TW202434214A - Compositions for ophthalmologic devices - Google Patents

Abstract

The present invention relates to ophthalmic device packaging compositions containing chlorous acid compound and a reductant for storing and/or packaging vinyl pyrrolidone containing polymeric ophthalmic device in the compositions. Methods of using the compositions of the present invention are also disclosed.

Description

Components of Ophthalmic Devices (II)

Cross-reference to related applications

This application claims priority to U.S. Provisional Patent Application Serial No. 63/476,548 filed on December 21, 2022, the entire text of which is incorporated herein by reference.

The present invention relates to an ophthalmic device packaging composition containing a chlorous acid compound and a reducing agent, which is used to store and/or package a polymeric ophthalmic device containing vinyl pyrrolidone in the composition. A method of using the composition of the present invention is also disclosed.

Methods of using the compositions of the invention are also disclosed.

Contact lenses are usually provided to consumers in the form of individually packaged products. The single unit containers that package such contact lenses generally use buffered saline as a storage solution or packaging solution.

At least in some cases, such a kit solution should provide an environment that does not promote the growth of harmful or undesirable microorganisms for a short period of time (e.g., between solution preparation and sterilization of the final stage packaged product). Such undesirable microorganisms include Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans , Bacillus subtilis , and Aspergillus brasiliensis . In addition, the kit solution should be gentle to the eye because at least some of the kit solution will most likely remain on the contact lens after the contact lens is removed from the kit solution and placed directly on the eye (i.e., by direct application to the eye).

Contact lens (or other ophthalmic device) packaging box solution/storage solution should also be compatible with the materials forming the contact lens (or other ophthalmic device) and the packaging box in which the solution and the ophthalmic device are stored.

A challenge in preparing a packaging kit solution/storage solution containing chlorous acid for use in an ophthalmic device is to formulate a solution that does not negatively impact eye comfort or negatively impact the compatibility of the solution with the polymeric material(s) forming the ophthalmic device. Although chlorous acid compounds (e.g., chlorite) can be used to retard the growth of microorganisms, prolonged exposure (e.g., through storage or packaging) of certain contact lenses to chlorous acid compounds in such compositions can result in adverse changes in certain contact lenses, such as a potential increase in the contact lens forward dynamic contact angle. This is particularly true in the case of contact lenses formed from polymeric materials containing polyvinylpyrrolidone.

The inventors have discovered that by incorporating a reducing agent into a contact lens storage/packaging composition containing a chlorous acid compound, the concentration of the chlorous acid compound is reduced during storage/packaging, thereby reducing the effect of the chlorous acid compound on the forward dynamic contact angle of the contact lens, as described in detail below.

The present invention relates to an ophthalmic product or kit comprising: a)    a composition comprising an admixture or mixture of: i.     a chlorous acid compound in an amount effective to inhibit the growth of microorganisms in the composition; ii.    a buffering compound; iii.   a reducing agent for neutralizing the chlorous acid compound, provided that after the reducing agent is admixed with the composition, the chlorous acid compound remains effective to inhibit the growth of microorganisms in the composition for a period of time; and iv.   an ophthalmologically acceptable carrier and b)   a container comprising a sealed compartment containing the composition and at least one polymeric ophthalmic device comprising a high molecular weight polyvinylpyrrolidone polymer.

The present invention also relates to a method for reducing or preventing the reaction between a chlorous acid compound and a polymeric ophthalmic device containing a high molecular weight polyvinyl pyrrolidone polymer, comprising the following steps: a.   Mixing a composition comprising: i.     a chlorous acid compound in an amount effective to inhibit the growth of microorganisms in the composition; ii.   A buffer compound; and iii.   A reducing agent for neutralizing the chlorous acid compound, provided that after the reducing agent is admixed with the composition, the chlorous acid compound remains effective to inhibit the growth of microorganisms in the composition for a period of time; b.   Placing the composition and the polymeric ophthalmic device containing a high molecular weight polyvinyl pyrrolidone polymer in a container.

The invention also relates to methods of making and using the disclosed compositions.

As indicated above, the present invention relates to compositions comprising one or more chlorous acid compounds and one or more phosphate compounds as an ophthalmologically acceptable carrier.

The compositions can be used to store ophthalmic devices or can be used as packaging solutions for ophthalmic devices. Specifically, the present invention provides ophthalmic solutions comprising a compound that temporarily inhibits the growth of microorganisms, which is bacteriostatic by heat sterilization such as autoclaving to formulate the composition, but is substantially or completely neutralized during sterilization to provide a non-preservative ophthalmic solution after sterilization. The present invention further provides a hermetically sealed contact lens packaging box comprising a contact lens and the ophthalmic solution of the present invention.

The compositions can be used for direct application to the eye to obtain eye care benefits, such as relief of eye discomfort.

The compositions and methods of the present invention may comprise, consist of, or consist essentially of the steps, essential elements, and limitations of the present invention described herein, as well as any additional or optional ingredients, components, or limitations described herein. As used herein, the term "comprising" (and its grammatical variations) is used in the inclusive sense of "having" or "including" rather than in the exclusive sense of "consisting only of". As used herein, the terms "a", "an" and "the" are understood to cover the plural as well as the singular.

Unless otherwise indicated, all documents cited are incorporated herein by reference. In addition, all documents incorporated herein by reference are incorporated herein only to the extent that such documents are not inconsistent with this patent specification. The citation of any document should not be interpreted as an admission that it is a prior art corresponding to the present invention.

The present invention as disclosed herein may be practiced in the absence of any compound or element (or group of compounds or elements) not specifically disclosed herein.

As used herein, the term "pharmaceutically acceptable" means biologically tolerated and otherwise biologically suitable for administration to or exposure to the eye and periocular tissues without undue adverse effects, such as toxicity, incompatibility, irritation, allergic response, and the like.

As used herein, the term "ophthalmically acceptable and/or compatible" means that the composition(s) or components, or other ingredients (including active ingredients) in the composition itself, are pharmaceutically acceptable and will not or will not substantially be adversely, negatively, or harmful to any part of the eye (or surrounding tissues).

As used herein, the term "water soluble" means that the components, alone or in combination with other components, do not form precipitates or gel particles visible to the human eye at selected concentrations and across temperature and pH conditions commonly encountered in the manufacture, sterilization, and storage of ophthalmic solutions or ophthalmic products.

As used herein, the term "cationic preservative" means a net positively charged compound having antimicrobial properties, and includes, but is not limited to, one or more of the following: polymyxin B sulfate, quaternary ammonium compounds, poly(quaternary ammonium) compounds, benzalkonium chloride, cetylpridinium chloride, benzethonium chloride, cetyltrimethyl ammonium bromide, chlorhexidine, poly(hexamethylene biguanide), and mixtures thereof. Poly(quaternary ammonium) compounds are compounds that act as positively charged surfactants (i.e., cationic surfactants) that destroy cell walls and cell membranes, and examples include BUSAN 77, ONAMERM, MIRAPOLA 15, IONENES A, POLYQUATERNIUM 11, POLYQUATERNIUM 7, BRADOSOL, and POLYQUAT D-17-1742.

As used herein, the term "lidstock" means a flexible film or sheet that is heat sealed to the concave side of a plastic blister package to form a sealed cavity. The lidstock is typically multi-layered and includes a support layer and a peelable sealing layer. The lidstock may further include additional layers, including printed layers, laminated layers, foil layers, combinations thereof, and the like.

As used herein, "advancing dynamic contact angle" means the angle measured when a contact lens is raised and lowered relative to a test solution surface and the test fluid-air interface is contacted with the contact lens surface as determined by lowering a test article (e.g., a contact lens) into the test solution. The advancing dynamic contact angle provides information about the wettability, topography, and homogeneity of the surface and is affected by experimental variables such as the speed at which the article moves within the test solution.

As used herein, the term "effective to inhibit" means an amount that causes inhibition of microbial growth.

The phrase "inhibition of in the growth of microorganisms" in the composition occurs under the following circumstances and means: there is less than 0.5 log, or less than 0.3 log, or less than 0.2 log increase, or no increase in the count of any microorganism present in the composition after 1 day, 2 days, 3 days, 5 days, 7 days, 8 days, 10 days, 13 days, 14 days, 15 days, 20 days, 21 days, or 22 days from the date of preparation of the composition of the present invention.

The term "hydrophilic monomers with at least one hydroxyl group (hydroxyalkyl monomer)" refers to an olefinically unsaturated compound comprising at least one hydroxyl alkyl group selected from _C2 - _C4 monohydroxy- or dihydroxy-substituted alkyl groups, and a poly(ethylene glycol) having 1 to 10 repeating units; or selected from 2-hydroxyethyl, 2,3-dihydroxypropyl, or 2-hydroxypropyl, and combinations thereof.

Examples of hydroxyalkyl monomers include 2-hydroxyethyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2,3-dihydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, 1-hydroxypropyl 2-(meth)acrylate, 2-hydroxy-2-methyl-propyl (meth)acrylate, 3-hydroxy-2,2-dimethyl-propyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, 2-hydroxyethyl (meth)acrylamide, N- -(2-hydroxypropyl)(meth)acrylamide, N,N-bis(2-hydroxyethyl)(meth)acrylamide, N,N-bis(2-hydroxypropyl)(meth)acrylamide, N-(3-hydroxypropyl)(meth)acrylamide, 2,3-dihydroxypropyl(meth)acrylamide, glycerol(meth)acrylate, polyethylene glycol monomethacrylate, and mixtures thereof.

The hydroxyalkyl monomer may also be selected from the group consisting of 2-hydroxyethyl methacrylate, glycerol methacrylate, 2-hydroxypropyl methacrylate, hydroxybutyl methacrylate, 3-hydroxy-2,2-dimethyl-propyl methacrylate, and mixtures thereof.

The hydroxyalkyl monomer may include 2-hydroxyethyl methacrylate, 3-hydroxy-2,2-dimethyl-propyl methacrylate, hydroxybutyl methacrylate or glycerol methacrylate.

The term "hydrophilic vinyl-containing monomer" refers to ethylenically unsaturated compounds containing a vinyl reactive group (such as hydrophilic N-vinyl lactam and N-vinyl amide monomers), including: N-vinyl pyrrolidone (NVP), N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-caprolactam, N-vinyl-3-methyl-2-piperidone, N-vinyl-4-methyl-2-piperidone, N-vinyl-4 -methyl-2-caprolactam, N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone, N-vinylacetamide (NVA), N-vinyl-N-methylacetamide (VMA), N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N-vinylformamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N-vinyl -2-methylpropionamide, N-vinyl-N,N'-dimethylurea, 1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone; 1-ethyl-5-methylene-2-pyrrolidone, N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-N-propyl-3-methylene-2-pyrrolidone, 1-N-propyl The invention also includes 1-isopropyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N-vinylformamide, N-vinylisopropylamide, N-vinylcaprolactam, N-carboxyvinyl-β-alanine (VINAL), N-carboxyvinyl-α-alanine, N-vinylimidazole, and mixtures thereof.

The term "hydrophilic O-vinyl carbamates and O-vinyl carbonates monomers" refers to ethylenically unsaturated compounds including O-vinyl carbamates or O-vinyl carbonates, including N-2-hydroxyethyl vinyl carbamate and N-carboxy-β-alanine N-vinyl ester. Further examples of hydrophilic vinyl carbonate or vinyl carbamate monomers are disclosed in U.S. Patent No. 5,070,215, and hydrophilic oxazolinone monomers are disclosed in U.S. Patent No. 4,910,277.

Examples of vinyl carbamates and vinyl carbonates include: N -2-hydroxyethyl vinyl carbamate, N -carboxy-β-alanine N -vinyl ester, other hydrophilic vinyl monomers including vinyl imidazole, ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, 2-ethyl oxazoline, vinyl acetate, acrylonitrile, and mixtures thereof.

The term "(meth)acrylamide monomers" refers to hydrophilic ethylenically unsaturated compounds containing a (meth)acrylamide group. Examples include N -N-dimethylacrylamide, acrylamide, N,N -bis(2-hydroxyethyl)acrylamide, acrylonitrile, N -isopropylacrylamide, N,N -dimethylaminopropyl(meth)acrylamide, and any of the hydroxyl-functional (meth)acrylamides listed above.

As used herein, "ophthalmic device" refers to an object that resides in or on the eye. Such devices may provide optical correction, cosmetic enhancement, light blocking (including UV, HEV, visible light, and combinations thereof), glare reduction, therapeutic effects (including preventing myopia progression), wound healing, delivery of medication or nutrients, diagnostic assessment or monitoring, or any combination thereof. Ophthalmic devices include (selected from the following or selected from the group consisting of the following) but are not limited to: soft contact lenses, artificial lenses, cover lenses, eye plugs, tear duct plugs, and optical plugs. The ophthalmic device may be a contact lens. Contact lenses (or "contacts") are placed directly on the surface of the eye (e.g., on the tear membrane covering the surface of the eye). Contact lenses include soft contact lenses (e.g., conventional or silicone hydrogels), hard contact lenses, or hybrid contact lenses (e.g., with a soft skirt or shell). Soft contact lenses can be formed from hydrogels. Contact lenses that can be used with these compositions can be manufactured using various known techniques to produce a shaped article with desired rear and front lens surfaces. Rotational casting methods are disclosed in U.S. Patent Nos. 3,408,429 and 3,660,545; static casting methods are disclosed in U.S. Patent Nos. 4,113,224; 4,197,266; and 5,271,875, each of which is incorporated herein by reference.

A "hydrogel" is a polymeric network that swells in water or aqueous solutions, typically absorbing at least 10 weight percent water. A "silicone hydrogel" is a hydrogel made from at least one silicone-containing component and at least one hydrophilic component. The hydrophilic component may also include a non-reactive polymer.

"Conventional hydrogel" refers to a polymeric network made of components that do not have any siloxy, siloxane, or carbosiloxane groups. Conventional hydrogels are prepared from a reactive mixture containing hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate ("HEMA"), N-vinyl pyrrolidone ("NVP"), N, N-dimethylacrylamide ("DMA"), or vinyl acetate. U.S. Patent Nos. 4,436,887, 4,495,313, 4,889,664, 5,006,622, 5,039,459, 5,236,969, 5,270,418, 5,298,533, 5,824,719, 6,420,453, 6,423,761, 6,767,979, 7,934,830, 8,138,290, and 8,389,597 disclose the formation of known hydrogels. Commercially available known hydrogels include, but are not limited to, etafilcon, genfilcon, hilafilcon, lenefilcon, nelficlon, nesofilcon, ocufilcon, omafilcon, polymacon, and vifilcon, including all variations thereof.

"Silicone hydrogel" refers to a polymeric network made of at least one hydrophilic component and at least one silicone-containing component. Examples of suitable families of hydrophilic components that may be present in the reactive mixture include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl urethanes, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof. Non-limiting examples of hydrophilic components include N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), N-vinyl pyrrolidone (NVP), N-vinyl acetamide (NVA), N-vinyl-N-methylacetamide (VMA), and mixtures thereof. Silicone-containing components are well known and have been extensively described in the patent literature. For example, the silicone-containing component may include at least one polymerizable group (e.g., (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl urethane, O-vinyl carbonate, vinyl, or a mixture of the foregoing), at least one siloxane group, and one or more linking groups (which may be bonds) connecting the polymerizable group(s) to the siloxane group(s). The silicone-containing component may, for example, contain 1 to 220 siloxane repeating units, 3 to 100, 3 to 40, or 3 to 20 siloxane repeating units. The silicone-containing component may also contain at least one fluorine atom.

The silicone hydrogel formulation may also include a polymeric humectant that is non-polymerizable and becomes entrapped in the silicone hydrogel upon polymerization, thereby forming a semi-interpenetrating network.

Alternatively, the polymeric wetting agent may be polymerizable, for example as a polyamide macromer or prepolymer, and in this case covalently incorporated into the silicone hydrogel. Mixtures of polymerizable and non-polymerizable polyamides may also be used.

Examples of suitable wetting agents include cyclic and linear polyamides, and specific examples include polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof. The polymeric wetting agent may be PVP, a mixture of PVP (e.g., PVP K90) and PVMA (e.g., having an M _w of about 570 KDa).

