% by weight, or 1% to 10% by weight (based on the total weight of the polymerizable composition). Another specific example of an acyclic tertiary amine monomer is 3-(dimethylamino)propyl methacrylate, which may be present in the polymerizable composition in an amount of 0.5% to 3%, or 1% to 2.5% by weight (based on the total weight of the polymerizable composition). Compositions including 3-(dimethylamino)propyl methacrylate have been found to provide contact lenses with particularly good dimensional stability.

[0024] Contact lenses as described herein are considered "dimensionally stable" if they are from a batch (i.e., lot) of contact lenses that exhibit an average dimensional stability variance of ≦±3.0% (i.e., no more than + or -3 percent) as determined by a shelf life test method that measures the chord diameter of 20 lenses from a single lot to obtain an "original" average diameter. At the same time, 20 unopened packages of lenses from the same lot are placed in an incubator set at 55°C. The lenses are maintained at this elevated temperature storage condition for three months to approximate a shelf life of approximately two years at 25°C. At the end of the three months, the packaged lenses are brought to room temperature, removed from their packaging, and measured to obtain a "final" average diameter. The dimensional stability variance is calculated according to the formula: (diameter x width x thickness x thickness) / (f / mm2). 最終 -diameter 本来 / diameter 本来 ) × 100. In some examples, the dimensional stability variance is ≦±2.5%, or ≦±2.0%, or ≦±1.5%, or ≦±1.0%.

[0025] In general, the non-cyclic tertiary amine monomers (and part of the polymeric lens body) form charged sites in acidic conditions, such as solutions of lower pH and / or low ionic strength, e.g., a pH below 8.0, or below 7, or a pH below 6 (e.g., a pH between 4 and 6). Under these conditions, the non-cyclic tertiary amine groups protonate to form positively charged sites in the lens material. As will be further explained, these positively charged sites can form ionic complexes with negatively charged comfort agents or other releasable anionic agents.

[0026] Advantageously, one or more acyclic tertiary amine monomers are included in the polymerizable composition to provide a polymeric lens body having a cation content of about 1.0%, or 2.0%, or 3.0% up to about 5.0%, 7.0%, or 10.0%. The "cation content" as used herein is defined by Formula I: Σ(a n1 ×b n1 / c n1 ) × 157 = % cation content (I) (In the formula, a n1is the mass percentage of cationic monomer n1 used in the monomer mixture, as defined below, and b n1 is the number of tertiary amine groups in monomer n1, and c n1 is the molecular weight of the tertiary amine-containing monomer n1). When more than one tertiary amine-containing monomer is used in the polymerizable composition, the % tertiary amine content of the resulting polymeric lens body is the sum of the % ion content contributed by each tertiary amine-containing monomer (i.e., 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 that are incorporated into the hydrogel. In other words, components of the monomer mixture that are not incorporated into the final hydrogel product, such as diluents that are removed from the hydrogel during the manufacturing process, are not included in determining the weight percentage. Formula I adjusts for molecular weight and charge differences compared to an exemplary tertiary amine-containing monomer, 2-(dimethylamino)ethyl methacrylate, which has a molecular weight of 157 and one tertiary amine group. Optionally, one or more hydrophobic monomers may be present as part of the polymerizable composition.

[0027] Examples of suitable hydrophobic monomers include, but are not limited to, one or more non-silicon containing hydrophobic monomers. 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 isobornyl methacrylate (IBM), or trifluoroethyl methacrylate, or hexafluoroisopropyl methacrylate, or tetrafluoropropyl methacrylate, or hexafluorobutyl methacrylate, or any combination thereof.

[0028] When used, the hydrophobic monomer may be present in the reaction product of the polymerizable composition in an amount of 1% by weight to about 30% by weight, for example, 1% by weight to 25% by weight, 1% by weight to 20% by weight, 1% by weight to 15% by weight, 2% by weight to 20% by weight, 3% by weight to 20% by weight, 5% by weight to 20% by weight, 5% by weight to 15% by weight, or 1% by weight to 10% by weight, based on the total weight of the polymerizable composition.

[0029] In addition to or instead of the hydrophilic monomer, the polymerizable composition may include a non-polymerizable hydrophilic polymer, resulting in a polymeric lens body that includes an interpenetrating polymer network (IPN) of the non-polymerizable hydrophilic polymer interpenetrating with the silicone hydrogel silicone hydrogel polymer matrix. In this example, the non-polymerizable hydrophilic polymer is referred to as an IPN polymer, which acts as an internal wetting agent in the contact lens. In contrast, the polymer chains in the silicone hydrogel network formed by 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, for example, from about 50,000 to about 500,000 Daltons. In a specific example, the IPN polymer is polyvinylpyrrolidone (PVP). In another example, the polymerizable composition is free or substantially free of polyvinylpyrrolidone or other IPN polymers.

