TW202439974A - Compositions for ophthalmic devices - Google Patents

Abstract

The present invention relates to microbial growth inhibiting compound and organic acid buffer containing compositions, especially eye care compositions, achieving physiologically compatible pH and tonicity as well as good bacteriostatic properties. Methods of using the compositions of the present invention are also disclosed.

Description

Ophthalmic device compositions

[Cross-reference to related applications]

This application claims priority to U.S. provisional patent application serial number 63/476,553 filed on December 21, 2022; and U.S. provisional patent application serial number 63/492,288 filed on March 27, 2023; the entire texts of which are incorporated herein by reference.

The present invention relates to compositions, particularly eye care compositions, containing microbial growth inhibiting compounds and organic acid buffers, achieving physiologically compatible pH and tonicity and good antimicrobial properties. Methods of using the compositions of the present 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).

The contact lens (or other ophthalmic device) packaging solution should also be compatible with the materials from which the contact lens (or other ophthalmic device) is formed and the contact lens packaging.

The challenge in preparing a package kit solution for an ophthalmic device is to formulate a solution that does not negatively affect eye comfort or negatively affect the compatibility of the solution with the material(s) forming the ophthalmic device. An important component of an ophthalmic composition including a package kit solution is an incorporated buffer solution that helps maintain the pH of the composition within an acceptable physiological range.

The inventors have discovered that by appropriately combining a microbial growth inhibitory compound and an organic acid buffer, a fully buffered antimicrobial composition (e.g., a packaging box solution) can be achieved. More specifically, such a buffer can be achieved by combining a microbial growth inhibitory compound with an organic acid at a specific ratio of microbial growth inhibitory compound to organic acid buffer, as described in detail below.

The present invention relates to an ophthalmic composition comprising: i.     a microbial growth inhibiting compound in an amount effective to inhibit the growth of microorganisms in the composition; ii.    an organic acid compound buffer; iii.   optionally, a reducing agent for neutralizing the microbial growth inhibiting compound, with the proviso that after the reducing agent is admixed with the composition, the microbial growth inhibiting compound remains effective to inhibit the growth of the microorganisms in the composition for a period of time; and iv.   an ophthalmically acceptable carrier comprising at least one of one or more tonic agents and a contact lens sealed in a container with the composition.

The present invention also relates to a method for inhibiting the growth of microorganisms in a composition during the period from preparation of the composition to sterilization of the composition in a sealed container, comprising the following steps: a.   Mixing a composition comprising: i.   A microorganism growth inhibiting compound in an amount effective to inhibit the growth of microorganisms in the composition; ii.   An organic acid compound buffer; and iii.   Optionally, a reducing agent for neutralizing the microorganism growth inhibiting compound after admixture with the composition; b.    Storing the composition for the period of time during which inhibition of microorganism growth occurs; c.    Placing the composition in a container; d.    Sealing the container of step c; e.    Sterilizing the container of step d; Optionally, the composition contains no or substantially no one or more of boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural gums, glycerin, polyoxyethylene-castor oil and derivatives thereof.

The present invention further relates to a method for packaging and sterilizing a composition in a sealed container, comprising the following steps: a.    Mixing a composition comprising: i.    A microbial growth inhibitory compound in an amount effective to inhibit the growth of microorganisms in the composition; ii.    An organic acid compound buffer; and iii.  Optionally, a reducing agent for neutralizing the microbial growth inhibitory compound after admixture with the composition; b.    Placing the composition in a container; c.    Sealing the container of step b; d.    Sterilizing the container of step c.

Optionally, the composition contains no or substantially no one or more of boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural gums, glycerin, polyoxyethylene-castor oil and derivatives thereof.

The present invention relates to a sealed ophthalmic product comprising: a)    a composition for storing contact lenses as an admixture or mixture: i.    a microbial growth inhibiting compound in an amount effective to inhibit the growth of microorganisms in the composition; ii.    an organic acid compound buffer; iii.  optionally, a reducing agent for neutralizing the microbial growth inhibiting compound, with the proviso that after the reducing agent is admixed with the composition, the microbial growth inhibiting compound remains effective to inhibit the growth of the microorganisms in the composition for a period of time; and iv.   an ophthalmically acceptable carrier comprising one or more tonic agents and b)   a container comprising a sealed compartment, the sealed compartment containing at least one contact lens in the presence of the composition.

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 microbial growth inhibiting compounds and one or more organic acid compounds as an ophthalmically 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.

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, instability, irritation, allergic response, and the like.

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, 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 deleterious to any part of the eye (or surrounding tissues).