When the polyamides are incorporated into the reactive monomer mixture, they may have a weight average molecular weight of at least 100,000 daltons; greater than about 150,000; between about 150,000 and about 2,000,000 daltons; between about 300,000 and about 1,800,000 daltons. Higher molecular weight polyamides may be used if they are compatible with the reactive monomer mixture.

The hydrogel or silicone hydrogel formulation may also contain additional components such as, but not limited to, diluents, initiators, light absorbing compounds (including UV, visible light absorbers), photochromic compounds, pharmaceuticals, nutrients, antimicrobial substances, colorants, pigments, copolymerizable dyes, non-polymerizable dyes, release agents, and combinations thereof. When light absorbing compounds, photochromic compounds, colorants, or dyes (polymerizable or non-polymerizable) are used, they are preferably stable in the presence of a chlorous acid compound at a selected chlorous acid compound concentration. One example of a UV absorber that is stable in the presence of a chlorous acid compound is Norbloc.

The silicone hydrogel lens may contain a coating, and the coating may be the same material as or different from the substrate.

Examples of silicone hydrogels include acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon (including all variants thereof), and the like as disclosed in U.S. Patent No. 4,659 ,782, No. 4,659,783, No. 5,244,981, No. 5,314,960, No. 5,331,067, No. 5,371,147, No. 5,998,498, No. 6,087,415, No. 5,760,100, No. 5,776,999, No. 5,789,461, No. 5,849,811, No. 5,965,631, No. 6,367,929, No. 6,822,016, No. 6,867,245, No. 6,943,203, No. 7,247,692, No. 7,249,848, No. 7,553,880, No. 7,666,921, No. 7,786,185, No. 7,956,131, No. 8,022,158, No. 8,273,802, No. 8,399,538, No. 8,470,906, No. 8,450,387, No. 8,487,058, No. 8,507,577, No. 8,637,621, No. 8,703,891, No. 8,937,110, No. 8,937,111, No. 8,940,812, No. 9,05 No. 6,878, No. 9,057,821, No. 9,125,808, No. 9,140,825, No. 9156,934, No. 9,170,349, No. 9,244,196, No. 9,244,197, No. 9,260,544, No. 9,297,928, No. 9,297,929, and WO03/22321, WO2008/061992, US2010/0048847, US2023/0037781, and US2021/0109255. The entire text of these patents is hereby incorporated by reference.

An "interpenetrating polymeric network" comprises two or more networks that are at least partially interlaced on a molecular scale, but are not covalently bonded to each other and cannot be separated without breaking chemical bonds. A "semi-interpenetrating polymeric network" comprises one or more networks and one or more polymers, characterized by some intermixing on a molecular level between at least one network and at least one polymer. A mixture of different polymers is a "polymer blend." A semi-interpenetrating network is technically a polymer blend, but in some cases the polymers are so entangled that they cannot be easily removed.

Unless otherwise specified, all percentages, parts and proportions are based on the total weight of the composition of the present invention. All weights of listed ingredients are based on active levels and, therefore, do not include carriers or by-products that may be included in commercially available materials unless otherwise specified.

The compositions of the present invention contain one or more chlorous acid compounds or salts thereof when mixed. The chlorous acid compounds and salts thereof are ophthalmically compatible with the eye and surrounding tissues, and are compatible with the ingredients in the compositions of the present invention. Upon degradation (e.g., sterilization or storage conditions), the chlorous acid compounds and salts degrade into ophthalmically compatible degradation agents. The degradation agents of the chlorous acid compounds and salts thereof do not interact with the contact lens in which they are stored or packaged, nor do they interact with the storage/packaging container (including the lid material). The chlorous acid compound may be an anhydride or a hydrate. The salt of chlorous acid may be a monosalt or a complex salt.

Examples of chlorous acid compounds suitable for use in the compositions or methods of the present invention include (selected from the following or selected from the group consisting of the following) but are not limited to: chlorous acid; alkali metal salts of chlorous acid, including lithium chlorite, sodium chlorite, sodium chlorite trihydrate, or potassium chlorite, and the like; alkali earth metal salts of chlorous acid, including magnesium chlorite, magnesium chlorite trihydrate, calcium chlorite, calcium chlorite trihydrate, barium chlorite, or barium chlorite dihydrate, and the like; earth metal salts of chlorous acid, such as aluminum chlorite; zinc salts of chlorous acid, such as zinc chlorite dihydrate; Transition metal salts of chloric acid, such as copper (II) chlorite, copper (III) chlorite, silver chlorite, nickel chlorite dihydrate, or manganese chlorite; ammonium chlorite; quaternary ammonium salts of chlorite, such as tetramethylammonium chlorite; quaternary phosphonium salts of chlorite, such as (2,4-dinitrophenyl)triethylphosphonium chlorite; amine salts of chlorite, such as methylamine salt of chlorite, tripropylamine salt of chlorite, hydrazine salt of chlorite, pyridinium salt of chlorite, 4-methylpyridinium salt of chlorite, 2,4-dimethylpyridinium salt of chlorite, or quinoline salt of chlorite; complex salts, such as KClO _{2 ·} NaClO ₂ , Cu (ClO ₂ ) ₂ · 2KClO ₂ · 2H ₂ O, Cu(ClO ₂ ) ₂ · Mg(ClO ₂ ) ₂ · 8H ₂ O, or Cu(ClO ₂ ) ₂ · Ba(ClO ₂ ) ₂ · 4H ₂ O, and the like, but not limited thereto. Chlorite compound sources such as stable oxychloride complexes (Purite, Bio-Cide International Inc., OK, USA) and/or stable peroxychlorite (SOC - Oxyd Tubilux.) can also be used in the composition of the present invention. A mixture of any of the above chlorite compounds or a chlorite compound source can also be used.

The salts of the chlorite compounds particularly preferably used herein are ophthalmically compatible salts, including but not limited to lithium chlorite, sodium chlorite, sodium chlorite trihydrate, or potassium chlorite, and the like; alkali earth metal salts of chlorite, including magnesium chlorite, magnesium chlorite trihydrate, calcium chlorite, calcium chlorite trihydrate, aluminum chlorite, ammonium chlorite; quaternary ammonium salts of chlorite , such as tetramethylammonium chlorite; quaternary phosphonium salts of chlorous acid, such as (2,4-dinitrophenyl)triethylphosphonium chlorite; amine salts of chlorous acid, such as methylamine salt of chlorous acid, tripropylamine salt of chlorous acid, pyridinium salt of chlorous acid, 4-methylpyridinium salt of chlorous acid, 2,4-dimethylpyridinium salt of chlorous acid, or quinoline salt of chlorous acid, and mixtures thereof.

Preferred for use in the composition of the present invention are chlorite compounds and salts thereof. Chlorite compounds suitable for use in the present invention include (selected from the following or selected from the group consisting of the following) but are not limited to: water-soluble alkali metal chlorites, water-soluble alkali metal chlorites, and mixtures thereof. Specific examples of chlorite compounds include (selected from the following or selected from the group consisting of the following): potassium chlorite, sodium chlorite, calcium chlorite, magnesium chlorite, and mixtures thereof. The chlorite compound may include sodium chlorite.

The chlorous acid compound is incorporated into the compositions of the present invention to provide antimicrobial properties for inhibiting the growth of microorganisms in the compositions. The antimicrobial properties for inhibiting the growth of microorganisms may appear and take effect during a period of time, which may begin when the composition of the present invention is prepared or manufactured and end when the composition is subjected to at least one sterilization method, which may be sterilization of the composition in a sealed package with at least one contact lens, as described below. In practice, this period of time may be as long as two weeks, during which the solution is stored in a sealed container at ambient temperature. During sterilization (particularly heat sterilization, such as autoclaving), the chlorous acid compound concentration is substantially or completely neutralized. For example, the concentration of the compound that inhibits microbial growth can be reduced by at least about 50%, about 70%, about 80%, about 90%, or 100%. If the chlorous acid is not completely neutralized during autoclaving, it can be completely neutralized during storage of the lens after autoclaving and before use.

When formulated, suitable concentrations of the chlorous acid compound include 0.0020% (or about 0.0020%) to 0.2000% (or about 0.2000%), or 0.0020% (or about 0.0020%) to 0.1000% (or about 0.1000%), or 0.0050% (or about 0.0050%) to 0.1000% (or about 0.1000%), or 0.0075% (or about 0.0075%) to 0.1000% (or about 0.1000%), based on the total weight of the composition. 0.0075%) to 0.1000% (or about 0.1000%), or 0.0080% (or about 0.0080%) to 0.0500% (or about 0.0500%), or 0.0090% (or about 0.0090%) to 0.0200% (or about 0.0200%), or 0.0095% (or about 0.0095%) to 0.0150% (or about 0.0150%), or 0.01% (or about 0.01%).

When formulated, the chlorous acid compound provides 0.0015% (or about 0.0015%) to 0.1500% (or about 0.1500%), or 0.0015% (or about 0.0015%) to 0.0750% (or about 0.0750%), or 0.0037% (or about 0.0037%) to 0.0750% (or about 0.0750%), or 0.0056% (or about 0.0056%), based on the total weight of the composition. 0.0056%) to 0.0750% (or about 0.0750%), or 0.0060% (or about 0.0060%) to 0.0370% (or about 0.0370%), or 0.0067% (or about 0.0067%) to 0.0150% (or about 0.0150%), or 0.0071% (or about 0.0071%) to 0.0110% (or about 0.0110%) of chlorite anion concentration.

The phrase "period of time" used in conjunction with the antibacterial properties of chlorous acid compounds means up to or at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days, 14 days, 15 days, 18 days, 20 days, 21 days, or 22 days from the date of preparation of the composition of the present invention. The period of time may be as long as two weeks, during which the solution is stored in a sealed container at ambient temperature. Buffering Compounds

The composition of the present invention comprises a buffer compound. Suitable buffer compounds include but are not limited to phosphate compounds, organic buffers, and mixtures thereof.

As used herein, the term "phosphate" or "phosphate compound" (used interchangeably herein) shall refer to phosphoric acid, salts of phosphoric acid, and other pharmaceutically acceptable phosphates (e.g., inorganic or organic pharmaceutically acceptable salts), or combinations thereof. Examples of phosphate compounds that can be used in the compositions are phosphate compounds selected from pharmaceutically acceptable organic or inorganic alkali metal and/or alkaline earth metal phosphates. Suitable phosphates can be incorporated as one or more monobasic phosphates, dibasic phosphates, and the like. The phosphate compound may include: one or more organic phosphates, such as phytic acid (or its salts, such as its potassium salt or sodium salt); _or one or more inorganic phosphates, such as dibasic sodium hydrogen phosphate ( _Na2HPO4 ), dibasic sodium phosphate ( _NaH2PO4 ), and _dibasic potassium phosphate ( _KH2PO4 ); or a mixture of any of the above phosphate compounds _.

When phosphate is provided as an inorganic phosphate compound, the inorganic phosphate compound may be present in the compositions at a concentration of 0.3% (or about 0.3%) w/v to 0.9% (or about 0.9%) w/v, or 0.4% (or about 0.4%) w/v to 0.85% (or about 0.85%) w/v, or 0.5% (or about 0.5%) w/v to 0.8% (or about 0.8%) w/v, or 0.6% (or about 0.6%) w/v to 0.75% (or about 0.75%) w/v of the total composition upon formulation.

When the phosphate compound is provided as an organophosphate compound, the organophosphate compound can be present in the composition at a concentration of 0.05% (or about 0.05%) w/v to 1.0% (or about 1.0%) w/v, or 0.10% (or about 0.10%) w/v to 0.50% (or about 0.50%) w/v, or 0.15% (or about 0.15%) w/v to 0.30% (or about 0.30%) w/v, or 0.17% (or about 0.17%) w/v to 0.25% (or about 0.25%) w/v of the total composition upon formulation.

The concentration of the phosphate compound may be at least 1.5 times (or about 1.5 times), or at least 2.0 times (or about 2.0 times) and/or at least 2.5 times (or about 2.5 times), but at most 4 times, or at most 3 times the amount of the borate compound by weight.

As used herein, the term "organic acid buffer" refers to a phosphate-free organic acid having two or more carboxylic acid groups.

The organic acid also has a buffering ability within a pH range consistent with ophthalmic compositions (e.g., eye drops and eye washes) and packaging solutions for eye care devices (e.g., contact lenses), and can buffer the composition of the present invention to about 6.0 pH to about 8.0 pH, or about 6.5 pH to about 8.0 pH, or about 6.5 pH to about 7.5 pH, or about 7.0 pH to about 7.5 pH, or greater than 7.2 (or about 7.2) pH to 7.5 (or about 7.5) pH.

Preferred organic acid buffers for use in the compositions of the present invention have a pK value in the range of 6 (or about 6) to 8 (or about 8), or 6 (or about 6) to 7 (or about 7).

Suitable diprotic acids include cis-butenedioic acid (pK ₂ = 6.5). Suitable hexaprotic acids include mellitic acid (pK ₆ = 7). Suitable hexaprotic acids include mellitic acid (pK ₆ = 7). Phytic acid (or a salt thereof, such as its potassium or sodium salt) may also be used herein. Phytic acid has 12 replaceable protons, six of which are strongly acidic (pKa of about 1.5), three are weakly acidic (pKa between 5.7 and 7.6), and three are very weakly acidic (pKa>10.0) (Costello, AJR; Glonek, T.; Myers, TC, 1976: ³¹ P-nuclear magnetic resonance-pH titrations of myo -inositol hexaphosphate. Carbohydrate Research 46, 159–171). Mixtures of the above acids may also be used.

The organic acid buffer may be selected from phytic acid, mellitic acid, maleic acid, and ophthalmically compatible salts thereof (such as sodium or potassium salts of organic acids), and mixtures thereof. In certain embodiments, the organic acid buffer may be selected from maleic acid, its sodium or potassium salts, and mixtures thereof. In some embodiments, the organic acid buffer may be selected from mellitic acid, its sodium or potassium salts, and mixtures thereof.

The content of the organic acid buffer in the composition of the present invention is in the range of about 0.10 wt % to about 0.4 wt %, or about 0.18 wt % to about 0.30 wt %, or about 0.20 wt % to about 0.28 wt % of the total weight of the composition when formulated.

The organic acid buffer is preferably a combination of a salt of a dibasic organic acid anion (e.g., dibasic sodium maleate monohydrate) and a salt of a monobasic organic acid anion (monobasic sodium maleate), wherein in the case of the dibasic organic acid when present as a metal (e.g., sodium) monohydrate, the concentration of the dibasic organic acid anion is from about 0.1% to about 0.3% by weight of the composition before sterilization, and the concentration of the monobasic organic acid anion is from 0.005% to about 0.002% by weight of the composition before sterilization. Reducing agent

The compositions of the present invention may optionally include a reducing agent for quenching (or reducing) the chlorous acid compound so as to neutralize it from the composition. Suitable reducing agents include, but are not limited to, the following salts or (metal ions thereof): iron (II); bisulfites such as sodium metabisulfite; tin metal, formates, phosphites, hypophosphites, sulfur, thiosulfates (such as sodium thiosulfate), zinc metal, disulfite, manganese metal, aluminum metal, magnesium metal, dithiothreitol, NADH ₂ , ascorbic acid salts, ferricyanide, hydroquinone, tyrosine, aldehydes (such as cinnamaldehyde), N-acetylcysteine, butylhydroxymethoxybenzene, dibutylhydroxytoluene, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and their ophthalmically compatible salts, cellulose disaccharides (classified as reducing sugars having the formula (C ₆ H ₇ (OH) ₄ O) ₂ O-disaccharides) and their analogs, glucose (L-isomers and D-isomers), reducing carbohydrates capable of reacting with oxidants (e.g., glucose, fructose, ribose, xylose, galactose, lactose, maltose, and the like, and L-isomers of mixtures thereof), phenols (e.g., butylhydroxymethoxybenzene, butylhydroxytoluene, tertbutylhydroquinone, and propyl gallate), polymeric aldehydes (e.g., polyvinylpyrrolidone (PVP) K-60 and K-90); and polymeric phenols, such as lignans; and copolymers of tyrosine acrylamide and N,N-dimethylacrylamide (such as polyacryl tyrosine methyl ester co-N,N-dimethylacrylamide), copolymers of Norbloc and N,N-dimethylacrylamide (such as poly Norbloc (2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2-hydroxyethyl)phenol) co-N,N-dimethylacrylamide), and/or mixtures thereof. The reducing agent may include 15:85 or 10:90 polyacryl tyrosine methyl ester co-N,N-dimethylacrylamide, L-glucose, 4-nitrophenol, vanillin, hydroquinone, ethylenediaminetetraacetic acid (EDTA), cellulose disaccharide, PVP, and mixtures thereof. In certain embodiments, the reducing agent may include 15:85 or 10:90 polyacryl tyrosine methyl ester co-N,N-dimethylacrylamide, L-glucose, ethylenediaminetetraacetic acid (EDTA), cellulose disaccharide, PVP, and mixtures thereof.