[0030] The polymerizable composition may further comprise at least one crosslinking agent. As used herein, a "crosslinking agent" is a molecule that has at least two polymerizable groups. Thus, the crosslinking agent can react with the functional groups of two or more polymer chains to crosslink one polymer with another. A variety of crosslinking agents suitable for use in silicone hydrogel polymerizable compositions are known in the art (see, for example, U.S. Patent No. 8,231,218, which is incorporated herein by reference). Examples of suitable crosslinking agents include, without limitation, 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 methacrylate, divinyl ethers such as triethylene glycol divinyl ether, diethylene glycol divinyl ether, 1,4-butanediol divinyl ether, and 1,4-cyclohexanedimethanol divinyl ether, divinyl sulfone; di- and trivinylbenzene; trimethylolpropane tri(meth)acrylate; pentaerythritol tetra(meth)acrylate; bisphenol A di(meth)acrylate; methylene bis(meth)acrylamide; triallyl phthalate; 1,3-bis(3-methacryloxypropyl)tetramethyldisiloxane; diallyl phthalate; triallyl isocyanurate, and combinations thereof.

[0031] As will be appreciated by those skilled in the art, the polymerizable composition may include one or more of the additional polymerizable or non-polymerizable components conventionally used in contact lens formulations, such as a polymerization initiator, an oxygen scavenger, a chain transfer agent, or a diluent. In some examples, the polymerizable composition may include an amount of an organic diluent that prevents or minimizes phase separation between the hydrophilic and hydrophobic components of the polymerizable composition, resulting in an optically clear lens. 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 or substantially free (e.g., less than 500 ppm) of an organic diluent. In such examples, the use of siloxane monomers containing hydrophilic moieties such as polyethylene oxide groups, pendant hydroxyl groups, or other hydrophilic groups may eliminate the need to include a diluent in the polymerizable composition. Non-limiting examples of these and additional components that may be included in the polymerizable composition are provided in U.S. Pat. No. 8,231,218.

[0032] A specific example of a silicone hydrogel contact lens of the present invention is based on a polymerizable composition comprising 25% to 55% by weight of a siloxane monomer, 30% to 55% by weight of a vinyl monomer selected from NVP, VMA, or a combination thereof, and optionally about 1% to about 20% by weight 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% to about 20% by weight 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 stenfilcon A, comfilcon A, somofilcon A, fanfilcon A, and enfilcon A. In a further example, the polymerizable composition may comprise stenfilcon A siloxanes, specifically those of formula (I):

[0033] [ka] (I) A first siloxane having a structure represented by: and formula (II)

[0034] [ka] (II) The base polymerizable composition described above is further modified to further include 0.1% to 15% by weight of at least one acyclic tertiary amine, such as 1% to 10% by weight of 2-(dimethylamino)ethyl methacrylate, or 0.5% to 3% by weight of 3-(dimethylamino)propyl methacrylate, and cured to provide a cationic polymeric lens body.

[0035] As part of the present invention, the contact lens is a silicone hydrogel contact lens that includes a polymeric lens body and at least one releasable anionic agent attached to the polymeric lens body. The anionic agent may be attached to the polymeric lens body by cationic and / or hydrophobic interactions and / or may be physically encapsulated within the polymer network of the polymeric lens body. The releasable anionic agent can be one or more (e.g., one, two, or more) releasable anionic agents. Alternatively, the releasable anionic drug may block TRPV1 receptors, such as in the cornea, and / or may interact with PPARa receptors.

[0036] 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 (i.e., having a molecular weight of less than about 900 Daltons). In some examples, the releasable anionic agent of choice is not a polymer. Optionally, the releasable anionic agent is not a polymer of a disaccharide. 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.

[0037] When a releasable anionic drug is in-situ complexed by ionic interaction with the polymeric lens body (e.g., due to low pH conditions and / or low ionic strength conditions, e.g., a pH less than about 7 or a pH less than about 6), the releasable anionic drug is itself an anionic drug or material that complexes by ionic interaction with a cationic moiety or molecule that forms part of the polymeric lens material. By way of example, a releasable anionic drug, upon deprotonation, may form a complex with at least a portion of the protonated moieties or molecules in the polymeric lens body, e.g., protonated tertiary amine groups present in the polymeric lens body. A releasable anionic drug that is complexed by ionic interaction with the polymeric lens body is released from the polymeric lens body, for example, under physiological conditions, by dissociation through ionic interaction with counterions in the tear fluid. The released anionic drug will at this point generally become a salt or ester (e.g., a salt of at least one acid, such as oleic acid, or an oleate ester).

[0038] The amount of releasable anionic drug attached to the polymer lens body is at least 25 μg, for example, 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. The releasable anionic agent may be from about 25 μg to about 500 μg, or from about 100 μg to about 300 μg, or from about 25 μg to about 300 μg, or from about 25 μg to about 250 μg, or from about 50 μg to about 750 μg, or from about 25 μg to about 300 μg, or from about 25 μg to about 500 μg, or from about 25 μg to about 3 ...