As used herein, the term "water soluble" means that a component, alone or in combination with other components, does not form precipitates or gel particles visible to the human eye at a selected concentration and across temperature and pH conditions common for the manufacture, sterilization, and storage of ophthalmic solutions.

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

The phrase "inhibition of growth of microorganisms" in the composition occurs under the following circumstances and means: there is less than 0.5 log, less than 0.3 log, 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.

Unless otherwise stated, 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 stated. Microbial Growth Inhibiting Compounds

The composition of the present invention comprises one or more microbial growth inhibiting compounds when mixed, which are selected from peroxides (or peroxide sources), chlorous acid compounds, salts thereof, and/or mixtures thereof. The microbial growth inhibiting compounds and their salts are ophthalmically compatible with the eye and surrounding tissues, and are compatible with the ingredients in the composition of the present invention. Upon degradation (e.g., sterilization or storage conditions), the microbial growth inhibiting compounds and their salts degrade into ophthalmically compatible degradation agents. The degradation agents of the microbial growth inhibiting compounds and their salts do not interact with the contact lenses in which they are stored or packaged, nor do they interact with the storage/packaging containers (including lids).

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.

The chlorite compounds applicable to the present invention include chlorous acid compounds and salts thereof, including (selected from the following or selected from the group consisting of the following) but 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 may be an anhydride or a hydrate. The chlorous acid salt may be a monosalt or a disalt.

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 0.0075%), 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 preferably 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 more preferably 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.

Also suitable for use in the microbial growth inhibiting compounds of the present invention are peroxides or peroxide sources. Peroxide sources are compounds or materials that release (or can release) peroxide or hydrogen peroxide in aqueous solution. Peroxides or peroxide sources suitable for use herein include, but are not limited to, hydrogen peroxide, barium peroxide, sodium peroxide, zinc peroxide, magnesium peroxide, calcium 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), mixtures thereof, and derivatives thereof.

Specific examples of preferred peroxides (or peroxide sources) are selected from benzoyl peroxide, hydrogen peroxide, and mixtures thereof, with hydrogen peroxide being most preferred.

When formulated, suitable concentrations of hydrogen peroxide (or a peroxide source) include 0.0001% (or about 0.0001%) to 0.02% (or about 0.02%), 0.0002% (or about 0.0002%) to 0.015% (or about 0.015%), or 0.0003% (or about 0.0003%) to 0.013% (or about 0.013%), or 0.0004 (or about 0.0004%) to 0.012% (or about 0.012%), or 0.0006 (or about 0.0006%) to 0.0007 (or about 0.0008%), or 0.0008 (or about 0.0009%) to 0.011% (or about 0.012%), or 0.0009 (or about 0.0010%) to 0.012% (or about 0.012%), or 0.0001% (or about 0.0010%) to 0.013% (or about 0.013%), or 0.0001% (or about 0.0010%) to 0.014% (or about 0.014%), or 0.0001% (or about 0.0010%) to 0.015% (or about 0.015%), or 0.0001% (or about 0.001 0.0005% (or about 0.0005%) to 0.011% (or about 0.011%), or 0.0006% (or about 0.0006%) to 0.01% (or about 0.01%), or 0.0007% (or about 0.0007%) to 0.005% (or about 0.005%), or 0.0008 (or about 0.0008%) to 0.002% (or about 0.002%), or 0.0009% (or about 0.0009%) to 0.001% (or about 0.001%).

Combinations of the above-mentioned microbial growth inhibiting compounds may also be used.

Microbial growth inhibiting compounds are 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 occur and take effect during a time period that 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 sterilizing the composition in a sealed package with at least one contact lens, as described below. During sterilization (particularly heat sterilization, such as autoclaving), the concentration of the microbial growth inhibiting compound is substantially or completely neutralized. For example, the concentration of the microbial growth inhibiting compound may be reduced by at least about 50%, about 70%, about 80%, about 90%, or 100%. If the microbial growth inhibitory compounds are not completely neutralized during autoclaving, they can be completely neutralized during storage of the lenses after autoclaving and prior to use.

The phrase "period of time" used in conjunction with the antibacterial properties of chlorous acid compounds means up to or at least one, two, three, four, five, six, seven, eight, ten, twelve, fourteen, fifteen, 18, 20, 21, 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. Organic Acid Buffer

The composition of the present invention comprises an organic acid buffer, wherein the organic acid buffer is added to the composition of the present invention in its undissociated form or its metal salt. As used herein, the term "organic acid buffer" means an 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 _pK2 values in the range of 6 (or about 6) to 8 (or about 8), preferably 6 (or about 6) to 7 (or about 7).