The reducing agent may comprise EDTA. EDTA may be used in a molar excess compared to the chlorous acid compound. EDTA may be used at a concentration of about 0.01 to about 0.075 wt % EDTA, or about 0.05 to about 0.075 wt % EDTA.

In the case where the reducing agent comprises PVP, the PVP reducing agent has a molecular weight of greater than 100,000 (or approximately 100,000) daltons, or greater than 100,000 (or approximately 100,000) daltons to 1,500,000 (or approximately 1,500,000) daltons, or 300,000 (or approximately 300,000) daltons to 1, The present invention relates to an alkylene oxide having a weight average molecular weight of 1,000,000 (or approximately 1,000,000) daltons, or 300,000 (or approximately 300,000) daltons to 750,000 (or approximately 750,000) daltons, or 320,000 (or approximately 320,000) daltons to 500,000 (or approximately 500,000) daltons.

Alternatively, the molecular weight of the PVP reducing agent of the present invention can also be expressed by a K value based on kinematic viscosity measurement, such as described by E.S. Barabas in N-Vinyl Amide Polymers in Encyclopedia of Polymer Science and Engineering, Second edition, Vol 17, pgs. 198-257, John Wiley & Sons Inc. When expressed in this manner, PVP reducing agents with a K value of 46-100 are preferred.

Preferred reducing agents used herein include PVP, ethylenediaminetetraacetic acid, polymeric phenols, reducing carbohydrates, and mixtures thereof. Preferably, the reducing agent is PVP.

When used herein, the PVP used as a reducing agent is PVP K-60, PVP K-90, PVP-120, or a mixture thereof. In certain embodiments, the PVP used as a reducing agent is PVP K-60, PVP K-90, or a mixture thereof.

The reducing agent and the chlorous acid compound may be present such that when formulated, the ratio of the chlorous acid compound to the reducing agent in molar equivalents is 1:1 to 1:20, or 1:1 to 1:15, preferably 1:1 to 1:10, or 1:1 to 1:5, or greater than 1:1 to 1:1.5.

When the reducing agent is EDTA, the molar equivalent of the chlorous acid compound to EDTA may be 1:2 to 1:5, or 1:3 to 1:5, or 1:4. When the reducing agent is EDTA and the chlorous acid compound is chlorite, the molar equivalent of chlorite to EDTA may be greater than 1:1 to 1.5, 1:2 to 1:5, or 1:3 to 1:5, or 1:4.

In some embodiments, the composition comprising a chlorous acid compound and a reducing agent is colorless or light colored even after autoclaving, which can be determined visually or measured by known methods such as APHA color technology. The autoclaved solution may have an APHA color value of less than about 180 or less than about 40. Ophthalmic device comprising a high molecular weight vinyl pyrrolidone polymer

The products of the present invention include hydrogel or silicone hydrogel ophthalmic devices, which include one or more high molecular weight vinyl pyrrolidone polymers, such as the high molecular weight vinyl pyrrolidone polymers disclosed in US6,367,929, WO03/22321, WO03/22322, US10,935,695, US8,053,539, US10,371,865, US10,370,476, US7,431,152, US7,841,716, and US7,262,232.

As used herein, "high molecular weight" means a weight average molecular weight of not less than about 100,000 Daltons. The term high molecular weight preferably refers to a weight average molecular weight greater than about 150,000 Daltons, between about 150,000 Daltons and about 2,000,000 Daltons, preferably between about 300,000 Daltons and about 1,800,000 Daltons, or about 500,000 to about 1,500,000 Daltons.

The high molecular weight vinyl pyrrolidone polymer may be a poly-N-vinyl pyrrolidone (PVP) homopolymer or copolymer, including a graft copolymer of PVP.

The PVP copolymer may contain 50 mol%, 30 mol%, or 20 mol% of additional repeating units (or comonomers) selected from hydroxyalkyl (meth)acrylates, alkyl (meth)acrylates, or other hydrophilic monomers and acrylates or methacrylates substituted with siloxanes. Suitable comonomers include hydrophilic monomers having at least one hydroxyl group (hydroxyalkyl monomers), hydrophilic vinyl-containing monomers, hydrophilic O-vinyl urethane and O-vinyl carbonate monomers, (meth)acrylamide monomers, and combinations thereof.

Specific examples of additional monomers that can be used to form PVP copolymers include 2-hydroxyethyl methacrylate, vinyl acetate, acrylonitrile, hydroxypropyl methacrylate, 2-hydroxyethyl acrylate, methyl methacrylate and hydroxybutyl methacrylate, glycerol monomethacrylate, polyethylene glycol, and the like, and mixtures thereof. Ionomers may also be included. Examples of ionomers include acrylic acid, methacrylic acid, 2-methacryloyloxyethylphosphocholine, 3-(dimethyl(4-vinylbenzyl)ammonium)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonium)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonium)propane-1-sulfonate (MAMPDAPS), 3-((3-(acrylamidopropyl)dimethylammonium)propane-1-sulfonate (APDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonium)propane-1-sulfonate (MAPDAPS).

PVP homopolymers and vinylpyrrolidone copolymers may also include N-vinylpyrrolidone substituted with hydrophilic substituents such as phosphocholine. Further examples of high molecular weight vinylpyrrolidone polymers include, but are not limited to, poly-N-vinylpyrrolidone, poly-N-vinyl-3-ethyl-2-pyrrolidone, and poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, and/or mixtures thereof.

When the high molecular weight vinyl pyrrolidone polymer is added to the hydrogel or silicone hydrogel reaction mixture, it can be included in a concentration of about 1% to about 20%, about 2% to about 15%, about 2% to about 12%, about 4% to about 15%, or about 4% to about 12%, based on the weight of the total composition excluding solvent, as disclosed in, for example, US6,367,929, US6,822,016, US7,052,131, US7,666,921, US7,691,916, US8,450,387, US2021/0163650, and US10,370,476. Thermal cure formulations may include lower amounts of PVP (e.g., about 5% or less) and still exhibit desirable properties, as disclosed in US2020/0399429.

Without intending to be bound by theory, when the high molecular weight vinyl pyrrolidone polymer is added to the silicone hydrogel reaction mixture, the high molecular weight vinyl pyrrolidone polymer acts as an internal wetting agent. The high molecular weight vinyl pyrrolidone polymer of the present invention may be non-polymerizable, and in this case is incorporated into the silicone hydrogel as a semi-interpenetrating network. The high molecular weight vinyl pyrrolidone polymer is entrapped or physically retained within the silicone hydrogel.

Alternatively, the high molecular weight vinyl pyrrolidone polymer may be polymerizable, for example as a high molecular weight vinyl pyrrolidone macromer or prepolymer, and in this case covalently incorporated into the silicone hydrogel. Mixtures of polymerizable and non-polymerizable high molecular weight vinyl pyrrolidone polymers may also be used.

Ophthalmic device (e.g., contact lens) polymers may also be used in which vinyl pyrrolidone monomers are included in the contact lens reaction mixture and polymerize primarily at the end of polymerization to form relatively long vinyl pyrrolidone chains. Examples of such silicone hydrogels include somofilcon, stenfilcon, and samfilcon.

When the high molecular weight vinyl pyrrolidone polymer is formed in situ during the polymerization of the contact lens polymer, the vinyl pyrrolidone may be included at a concentration of about 20%, about 25%, about 30%, about 25% to about 75%, about 20% to about 70%, about 20% to about 60%, about 30% to about 70%, about 30% to about 60%, or about 37% to about 60% vinyl pyrrolidone by weight of the total composition excluding solvent. Examples include US2010/0048847, US8,937,110, US7,915,323, US7,994,356, US8,420,711, US8,827,447, and US9,039,174.

High molecular weight vinyl pyrrolidone polymers can also be incorporated into the packaging composition and entrapped in the finished contact lens, as disclosed in US 9,395,559. In this embodiment, the high molecular weight vinyl pyrrolidone polymer is added to the packaging box solution at a concentration of about 100 ppm to about 3,000 ppm, about 200 ppm to about 1000 ppm, or less than 500 ppm, as disclosed in US 9,395,559.

The inventors have discovered that the advancing dynamic contact angle of a contact lens comprising a polymeric material having a vinyl pyrrolidone polymer can increase over time to an angle exceeding 100° in the presence of a chlorous acid compound. Without being limited by theory, it is believed that the high molecular weight vinyl pyrrolidone polymer in the polymeric material of the hydrogel or silicone hydrogel contact lens reacts with the chlorous acid compound, causing the high molecular weight vinyl pyrrolidone polymer to break chains, thereby causing a depletion of the high molecular weight vinyl pyrrolidone polymer at and near the lens surface, resulting in an undesirable increase in the advancing dynamic contact angle.

The inventors have discovered that by incorporating a reducing agent with the chlorous acid compound to reduce the concentration of the chlorous acid compound in the packaging/storage composition (e.g., by consuming the chlorous acid compound) to less than 0.001 wt % (or about 0.001 wt %) of the total packaging/storage composition, the forward dynamic contact angle of a contact lens comprising a polymer having a high molecular weight vinyl pyrrolidone can be maintained at a forward dynamic contact angle of about 40° to about 80°, about 40° to about 70°, about 40° to about 60°, or about 45° to about 55°. In certain embodiments, by incorporating the reducing agents disclosed herein, the forward dynamic contact angle of a contact lens comprising a polymer having a high molecular weight vinyl pyrrolidone can maintain a forward dynamic contact angle within about 20%, or about 15%, or about 10% of the initially measured forward dynamic contact angle value of such contact lens. Without being bound by any theory, it is believed that when a contact lens containing PVP is packaged in a packaging kit solution composition, the PVP added to the packaging kit solution composition acts in a sacrificial manner to "protect" the PVP within and at the lens surface. EDTA also acts as a reducing agent for chlorite during the autoclave cycle, thereby reducing the chlorite concentration to a level that does not adversely affect the wettability of PVP-containing lenses.

The contact lens of the present invention may include a free radical reaction product of a reaction mixture of one or more monomers suitable for making the desired lens (also referred to herein as device-forming monomers or hydrogel-forming monomers) and optional components. When polymerized, the reactive mixture results in the formation of a polymeric network, and the lens may include the polymeric network. The polymeric network may, for example, be a hydrogel (e.g., a conventional hydrogel or a silicone hydrogel).

As a further example, the polymeric network can be made from a reactive mixture comprising one or more of a hydrophilic component, a hydrophobic component, a silicone-containing component, a high molecular weight vinyl pyrrolidone polymer wetting agent, a crosslinking agent, and further components such as diluents and initiators. Hydrophilic Component

Hydrophilic components include hydrophilic monomers, macromonomers, and polymers. Examples of suitable families of hydrophilic monomers that may be present in the reactive mixture include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl amines, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof.

Non-limiting examples of hydrophilic (meth)acrylate and (meth)acrylamide monomers include: acrylamide, N-isopropylacrylamide, N,N-dimethylaminopropyl (meth)acrylamide, N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2,3-dihydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, N-(2-hydroxyethyl) (meth)acrylamide, N,N-bis(2-hydroxyethyl) (meth)acrylamide, N-(2-hydroxypropyl) (Meth)acrylamide, N,N-bis(2-hydroxypropyl) (meth)acrylamide, N-(3-hydroxypropyl) (meth)acrylamide, N-(2-hydroxybutyl) (meth)acrylamide, N-(3-hydroxybutyl) (meth)acrylamide, N-(4-hydroxybutyl) (Meth)acrylamide, 2-aminoethyl (meth)acrylate, 3-aminopropyl (meth)acrylate, 2-aminopropyl (meth)acrylate, N-2-aminoethyl (meth)acrylamide), N-3-aminopropyl (meth)acrylamide, N-2-aminopropyl (meth)acrylamide, N,N-bis-2-aminoethyl (meth)acrylamide, N,N-bis-3-aminopropyl (meth)acrylamide), N,N-bis-2-aminopropyl (meth)acrylamide, glyceryl methacrylate, polyethylene glycol monomethacrylate, (meth)acrylic acid, vinyl acetate, acrylonitrile, and mixtures thereof.

The hydrophilic monomer may also be ionic, including anions, cations, zwitterions, betaine, and mixtures thereof. Non-limiting examples of such charged monomers include (meth)acrylic acid, N-[(vinyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropionic acid (ACA1), 5-acrylamidovaleric acid (ACA2), 3-acrylamido-3-methylbutyric acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), 1-propanediol, N-( 2-Carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, inner salt (CBT), 1-propanediol, N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfonic acid-, inner salt (SBT), 3,5-dioxo-8-nitro-4-phosphounde-10-en-1-ammonium, 4-hydroxy-N,N,N-trimethyl-9-oxo-, inner salt, 4-oxide (9CI) (PBT), 2-methacryloyloxyethyl phosphinoylcholine, 3-(dimethyl(4-vinylbenzyl)ammonium)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonium)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonium)propane-1-sulfonate (MAMPDAPS), 3-((3-(acrylamidopropyl)dimethylammonium)propane-1-sulfonate (APDAPS), and 3-((3-(acrylamidopropyl)dimethylammonium)propane-1-sulfonate (MAPDAPS).

Non-limiting examples of hydrophilic N-vinyl lactams and N-vinyl amide monomers include: N-vinyl pyrrolidone (NVP), N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-caprolactam, N-vinyl-3-methyl-2-piperidone, N-vinyl-4-methyl-2-piperidone, N-vinyl-4-methyl-2-caprolactam, N -vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone, N-vinylacetamide (NVA), N-vinyl-N-methylacetamide (VMA), N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N-vinylformamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N- Vinyl-2-methylpropionamide, N-vinyl-N,N'-dimethylurea, 1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone; 1-ethyl-5-methylene-2-pyrrolidone, N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-N-propyl- 3-methylene-2-pyrrolidone, 1-N-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N-vinylformamide, N-vinylisopropylamide, N-vinylcaprolactam, N-vinylimidazole, and mixtures thereof.

Non-limiting examples of hydrophilic O-vinylcarbamate and O-vinyl carbonate monomers include N-2-hydroxyethylvinylcarbamate and N-carboxy-β-alanine N-vinyl ester. Further examples of hydrophilic vinyl carbonate or vinylcarbamate monomers are disclosed in U.S. Patent No. 5,070,215. Hydrophilic oxazolinone monomers are disclosed in U.S. Patent No. 4,910,277.

Other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, and 2-ethylhexazine.

The hydrophilic monomer may also be a macromonomer or prepolymer of a linear or branched poly(ethylene glycol), poly(propylene glycol), or a statistical random or block copolymer of ethylene oxide and propylene oxide, having a polymerizable moiety such as (meth)acrylate, styrene, vinyl ether, (meth)acrylamide, N-vinylamide, and the like. The macromonomer of these polyethers has one polymerizable group; the prepolymer may have two or more polymerizable groups.

In one embodiment, the hydrophilic monomer includes DMA, NVP, HEMA, VMA, NVA, and mixtures thereof. In another embodiment, the hydrophilic monomer includes NVP, DMA, HEMA, and combinations thereof. Other suitable hydrophilic monomers will be apparent to those of ordinary skill in the art.