[0039] Alternatively, the releasable anionic agent may be distributed uniformly throughout the polymeric lens body via ionic interactions as described herein. Alternatively, the releasable anionic agent may be distributed non-uniformly. For example, the releasable anionic agent may be present in a higher amount on one side of the contact lens or on both sides of the contact lens (i.e., the posterior and anterior sides) compared to an interior portion of the contact lens (the region located between the posterior and anterior sides). The releasable anionic drugs present in silicone hydrogel contact lenses are not covalently bound to the polymeric lens body. Alternatively or in addition to the ionic interactions described herein between the polymeric lens body and the releasable anionic agent, the releasable anionic agent can alternatively be considered to be embedded, encapsulated, dispersed, absorbed, and / or located within the contact lens. As mentioned, the releasable anionic agent is preferably present within and / or on the contact lens due to the releasable anionic agent forming a complex with the lens material or a portion of the lens material, which is believed to be an ionic interaction.

[0040] A further example of a contact lens of the present invention is an unworn, sterile silicone hydrogel contact lens comprising a polymeric lens body that is the reaction product of a polymerizable composition comprising 15% to 65% by weight of at least one siloxane monomer, 25% to 75% by weight of at least one non-ionic hydrophilic monomer, and 0.1% to 15% by weight of at least one acyclic tertiary amine monomer. The unworn, sterile silicone hydrogel contact lens is capable of releasing a releasable anionic drug at a release rate of at least 6 μg / hour for at least 8 hours. References herein to the amount or duration of release of anionic drug from a contact lens are intended to mean the amount and / or duration of release from the contact lens when tested in the in vitro release assay described in Example 2. The at least one acyclic tertiary amine monomer facilitates uptake and / or sustained release of the releasable anionic drug by the polymeric lens body.

[0041] With respect to at least one non-cyclic tertiary amine monomer that promotes the uptake and / or sustained release of at least one releasable anionic agent by the polymeric lens body, it is believed that when a "control lens" that is a silicone hydrogel contact lens comprising a polymeric lens body formed from a polymerizable composition in which the non-cyclic tertiary amine monomer is absent (instead of the amount of the non-cyclic tertiary amine monomer, this amount is replaced with a hydrophobic monomer such as MMA, but otherwise the same polymerizable composition) is compared to a "cationic lens" that is a silicone hydrogel contact lens comprising a polymeric lens body formed from a polymerizable composition in which the non-cyclic tertiary amine monomer is present, the uptake by the polymeric lens body containing the non-cyclic tertiary amine monomer will be higher than the control lens using the same concentration of releasable anionic agent in the loading solution. Similarly, due to the enhanced sustained release, the polymeric lens body containing the non-cyclic tertiary amine monomer in the polymerizable composition will have a longer release time, e.g., 8 hours or 9 hours, compared to the control lens, and / or will have a more linear release profile over the 8 hour or 9 hour period compared to the control lens. As used herein, the term "release profile" refers to the shape of the line that represents the amount of anionic drug released from a lens at 1 hour, 3 hours, 6 hours, and 9 hours using the release media and release assay method described in Example 2 below, as shown in FIG. 1A.

[0042] In one example, the cationic contact lens exhibits a substantially linear release of the anionic drug over a period of at least 8 hours. As used herein, a substantially linear release over a period of at least 8 hours is indicated when a linear regression of the anionic drug release profile has an R-squared value of at least 0.90 with the amount of release measured at 1 hour, 3 hours, 6 hours, and 9 hours (n=3 at each time point). In one example, the cationic contact lens exhibits a substantially linear release of the anionic drug over a period of at least 8 hours and has an R-squared value of at least 0.90. In some examples, the cationic contact lens exhibits a substantially linear release of the anionic drug over a period of at least 8 hours and has an R-squared value of at least 0.90, and the control lens exhibits a burst release in which 50% or more by weight of the anionic drug releasable from the contact lens is released in a period of 3 hours or less.

[0043] In some examples, the present cationic contact lenses may have an anionic drug release of from 2 μg to 50 μg (e.g., from 5 μg to 50 μg, or from 10 μg to 40 μg, or from 10 μg to 30 μg) of anionic drug per hour for a period of at least 8 hours, at least 9 hours, or at least 10 hours, such as from 8 hours to 16 hours, or from 10 hours to 16 hours, or from 12 hours to 16 hours.

[0044] The present invention preferably avoids burst release of the anionic drug. An example of a burst release (or burst effect) is when 50% or more by weight of the releasable anionic drug from the contact lens is released in a time period of 3 hours or less. Thus, in accordance with the present invention, the contact lenses of the present invention are capable of providing at least one or more of the following properties: a) a substantially linear release profile of the anionic drug; b) the ability to upload large amounts of the anionic drug (at least 50 μg, or at least 100 μg, or at least 150 μg, or at least 200 μm to the lens); c) release of the anionic drug over an extended period of time (at least 8 hours, e.g., 8 to 16 hours, or 9 to 16 hours, or 10 to 16 hours, or 8 to 12 hours); and / or d) avoidance of any burst release.