Suitable diprotic acids include cis-butenedioic acid ( _pK2 = 6.5). Suitable hexaprotic acids include mellitic acid ( _pK6 = 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, citric acid, and salts thereof (such as sodium or potassium salts of organic acids), and mixtures thereof. The organic acid buffer may be selected from citric acid, sodium or potassium salts thereof, and mixtures thereof. The organic acid buffer may be selected from mellitic acid, sodium or potassium salts thereof, and mixtures thereof.

When formulated, the organic acid content of the composition of the present invention (as the sum of the monobasic salt and the dibasic salt) 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.

The organic acid buffer may be 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 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 sterilization of the composition.

The composition of the present invention may also contain a neutral salt (e.g. sodium chloride) to meet the physiological osmotic pressure requirements of humans.

When formulated, the neutral salt (e.g., sodium chloride) can be present in a concentration of 0.62% (or about 0.62%) to 0.66% (or about 0.66%), or 0.58% (or about 0.58%) to 0.75% (or about 0.75%), or 0.10% (or about 0.10%) to 0.28% (or about 0.28%), or 0.00% to 0.35% (or about 0.35%), based on the weight of the composition of the present invention.

Depending on the concentration of the neutral salt in the composition, the composition of the present invention contains the following ratios of monobasic organic acid anions and dibasic organic acid anions: Neutral salt (e.g. sodium chloride) concentration (%) Ratio of monobasic organic acid anions to dibasic organic acid anions (molar ratio) 0.72% to 0.81% 0.042:1 to 0.068:1 0.65% to 0.93% 0.04:1 to 0.08:1 0.58% to 1.15% 0.02:1 to 0.09:1 0.25% to 1.45% 0.008:1 to 0.14:1 Reducing agent

The compositions of the present invention may optionally include a reducing agent for quenching (or reducing) the microbial growth inhibitory compound so as to neutralize it from the composition. Suitable reducing agents include, but are not limited to, the following salts (or their metal ions): 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 , ascorbate, ferricyanide, hydroquinone, tyrosine, tyrosine copolymers, aldehydes (such as cinnamaldehyde), N-acetylcysteine, butylhydroxymethoxybenzene, dibutylhydroxytoluene, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and their ophthalmically compatible salts, cellulose disaccharides (disaccharides with the formula (C₆H₇(OH)₄O)₂O classified as reducing sugars) and their analogs, glucose (L-isomers and D-isomers), reducing carbohydrates capable of reacting with oxidants (such as glucose, fructose, ribose, xylose, galactose, lactose, maltose, and and mixtures thereof), vanillin and its analogs, phenols (such as butylhydroxymethoxybenzene, butylhydroxytoluene, tertbutylhydroquinone, and propyl gallate), polymeric aldehydes (such as polyvinylpyrrolidone (PVP)); and polymeric phenols, such as lignans; and copolymers of tyrosine acrylamide and N,N-dimethylacrylamide (such as polyacrylyl 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), 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.

The reducing agent and the microbial growth inhibitory compound are present so that the molar equivalent ratio of the microbial growth inhibitory compound to the reducing agent is 1:1 to 1:20, or 1:1 to 1:15, or 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. In the case where 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. When the microbial growth inhibitory compound is a peroxide, the molar equivalent of peroxide 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 lightly colored even after autoclaving, which can be visually determined 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. Ophthalmically acceptable carrier

The compositions of the present invention include an ophthalmically acceptable carrier . The ophthalmically 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% by weight, or at least about 75% by weight, or at least about 90% by weight, and up to about 95% by weight, or about 99% by weight of water.

The compositions of the present invention 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 0.05% by weight, or less than 0.025% by weight, or less than 0.01% by weight, or less than 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 ophthalmically 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 ophthalmically acceptable carrier may be present in 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 is statistically demonstrated to the extent required for such products prior to release or use. Such compositions may be selected to have no or substantially no adverse, negative, or deleterious effects on the contact lenses therein 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 to be placed directly on the eye or applied directly to the eye without rinsing, that is, the solution is safe and comfortable for any frequency of use of ophthalmic devices wetted by the solution, including contact lenses of any frequency of wear. Ophthalmically safe compositions have a tonicity and pH compatible with the eye and include ophthalmically 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 tears, 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, about 200 mOsm/kg to about 450 mOsm/kg, or about 205 mOsm/kg to about 380 mOsm/kg, or about 210 to about 360 milliosmoles/kilogram (mOsm/kg), or about 250 mOsm/kg to about 350 mOsm/kg, or about 270 mOsm/kg to about 330 mOsm/kg as measured using the osmotic pressure measurement method USP <785> (as of November 2022). Ophthalmic compositions will typically be formulated as sterile aqueous compositions, or as non-sterile compositions that are subsequently sterilized.