The amount of hydrophilic monomer can be selected based on the desired characteristics of the resulting hydrogel, including water content, clarity, wettability, protein absorption, and the like. Wettability can be measured by contact angle, and the desired contact angle is less than about 100°, less than about 80°, and less than about 60°. The hydrophilic monomer can be present in an amount ranging from, for example, about 0.1 to about 100 weight percent, alternatively from about 1 to about 80 weight percent, alternatively from about 5 to about 65 weight percent, alternatively from about 40 to about 60 weight percent, or alternatively from about 55 to about 60 weight percent, based on the total weight of the reactive components in the reactive monomer mixture. Silicone-Containing Component

The silicone-containing component suitable for use in the lens comprises one or more polymerizable compounds, wherein each compound independently comprises at least one polymerizable group, at least one siloxane group, and one or more linking groups connecting the polymerizable group(s) to the siloxane group(s). The silicone-containing component may, for example, contain 1 to 220 siloxane repeating units, such as the groups defined below. The silicone-containing component may also contain at least one fluorine atom.

The silicone-containing component may comprise: one or more polymerizable groups as defined above; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable group to the siloxane units. The silicone-containing component may comprise: one or more polymerizable groups, which are independently (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, O-vinyl urethane, O-vinyl carbonate, vinyl, or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable group to the siloxane units.

The silicone-containing component may include: one or more polymerizable groups, which are independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinyl amide, styryl, or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable group to the siloxane unit.

The silicone-containing component may include: one or more polymerizable groups, which are independently (meth)acrylates, (meth)acrylamides, or mixtures thereof; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.

The silicone-containing component may include one or more polymerizable compounds of formula A: wherein: at least one ^RA is a group of the formula _Rg- L-, wherein _Rg is a polymerizable group, and L is a linking group, and the remaining ^RAs are each independently: (a) _Rg -L-, (b) _C1 - _C16 alkyl, which is optionally substituted with one or more hydroxyl groups, amino groups, amide groups, oxadiazole groups, carboxyl groups, alkylcarboxyl groups, carbonyl groups, alkoxy groups, amide groups, carbamate groups, carbonate groups, halogen groups, phenyl groups, benzyl groups, or combinations thereof, (c) _C3 - _C12 cycloalkyl, which is optionally substituted with one or more alkyl groups, hydroxyl groups, amino groups, amide groups, oxadiazole groups, carbonyl groups, alkoxy groups, amide groups, carbamate groups, carbonate groups, halogen groups, phenyl groups, benzyl groups, or combinations thereof, (d) _C6 -C ₁₄ aryl, which is optionally substituted with one or more alkyl, hydroxyl, amino, amide, oxo, carboxyl, alkylcarboxyl, carbonyl, alkoxy, amide, carbamate, carbonate, halide, phenyl, benzyl, or a combination thereof, (e) halide, (f) alkoxy, cycloalkoxy, or aryloxy, (g) siloxy, (h) alkoxy-alkyl or alkoxy-alkoxy-alkyl, such as polyethoxyalkylene, polypropoxyalkylene, or poly(ethoxy-co-propoxyalkylene), or (i) A monovalent siloxane chain comprising 1 to 100 siloxane repeating units, which may be optionally substituted with alkyl, alkoxy, hydroxyl, amine, oxo, carboxyl, alkylcarboxyl, alkoxy, amide, carbamate, halogen, or a combination thereof; and n is 0 to 500, or 0 to 200, or 0 to 100, or 0 to 20, wherein it is understood that when n is not 0, n is a distribution having a plurality of values equal to the specified value. When n is 2 or greater, the SiO units may carry the same or different ^RA substituents, and if different ^RA substituents are present, the n groups may be in a random or block configuration.

In Formula A, the three ^RAs may each include a polymerizable group, alternatively two ^RAs may each include a polymerizable group, or alternatively one ^RA may include a polymerizable group.

Examples of polysiloxane-containing components suitable for use in the present invention include, but are not limited to, the compounds listed in Table A. In the case of compounds in Table A containing polysiloxane groups, unless otherwise indicated, the number of SiO repeating units in such compounds is preferably 3 to 100, more preferably 3 to 40, or even more preferably 3 to 20. Table A 1 Mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxane (mPDMS) (preferably containing 3 to 15 SiO repeating units) 2 Mono-acryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxane 3 Mono(meth)acryloxypropyl-terminated mono-n-methyl-terminated polydimethylsiloxane 4 Mono(meth)acryloxypropyl-terminated mono-n-butyl-terminated polydiethylsiloxane 5 Mono(meth)acryloxypropyl-terminated mono-n-methyl-terminated polydiethylsiloxane 6 Mono(meth)acrylamide alkyl polydialkylsiloxane 7 Mono(meth)acryloxyalkyl-terminated monoalkyl polydiarylsiloxane 8 3-Methacryloyloxypropyltris(trimethylsiloxy)silane (TRIS) 9 3-Methacryloyloxypropylbis(trimethylsiloxy)methylsilane 10 3-Methacryloyloxypropyl pentamethyldisiloxane 11 Mono(meth)acrylamide alkyl polydialkylsiloxane 12 Mono(meth)acrylamidoalkyl dimethicone 13 N-(2,3-Dihydroxypropane)-N'-(propyltetra(dimethylsiloxy)dimethylbutylsilane) acrylamide 14 N-[3-Tris(trimethylsilyloxy)silyl]-propylacrylamide (TRIS-Am) 15 2-Hydroxy-3-[3-methyl-3,3-bis(trimethylsilyl)silylpropoxy]-propyl methacrylate (SiMAA) 16 2-Hydroxy-3-methacryloyloxypropyloxypropyl-tris(trimethylsiloxy)silane 17 Mono(2-hydroxy-3-methacryloyloxypropyloxy)-propyl terminated mono-n-butyl terminated polydimethylsiloxane (OH-mPDMS) (containing 4 to 30, or 4 to 20, or 4 to 15 SiO repeating units) 18 19 20 twenty one twenty two twenty three twenty four

Additional non-limiting examples of suitable silicone-containing components are listed in Table C. Unless otherwise indicated, where applicable, j2 is preferably 1 to 100, more preferably 3 to 40, or even more preferably 3 to 15. In compounds containing j1 and j2, the sum of j1 and j2 is preferably 2 to 100, more preferably 3 to 40, or even more preferably 3 to 15. Table B 25 26 p is 1 to 10 27 p is 5 to 10 28 29 30 1,3-Bis[4-(vinyloxycarbonyloxy)but-1-yl]tetramethyl-disiloxane 31 3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane] 32 3-[Tris(trimethylsiloxy)silyl]propyl allylcarbamate 33 3-[Tris(trimethylsiloxy)silyl]propyl vinyl carbamate 34 Tris(trimethylsiloxy)silylstyrene (styryl-TRIS) 35 36 37 38 39 40 41 42

Mixtures of silicone-containing components may be used. In one embodiment, the polysiloxane-containing component may include one or more mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxane (mPDMS) (preferably containing 3 to 15 SiO repeating units), mono-(meth)acryloxypropyl-terminated mono-n-methyl-terminated polydimethylsiloxane (preferably containing 3 to 15 SiO repeating units); polysiloxane-based crosslinking agents, such as bis-3-acryloxy-2-hydroxypropoxypropyl polydimethylsiloxane (ac-PDMS); 2-hydroxy-3-[3-methyl-3,3-bis(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA), and mixtures thereof alone or with additional polysiloxane-containing components.

The silicone-containing component(s) may be present in an amount up to about 95 weight percent, or about 10 to about 80 weight percent, or about 20 to about 70 weight percent, based on all reactive components of the reactive mixture (excluding diluent).

In the case where it is desired that a concentration of the high molecular weight vinyl pyrrolidone polymer greater than about 3% or about 5% be included in the reactive mixture, the reactive mixture may also include a compatibilizing component, such as a hydroxyl-functionalized polysiloxane, including compounds 13, 15, 16, 17, 21, 36 and 42 in Table A and Table B, those disclosed in US6,822,016, or a polysiloxane-free compatibilizing component as disclosed in US2021/063650. The high molecular weight vinyl pyrrolidone polymer can be introduced into the lens by adding it as a component to the reaction mixture, first forming the lens, and then polymerizing the high molecular weight vinyl pyrrolidone polymer in a separate step as disclosed in US7,262,232, and adding it to the packaging kit solution as disclosed in US7,841,716.

The reactive mixture may contain additional components such as, but not limited to, crosslinking agents, diluents, initiators, UV absorbers, HEV absorbers, visible light absorbers, photochromic compounds that reversibly darken when exposed to light of a specific wavelength, pharmaceuticals, nutrients, antimicrobial substances, colorants, pigments, copolymerizable dyes, non-polymerizable dyes, release agents, and combinations thereof.

The reactive mixture may include: and a hydrophilic component selected from DMA, NVP, HEMA, VMA, NVA, methacrylic acid, and mixtures thereof.

The reactive mixture may include: a hydrophilic component selected from NVP, DMA, VMA, HEMA, and mixtures thereof; a polysilicone-containing component selected from 2-hydroxy-3-[3-methyl-3,3-bis(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA), mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxane (mPDMS), mono-methacryloxypropyl-terminated mono-n-methyl-terminated polydimethylsiloxane (methyl-MPDMS), mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether-terminated mono-n-butyl-terminated polydimethylsiloxane (OH-mPDMS), and mixtures thereof; and optionally a high molecular weight vinyl pyrrolidone polymer.

The reactive mixture may comprise: between 20 to 70 wt%, 25 to 65 wt%, or 30 to 60 wt% of at least one silicone-containing component; about 30 to 80, 35 to 75 wt%, or 40 to 70% of at least one hydrophilic monomer; optionally at least one high molecular weight vinyl pyrrolidone polymer.

The reactive mixture may comprise: between 20 to 70 wt%, 25 to 65 wt%, or 30 to 60 wt% of at least one silicone-containing component; about 35 to 70 wt% or 40 to 60% of at least one hydrophilic monomer selected from NVP, VMA, or a combination thereof; optionally additional hydrophilic monomers and optionally at least one high molecular weight vinyl pyrrolidone polymer. The aforementioned reactive mixture may contain optional ingredients such as, but not limited to, one or more initiators, reactive or non-reactive wetting agents, crosslinking agents, other UV or HEV absorbers, pigments, polymerizable dyes, polymerizable dyes, non-polymerizable dyes, and non-photochromic compounds that can reversibly change color, darken, or reflect light when exposed to light of various wavelengths, release agents, diluents, and the like. When UV absorbers, HEV absorbers, visible light absorbers, photochromic compounds, colorants, or dyes (polymerizable or non-polymerizable) are used, they are preferably stable in the presence of a chlorous acid compound at a selected chlorous acid compound concentration. An example of a UV absorber that is stable in the presence of chlorous acid compounds is Knoblock.

Silicone hydrogel formulations comprising at least one high molecular weight polyvinylpyrrolidone polymer as an internal wetting agent include all variants of aquafilcon, galyfilcon, senofilcon, narafilcon, and formulations disclosed in US6,367,929, WO03/22321, WO03/22322, US10,935,695, US8,053,539, US10,371,865, and US10,370,476. Silicone hydrogel formulations including large amounts of NVP that can be polymerized into PVP blocks include comfilcon, formofilcon, riofilcon, somofilcon, kalifilcon, verofilcon; silicone hydrogel formulations disclosed in US9,588,258, US9,156,934, US8,937,110, US8,937,111, and the like. The present invention may also be used with conventional lenses containing at least one high molecular weight polyvinylpyrrolidone polymer as an internal wetting agent, such as lenses disclosed in US7,431,152, US7,841,716, and conventional lenses or silicone hydrogel lenses disclosed in US7,262,232. Ophthalmologically Acceptable Carriers

The compositions of the present invention include an ophthalmologically acceptable carrier. The ophthalmologically acceptable carrier may be water or an aqueous solution of an excipient. The term "aqueous" generally refers to a formulation in which the excipient is at least about 50%, at least about 75%, at least about 90%, up to about 95%, about 99% water by weight.

The compositions of the present invention may contain no or substantially no oil or oily substances (e.g., medium chain triglycerides, castor oil, linseed oil, and the like, or mixtures thereof). As used with respect to oil or lipid compounds, the term "substantially free" means that the compositions of the present invention contain less than about 0.05%, less than about 0.025%, less than about 0.01%, less than about 0.005% by weight of such oil or oily components based on the total composition. Thus, in certain embodiments, the compositions are not multiphase compositions such as oil-in-water emulsions.

The water is preferably distilled water. The carrier preferably does not contain _C1-4 alcohols, such as methanol, ethanol, propanol, isopropanol, butanol, and the like, which may sting, irritate, or otherwise cause eye discomfort.

Water may be present in the ophthalmologically acceptable carrier at a concentration of about 96% to about 99.9%, about 98% to about 99.5%, or about 99.0% to about 99.5% by weight of the total composition.

The ophthalmologically acceptable carrier may be present at a concentration of about 96% to about 99.5%, about 98% to about 99.5%, or about 98.5% to about 99.2% by weight of the total composition.

Such compositions may be sterile, i.e., such that the absence of microbial contamination in the product prior to release or use is statistically demonstrated to be to the extent required for such products. Such compositions may be selected to have no or substantially no adverse, negative, or deleterious effects on contact lenses or on the eye (or on the area surrounding the eye).

The compositions according to the present invention are physiologically compatible with the eye and ophthalmic devices. Specifically, the composition should be "ophthalmically safe" for use in ophthalmic devices such as contact lenses, which means that the contact lenses treated with the solution are generally suitable and safe for direct placement on the eye or direct application to the eye without rinsing, that is, the solution is safe and comfortable for ophthalmic devices immersed in the solution, rinsed with the solution, or moistened with the solution, including contact lenses worn at any frequency. Ophthalmologically safe compositions have a tonicity and pH compatible with the eye and include ophthalmologically compatible and non-cytotoxic materials and amounts thereof according to ISO standards and U.S. Food and Drug Administration (FDA) regulations.

The compositions of the present invention can be adjusted using tonicity agents to approximate the osmotic pressure of normal tear fluid, which is equivalent to a 0.9 percent sodium chloride solution. The compositions can be rendered substantially isotonic by physiological saline, used alone or in combination with other tonicity agents (e.g., dextrose), otherwise ocular devices such as contact lenses may lose their desired optical parameters if mixed with sterile water alone and made hypotonic or hypertonic. In contrast, excess saline may result in the formation of hypertonic compositions, which will cause stinging and eye irritation. The osmotic pressure of the composition may be at least about 200 mOsm/kg to less than 500 mOsm/kg, preferably about 200 mOsm/kg to about 450 mOsm/kg, preferably about 205 mOsm/kg to about 380 mOsm/kg, preferably about 210 to about 360 milliosomoles/kilogram (mOsm/kg), preferably about 250 mOsm/kg to about 350 mOsm/kg, or preferably about 270 mOsm/kg to about 330 mOsm/kg, as measured using osmotic pressure measurement method USP <785> (as of November 2022). Ophthalmic compositions will generally be formulated as sterile aqueous compositions, or as non-sterile compositions which are subsequently sterilized.

Examples of suitable tonicity adjusting agents include (selected from the following or selected from the group consisting of) but are not limited to: sodium chloride, potassium chloride, calcium chloride, zinc chloride, and magnesium chloride, alkali metal halides, dextrose, and the like, and mixtures thereof. These agents may be used individually in an amount ranging from about 0.01% w/v to about 2.5% w/v and preferably from about 0.2% w/v to about 1.5% w/v.

The tonicity adjusting agent may be sodium chloride, which may be incorporated at a concentration of about 0.4% w/v to about 0.9% w/v, preferably about 0.4% w/v to about 0.7% w/v, or preferably about 0.5% w/v to about 0.6% w/v.

The ophthalmically acceptable carrier may contain one or more of the above-mentioned tonicity adjusting agents.

The compositions of the present invention may have a pH of about 6.0 to about 8.0, about 6.5 to about 8.0, about 6.5 to about 7.5, or about 7.0 to about 7.5, or about 7.2 to about 7.4. The compositions (as indicated above) may have a pH that matches the physiological pH of the human tissues to which the composition will be contacted or to which the composition will be directly applied.

The pH of ophthalmic compositions can be adjusted using acids and bases such as: inorganic acids such as, but not limited to, hydrochloric acid; and bases such as sodium hydroxide.

The composition of the present invention can also be used as a packaging kit solution for packaging ophthalmic devices and for storing such ophthalmic devices. The packaging kit solution of the present invention can have a viscosity of less than about 5.2 cP at 25°C.