[0045] The incorporation or loading of the releasable anionic agent by the silicone hydrogel contact lens may occur during the extraction step, and / or the hydration step, and / or the packaging step. For example, the incorporation of the releasable anionic agent may occur during the solvent extraction step after the contact lens material has been cured, and / or during one or more hydration steps when at least one releasable anionic agent is present in the extraction solvent and / or hydration solution. Generally, if the anionic agent is not water soluble, it is added to an organic extraction solvent, such as ethanol or a mixture of ethanol and water. After curing, the polymeric lens body is swollen in the extraction solvent containing the anionic agent. When the extracted polymeric 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 polymeric lens body. Generally, if the anionic agent is hydrophilic, it is included in the hydration solution or in the final packaging solution from which the anionic agent dissolves into the polymeric lens body.

[0046] For example, the extraction and hydration liquids used in the extraction and hydration process can consist of denatured ethanol, a 50 / 50 (by volume) mixture of denatured ethanol and deionized water, and deionized water. By way of example, the extraction and hydration process can include at least one extraction step in a 50:50 mixture of denatured ethanol followed by ethanol water, followed by at least one hydration step in deionized water, with each extraction and hydration step lasting from about 15 minutes to about 3 hours at a temperature of about 20° C. to about 30° C. For purposes of the present invention, any one or more or all of the liquids used in the extraction and / or hydration can further contain one or more releasable anionic drugs to achieve uploading of the releasable anionic drugs to the polymeric lens body. To more effectively achieve uploading, the liquids can be adjusted to have a pH of 7 or less, such as from about 4 to about 6. In one example, the cationic silicone hydrogel contact lenses contain at least 25% more (by weight) of releasable anionic agent than the control lenses, such as at least 50% more, or at least 75% more.

[0047] As described further below, the unworn contact lens after the extraction and hydration steps is generally placed into a base member containing a packaging solution, and then the base member and packaging solution with the contact lens are sealed and subjected to a sterilization process (e.g., autoclaving). Optionally, the packaging solution contains a quantity of a releasable anionic drug, which is uploaded to the contact lens during packaging. Preferably, the sterilization step does not affect the upload or stability of the drug in the contact lens or in the packaging solution. Alternatively, the eye drops and / or multi-purpose contact lens care solution (MPS) may contain a releasable anionic agent. This option is particularly effective for reloading the contact lens with additional releasable anionic agents. Thus, a further aspect of the present invention is the ability to reload the contact lens with an upload solution containing a releasable anionic agent.

[0048] Any liquid used as an upload solution for a releasable anionic agent may contain a concentration of releasable anionic agent of at least 50 ppm of 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 anionic agent. For example, the concentration may be from 50 ppm to 2000 ppm or more of anionic agent in the upload solution (or solution used to upload an anionic agent to a contact lens).

[0049] In some instances, the releasable anionic agent once attached to the polymeric lens body is stable and does not substantially release from the polymeric lens body or degrade during autoclaving of a sealed contact lens package containing an unworn silicone hydrogel contact lens in a packaging solution or during storage of the packaging solution, but is released during lens wear. Thus, the packaging solution in which the contact lens is immersed prior to autoclaving or immediately thereafter, or 1 day, or 30 days, or 60 days, or 120 days after autoclaving, has less than 10 ppm of releasable anionic agent released from the contact lens into the packaging solution, or has 5 ppm or less, or less than 1 ppm, or 0 ppm of releasable anionic agent released from the contact lens into the packaging solution. Whether or not a releasable anionic agent is released from the contact lens during autoclaving or storage can be determined by testing for the presence of the releasable anionic agent in the packaging solution using HPLC, LCMS, or other suitable analytical methods.

[0050] One of the features that can be achieved by the present invention is to improve the comfort level of soft contact lenses, which involves reducing corneal sensitivity by releasing drugs that block TRPV1 receptors or interact with PPARa receptors at the cornea. The present invention further relates to a method of making an unworn, sterile silicone hydrogel contact lens comprising the sealed contact lens package or polymeric lens body of the present invention, the method comprising 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 and hydrating the removed hydrogel contact lens one or more times, d) sealing the hydrated silicone hydrogel contact lens in a package with a packaging solution, and e) autoclaving the package. Silicone hydrogel materials molded into the shape of a contact lens can typically be formed by curing a polymerizable composition (i.e., a monomer mixture) that includes at least one siloxane monomer, at least one hydrophilic monomer, at least one tertiary amine monomer, and optionally at least one hydrophobic monomer.

[0051] Conventional methods can be used to manufacture the contact lenses of the present invention. By way of example, a polymerizable silicone hydrogel composition is dispensed into a female mold member having a concave surface that defines the front surface of the contact lens. A male mold member having a convex surface that defines the rear surface, i.e., the corneal contact surface, of the contact lens is mated with the female mold member to form a contact lens mold assembly that is subjected to curing conditions, e.g., UV or thermal curing conditions, under which the curable composition is formed into a polymeric lens body. The female and male mold members can be of either a non-polar or polar type. The mold assembly is disassembled (i.e., demolded), and the polymeric 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, such as water or an aqueous solution. As indicated, the releasable anionic drug may 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. If a releasable anionic drug is included in the extraction solvent, the hydration step replaces the solvent with a hydration fluid, thereby hydrating the polymeric lens body to form a silicone hydrogel, and the releasable anionic drug (or a portion thereof) may remain due to ionic interactions within the resulting silicone hydrogel. An exemplary method for making silicone hydrogel contact lenses is described in U.S. Patent No. 8,865,789.