Examples of suitable tonicity adjusting agents include (selected from 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, or from about 0.2% w/v to about 1.5% w/v, based on the total composition.

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

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

The compositions of the present invention may have 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 about 7.5, or a pH of about 7.0 to about 7.5, or a pH of 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.

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), rigid 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.

Contact lens polymer materials suitable for making suitable contact lenses include (selected from the following or selected from the group consisting of) but are not limited to: acofilcon A, alofilcon A, alphafilcon A, amifilcon A, aquafilcon A, astifilcon A, atalafilcon A, balafilcon A, bisfilcon A, bufilcon A, comfilcon, crofilcon A, cyclofilcon A, darfilcon A, deltafilcon A, delefilcon, deltafilcon B, dimefilcon A, drooxifilcon A, epsifilcon A, esterifilcon A, etafilcon A, fanfilcon A, focofilcon A, galyfilcon A, genfilcon A, govafilcon A, hefilcon A, hefilcon B, hefilcon D, hilafilcon A, hilafilcon B, hioxifilcon B, hioxifilcon C, hixoifilcon A, hydrofilcon A, lenefilcon A, licryfilcon A, licryfilcon B, lidofilcon A, lidofilcon B, lotrafilcon A, lotrafilcon B, mafilcon A, mesifilcon A, methafilcon B, mipafilcon A, narafilcon A, narafilcon B, nelfilcon A, netrafilcon A, ocufilcon A, ocufilcon B, ocufilcon C, ocufilcon D. ocufilcon E, ofilcon A, omafilcon A, oxyfilcon A, pentafilcon A, perfilcon A, pevafilcon A, phemfilcon A, polymacon, riofilcon A, samfilcon A, senofilcon A, senofilcon C, silafilcon A, siloxyfilcon A, somofilcon A, stenfilcon A, tefilcon A, tetrafilcon A, trifilcon A. vasurfilcon, vifilcon, and xylofilcon A. The contact lens may be made of a polymer material selected from the group consisting of comfilcon, etafilcon A, galyfilcon A, senofilcon A, senofilcon C, samfilcon, serafilcon, nelfilcon A, hilafilcon, tetrafilcon A, vasurfilcon, vifilcon, and polymacon.

Conventional hydrogel contact lenses do not contain silicone-containing components and generally have higher water content, lower oxygen permeability, and modulus than silicone hydrogels. Conventional hydrogels are made from monomer mixtures that primarily contain hydrophilic monomers, such as 2-hydroxyethyl methacrylate ("HEMA"), N-vinyl pyrrolidone ("NVP"), or polyvinyl alcohol. 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. Conventional hydrogels may be ionic or nonionic and include (selected from or consisting of) polymacon, etafilcon, genfilcon, hilafilcon, nesofilcon, nelfilcon, ocufilcon, omafilcon, lenefilcon, and the like. The oxygen permeability of these conventional hydrogel materials is generally less than 20 to 30 barrers.

Silicone hydrogel formulations can include aquafilcon, balafilcon, samfilcon, lotrafilcon A and B, delefilcon, galyfilcon, senofilcon A, B, and C, narafilcon, comfilcon, formofilcon, riofilcon, fanfilcon, serafilcon, stenfilcon, somofilcon, kalifilcon, verofilcon, and the like.

"Silicone hydrogel" refers to a polymeric network made of at least one hydrophilic component and at least one silicone-containing component. Suitable hydrophilic components and silicone-containing components are known. Examples of suitable families of hydrophilic components that may be present in silicone hydrogel formulations 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-vinylpyrrolidone (NVP), N-vinylacetamide (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 can include at least one polymerizable group (e.g., (meth)acrylate, styryl, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinylamide, O-vinylcarbamate, O-vinyl carbonate, vinyl, or a mixture of the foregoing), at least one siloxane group, and one or more linking groups (which can be bonds) connecting the polymerizable group(s) to the siloxane group(s). The silicone-containing component may, for example, contain 1 to 220, 3 to 100, 3 to 40, or 3 to 20 siloxane repeating units.

The ophthalmic device may also include a polymeric wetting agent, which may be incorporated into the ophthalmic device in a variety of ways, including but not limited to as a non-reactive polymer and, when polymerized, is entrapped in the hydrogel to form a semi-IPN, may be polymerized (with or without crosslinking) in a preformed contact lens to form a complete or semi-IPN, respectively, or may be added to the packaging kit solution of the present invention and absorbed into the contact lens during sterilization, examples of which are disclosed in US6,367,929, US10,935,695, US8,053,539, US10,371,865, US10,370,476, US6,822,016, US7,431,152, US7,841,716, and US7,262,232.