The compositions may also be used for direct application to the eye as wetting or rewetting eye drops to relieve eye discomfort (e.g., eye-related burning sensation or general eye irritation) during contact lens wear.

Once manufactured, the composition of the present invention is not further mixed with (multiple) additional or separate components before direct application to the eye, or is not further mixed with (multiple) additional or separate components to store an ophthalmic device (e.g., contact lens) (or as a packaging box solution for an ophthalmic device), that is, the composition of the present invention (or its product) is not in the form of 2 or more components or products.

The compositions described herein, when mixed, may be free or substantially free of boric acid, borates, non-chlorous acid preservatives (especially cationic preservatives), peroxides (e.g., hydrogen peroxide) or peroxide sources, persulfates, carboxyvinyl polymers, natural gums, glycerin, polyoxyethylene-castor oil, and/or derivatives thereof.

As used herein, the term "borate" refers to salts of boric acid and other pharmaceutically acceptable borate salts, or combinations thereof. Suitable borate salts include, but are not limited to, boric acid; pharmaceutically acceptable salts such as alkaline metal salts such as sodium borate, potassium borate; alkali earth metal salts such as calcium borate, magnesium borate; transition metal salts such as manganese borate; and mixtures thereof. However, recent proposals by EU member states to limit the concentration of boric acid and/or borate salts in eye care formulations reduce the desirability of incorporating such compounds into the compositions of the present invention. (See CLH REPORT FOR BORIC ACID AND BORATES, Proposal for Harmonized Classification and Labeling Based on Regulation (EC) No 1272/2008 (CLP Regulation), Annex VI, Part 2, Swedish Chemicals Agency Nov. 2, 2018. )

The term "non-chlorous acid preservative" means a compound that is not a chlorous acid compound but has antimicrobial properties. Examples of specific preservatives include, but are not limited to, 4-chlorocresol, 4-chloroxylenol, benzalkonium, benzalkonium chloride (BAK), benzoic acid, benzyl alcohol, chlorhexidine, chlorobutanol, imidurea, m-cresol, methylparaben, 0.5% phenol, phenoxyethanol, sorbate, propionic acid, propylparaben, sodium benzoate, sorbic acid, thimerosol, polyquaternary ammonium salt compounds (such as polyquaternary ammonium salt-42 and polyquaternary ammonium salt-1), biguanide compounds (e.g., polyhexamethylene biguanide or polyaminopropyl biguanide). Non-chlorous acid preservatives, especially cationic preservatives, may cause eye irritation and/or allergic reactions, which may undesirably affect consumers using eye care compositions or contact lenses containing such non-chlorous acid preservatives (on their surfaces) due to storage of contact lenses with such compounds. See, for example: • Baudouin See C, Labbé A, Liang H, Pauly A, Brignole-Baudouin F. Preservatives in eyedrops: the good, the bad and the ugly . Prog Retin Eye Res. 2010 Jul;29(4):312-34 (concluding that the cationic preservative "BAK may cause or aggravate deleterious effects on anterior ocular structures, tear membranes, cornea, conjunctiva, and even trabecular meshwork.") • Lakshman Subbaraman, Contact lens material properties that influence preservative uptake, Contact Lens Update, October 1, 2013 (https://contactlensupdate.com/2013/10/01/contact-lens-material-properties-that-influence-preservative-uptake/) (When contact lenses are involved, please pay special attention: "When lens care products interact with contact lenses, components such as preservatives present in the solution will be absorbed by the lens material. When these preservatives are released from the contact lens into the eye during lens wear, they may have a significant impact on the comfort of the lens during wear.")

As used herein, the term "source of peroxides" as used herein means a compound or material that releases (or can release) peroxide or hydrogen peroxide in aqueous solution, and includes, but is not limited to, barium peroxide, sodium peroxide, zinc peroxide, magnesium peroxide, calcium peroxide, strontium peroxide, lithium peroxide, methyl ethyl ketone peroxide, cyclohexanone peroxide, benzoyl peroxide, urea hydrogen peroxide (carbamide peroxide, carbamide perhydrate, or percarbamide), percarbonate (e.g., calcium percarbonate or magnesium percarbonate), tertiary butyl hydroperoxide, perborate (e.g., sodium perborate), peroxyacid (e.g., methyl ethyl ketone peroxide), Peroxides (e.g., hydrogen peroxide) and/or peroxide sources may cause stinging and irritation to the eyes, and may undesirably affect consumers using contact lenses containing peroxides (e.g., hydrogen peroxide) and/or peroxide sources (on their surfaces) due to the storage of contact lenses with such compounds. As used herein, the term "persulfates" as used herein means persulfate anions or salts of such persulfates and other pharmaceutically acceptable persulfates, or combinations thereof. Suitable persulfates include, but are not limited to, sodium peroxymonosulfate, potassium peroxymonosulfate, sodium persulfate, ammonium persulfate, potassium persulfate, and mixtures thereof. Persulfates may cause eye stinging and irritation and may have undesirable effects on consumers using contact lenses that have persulfates on their surface due to storage of contact lenses with these compounds.

Humectants and/or buffers, such as carboxyvinyl polymers (e.g., carbomers), natural gums (e.g., guar gum, tragacanth gum), glycerin, polyoxyethylene-castor oil, and/or derivatives thereof are well-known thickening agents that, when present on the surface of contact lenses, may undesirably affect a consumer's vision through the contact lenses by causing blurring or otherwise reducing visual clarity by interacting with the contact lens surface or by slowly diffusing from tears trapped between the eye-facing side of the contact lens and the corneal surface. Although the latter effect is usually temporary, dissipating within a few minutes of insertion and the trapped tears are cleared by repeated blinking, such visually impairing effects may be undesirable.

The term “substantially free” as it relates to a compound selected from boric acid, borates, non-chlorous acid preservatives, peroxides (e.g., hydrogen peroxide) or peroxide sources, persulfates, carboxyvinyl polymers (e.g., carbomer), natural gums (e.g., guar gum, tragacanth gum), glycerin, polyoxyethylene castor oil, and/or derivatives thereof. "free)" means that such compounds exist as impurities in the composition of the present invention, such impurities are not intentionally added, or their concentration is less than 2% by weight (or about 2% by weight), less than 1.5% by weight (or about 1.5% by weight), less than 1% by weight (or about 1% by weight), less than 0.5% by weight (or about 0.5% by weight), less than 0.1% by weight (or about 0.1% by weight), less than 0.05% by weight (or about 0.05% by weight), less than 0.01% by weight (or about 0.01% by weight), less than 0.005% by weight (or about 0.005% by weight) of the total composition. The composition of the present invention may not contain such compounds.

As described above, the contact lens can be immersed in the composition of the present invention and stored in a suitable packaging container, in some embodiments, stored in a packaging container for a single contact lens unit. Typically, the packaging container for storing the contact lens includes at least one sealing layer that seals the container containing the unused contact lens immersed in the composition of the present invention. The sealed container can be a hermetically sealed packaging container and can have any form that creates a sealed space to contain the composition and the contact lens. The hermetically sealed packaging container may have any suitable form, including a sealed package formed from two sheets of plastic, metal, or a multi-layer structure, or a blister package in which a base having a recess for receiving the contact lens is covered by a metal, plastic, or laminate sheet suitable for peeling off to open the blister package. The sealed container may be formed of any suitable, generally inert packaging material that provides a reasonable degree of protection for the lens. The packaging material may be formed from plastic materials such as polypropylene, polysulfone (PSU), polyethersulfone (PESU), polycarbonate (PC), polyetherimide (PEI), polyamide (including nylon), polyolefin (including polypropylene), polymethylpentene (PMP), and olefin copolymers (including cyclic olefin polymer (COP) and cyclic olefin copolymer (COC)), acrylic, rubber, urethane, fluorocarbon, polyoxymethylene, polyvinyl chloride (PVC), polyphenylene sulfide (PPS), polycarbonate copolymer, polyvinylidene fluoride (PVDF), and the like, and copolymers and blends of the foregoing. Blends include polybutylene terephthalate polyester blends, including PBT and PC blends, PC/polyester blends, and polypropylene blended with COP or COC. In one embodiment, the plastic material can be selected from polypropylene, COP (cyclic olefin polymer) and COC (cyclic olefin copolymer), and blends thereof.

In addition to the specific buffers mentioned above, any water-soluble buffer (or buffer-like, e.g., having buffering properties, such as viscosity-increasing ability) polymer may also be used in the compositions of the present invention, provided that it does not have (or does not have substantially) a deleterious effect (e.g., blurring or otherwise reducing visual clarity) on the stored contact lens or on the contact lens wearer, or on the eye (or on the area surrounding the eye) at the concentrations used in the compositions of the present invention. Particularly useful components are water-soluble components, e.g., components that are soluble at the concentrations used in the currently useful liquid aqueous media. Suitable water-soluble buffer polymers include, but are not limited to, buffer polymers, such as block copolymer surfactants (e.g., block copolymers of polyethylene oxide (PEO) and polypropylene oxide (PPO)); polyvinyl alcohol, polyvinyl pyrrolidone; polyacrylic acid; polyethers, such as polyethylene glycol (e.g., polyethylene glycol 300, polyethylene glycol 400) and polyethylene oxide; hyaluronic acid and hyaluronic acid derivatives (e.g., sodium hyaluronate); chitosan; polysorbates, such as polysorbate 80, polysorbate 60, and polysorbate 40; polydextrose, such as polydextrose 70; Cellulose derivatives, such as carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, and methylethyl cellulose; non-cyclic polyamides, such as non-cyclic polyamides having a weight average molecular weight of 2,500 to 1,800,000 Daltons disclosed in US7,786,185, which is incorporated herein by reference in its entirety; salts of any of the foregoing and mixtures of any of the foregoing. Block copolymers of PEO and PPO include poloxamers and poloxamines, including poloxamers and poloxamines disclosed in US6,440,366, which is incorporated herein by reference in its entirety. Preferably, the water-soluble buffer polymer is selected from polyvinyl pyrrolidone, methylethyl cellulose, polymethacrylic acid, carboxymethyl cellulose, propylene glycol, 1,3-propylene glycol, polyethylene glycol, and mixtures thereof.

The water-soluble modifier polymer may have a molecular weight of more than 100,000. When propylene glycol and/or 1,3-propanediol are used as the water-soluble modifier polymer, they may have a molecular weight of less than 100,000.

When any water-soluble polymer is used in the packaging solution of the present invention, the water-soluble polymer can be included and present in an amount up to about 0.5 wt %, about 1 wt % or about 2 wt %, preferably between about 0.001 wt % and about 2 wt %, between about 0.005 wt % and about 1 wt %, between about 0.01 wt % and about 0.5 wt %, or between about 100 ppm and about 0.5 wt %, all based on the weight of the total composition.

When any water-soluble polymer is used in the direct-use eye care formulations such as the eye drops of the present invention, the water-soluble polymer may be included and present in an amount up to about 2 wt%, about 5 wt%, or about 10 wt%, between about 0.001 wt% and about 10 wt%, between about 0.005 wt% and about 2 wt%, between about 0.01 wt% and about 0.5 wt%, or between about 100 ppm and about 2 wt%, all based on the weight of the total composition.

Without being limited by theory, it is believed that the water-soluble modifier polymer helps prevent the ophthalmic device from sticking to the packaging container and can enhance the initial (and/or extended) comfort of the contact lens when the contact lens packaged in the composition is placed on the eye after being removed from the packaging container.

The water-soluble modifier polymer may be a cellulose derivative. The cellulose derivative may be present in a concentration of about 0.002 to about 0.01, or preferably about 0.004 to about 0.006, based on the weight of the total composition of the present invention.

The compositions described herein may include various other materials.

In the case of the compositions of the present invention for direct application to the eye, a surfactant may be included. Suitable surfactants for this purpose include, but are not limited to, ionic surfactants and non-ionic surfactants (although non-ionic surfactants are preferred), RLM 100, POE 20 cetyl stearyl ether such as ^Procol® CS20, poloxamer block copolymers such as ^Pluronic® F68, and block copolymers of poly(oxyethylene)-poly(oxybutylene) compounds such as those described in US 2008/0138310 (which publication is incorporated herein by reference). The poly(oxyethylene)-poly(oxybutylene) block copolymer may have the formula (EO) _m (BO) _n , wherein EO is oxyethylene and BO is oxybutylene, and wherein m is an integer with an average value of 10 to 1000 and n is an integer with an average value of 5 to 1000, as disclosed in US Pat. No. 8,318,144; m may also be 10 and n may be 5.

The surfactant may be present in a concentration of about 0.01% to about 3%, preferably about 0.01% to about 1%, preferably about 0.02% to about 0.5%, or preferably about 0.02% to about 0.1%, based on the weight of the total composition of the present invention. It will be appreciated that some components may perform more than one function, for example, some moderators may also act as surfactants (e.g., PEO-PPO and PEO-PBO block copolymers).

If desired, one or more additional components may be optionally included in the composition. The optional component(s) are selected to impart or provide at least one beneficial or desired property to the composition. Such additional but optional components may be selected from components known to be used in ophthalmic device care compositions. Examples of such optional components include (or are selected from the following, or are selected from the group consisting of): cleansers (e.g., in direct application eye drops or cleansing [or eye care solutions]), moisturizers, nutrients, therapeutic agents, sequestering agents, viscosity increasing agents, contact lens conditioning agents, antioxidants, and the like, and mixtures thereof. Each of these optional components can be included in the compositions in an amount effective to impart or provide a beneficial or desired property to the compositions so that the beneficial or desired property is apparent to the user. For example, such optional components can be included in the compositions in an amount similar to the amount of such components used in other eye or ocular device care composition products.

In one embodiment, the ophthalmic solution comprises about 0.01 to about 0.02 wt% sodium chlorite, phosphate buffer, about 0.01 to about 0.075 wt% EDTA, or about 0.05 to about 0.075 wt% EDTA, up to about 1, 1.5 or 2 wt% PVP K60 or K90, and optionally about 0.005 to about 0.01 wt% methylethylcellulose, all based on the ophthalmic solution formulated before autoclaving. These ranges can be combined in any arrangement.

The ophthalmic solution can be used as a packaging solution for contact lenses, including silicone hydrogel contact lenses containing PVP.

All components of the ophthalmic solution of the present invention should be water-soluble.

One or more therapeutic agents may also be incorporated into the ophthalmic solution. A wide variety of therapeutic agents may be used, provided that the active agent selected is generally inert in the presence of the chlorous acid compound (e.g., chlorite) or oxidizing agent. Suitable therapeutic agents include those that treat or target any part of the ocular environment, including the anterior and posterior portions of the eye, and include pharmaceutical agents, vitamins, nutrients, combinations thereof, and the like. Suitable classes of active agents include antihistamines, antibiotics, glaucoma medications, carbonic anhydrase inhibitors, antivirals, anti-inflammatory agents, nonsteroidal anti-inflammatory drugs, antifungals, anesthetics, mydriatics, mydriatics, immunosuppressants, antiparasitics, antiprotozoals, combinations thereof, and the like. When an active agent is included, it is included in an amount sufficient to produce the desired therapeutic result (a "therapeutically effective amount").

Useful alternative chelating agents include, but are not limited to, citric acid, sodium citrate, and the like, and mixtures thereof.

A method of packaging and storing contact lenses (or other ophthalmic devices) comprises immersing the device in the compositions described above in a suitable container. The method may include immersing the device in the compositions directly after manufacturing the contact lenses and before delivery to the customer/wearer. Alternatively, incorporation and storage of the device in the compositions (all in a packaging box) may occur at an intermediate point before delivery to the final customer (wearer), but after manufacturing and shipping the device in a dry state, wherein the dry device is hydrated by immersing the device in the compositions. Thus, a package for delivery to a customer may include a hermetically sealed container containing one or more unused devices (e.g., contact lenses) immersed in the compositions.

Steps for packaging an ophthalmic device in the composition of the present invention may include: (1) molding an ophthalmic device (e.g., a contact lens) in a mold comprising at least a first mold portion and a second mold portion, (2) removing the device from the mold portion and removing unreacted monomer and processing agent, (3) introducing the composition and the device into the packaging box (or container), and (4) sealing the packaging box.