[0052] The contact lenses in the present invention can be considered to be soft contact lenses, particularly soft silicone hydrogel contact lenses. The contact lenses sealed in the contact lens packaging of the present disclosure can be of any lens wear mode. The lens wear mode refers to the number of consecutive days and nights the lens can be worn without removal. In one example, the contact lenses sealed in the contact lens packaging of the present disclosure are daily disposable lenses. Daily disposable lenses are indicated for a single use with a maximum of 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 disclosure are daily wear lenses. Daily wear lenses are worn during waking hours, typically for a maximum of about 12-16 hours, and removed before going to bed. Daily wear lenses are typically stored in a contact lens case that contains a contact lens care solution for cleaning and disinfecting the lenses during non-use times. Daily wear lenses are typically discarded after a maximum of 30 days of wear. In yet another example, the contact lenses are extended wear lenses. Extended wear lenses are typically worn for up to 6, 14, or 30 consecutive days and nights.

[0053] The packaging solution sealed within the contact lens packaging of the present disclosure may 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 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 the lens from sticking to the packaging. The packaging solution may have a pH ranging from about 6.8 or 7.0 up to about 7.8 or 8.0. In one example, the packaging solution includes a phosphate buffer or a borate buffer. In another example, the packaging solution includes a tonicity agent selected from sodium chloride or sorbitol in an amount to maintain an osmolality of about 200 to 400 mOsm / kg, typically ranging from about 270 mOsm / kg up to about 310 mOsm / kg. In some examples, the packaging solution may include polysaccharides (e.g., hyaluronic acid, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, etc.) or other high molecular weight polymers, such as polyvinylpyrrolidone, which are commonly used as comfort polymers or thickening agents in ophthalmic solutions and contact lens packaging solutions.

[0054] With respect to contact lens packaging, the packaging may include or comprise a base member, such as a plastic base member, that includes a cavity configured to hold a contact lens and a packaging solution, and a flange region that extends outwardly around the cavity. A removable foil or seal is attached to the flange region to provide a sealed contact lens package. Such contact lens packages are commonly referred to as "blister packs" and are well known in the art (see, e.g., U.S. Pat. No. 7,426,993).

[0055] It is recognized that conventional manufacturing methods can be used to manufacture the sealed contact lens package. Accordingly, one aspect of the present disclosure is a method of manufacturing a contact lens package, comprising the steps of placing an unworn contact lens and a contact lens packaging solution in a receptacle, placing a cover in the receptacle, and sealing the cover to the receptacle. Generally, the receptacle is configured to receive a single contact lens and a sufficient amount of packaging solution to completely cover the contact lens, typically about 0.5 to 1.5 ml. The receptacle may be made of any suitable material, such as glass or plastic. In one example, the receptacle includes a plastic base member including a cavity configured to hold the contact lens and the packaging solution, and a flange region that flares outwardly around the cavity, and the cover includes a removable foil attached to the flange region to provide a sealed contact lens package. The removable foil may be sealed by any conventional method, such as heat sealing or gluing. In another example, the receptacle is in the form of a plastic base member including a plurality of threads, and the cover includes a plastic cap member including a matching set of threads for mating with the threads of the base member, thereby providing a removable cover. It will be appreciated that other types of packaging can also be used to provide the removable packaging. For example, a contact lens packaging may include a plastic cover including features that mate with matching features of the receptacle to form an interference fit.

[0056] The method of producing a sealed contact lens package may further include sterilizing an unworn contact lens by autoclaving the sealed contact lens package. Autoclaving typically 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 ophthalmically acceptable surface wettability. In an embodiment, the present invention provides a contact lens package having a base member having a cavity for receiving 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. The following examples are illustrative of certain aspects and advantages of the present invention, but it should be understood that they are not limiting thereby. EXAMPLES

[0057] Example 1 Oleic acid uptake from cationic silicone hydrogel lenses. Silicone hydrogel contact lenses were prepared using a polymerizable composition of stenfilcon A (control lenses) or stenfilcon A modified to contain approximately 4.5% by weight 2-(dimethylamino)ethyl methacrylate (cationic lenses). The polymerizable composition was cured in polypropylene contact lens molds. The polymeric lens bodies were removed from the molds and extracted by immersing them in ethanol (EtOH) containing oleic acid (Sigma) at the concentration shown in Table I for 215 minutes. The lenses were removed from the EtOH and washed in a 50 / 50 mixture of EtOH / water for approximately 30 minutes, followed by three changes of DI water for approximately 6 minutes, 30 minutes, and 30 minutes, respectively.