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, HEV, or 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 with chlorous acid compounds, they are preferably stable in the presence of a microbial growth inhibitory compound at a selected microbial growth inhibitory compound concentration. Examples of light absorbing compounds that are stable in the presence of hydrogen peroxide are Norbloc and 2-(2-cyano-2-(9H-sulfuronium) 2-(2-cyano-2-(9H-thioxanthen-9-ylidene)acetamido)ethyl methacrylate.

The silicone hydrogel can have a modulus in the range of 60 to 200, 60 to 150, or 80 to 130 psi, a water content in the range of 20 to 60%, and a contact angle of less than about 100°, less than about 80°, and less than about 60°. Examples of silicone hydrogels include acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, kalifilcon, narafilcon, riofilcon, samfilcon, senofilcon, serafilcon, somofilcon, stenfilcon, unifilcon, and verofilcon (including the like). and all variations thereof), and U.S. Patent Nos. 4,659,782, 4,659,783, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,998,498, 6,087,415, 5,760,100, 5,776,999, 5,789,461, 5,849,811, 5,965,631, 6,367,929, 6,822,016, 6,867,245, 6,943,203, 7,247,692, 7, No. 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. 9,056,878, No. 9,057,821, No. 9,125, 808, 9,140,825, 9156,934, 9,170,349, 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,929, and WO03/22321, WO2008/061992, US2010/0048847, US20230037781, US20210109255, US10,935,695, US8,053,539, US10,371,865, and US10,370,476. The entire text of these patents is hereby incorporated by reference.

The contact lens polymer material may be a silicone hydrogel polymer. The silicone hydrogel may be selected from the following (or a group consisting of the following): acquafilcon, asmofilcon, balafilcon A, comfilcon, delefilcon, enfilcon, fanfilcon, galyfilcon, lehfilcon, kalificlon, lotrafilcon, riofilcon, senofilcon, samfilcon, serafilcon, somofilcon, stenfilcon, unifilcon, and verofilicon.

The compositions may also be used for direct application to the eye as wetting or rewetting eye drops to relieve eye discomfort (e.g., burning sensations associated with the eye or general eye irritation).

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, certain non-chlorous acid or non-peroxide preservatives (particularly cationic preservatives), persulfates, carboxyvinyl polymers, natural gums, glycerin, polyoxyethylene-castor oil, and/or their derivatives.

As used herein, the term "borate" shall refer 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 Harmonised Classification and Labelling Based on Regulation (EC) No 1272/2008 (CLP Regulation), Annex VI, Part 2, Swedish Chemicals Agency Nov. 2, 2018. ) The term “non-chlorous acid or non-peroxide preservative” or “non-chlorous acid/non-peroxide preservative” means compounds mentioned above which are not chlorous acid compounds or certain peroxides (or peroxide sources) but have 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 or non-peroxide preservatives, especially cationic preservatives, may cause eye irritation and/or allergic reactions, undesirably affecting consumers using eye care compositions or contact lenses containing such non-chlorous acid/non-peroxide 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 enhance deleterious consequences to the anterior segment, tear membrane, cornea, conjunctiva, and even the 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, special attention should be paid: “When lens care products interact with contact lenses, components such as preservatives present in the solution will be absorbed into 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 "persulfates" as used herein refers to 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 stinging and irritation to the eyes, and may undesirably affect consumers using contact lenses containing persulfates on their surfaces due to storage of the contact lenses with such 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 are still undesirable.

The term “substantially free” as it relates to compounds selected from boric acid, borates, non-chlorous acid/non-peroxide preservatives, 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 are present in the composition of the present invention at a concentration of less than 2% by weight (or about 2% by weight), or less than 1.5% by weight (or about 1.5% by weight), or less than 1% by weight (or about 1% by weight), or less than 0.5% by weight (or about 0.5% by weight), or less than 0.1% by weight (or about 0.1% by weight), or less than 0.05% by weight (or about 0.05% by weight), or less than 0.01% by weight (or about 0.01% by weight), or less than 0.005% by weight (or about 0.005% by weight) of the total composition. In certain embodiments, the composition of the present invention may be free of 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; chitosan; polysorbates such as polysorbate 80, polysorbate 60, and polysorbate 40; polydextrose such as polydextrose 70; cellulose derivatives; Biologicals, such as carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, and methylethyl cellulose; non-cyclic polyamides, such as non-cyclic polyamides with a weight average molecular weight of 2,500 to 1,800,000 Daltons disclosed in U.S. Pat. No. 7,786,185, 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 U.S. Pat. No. 6,440,366, which is incorporated herein by reference in its entirety. Preferably, the water-soluble buffer polymer is selected from polyvinyl pyrrolidone, methylethyl cellulose, polyvinyl alcohol, 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 of up to about 0.5 wt %, 1 wt %, or 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 of up to about 2 wt%, 5 wt%, or 10 wt%, preferably 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, poloxamers such as Pluronic® F68, and block copolymers of poly ⁽ oxyethylene)-poly(oxybutylene) compounds such as those described in U.S. Patent Application Publication No. 2008/0138310 (which 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.