The method may also include a step of sterilizing the contents of the packaging box. Sterilization may be performed before or, most conveniently, after the sealing of the container, and may be performed by any suitable method known in the art, such as by autoclaving the sealed container at a temperature of about 120° C. or higher (autoclave or steam sterilization), or by using ultraviolet (UV) sterilization or gamma electron beam sterilization. Preferably, the composition of the present invention is sterilized by autoclave sterilization. The packaging box may be a plastic blister packaging box (packaging or package), which includes a recess for accommodating the ophthalmic device and the composition, wherein the recess is hermetically sealed with a cover material before sterilization.

The following examples are provided to enable those skilled in the art to implement the compositions and are merely illustrative examples of the present invention. These examples should not be interpreted as limiting the scope of the present invention as defined in the scope of the patent application.

The compositions of the present invention described in the following examples illustrate specific embodiments of the compositions of the present invention, but are not intended to be limiting thereof. Other modifications may be made by a person skilled in the art without departing from the spirit and scope of the present invention.

The materials used in the following examples are provided as follows: Material Suppliers Sodium chloride JT Baker Sodium Chlorite, Anhydrous (80% Sodium Chlorite/20% Sodium Chloride) Spectrum Disodium ethylenediaminetetraacetate (EDTA) Sigma-Aldrich Methyl ether cellulose Fisher water JJVC House DI 3% hydrogen peroxide solution EMD Sodium Appleate Sigma-Aldrich Sodium dimaleate Sigma-Aldrich Sodium Phytate Sigma-Aldrich Citric Acid Sigma-Aldrich PVP K-60 Chempilots Sodium hydroxide Fluka Forward dynamic contact angle measurement

The advancing dynamic contact angle was determined using a modified Wilhelmy plate method at room temperature (23 ± 4 °C) using a calibrated Kruss K100 tensiometer and the following borate buffer solutions. Components weight % Deionized water 98.06% Sodium chloride 0.83% Boric acid 0.89% Sodium borate decahydrate 0.21% EDTA 0.01% 10% PVP solution N/A Methyl ether cellulose (MEC) 0.005%

All equipment was clean and dry; vibrations around the instrument were minimized during testing. The tensiometer was equipped with a humidity generator, and a temperature and humidity meter was placed in the tensiometer chamber. Relative humidity was maintained at 70 ± 5%. The experiment was performed by immersing the contact lens test strips in borate buffer while measuring the force exerted on the contact lens sample in each case due to the wetting of the probe solution using an inductive balance (i.e., in the case of Kruss K100). The forward dynamic contact angle of the contact lens sample was determined based on the force data collected during the sample immersion.

The receding contact angle is determined from the force data when the contact lens sample (in the form of a test strip) is removed from the test liquid. The Veegan plate method is based on the following formula: Fg = γρ cos θ-B, where F = wetting force between the liquid and the lens (mg), g = acceleration due to gravity (980.665 cm/sec), γ = surface tension of the probe liquid (dynes/cm), ρ = circumference of the contact lens at the liquid/lens meniscus (cm), θ = dynamic contact angle (degrees), and B = buoyancy (mg). At zero depth of immersion, B is zero.

Contact lens test strips were cut from the center area of the sample contact lens. Each strip was approximately 5 mm wide and 14 mm long, attached to a metal clamp using a plastic tweezer, pierced with a metal wire hook, and equilibrated in the packaging solution for at least 3 hours. Each sample was then cycled four times and the results averaged to obtain the lens forward and backward contact angles. The typical measurement speed was 12 mm/min. During data acquisition and analysis, the contact lens test sample was completely immersed in the packaging solution without touching the metal clamp.

The values for five individual contact lens test samples were averaged to obtain the reported dynamic contact angles of the sample lens in advance (and retreat). Example 1

Effect of chlorous acid compounds on the forward dynamic contact angle of PVP-containing contact lenses.

Table 1 shows the comparative compositions evaluated for storage of (or use of packaging solutions for) polymeric ophthalmic devices (e.g., contact lenses) containing poly(vinyl pyrrolidone) polymers, such as ACUVUE ^® OASYS 1-Day Disposable Contact Lenses with HydraLuxe ^® Technology (“ACUVUE OASYS 1-Day Disposable Lenses”). The comparative solutions were prepared using standard mixing techniques. One ml of the comparative composition of Table 1 was individually packaged with the ACUVUE OASYS 1-Day Disposable Lenses in sealed polypropylene blister boxes without further sterilization. This comparative contact lens/solution box is referred to as “Test” in Table 2. Table 1 (Comparative Compositions) Components Comparative composition weight (gm) Weight of control group (gm) Sodium chloride 4.14 4.14 Sodium dihydrogen phosphate 0.50 0.50 Sodium Hydrogen Phosphate 3.13 3.13 EDTA 0.056 0.056 MEC 0.024 0.024 Sodium chlorite* 0.061 0. water 492.03 492.091 Composition characteristics pH 7.2 Osmotic pressure (mOsm) 338 *Supplied as a stable 80% sodium chlorite and 20% sodium chloride. The nominal chlorite content in the composition in Table 1 is approximately 72 µg/mL

A "control" formulation identical to the comparative composition of Table 1, except excluding sodium chlorite (control), was also prepared as a test control and packaged similarly with ACUVUE OASYS daily disposable lenses in a sealed polypropylene blister box. This contact lens/solution box is referred to as the "control" in Tables 1 and 2.

Contact lenses containing poly(vinyl pyrrolidone) polymer and Example 1 or control solutions were sealed in polypropylene blister packages and then placed in a stabilization chamber (ES2000 REACH-IN, supplied by Environmental Specialties) set at 55°C and 35% relative humidity to determine the availability of chlorite over time and the results of the forward dynamic contact angle measurement. (Accelerated aging analysis - ASTM F1980 Standard Guide For Accelerated Ageing of Sterile Medical Device Packages generally accepts temperatures below 60°). Samples were analyzed by ion chromatography and conductivity detection for chlorite concentration at the time periods shown in Table 2 below. Separation was performed using a 4 mm diameter × 250 mm length Dionex AS9-HC column and a matching guard column. The mobile phase was 9 mmol.L sodium bicarbonate and the suppressor eluent was 500 mL sulfuric acid. Injection volume and flow rate parameters were typically set at 20 µL and 1 mL/min, respectively. Standardization was performed using certified chlorite reference standards diluted to the appropriate concentrations, typically 0.1 to 20 µg/mL. The chlorite peak areas of the standard solutions were least squares fit to the corresponding chlorite concentrations. The chlorite concentrations of the test solutions were calculated using the least squares regression equation.

The results are summarized in Table 2. Real (actual) time (days) Analysis results (standard deviation) Simulated Aging* (months) Chlorite(µg/mL) Forward dynamic contact angle, ^° Test Control group Test Control group 0 0 61.3 N/A 48 (2) 51 (2) twenty one 6 13.5 N/A 103 (13) 46 (6) 42 12 0.7 N/A 115 (13) 47 (2) 84 twenty four Below detection level N/A 115 (25) 55 (2)

As shown in Table 2, virtually no chlorite remained within the detection limit of the test method (approximately 1 µg/mL) after six weeks at 55°C. As the chlorite concentration decreased, an upward increase in the advancing dynamic contact angle to greater than 100° was observed for the contact lenses containing poly(vinyl pyrrolidone) polymers in the composition of Table 1 (i.e., containing 0.01% chlorite) in the test sealed packages. No such increase in contact angle was observed for the contact lenses containing poly(vinyl pyrrolidone) polymers sealed in the control solution. Throughout the stability testing, the AOA for contact lenses packaged in the control solution remained within the range of 46° to 55°, indicating that the shift in AOA was due to the presence of chlorite in the packaging solution of Example 1. Due to this increase in AOA, the contact lenses became unacceptably hydrophobic rather than having the desired hydrophilic properties. While not necessarily limited to any specific mechanism for this behavior, the data supports a mechanism that indicates oxidative cleavage of the PVP internal wetting agent resulting in PVP depletion from the lens. No significant changes or deleterious effects to other contact lens properties were observed.

As shown in Table 2, exposure of OASYS lenses to solutions containing 0.01% sodium chlorite (or 0.0075% chlorite) resulted in an unacceptable time-dependent increase in the advancing dynamic contact angle. While not necessarily limited to any specific mechanism for this behavior, analytical data support a mechanism that indicates oxidative cleavage of the PVP internal wetting agent resulting in depletion of PVP at least on the lens surface. Example 2

Table 3 shows the compositions of the present invention (containing 1% PVP K90 and a chlorous acid compound as a reducing agent) evaluated for storing (or using packaging solutions for) polymeric ophthalmic devices (e.g., contact lenses) containing poly(vinyl pyrrolidone) polymers, such as ^ACUVUE® OASYS ^™ daily disposable lenses (senofilcon A). 1 ml of the compositions of the present invention in Table 3 was individually packaged in sealed polypropylene blister packaging boxes together with ^ACUVUE® OASYS ^™ daily disposable lenses. Sealed polypropylene blister packages containing the composition shown in Table 3 and ACUVUE ^® OASYS daily disposable lenses were sterilized in a Tuttnauer Model 2540E-B/L autoclave at 121°C (with the temperature increasing at the start and end of autoclave) for 15 minutes. Table 3 Components weight% Sodium chloride 0.83 Sodium dihydrogen phosphate 0.10 Sodium Hydrogen Phosphate 0.62 EDTA 0.01 MEC 0.005 Sodium chlorite 0.013 PVP K-90 Changing water 100% balance *Supplied as a stable 80% sodium chlorite and 20% sodium chloride. The nominal chlorite content in the composition in Table 3 is approximately 78 µg/mL

Contact lenses that had been packaged and sterilized in the composition of the present invention in Table 3 were tested for the ADCA (using the ADCA procedure described above) and chlorite concentration immediately after autoclaving and 2 weeks later (from the date of autoclaving) at room temperature ("RT", about 25°C). The test results are summarized in Table 4. Table 4 Reducing agent Reducing agent concentration, % Forward dynamic contact angle Measured immediately after autoclaving* Measured at RT 2 weeks after autoclaving PVP K-90 0.0 50 (4) 48 (5) 0.2 54 (2) 48 (2) 0.4 53 (2) 46 (1) 1.0 52 (3) 49 (3) *The compositions of the present invention in Table 3 were packaged with ACUVUE OASYS daily disposable lenses in sealed polypropylene blister packs.

As shown in Table 4, the incorporation of the PVP reducing agent resulted in the forward dynamic contact angle being maintained within approximately 10% of the initial measurement of the tested contact lens. Example 3

Table 5 shows the formulation of a composition that can be used as a solution for storing a polymeric ophthalmic device (e.g., contact lens) containing a poly(vinyl pyrrolidone) polymer (or can be used as a packaging box for such a polymeric ophthalmic device), or can be used as a direct administration eye drop solution, which composition can be prepared using known mixing techniques. Table 5 Components Weight, g Weight % (balance is water) Sodium chloride 2.3355 0.7798% Sodium maleate 0.0292 0.0097% Sodium maleate monohydrate 0.684 0.2284% Sodium Chlorite (Anhydrous)* 0.0362 0.0121% EDTA 0.031 0.0103% Methylethylcellulose (MEC) 0.0158 0.0053% PVP K-60 3.006 1.0035% water 293.38 Remaining amount *Supplied in a stable form of 80% sodium chlorite and 20% sodium chloride. The nominal chlorite content in the composition of Table 5 is approximately 72 µg/mL Example 4

Table 6 shows the formulation of the composition containing chlorous acid compound of the present invention, which is incorporated with organic maleic acid salt buffer and can be used as a solution for storing ophthalmic devices (such as contact lenses) (or can be used as a packaging solution for such ophthalmic devices) or a direct application eye drop solution, and the composition is prepared using known mixing techniques. Table 6 Components Weight % (balance is water) Sodium maleate 0.01008% Sodium maleate monohydrate 0.22653% Sodium chloride 0.77489% Sodium chlorite* 0.012% EDTA 0.075% Methylethylcellulose (MEC) 0.005% PVP K-60 1.000% water Remaining amount *Supplied as a stable 80% sodium chlorite and 20% sodium chloride. The nominal chlorite content in the composition in Table 6 is approximately 72 µg/mL

A pot life analysis was performed on the composition of Table 6 to determine the useful life of the composition for inhibiting microbial growth over a period of time as a function of the decrease in the chlorite concentration in the composition over time. The chlorite-containing composition of Table 6 was sufficient to inhibit microbial growth of the group of organisms for a period of at least 5 days.

Pot Life samples were prepared as follows: 1.     Place approximately 10 mL of the composition of Table 6 in several 20 mL glass screw-top flash bottles. 2.     Seal the vials from step 1 with gray butylene caps and store in light-proof containers at room temperature. 3.     Place the vials in the freezer for a period of time to delay the reduction of chlorite. 4.     Analyze chlorite concentration by ion chromatography as described above.

The results of the applicable period are summarized in Table 7. Table 7 Aging (days) Chlorite, µg/ml Initial chlorite concentration % 0 52.9 100.0 1 51.7 97.7 2 53.0 100.2 3 50.7 95.9 4 50.7 95.9 5 DNT 95.0 ^{a aEstimation} based on linear extrapolation.

In Table 7, the pot life study shows that in the presence of EDTA and PVP reducing agents, at least 95% of the initial chlorite concentration in the composition of Table 6 remains viable for at least 5 days. This viability over this time period is useful in packaging/storing compositions that may need to be held for a period of time prior to sterilization (e.g., by autoclaving). (An initial concentration of at least 95% of the active ingredient remaining is considered commercially/consumer acceptable.)

It should be noted that when the composition of Table 6 (i.e., with reducing agents PVP and EDTA) was autoclaved in a Tuttnauer Model 2540E-B/L autoclave at 121°C for 15 minutes (note: also increasing in both directions), the chlorite concentration was determined to have decreased by approximately 40% (i.e., from an initial concentration of 52.9 µg/ml to a concentration of 31.3 µg/ml). For perspective, the chlorite concentration was determined to have decreased (relative to its initially measured chlorite concentration) by only 17% after the composition containing chlorite, but not a reducing agent, was autoclaved.

Prepare contact lenses containing test kit solution/storage solution for accelerated weathering analysis using the composition of Table 6 and ACUVUE ^® OASYS 1-Day Disposable Contact Lenses with HydraLuxe ^® Technology (“OASYS 1-Day Disposable Lenses”) as follows: 1. Pipette 3 mL of the solution of Table 6 into 7 mL glass crimp top flash bottles (total bottles = typically 100 bottles); 2. Remove the OASYS 1-Day Disposable Lenses from their blister packs and place in a beaker of DI water to remove adhering blister pack solution; 3. Tap the OASYS 1-Day Disposable Lenses onto blotting paper to remove excess DI water; 4. Add one (1) OASYS 1-Day Disposable Lens to each vial from step 1; 5. The vials containing OASYS daily disposable lenses and the composition of Table 6 were sealed with gray butylene caps and autoclaved at 121°C for 15 minutes. 6. The vials from step 5 were recovered from the autoclaved vials at T=0 and immediately placed in a stabilization chamber (ES2000 REACH-IN, supplied by Environmental Specialties) set at 55°C and 35% relative humidity to determine the availability of chlorite over time and to determine the forward dynamic contact angle of the contact lens in the test box solution/storage solution. Temperatures below 60°C are generally acceptable for accelerated aging analysis. (ASTM F1980 Standard Guide for Accelerated Aging of Sterile Medical Device Packages.) 7. After simulating real-world aging in a stability chamber for approximately 6, 12, and 24 months, the vials were recovered and tested for accelerated aging stability (i.e., residual chlorite concentration) as a function of time.

The forward dynamic contact angle measurement was also performed as described in detail above. The results of the accelerated aging and forward dynamic contact angle tests are shown in Table 8. Table 8 Real (actual) time (days) Simulated Aging* (months) Chlorite(µg/mL) Forward dynamic contact angle (standard deviation) 0 0.0 31.3 53.5 (4.0) twenty two 6.7 Below detectable level 48.4 (3.1) 43 13.2 Not tested 44.5 (4.1) 76 23.3 Not tested 50.7 (6.1) *Based on the Arrhenius equation, which states that a 10°C increase in temperature doubles the rate of a chemical reaction (also known as the Q10 factor; a Q10 factor of 2 was used).