[0058] The amount of oleic acid (OA) in each lens (n=3) was determined by extracting the lenses with isopropanol (IPA) and measuring the oleic acid in the extract by liquid chromatography mass spectrometry (LCMS). Briefly, each lens was removed from its container, lightly blotted to remove excess packaging solution, and placed in a 20 mL glass vial containing 10 mL of 100% isopropanol (IPA). The vial was placed on a benchtop shaker at 300 rpm at room temperature overnight (approximately 16 hours). For stenfilcon A, a single overnight extraction step is sufficient to extract virtually all of the oleic acid from the lens. Silicone hydrogel lens materials, which are more hydrophobic, may require a second overnight extraction to extract all of the oleic acid, in which case the IPA from the first extraction step is removed and replaced with 3 mL of fresh IPA and shaken overnight at room temperature at 300 rpm. The amount of oleic acid in the IPA extract from each lens is determined by liquid chromatography mass spectrometry (LCMS). The oleic acid loading concentration and average oleic acid uptake per lens are shown in Table 1.

[0059] [Table 1]

[0060] Example 2 Oleic acid release from cationic silicone hydrogel lenses. An artificial tear film (ATF) having the composition shown in Table 2 was used as the in vitro release medium. [Table 2]

[0061] 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-warmed to 35° C. was added to each vial. The vials were placed in an incubator at 35° C. and shaken at 125 rpm. The release medium was replaced with 4.5 mL of fresh ATS at 1, 3, and 7 hours. The amount of oleic acid in the lenses at each time point was determined using the IPA extraction method described in Example 1. The results are shown in Table 3 and plotted in Figures 1A and 1B.

[0062] [Table 3] The linear regression equations and R-squared values ​​for the release profiles are presented in Table 4.

[0063] [Table 4]

[0064] Example 3 Dimensionally stable cationic silicone hydrogel lenses. Silicone hydrogel contact lenses were prepared using polymerizable compositions of stenfilcon A modified to contain 3-(dimethylamino)propyl methacrylate (DMAPMA) at approximately 1.0%, 1.5%, 2.0%, and 2.5% by weight. The compositions were used to prepare contact lenses using the method described in Example 1, except that oleic acid was not included in the extraction solvent. The dimensional stability of the lenses was determined using the shelf life test method described above (i.e., storage at 55°C for 3 months to approximate a shelf life of 2 years at 25°C). The average chord length of the lenses changed by less than 1.0% from the original average chord length, indicating that the lenses made with DMAPMA monomer are dimensionally stable.

[0065] The present invention includes the following numbered aspects / embodiments / features in any order and / or in any combination: 1. An unworn, sterile silicone hydrogel contact lens that has been immersed in a packaging solution and sealed in a package, comprising: a. a polymeric lens body that is a reaction product of a polymerizable composition that includes 15% to 65% by weight of at least one siloxane monomer, 25% to 75% by weight of at least one nonionic hydrophilic monomer, and 0.5% to 3% by weight of 3-(dimethylamino)propyl methacrylate; b. at least one releasable anionic drug attached to the polymeric lens body; wherein 3-(dimethylamino)propyl methacrylate advantageously promotes the uptake and / or sustained release of at least one releasable anionic drug by the polymeric lens body.

[0066] 2. A contact lens of any preceding or following embodiment / feature / aspect, wherein the polymerizable composition comprises 1.0% to 2.5% by weight of 3-(dimethylamino)propyl methacrylate. 3. A contact lens of any preceding or following embodiment / feature / aspect, wherein the polymerizable composition comprises 1.5% to 2.0% by weight of 3-(dimethylamino)propyl methacrylate. 4. A contact lens of any preceding or following embodiment / feature / aspect, wherein the polymerizable composition comprises a first siloxane monomer represented by formula I, and a second siloxane monomer represented by formula II. 5. A contact lens of any preceding or following embodiment / feature / aspect that is dimensionally stable.

[0067] 6. A contact lens of any preceding or following embodiment / feature / aspect, wherein at least one releasable anionic agent is a fatty acid. 7. A contact lens of any preceding or following embodiment / feature / aspect, wherein at least one releasable anionic agent is a small molecule. 8. A contact lens of any preceding or following embodiment / feature / aspect, wherein the sustained release of the at least one releasable anionic agent by the polymeric lens body is substantially linear over a period of at least 8 hours when placed in an artificial tear film solution. 9. A contact lens of any preceding or following embodiment / feature / aspect, wherein the sustained release of at least one releasable anionic agent by the polymeric lens body when placed in an artificial tear film solution is substantially linear over a period of at least 8 hours, and a linear regression of the release profile has an R-squared value of at least 0.90.