It will be appreciated that some components may perform more than one function, for example, some modifiers may also act as surfactants (e.g., PEO-PPO and PEO-PBO block copolymers).

Surfactant can 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 should be understood that some components can perform more than one function, for example, some mitigants can 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. This (class) optional component is selected to give or provide at least one beneficial or desired characteristic to the composition. Such additional but optional components can be selected from the components in the ophthalmic device care composition known to be used. 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-applied eye drops or cleansing [or eye care solutions]), moisturizers, nutrients, therapeutic agents, sequestering agents, viscosity increasing agents, contact lens adjustment 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, such that the beneficial or desired property is apparent to the user. For example, such optional components can be included in the compositions in amounts similar to the amounts of such components used in other eye or ocular device care composition products.

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

In one embodiment, the ophthalmic solution comprises about 0.01 to about 0.02 wt % sodium chlorite, an organic acid buffer, about 0.5 to about 0.75 wt % EDTA, about 0.005 to about 0.01 wt % methylethylcellulose, and optionally up to about 1, about 1.5, or about 2 wt % PVP K30, K60, or K90, 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.

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 microbial growth inhibiting compounds (e.g., chlorites or peroxides) or oxidizing agents. 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 drugs, 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 housing 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) comprising a recess for accommodating the ophthalmic device and the composition, wherein the recess is hermetically sealed with a lid material before the contents of the packaging box are sterilized.

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 Hydrogen peroxide, 3% solution (the percentages/amounts in the examples represent pure hydrogen peroxide in the composition). 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 a borate buffer solution while using an inductive balance to measure the force exerted on the contact lens sample in each case due to the wetting of the probe solution (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 Vespa 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 from five individual contact lens test samples were averaged to obtain the reported dynamic contact angle of the lens as it advances (and recedes). Sessile Drop Contact Angle

The sessile drop contact angle of the lens is determined using the sessile drop technique at room temperature using a KRUSS DSA-100 TM instrument and deionized water as the probe solution (Sessile Drop). The lenses to be tested are wetted in deionized water to remove carryover from the packaging solution. Each test lens is placed on an absorbent, lint-free wipe moistened with the packaging solution. Both sides of the lens are contacted with the wipe to remove surface moisture but not to dry the lens. To ensure proper flattening, the lens is placed "bowl side down" on the convex surface of a contact lens plastic mold. The plastic mold and lens are placed in the sessile drop instrument holder, ensuring proper central syringe alignment. Using the DSA 100-Drop Shape Analysis software, form a 3 to 4 microliter drop of deionized water on the tip of a syringe, ensuring that the drop is suspended from the lens. Move the needle down to release the drop smoothly onto the lens surface. Immediately after releasing the drop, remove the needle. Allow the drop to equilibrate on the lens for 5 to 10 seconds and measure the contact angle between the drop image and the lens surface. Generally, three to five lenses are evaluated and the average contact angle is reported.

Water content is measured gravimetrically. Allow the lenses to equilibrate in the packaging solution for 24 hours. Use a sponge-tipped swab to remove each of the three test lenses from the packaging solution and place on an absorbent wipe moistened with the packaging solution. Both sides of the lens are in contact with the wipe. Using tweezers, place the test lens in a tared weigh pan and weigh. Then prepare and weigh two additional sets of samples. All weight measurements are performed in triplicate and the average of those values is used in the calculations. Wet weight is defined as the combined weight of the pan and wet lens minus the weight of the weigh pan alone.

Dry weight is measured by placing the sample pan in a vacuum oven preheated to 60°C for 30 minutes. Apply vacuum until the pressure reaches at least 1 inch Hg; lower pressures are allowed. Close the vacuum valve and pump and dry the lens for at least 12 hours, usually overnight. Open the purge valve to allow dry air or dry nitrogen to enter. Allow the oven to reach atmospheric pressure. Remove the sample pan and weigh it. Dry weight is defined as the combined weight of the pan and dried lens minus the weight of the pan weighed alone. The water content of the test lens is calculated as follows: % Water Content (%WC) = (Wet Weight – Dry Weight) / Wet Weight x 100. Calculate the average water content and its standard deviation, and report the average as the percent water content of the test lens. The standard deviations are given in parentheses in the table.