As shown in Table 8, the advancing dynamic contact angles of the test contact lenses (i.e., polymeric contact lenses containing poly(vinyl pyrrolidone) polymers) stored in the packaging box solutions containing the reducing agent of Table 6 did not exhibit an increase over time (i.e., indicating that the surface of the contact lens did not lose wettability). Statistical analysis of the contact angles after approximately two years of simulated aging confirmed that there were no statistically significant changes relative to the initial advancing contact angles. On this basis, it can be concluded that after autoclaving and during the 22-day storage period (at 55°C) from autoclaving, the chlorite concentration decreases sufficiently that no significant degradation of PVP occurs in or on the contact lenses. Examples 5 to 9

Table 9 shows the formulation of a composition having a range of chlorite concentrations, which can be used as a solution for storing ophthalmic devices (e.g., contact lenses) (or can be used as a packaging solution for such ophthalmic devices) or a direct administration eye drop solution, which is prepared using known mixing techniques. Table 9 Components Weight % (balance is water) Example 5 (15 µg/mL chlorite ion) Example 6 (7.6 µg/mL chlorite ion) Example 7 (3.7 µg/mL chlorite ion) Example 8 (1.7 µg/mL chlorite ion) Example 9 (0.84 µg/mL chlorite ion) Sodium chloride 0.58% 0.58% 0.58% 0.58% 0.58% Sodium dihydrogen phosphate*H ₂ O 0.09% 0.09% 0.09% 0.09% 0.09% Sodium Hydrogen Phosphate*7H ₂ O 0.70% 0.70% 0.70% 0.70% 0.70% Sodium Chlorite (Anhydrous)* 0.00252% 0.00126% 0.00062% 0.00028% 0.00014% EDTA 0.075% 0.075% 0.075% 0.075% 0.075% Methylethylcellulose (MEC) 0.01% 0.01% 0.01% 0.01% 0.01% PVP K-60 1.5% 1.5% 1.5% 1.5% 1.5% *Supplied as a stable solution of 80% sodium chlorite and 20% sodium chloride.

Once prepared, samples of each of the compositions of Examples 5 to 9 were poured from the original sample cup containers and filter sterilized through a 0.22 µm membrane using a 150-mL analytical filter unit. The filtered individual compositions were then aseptically transferred to new individual sterile sample cups for storage and testing.

The following microorganisms were used to evaluate microbial activity: • (AB) Aspergillus brasiliensis (Quanti-Cult ^™ ) - ATCC 16404 (Remel Inc.) • (BS) Bacillus subtilis – Steinernema (Epower ^™ ) - ATCC 6633 ( ^{Microbiologics®} ) • (CA) Candida albicans (Epower ^™ ) - ATCC 10231 ( ^{Microbiologics®} )

The test organisms were resuspended and approximately 0.5 mL aliquots were spread onto two separate tryptic soy agar (TSA) and Sabouraud dextrose agar (SDA) plates following the manufacturer's instructions. TSA and SDA plates were incubated at 30 to 35°C and 20 to 25°C, respectively, for 2 to 7 days.

Resuspend the designated test microorganisms from the plate surface using sterile filtered deionized (DI) water and an inoculation loop and aseptically transfer the suspension to individual 50 mL centrifuge tubes using a sterile pipette.

Dilute the test microorganism suspension until its colony count can be estimated using a hemocytometer. The target colony count for each final test microorganism suspension is approximately 1.0 × 10 ⁷ cells/mL.

Depending on the test microorganism target suspension count, aliquots ranging from 2.5 µL to 100 µL were inoculated into 20 mL of each of the test compositions of Table 3 to obtain an average starting microbial population count of approximately 7000 CFU/mL.

Each inoculated sample of the compositions of Table 9 containing the specified test microorganisms was stored at room temperature and plated with thawed TSA or SDA containing chloramphenicol in duplicate (day 0 only) or triplicate as needed on days 0, 1, 2, and 3.

Aliquot volumes are placed in parentheses to increase the chances that the pour plate count will be within the countable range of 25 CFU to 300 CFU. All pour plate sample volumes were adjusted to 1 mL using sterile water for injection (WFI) (i.e., 50 µL + 950 µL WFI) to allow for adequate sample dispersion.

Splash plates were performed for AB with both TSA and SDA + chloramphenicol. When the splash plates were performed in parallel, the A. agricultura counts were similar with TSA and SDA + chloramphenicol. Thus, TSA achieved counts of A. agricultura on the plate without interference due to sporulation.

Results for Aspergillus brasiliensis and the bacterium Bacillus subtilis-Steinerria sp. are shown. The log counts for Candida albicans are shown in Table 10 below. Table 10 Candida albicans log count Time (days) ClO2- concentration, (ug/mL) 0.84 1.7 3.7 7.6 15.0 0 1.40 1.43 1.40 1.40 1.40 2 1.11 1.26 0.95 0 0.85 8 0 0.48 0 0 0 13 0 0 0 0 0 twenty two 0 0 0 0 0

The results of the study showed that microbial growth was significantly inhibited at all concentrations evaluated. Microbial growth was less than 0.2 log or counts did not increase over the entire test period, including 2, 8, 13, and 22 days after incorporation for the yeast Candida albicans, the fungus Aspergillus brasiliensis, and the bacterium Bacillus subtilis-Steinerbini. When each microorganism was incorporated into the composition of Table 9 containing at least 0.84 µg/ml chlorite, Candida albicans and the bacterium Bacillus subtilis-Steinerbini were reduced over the test period for all chlorite concentrations evaluated. The fungus Aspergillus brasiliensis counts remained unchanged (within the test limits) at the lowest chlorite concentrations (0.84 and 1.7 µg/ml) and decreased over the test period at higher concentrations (about 0.2 to about 0.5 log reduction at 3.7 and 7.6 µg/ml, and 2.5 log reduction at 15 µg/ml). Examples 5-9 show that a range of chlorite concentrations provide effective inhibition of microbial growth for at least 22 days. Examples 5-9 also show that elevated concentrations of EDTA of about 0.075% reduce microbial growth in a single autoclave, and that PVP ensures that the advancing contact angle is not adversely affected, particularly when used in combination with chlorite.

It should be understood that the embodiment illustrated and described herein is one of countless embodiments within the scope of the present invention as set forth in the attached patent claims. For the purpose of explanation, the foregoing description uses specific terms to provide a thorough understanding of the described embodiments so that others can easily change, modify and/or adapt various applications of such specific embodiments by applying the knowledge in the art to which they belong without undue experimentation and without departing from the general concept of the present invention. Based on the teachings and guidance presented herein, such changes, modifications, and adaptations are intended to be within the meaning and scope of equivalents of the disclosed embodiments.

It will be apparent to one of ordinary skill in the art that many of the specific details may not be required to implement the described embodiments. Therefore, the descriptions of the specific embodiments described herein are presented for illustrative purposes and are not intended to be exhaustive or to limit the embodiments to the precise forms disclosed.

The breadth and scope of the present invention should not be limited by any of the above-described embodiments, but should be defined only in accordance with the following embodiments, claims and their equivalents.