[0068] 10. A contact lens of any preceding or following embodiment / feature / aspect, wherein the sustained release of at least one releasable anionic agent by the polymeric lens body when placed in an artificial tear film solution is substantially linear over a period of at least 8 hours, a linear regression of the release profile having an R-squared value of at least 0.90, and a release profile of a control lens exhibiting a burst release in which 50% or more by weight of the releasable anionic agent from the control lens is released in a period of 3 hours or less. 11. A contact lens of any preceding or following embodiment / feature / aspect, wherein the sustained release of at least one releasable anionic agent by the polymeric lens body when placed in an artificial tear film solution is substantially linear over a period of at least 8 hours, a linear regression of the release profile having an R-squared value of at least 0.90, and the release profile of a control lens exhibits a burst release in which 50% or more by weight of the releasable anionic agent from the contact lens is released in a period of 3 hours or less, and the releasable anionic agent is oleic acid. 12. A contact lens of any preceding or following embodiment / feature / aspect, wherein the packaging solution comprises an additional releasable anionic agent that is the same as or different from the at least one releasable anionic agent.

[0069] 13. A contact lens of any preceding or following embodiment / feature / aspect, wherein about 25 μg to about 1000 μg of a releasable anionic agent is attached to the polymeric lens body. 14. A 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 the polymeric lens body, and the releasable anionic agent is oleic acid. 15. Packaging c. a base member having a cavity for holding a packaging solution; and d. A cover that forms a liquid-tight seal with the base member A contact lens according to any preceding or following embodiment / feature / aspect.

[0070] 16. A silicone hydrogel contact lens comprising a polymeric lens body that is the reaction product of a polymerizable composition comprising 25% to 55% by weight of a siloxane monomer; 30% to 55% by weight of a vinyl monomer selected from N-vinylpyrrolidone, N-vinyl-N-methylacetamide, or combinations thereof; 0.5% to 3% by weight of 3-(dimethylamino)propyl methacrylate; and optionally, from about 1% to about 20% by weight 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 combinations thereof; and optionally, from about 1% to about 20% by weight of a hydrophobic monomer selected from methyl methacrylate (MMA), isobornyl methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB), or any combinations thereof.

[0071] 17. A method of making a silicone hydrogel contact lens of any preceding or following embodiment / feature / aspect, comprising: a) polymerizing the polymerizable composition in a contact lens mold to obtain a polymeric lens body; b) removing the polymeric lens body from the contact lens mold; c) extracting the polymeric lens body in an extraction solvent; d) hydrating the polymeric lens body in a hydration liquid to obtain a silicone hydrogel contact lens; e) sealing the silicone hydrogel contact lens in a package with a packaging solution; and e) autoclaving the package, wherein at least one of the extraction solvent, hydration liquid, or packaging solution contains at least one releasable anionic drug. 18. The method of any preceding or following embodiment / feature / aspect, wherein the extraction solvent comprises the at least one releasable anionic drug. 19. An unworn, sterile silicone hydrogel contact lens comprising a polymeric lens body that is the reaction product of a polymerizable composition comprising 15% to 65% by weight of at least one siloxane monomer, 25% to 75% by weight of at least one nonionic hydrophilic monomer, and 0.5% to 3% by weight of 3-(dimethylamino)propyl methacrylate, wherein when tested in an in vitro release assay, the lens is capable of a substantially linear release of a releasable anionic agent at a release rate of at least 6 μg / hour over a period of at least 8 hours, and the 3-(dimethylamino)propyl methacrylate advantageously promotes uptake and / or sustained release of the releasable anionic agent by the polymeric lens body.

[0072] It should be understood that the disclosure herein refers to certain illustrated examples, which are presented by way of example and not by way of limitation. The intent of the foregoing detailed description, while discussing illustrative examples, is to be construed as including all modifications, alternatives, and equivalents of those examples as may fall within the spirit and scope of the invention as defined by the appended claims.

[0073] Reference herein to an "example" or "embodiment" or "aspect" or "embodiment" or similar phrase is intended to introduce one or more features of the cationic silicone hydrogel contact lenses or components thereof, the sealed contact lens packaging or components thereof, or the method of making the cationic silicone hydrogel contact lenses (as the context requires), which may be combined in any combination of the examples, aspects, embodiments (i.e., features) described above or subsequently, unless a particular combination of features is mutually exclusive or the context indicates otherwise. Furthermore, as used herein, the singular forms "a," "an," and "the" include plural references (e.g., at least one or more) unless the context clearly dictates otherwise. Thus, for example, a reference to a "contact lens" includes a single lens as well as two or more of the same or different lenses.

[0074] The entire contents of all references cited in this disclosure are incorporated herein by reference to the extent they are not inconsistent with this disclosure. The present invention may include any combination of the various features or embodiments described above and / or in the following claims, as set forth in sentences and / or paragraphs. Any combination of features disclosed herein is considered to be part of the invention, and no limitations as to which features may be combined are intended.

[0075] 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 as exemplary only, with a true scope and spirit of the invention being indicated by the following claims and equivalents thereof.