The mechanical properties of contact lenses are measured using a tensile testing machine (such as Instron Model 1122 or 5542) equipped with a load cell and pneumatic gripper controller. A negative one diopter lens (spherical) is a preferred lens geometry because of its uniform thickness around the center profile. A dog-bone shaped specimen (having a length of 0.522 inches, an "ear" width of 0.276 inches, and a "neck" width of 0.213 inches) cut from a -1.00 diopter lens is loaded into a fixture and stretched at a constant strain rate of 2 inches per minute until it breaks. Prior to testing, the center thickness of the dog-bone specimen is measured using an electronic thickness gauge. Measure the initial gauge length (L _o ) and the length at break (L _f ) of the sample. Measure at least five samples of each composition and use the average value to calculate the percent elongation at break: percent elongation = [(L _f – L _o )/L _o ] × 100.

The tensile modulus (M) is calculated as the slope of the initial linear portion of the stress-strain curve; the units of modulus are pounds per square inch or psi. The tensile strength (TS) is calculated from the peak load and the original cross-sectional area: tensile strength = peak load divided by the original cross-sectional area; the units of tensile strength are psi.

Toughness is calculated from the fracture energy and the original sample volume: Toughness = fracture energy divided by original sample volume; the unit of toughness is in-lbs/in ³ .

Elongation to break (ETB) is also recorded as a percentage of the strain at break. Example 1

Table 1 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 1 Components Weight % (balance is water) Sodium maleate 0.01008% Sodium maleate monohydrate 0.22653% Sodium chloride 0.77489% Sodium Chlorite (Anhydrous)* 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 1 is approximately 71 µg/mL

A pot life analysis was performed on the composition of Table 1 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 1 was sufficient to inhibit microbial growth of the group of organisms for a period of at least 5 days.

Pot Life samples are prepared as follows: 1.    Place approximately 10 mL of the composition in Table 1 in several 20 mL glass screw-top flash bottles. 2. Seal the vials from step 1 with gray butylene caps, store in a light-proof container at room temperature, and place in a refrigerator as needed (generally 1 vial per day for 5 days). 3.    Analyze the chlorite concentration of the samples at the time periods shown in Table 2 below.

Chlorite concentrations were measured by ion chromatography with conductivity detection. Separations were 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 concentration of the test solution was calculated using a least squares regression equation.

The results of the applicable period are summarized in Table 2. Table 2 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.

Pot life studies have shown that in the presence of EDTA and PVP reducing agents, at least 95% of the initial chlorite concentration in the composition of Table 1 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 residual amount of active agent is considered commercially/consumer acceptable.

It should be noted that after autoclaving (at 121°C for 15 minutes) the composition of Table 1 (i.e., with the reducing agents PVP and EDTA) in an autoclave model 2540E-B/L from Tuttnauer (note: there is a temperature ramp at the start and end of autoclaving), the chlorite concentration was determined to have decreased by about 40% (i.e., from an initial concentration of 52.9 µg/ml to a concentration of 31.3 µg/ml). In the long run, the chlorite concentration (with respect to its initially measured chlorite concentration) was determined to have decreased by only 17% after autoclaving the composition containing chlorite but without reducing agents. Example 2

Table 3 shows the formulation of the composition of the present invention containing peroxide or peroxide source, which is incorporated with an organic maleate 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 3 Components Weight % (balance is water) Sodium chloride 0.7903% Sodium maleate 0.0098% Sodium maleate monohydrate 0.2342% Hydrogen peroxide* 0.0101% water QS Example 3

Table 4 shows the formulation of another composition containing a chlorous acid compound of the present invention, which is incorporated with an 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. The composition is prepared using a known mixing technique. Table 4 Components Weight % (balance is water) Sodium chloride 0.7798% Sodium maleate 0.0097% Sodium maleate monohydrate 0.2284% Sodium Chlorite (Anhydrous)* 0.0121% Methylethylcellulose (MEC) 0.0053% water QS *Supplied in a stable form of 80% sodium chlorite and 20% sodium chloride. The nominal chlorite content in the composition of Table 4 is approximately 72 µg/mL Example 4