Embodiments of the present invention: 1. An ophthalmic product or kit comprising: a) a composition comprising an admixture or mixture of: i. a chlorous acid compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. a buffering compound; iii. a reducing agent for neutralizing the chlorous acid compound, provided that after the reducing agent is admixed with the composition, the chlorous acid compound remains effective to inhibit the growth of microorganisms in the composition for a period of time; and iv. an ophthalmologically acceptable carrier and b) a container comprising a sealed compartment, the sealed compartment containing the composition and at least one polymeric ophthalmic device comprising a high molecular weight polyvinylpyrrolidone polymer. 2. The product or kit as described in any of the embodiments 1 and 2, wherein the polymeric ophthalmic device containing high molecular weight polyvinyl pyrrolidone polymer is a contact lens. 3. The product or kit as described in any of the embodiments 1 and 2, wherein the contact lens containing high molecular weight polyvinyl pyrrolidone polymer maintains a forward dynamic contact angle of about 40° to about 80°. 4. The product or kit of any of the preceding and subsequent embodiments, wherein upon formulation, the chlorous acid compound is present in a concentration of about 0.002% to about 0.200% by weight, about 0.0020% to about 0.1000% by weight, or about 0.0050% to about 0.1000% by weight, or about 0.0075% to about 0.1000% by weight, or about 0.0080% to about 0.0500% by weight, or about 0.0090% to about 0.0200% by weight, or about 0.0095% to about 0.0150% by weight, or about 0.01% by weight, based on the total weight of the composition. 5. The product or kit as described in any of the preceding and subsequent embodiments, wherein the chlorite compound is selected from water-soluble alkali metal chlorites, water-soluble alkaline metal chlorites, and mixtures thereof. 6. The product or kit as described in any of the preceding and subsequent embodiments, wherein the chlorite is selected from potassium chlorite, sodium chlorite, calcium chlorite, magnesium chlorite, and mixtures thereof. 7. The product or kit as described in any of the preceding and subsequent embodiments, wherein the chlorite comprises sodium chlorite. 8. A product or kit as described in any of the preceding and subsequent embodiments, wherein when formulated, the reducing agent and the chlorous acid compound are present in a ratio (in molar equivalents) of 1:1 to 1:20, 1:1 to 1:15, 1:1 to 1:10, or 1:1 to 1:5, or greater than 1:1 to 1:1.5 of the chlorous acid compound relative to the reducing agent. 9. A product or kit as described in any of the preceding and subsequent embodiments, wherein the reducing agent comprises EDTA, the chlorous acid compound comprises at least one chlorite compound, and when the composition is formulated, the chlorite compound and the EDTA are present in a molar equivalent of 1:2 to 1:5, or 1:3 to 1:5, or 1:4. 10. The product or kit as described in any of the preceding embodiments and any of the following embodiments, wherein the reducing agent is selected from iron (II), hydrogen sulfite, tin metal, formates, phosphites, hypophosphites, sulfur, thiosulfates, zinc metal, disulfites, manganese metal, aluminum metal, magnesium metal, disulfites, dithiothreitol, NADH ₂ , ascorbate, ferricyanide, hydroquinone, tyrosine, aldehyde, N-acetylcysteine, butylhydroxymethoxyphenyl, dibutylhydroxytoluene, ethylenediaminetetraacetic acid (EDTA), cellulose disaccharides, reducing carbohydrates, phenols, polymeric aldehydes, polymeric phenols, copolymers of tyrosine acrylamide and N'N-dimethylacrylamide, polynoblock (2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2-hydroxyethyl)phenol) co-N,N-dimethylacrylamide, and mixtures thereof. 11. A product or kit as described in any of the preceding and subsequent embodiments, wherein the reducing agent is selected from polymeric aldehydes, ethylenediaminetetraacetic acid, polymeric phenols, reducing carbohydrates, and mixtures thereof. 12. The product or kit of any of the preceding and following embodiments, wherein the polymeric aldehyde is polyvinyl pyrrolidone. 13. The product or kit of embodiment 12, wherein the reducing agent polyvinyl pyrrolidone has a weight average molecular weight of greater than about 100,000 Daltons to about 1,500,000 Daltons, about 300,000 Daltons to about 1,000,000 Daltons, about 300,000 Daltons to about 750,000 Daltons, or about 320,000 Daltons to about 500,000 Daltons. 14. The product or kit as described in Example 12, wherein the reducing agent polyvinyl pyrrolidone is PVP K-60, PVP K-90, PVP-120, or a mixture thereof. 15. The product or kit as described in Examples 12 to 14, wherein the reducing agent polyvinyl pyrrolidone is selected from polyvinyl pyrrolidone K-60, polyvinyl pyrrolidone K-90, or a mixture thereof. 16. The product or kit as described in any of the preceding and subsequent examples, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 1 day. 17. The product or kit as described in any of the preceding and subsequent examples, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 2 days. 18. The product or kit as described in any of the preceding and subsequent embodiments, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 3 days. 19. The product or kit as described in any of the preceding and subsequent embodiments, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 7 days. 20. The product or kit of any of the preceding and subsequent embodiments, wherein the osmotic pressure is about 200 mOsm/kg to less than about 500 mOsm/kg, about 200 to about 450 mOsm/kg, about 205 to about 380 mOsm/kg, about 210 to about 360 (mOsm/kg), about 250 to about 350 mOsm/kg, about 270 to about 330 mOsm/kg, or about 205 mOsm/kg to about 350 mOsm/kg. 21. A product or kit as described in any of the preceding and subsequent embodiments, wherein the composition has a pH of about 6.0 to about 8.0, or a pH of about 6.5 to about 8.0, or a pH of about 6.5 to 7.5, or a pH of about 7.0 to about 7.5. 22. A product or kit as described in any of the preceding and subsequent embodiments, wherein the buffer compound is selected from a phosphate compound, an organic acid buffer, a salt thereof, or a mixture thereof. 23. A product or kit as described in any of the preceding and subsequent embodiments, wherein the buffer compound is a phosphate compound. 24. The product or kit of embodiment 23, wherein the phosphate compound is a combination of a salt of a dibasic phosphate anion (HPO ₄ ) ^2- and a salt of a monobasic phosphate anion (H ₂ PO ₄ ) ^- . 25. The product or kit of embodiment 23, wherein the phosphate compound is sodium dihydrogen phosphate (Na ₂ HPO ₄ ), sodium dihydrogen phosphate (NaH ₂ PO ₄ ), or a mixture thereof. 26. The product or kit of any of the preceding and following embodiments, wherein the buffer compound is an organic acid buffer. 27. The product or kit of embodiment 27, wherein the organic acid buffer is a phosphate-free organic acid having two or more carboxylic acid groups. 28. The product or kit of embodiment 27, wherein the organic acid buffer is selected from phytic acid, mellitic acid, maleic acid, and ophthalmically compatible salts thereof. 29. The product or kit of embodiment 27, wherein the organic acid buffer is selected from maleic acid, its sodium or potassium salt, and mixtures thereof. 30. The product or kit of embodiment 27, wherein the organic acid buffer is selected from mellitic acid, its sodium or potassium salt, and mixtures thereof. 31. The product or kit of embodiment 28, wherein the organic acid buffer comprises a salt of a dibasic organic acid anion (e.g., dibasic sodium maleate monohydrate) and a salt of a monobasic organic acid anion (monobasic sodium maleate). 32. The product or kit of embodiment 32, wherein in the case of the dibasic organic acid, when present in the form of a metal (e.g., sodium) monohydrate, the concentration of the dibasic organic acid anion is about 0.1% to about 0.3% by weight of the composition and the concentration of the monobasic organic acid anion is 0.005% to about 0.002% by weight of the composition before sterilizing the composition. 33. A product or kit as described in any of the preceding and subsequent embodiments, wherein the composition is free of boric acid and borate. 34. A product or kit as described in any of the preceding and subsequent embodiments, wherein the composition has a pH of about 7.0 to about 7.5, or about 7.2 to about 7.4. 35. A product or kit as described in any of the preceding and subsequent embodiments, wherein the composition is manufactured under sterile conditions, or is sterilized during and/or after the time period. 36. A product or kit as described in any of the preceding and subsequent embodiments, wherein the composition is sterilized after the time period by a sterilization process selected from autoclave sterilization, UV sterilization, and gamma electron beam sterilization. 37. A product or kit as described in any of the preceding and subsequent embodiments, wherein the composition further comprises one or more softeners. 38. A product or kit as described in embodiment 38, wherein the softener polymer is selected from block copolymer surfactants; polyvinyl alcohol, polyvinyl pyrrolidone; polyacrylic acid; polyether; hyaluronic acid and hyaluronic acid derivatives; chitosan; polysorbate; dextran; cellulose derivatives; acyclic polyamides, and mixtures thereof. 39. A method of reducing or preventing the reaction between a chlorous acid compound and a polymeric ophthalmic device containing a high molecular weight polyvinyl pyrrolidone polymer, comprising the steps of: a. mixing a composition comprising: i. a chlorous acid compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. a buffering compound; and iii. a reducing agent for neutralizing the chlorous acid compound, provided that after the reducing agent is admixed with the composition, the chlorous acid compound remains effective to inhibit the growth of microorganisms in the composition for a period of time; b. placing the composition and the polymeric ophthalmic device containing a high molecular weight polyvinyl pyrrolidone polymer in a container. 40. The method of any of the method embodiments described in Example 40 and thereafter, wherein the container and contents of step b. are sterilized. 41. The method as described in any of the foregoing method embodiments and any of the following method embodiments, wherein the sterilization is selected from autoclave sterilization, UV sterilization, and gamma electron beam sterilization. 42. The method as described in any of the foregoing method embodiments and any of the following method embodiments, wherein the sterilization is performed by autoclave sterilization. 43. The method as described in any of the foregoing method embodiments and any of the following method embodiments, wherein the ocular device containing a high molecular weight polyvinyl pyrrolidone polymer is a contact lens. 44. The method as described in any of the foregoing method embodiments and any of the following method embodiments, wherein the contact lens containing a high molecular weight polyvinyl pyrrolidone polymer maintains a forward dynamic contact angle of about 40° to about 80°. 45. The method of any of the preceding method embodiments and any of the following method embodiments, wherein the composition is manufactured under aseptic conditions or sterilized during and/or after the time period. 46. The method of any of the preceding method embodiments, wherein the composition is sterilized after the time period by a sterilization process selected from autoclave sterilization, UV sterilization, and gamma electron beam sterilization. 47. The method of any of the foregoing and subsequent embodiments, wherein when the composition is formulated, the chlorous acid compound is present in a concentration of about 0.002% to about 0.200%, about 0.0020% to about 0.1000%, or about 0.0050% to about 0.1000%, or about 0.0075% to about 0.1000%, or about 0.0080% to about 0.0500%, or about 0.0090% to about 0.0200%, or about 0.0095% to about 0.0150%, or about 0.01% by weight, based on the total weight of the composition. 48. The method as described in any of the preceding and subsequent embodiments, wherein the chlorous acid compound is selected from water-soluble alkali metal chlorites, water-soluble alkali metal chlorites, and mixtures thereof. 49. The method as described in any of the preceding and subsequent embodiments, wherein the chlorite is selected from potassium chlorite, sodium chlorite, calcium chlorite, magnesium chlorite, and mixtures thereof. 50. The method as described in any of the preceding and subsequent embodiments, wherein the chlorite comprises sodium chlorite. 51. The method of any of the preceding and subsequent embodiments, wherein when the composition is formulated, the reducing agent and the chlorous acid compound are present in a ratio of 1:1 to 1:20, 1:1 to 1:15, 1:1 to 1:10, or 1:1 to 1:5, or greater than 1:1 to 1:1.5 of the chlorous acid compound to the reducing agent. 52. The method of any of the preceding and subsequent embodiments, wherein the reducing agent comprises EDTA, and when the composition is formulated, the EDTA and the chlorous acid compound are present in a ratio of 1:2 to 1:5, or 1:3 to 1:5, or 1:4 of the chlorous acid compound to EDTA in molar equivalents. 53. The method of any of the preceding embodiments and any of the following embodiments, wherein the reducing agent is selected from iron (II), hydrogen sulfite, tin metal, formates, phosphites, hypophosphites, sulfur, thiosulfates, zinc metal, disulfite, manganese metal, aluminum metal, magnesium metal, disulfite, dithiothreitol, NADH ₂ , ascorbate, ferricyanide, hydroquinone, tyrosine, aldehyde, N-acetylcysteine, butylhydroxymethoxybenzene, dibutylhydroxytoluene, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ophthalmically compatible salts thereof, cellulose disaccharides, reducing carbohydrates, phenols, polymeric aldehydes, polymeric phenols, copolymers of tyrosine acrylamide and N'N-dimethylacrylamide, polynoblock (2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2-hydroxyethyl)phenol) co-N,N-dimethylacrylamide, and mixtures thereof. 54. The method as described in any of the preceding and subsequent embodiments, wherein the reducing agent is selected from polymeric aldehydes, ethylenediaminetetraacetic acid, polymeric phenols, reducing carbohydrates, and mixtures thereof, or comprises EDTA. 55. The method as described in any of the preceding and subsequent embodiments, wherein the polymeric aldehyde is polyvinylpyrrolidone. 56. The method of embodiment 55, wherein the reducing agent polyvinyl pyrrolidone has a weight average molecular weight of greater than about 100,000 Daltons to about 1,500,000 Daltons, about 300,000 Daltons to about 1,000,000 Daltons, about 300,000 Daltons to about 750,000 Daltons, or about 320,000 Daltons to about 500,000 Daltons. 57. The method of embodiment 55, wherein the reducing agent polyvinyl pyrrolidone is PVP K-60, PVP K-90, PVP-120, or a mixture thereof. 58. The method of any of the preceding and subsequent embodiments, wherein the total polyvinylpyrrolidone component has a weight average molecular weight greater than about 100,000 Daltons. 59. The method of any of the preceding and subsequent embodiments, wherein the polyvinylpyrrolidone is selected from polyvinylpyrrolidone K-60, polyvinylpyrrolidone K-90, or a mixture thereof. 60. The method of any of the preceding and subsequent embodiments, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 1 day. 61. The method of any of the preceding and subsequent embodiments, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 2 days. 62. The method of any of the preceding and subsequent embodiments, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 3 days. 63. The method of any of the preceding and subsequent embodiments, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 7 days. 64. The method of any of the preceding and subsequent embodiments, wherein the osmotic pressure is about 200 mOsm/kg to less than about 500 mOsm/kg, about 200 to about 450 mOsm/kg, about 205 to about 380 mOsm/kg, about 210 to about 360 (mOsm/kg), about 250 to about 350 mOsm/kg, about 270 to about 330 mOsm/kg, or about 205 mOsm/kg to about 350 mOsm/kg. 65. The method of any of the preceding and subsequent embodiments, wherein the composition has a pH of about 6.0 to about 8.0, or a pH of about 6.5 to about 8.0, or a pH of about 6.5 to 7.5, or a pH of about 7.0 to about 7.5. 66. The method as described in any of the preceding and subsequent embodiments, wherein the buffer compound is selected from a phosphate compound, an organic acid buffer, a salt thereof, or a mixture thereof. 67. The method as described in any of the preceding and subsequent embodiments, wherein the buffer compound is a phosphate compound. 68. The method as described in embodiment 67, wherein the phosphate compound is a combination of a salt of a dibasic phosphate anion (HPO ₄ ) ^2- and a salt of a monobasic phosphate anion (H ₂ PO ₄ ) ^- . 69. The method as described in embodiment 67, wherein the phosphate compound is sodium dihydrogen phosphate (Na ₂ HPO ₄ ), sodium dihydrogen phosphate (NaH ₂ PO ₄ ), or a mixture thereof. 70. The method of any of the preceding and subsequent embodiments, wherein the buffer compound is an organic acid buffer. 71. The method of embodiment 70, wherein the organic acid buffer is a phosphate-free organic acid having two or more carboxylic acid groups. 72. The method of embodiment 70, wherein the organic acid buffer is selected from phytic acid, mellitic acid, citric acid, and ophthalmically compatible salts thereof. 73. The method of embodiment 70, wherein the organic acid buffer is selected from citric acid, its sodium or potassium salt, and mixtures thereof. 74. The method of embodiment 70, wherein the organic acid buffer is selected from mellitic acid, its sodium or potassium salt, and mixtures thereof. 75. The method of embodiments 70 to 74, wherein the organic acid buffer comprises a salt of a dibasic organic acid anion (e.g., dibasic sodium maleate monohydrate) and a salt of a monobasic organic acid anion (monobasic sodium maleate). 76. The method of embodiment 32, wherein in the case of the dibasic organic acid, when present as a metal (e.g., sodium) monohydrate, the concentration of the dibasic organic acid anion is from about 0.1% to about 0.3% by weight of the composition and the concentration of the monobasic organic acid anion is from 0.005% to about 0.002% by weight of the composition before sterilizing the composition. 77. The method of any of the preceding and subsequent embodiments, wherein the composition is free of boric acid and borate. 78. The method of any of the preceding and subsequent embodiments, wherein the composition has a pH of from about 7.0 to about 7.5, or from about 7.2 to about 7.4. 79. The method of any of the preceding method embodiments and any of the following method embodiments, wherein the composition is manufactured under aseptic conditions or sterilized during and/or after the time period. 80. The method of any of the preceding method embodiments and any of the following method embodiments, wherein the composition is sterilized after the time period by a sterilization process selected from autoclave sterilization, UV sterilization, and gamma electron beam sterilization. 81. The method of any of the preceding method embodiments and any of the following method embodiments, wherein the composition further comprises one or more mitigating agents. 82. The method of embodiment 81, wherein the modifier polymer is selected from the group consisting of block copolymer surfactants; polyvinyl alcohol, polyvinyl pyrrolidone; polyacrylic acid; polyethers; hyaluronic acid and hyaluronic acid derivatives; chitosan; polysorbate; dextran; cellulose derivatives; acyclic polyamides, and mixtures thereof. 83. The product or method of any preceding or following embodiment, wherein the chlorous acid compound concentration is reduced by at least about 50%, about 70%, about 80%, or about 90% after autoclaving. 84. The product or method of any preceding or following embodiment, wherein the composition inhibits microbial growth prior to sterilization, and the microbial growth inhibiting compounds degrade into ophthalmically compatible degradation agents during and after sterilization. 85. The method or product of any preceding or following embodiment, wherein the hydrogel contact lens is a silicone hydrogel contact lens. 86. The method or product of any preceding or following embodiment, wherein the contact lens is a hybrid contact lens. 87. The method or product of any preceding embodiment, wherein, when formulated, the reducing agent comprises EDTA at a concentration of about 0.01 to about 0.075 wt % based on the total composition.

without

[ FIG. 1 ] to [ FIG. 3 ] respectively show the growth inhibition of the fungi Candida albicans, Aspergillus brasiliensis, and the bacteria Bacillus subtilis-subspecies spizizenii when each microorganism is mixed into the composition containing various concentrations of the compound that inhibits the growth of microorganisms in Table 9.

Claims (33)

An ophthalmic product or kit comprising, a)     a composition comprising an admixture or mixture of: i.      a chlorous acid compound in an amount effective to inhibit the growth of microorganisms in the composition; ii.     a buffering compound; iii.    a reducing agent for neutralizing the chlorous acid compound, provided that after the reducing agent is admixed with the composition, the chlorous acid compound remains effective to inhibit the growth of microorganisms in the composition for a period of time; and iv.    an ophthalmologically acceptable carrier; and b)     a container comprising a sealed compartment containing the composition and at least one polymeric ophthalmic device comprising a high molecular weight polyvinylpyrrolidone polymer. A product or kit as described in claim 1, wherein the polymeric ophthalmic device containing a high molecular weight polyvinyl pyrrolidone polymer is a contact lens. The product or kit of claim 1, wherein after sterilization and storage of the ophthalmic product or kit, the contact lens containing the high molecular weight polyvinyl pyrrolidone polymer maintains a forward dynamic contact angle of about 40° to about 80°. The product or kit of claim 1, wherein when the composition is formulated, the chlorous acid compound is present in a concentration of about 0.002 wt % to about 0.200 wt %. The product or kit as claimed in claim 1, wherein the chlorous acid compound is selected from water-soluble alkali metal chlorites, water-soluble alkaline metal chlorites, and mixtures thereof. The product or kit of claim 5, wherein the chlorite is selected from potassium chlorite, sodium chlorite, calcium chlorite, magnesium chlorite, and mixtures thereof. A product or kit as described in claim 1, wherein the reducing agent and the chlorous acid compound are present in a ratio of 1:1 to 1:20 of the chlorous acid compound to the reducing agent (in molar equivalents). The product or kit as claimed in claim 1, wherein the reducing agent is selected from iron (II), hydrogen sulfite, tin metal, formate, phosphite, hypophosphite, sulfur, thiosulfate, zinc metal, disulfite, manganese metal, aluminum metal, magnesium metal, disulfite, dithiothreitol, NADH ₂ , ascorbate, ferricyanide, hydroquinone, tyrosine, aldehyde, N-acetylcysteine, butylhydroxymethoxybenzene, dibutylhydroxytoluene, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ophthalmically compatible salts thereof, cellulose disaccharides, reducing carbohydrates, phenols, polymeric aldehydes, polymeric phenols, copolymers of tyrosine acrylamide and N'N-dimethylacrylamide, poly Norbloc (2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2-hydroxyethyl)phenol) co-N,N-dimethylacrylamide, and mixtures thereof. A product or kit as described in claim 8, wherein the reducing agent is selected from polymeric aldehydes, ethylenediaminetetraacetic acid, polymeric phenols, reducing carbohydrates, and mixtures thereof. A product or kit as described in claim 9, wherein the polymeric aldehyde is polyvinylpyrrolidone. The product or kit of claim 10, wherein the total polyvinylpyrrolidone component has a weight average molecular weight greater than about 100,000 Daltons. The product or kit as described in claim 11, wherein the polyvinyl pyrrolidone is selected from polyvinyl pyrrolidone K-60, polyvinyl pyrrolidone K-90, or a mixture thereof. A product or kit as described in claim 1, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 1 day. A product or kit as described in claim 13, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 2 days. A product or kit as described in claim 14, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 3 days. A product or kit as described in claim 15, wherein the chlorous acid compound remains effective in inhibiting the growth of microorganisms in the composition for at least 7 days. The product or kit of claim 1, wherein the osmotic pressure is about 205 mOsm/kg to about 450 mOsm/kg. The product or kit as claimed in claim 1, wherein the buffer compound is selected from phosphate compounds, organic acid buffers, salts thereof, or mixtures thereof. The product or kit of claim 18, wherein the buffer compound is a phosphate compound. The product or kit of claim 18, wherein the buffer compound is an organic acid buffer. A product or kit as claimed in claim 1, wherein the components are manufactured under aseptic conditions, or are sterilized during and/or after the time period. The product or kit of claim 21, wherein the composition is sterilized after the time period by a sterilization process selected from autoclave sterilization, UV sterilization, and gamma beam sterilization. A product or kit as described in any one of claims 1 to 22, wherein the ophthalmic device is a silicone hydrogel contact lens. A product or kit as described in claim 23, wherein the reducing agent comprises EDTA, and when the composition is formulated, the EDTA and the chlorous acid compound are present in a ratio of chlorous acid compound to EDTA in molar equivalents of 1:2 to 1:5, or 1:3 to 1:5, or 1:4. A method for reducing or preventing the reaction between a chlorous acid compound and a polymeric ophthalmic device containing a high molecular weight polyvinyl pyrrolidone polymer, comprising the following steps: a.     Mixing a composition comprising: i.      a chlorous acid compound in an amount effective to inhibit the growth of microorganisms in the composition; ii.     a buffer compound; and iii.    a reducing agent for neutralizing the chlorous acid compound, provided that after the reducing agent is admixed with the composition, the chlorous acid compound remains effective to inhibit the growth of microorganisms in the composition for a period of time; b.     Placing the composition and the polymeric ophthalmic device containing a high molecular weight polyvinyl pyrrolidone polymer in a container. The method as described in claim 25, wherein the contents are hermetically sealed in the container, and the hermetically sealed container and the contents are sterilized. The method of claim 26, wherein the sterilization is selected from autoclave sterilization, UV sterilization, and gamma beam sterilization. The method of claim 26, wherein the sterilization is performed by autoclave sterilization. The method of claim 25, wherein the ophthalmic device containing the high molecular weight polyvinyl pyrrolidone polymer is a contact lens. The method of claim 29, wherein after sterilization and storage, the contact lens comprising the high molecular weight polyvinyl pyrrolidone polymer maintains a forward dynamic contact angle of about 40° to about 80°. The method of any one of claims 24 to 30, wherein the ophthalmic device is a silicone hydrogel contact lens. The method of claim 31, wherein the reducing agent comprises EDTA, and when the composition is formulated, the EDTA and the chlorous acid compound are present in a ratio of chlorous acid compound to EDTA in a molar equivalent of 1:2 to 1:5. The method of claim 31, wherein when formulated, the reducing agent comprises EDTA at a concentration of about 0.01 to about 0.075 wt % based on the total composition.