Claims

1. 1. An unworn, sterile silicone hydrogel contact lens immersed in a packaging solution and sealed in a package, comprising: (a) a polymeric lens body that is the reaction product of a polymerizable composition comprising 15% to 65% by weight of at least one siloxane monomer, 25% to 75% by weight of at least one nonionic hydrophilic monomer, and 0.5% to 3% by weight of 3-(dimethylamino)propyl methacrylate; (b) at least one releasable anionic drug attached to the polymeric lens body; wherein 3-(dimethylamino)propyl methacrylate promotes the uptake and / or sustained release of at least one releasable anionic drug by the polymeric lens body.

2. 2. The contact lens of claim 1, wherein the polymerizable composition comprises 1.0% to 2.5% by weight of 3-(dimethylamino)propyl methacrylate.

3. The contact lens of claim 1 , wherein the polymerizable composition comprises a first siloxane monomer represented by Formula I and a second siloxane monomer represented by Formula II.

4. The contact lens of claim 3 which is dimensionally stable.

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

6. The contact lens of claim 1 , wherein the at least one releasable anionic agent is a small molecule.

7. 10. The contact lens of claim 1, wherein the sustained release of the at least one releasable anionic agent by the polymeric lens body is substantially linear over a period of at least 8 hours when placed in an artificial tear film solution.

8. 2. The contact lens of claim 1, wherein the sustained release of at least one releasable anionic drug by the polymeric lens body when placed in an artificial tear film solution is substantially linear over a period of at least 8 hours, and a linear regression of the release profile has an R-squared value of at least 0.

90.

9. 2. The contact lens of claim 1, wherein the sustained release of at least one releasable anionic drug by the polymeric lens body when placed in an artificial tear film solution is substantially linear over a period of at least 8 hours, a linear regression of the release profile has an R-squared value of at least 0.90, and the release profile of a control lens exhibits a burst release in which at least 50% by weight of the releasable anionic drug from the control lens is released in a period of 3 hours or less.

10. 2. The contact lens of claim 1, wherein the sustained release of at least one releasable anionic drug by the polymeric lens body when placed in an artificial tear film solution is substantially linear over a period of at least 8 hours, a linear regression of the release profile has an R-squared value of at least 0.90, and the release profile of a control lens exhibits a burst release in which 50% or more by weight of the releasable anionic drug is released from the contact lens in a period of 3 hours or less, and the releasable anionic drug is oleic acid.

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

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

13. 10. The contact lens of claim 1, wherein about 100 μg to about 300 μg of a releasable anionic agent is attached to the polymeric lens body, the releasable anionic agent being oleic acid.

14. The packaging, (a) a base member having a cavity for holding a packaging solution; and (b) a cover that forms a liquid-tight seal with the base member The contact lens of claim 1 , comprising:

15. 1. A silicone hydrogel contact lens comprising a polymeric lens body that is the reaction product of a polymerizable composition comprising 25% to 55% by weight of a siloxane monomer; 30% to 55% by weight of a vinyl monomer selected from N-vinylpyrrolidone, N-vinyl-N-methylacetamide, or a combination thereof; 0.5% to 3% by weight of 3-(dimethylamino)propyl methacrylate; and optionally, from about 1% to about 20% by weight 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, from about 1% to about 20% by weight of a hydrophobic monomer selected from methyl methacrylate (MMA), isobornyl methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB), or any combination thereof.

16. The contact lens of claim 15, wherein the polymerizable composition comprises 1.0% to 2.5% by weight of 3-(dimethylamino)propyl methacrylate.

17. 16. The contact lens of claim 15, wherein the polymerizable composition comprises a first siloxane monomer represented by formula I and a second siloxane monomer represented by formula II.

18. 16. The contact lens of claim 15 which is dimensionally stable.

19. 13. A method of making a silicone hydrogel contact lens according to claim 1, comprising the steps of: a) polymerizing the polymerizable composition in a contact lens mold to obtain a polymeric lens body; b) removing the polymeric lens body from the contact lens mold; c) extracting the polymeric lens body in an extraction solvent; d) hydrating the polymeric lens body in a hydration liquid to obtain a silicone hydrogel contact lens; e) sealing the silicone hydrogel contact lens in a package with a packaging solution; and e) autoclaving the package, wherein at least one of the extraction solvent, hydration liquid, or packaging solution contains at least one releasable anionic drug.

20. 20. The method of claim 19, wherein the extraction solvent comprises the at least one releasable anionic drug.

21. 1. An unworn, sterile silicone hydrogel contact lens comprising a polymeric lens body that is the reaction product of a polymerizable composition comprising 15% to 65% by weight of at least one siloxane monomer, 25% to 75% by weight of at least one non-ionic hydrophilic monomer, and 0.5% to 3% by weight of at least one acyclic tertiary amine monomer, 3-(dimethylamino)propyl methacrylate, wherein the contact lens is capable of a substantially linear release of a releasable anionic drug at a release rate of at least 6 μg / hour over a period of at least 8 hours when tested in an in vitro release assay, and the 3-(dimethylamino)propyl methacrylate promotes the uptake and / or sustained release of the releasable anionic drug by the polymeric lens body.

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