Accelerated aging studies were performed at 55°C using OASYS 1-Day contact lenses (senofilcon A, -1.00D) and the maleate buffered packaging solution of Example 1 (0.012% sodium chlorite, 0.075% EDTA, and 1% PVP K-60). 3 ml of maleate buffered packaging solution and one OASYS 1-Day contact lens were placed in each glass vial and sealed with a gray butylene cap. The sealed vials were subjected to a single autoclave cycle as described in Example 1 and placed in an accelerated aging chamber. The contact angles and chlorite concentrations were measured at the time periods listed in Table 5 (using the method described in Example 1). After a single autoclave cycle, chlorite concentrations decreased by approximately 40% to a concentration of 31.3 µg/mL. No chlorite was detected at subsequent time points. Contact angles were measured at each of the time points listed in Table 5 below, and no contact angle shift was observed, as measured by dynamic or static techniques. Mechanical properties and light transmittance were tested at the final time point and were consistent with typical results for ACUVUE ^® OASYS 1-Day lenses. Overall, these results show that maleate buffered packaging solutions containing 1% PVP K-60 and increasing concentrations of EDTA are compatible with silicone hydrogel contact lenses such as senofilcon A. Table 5. Summary of accelerated aging studies Simulated aging, months Chlorite, µg/mL Wettability Adv.Contact Angle FC is not wet BC is not wet 0.0 31.3 53.5 (4.0) 56.9 (3.8) DNT 6.7 BDL 48.4 (3.1) 66.8 (4.8) DNT 13.2 DNT 44.5 (4.1) DNT 76.5 (10.7) 23.3 DNT 50.7 (6.1) 59.1 (6.9) 67.9 (8.7) Table 6 Nature Water content, % 40.9 (0.4) Modulus, psi 85 (4) Elongation, % 238 (65)

It should be understood that the embodiments depicted and described herein are among many embodiments within the scope of the present invention as described in the accompanying patent claims. For the purpose of explanation, specific nomenclature is used to provide a thorough understanding of the described embodiments so that others can easily change, modify, and/or adapt for various applications of such specific embodiments by applying knowledge in the art without experimentation and without departing from the general concept of the 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.

Those skilled in the art will appreciate that many of the specific details may not be required to practice the described embodiments. Therefore, the descriptions of the specific embodiments described herein are presented for illustrative purposes only and are not intended to be exhaustive or to limit the embodiments to the precise form disclosed.

The breadth and scope of the present invention should not be limited by any of the above embodiments, but should be defined only according to the following embodiments, claims, and their equivalents. Embodiments of the present invention: 1. An ophthalmic composition comprising: i. a microbial growth inhibitory compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. an organic acid buffer; iii. optionally, a reducing agent for neutralizing the microbial growth inhibitory compound, provided that after the reducing agent is admixed with the composition, the microbial growth inhibitory compound remains effective to inhibit the growth of the microorganisms in the composition for a period of time; and iv. an ophthalmically acceptable carrier comprising at least one of one or more tonicity agents and a contact lens sealed in a container with the composition. 2. The composition as described in any of the embodiments 1 and the following, wherein the microbial growth inhibiting compound is selected from peroxides, peroxide sources, chlorous acid compounds, salts thereof, and/or mixtures thereof. 3. The composition as described in any of the embodiments 1 and 2 and the following, wherein the microbial growth inhibiting compound is a chlorous acid compound. 4. The composition as described in any of the preceding embodiments and the following, wherein the chlorous acid compound is a chlorite selected from water-soluble alkali metal chlorites, water-soluble alkali metal chlorites, and mixtures thereof. 5. The composition as described in any of the preceding embodiments and the following, wherein the chlorite is selected from potassium chlorite, sodium chlorite, calcium chlorite, magnesium chlorite, and mixtures thereof. 6. The composition of any of the preceding and subsequent embodiments, wherein the chlorite comprises sodium chlorite. 7. The composition of any of the preceding and subsequent embodiments, wherein when formulated, the chlorous acid compound is present at 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 of the total composition. 8. The composition of any of the preceding and subsequent embodiments, wherein the microbial growth inhibiting compound is a peroxide or a peroxide source. 9. The composition of any of the preceding and subsequent embodiments, wherein the peroxide or the peroxide source is selected from benzoyl hydrogen peroxide, hydrogen peroxide, and mixtures thereof. 10. A composition as described in any of the preceding and subsequent embodiments, wherein the peroxide or the peroxide source is present at a concentration of about 0.0001% to about 0.02%, about 0.0002% to about 0.015%, or about 0.0003% to about 0.013%, or about 0.0004% to about 0.012%, or about 0.0005% to about 0.011%, or about 0.0006% to about 0.01% by weight of the total composition when formulated. 11. A composition as described in any of the preceding and subsequent embodiments, wherein the organic acid buffer is a phosphate-free organic acid having two or more carboxylic acid groups. 12. The composition as described in any of the preceding and subsequent embodiments, wherein the organic acid buffer is selected from phytic acid, mellitic acid, citric acid, and ophthalmically compatible salts thereof. 13. The composition as described in any of the preceding and subsequent embodiments, wherein the organic acid buffer is selected from mellitic acid, citric acid and its salts, and mixtures thereof. 14. The composition as described in any of the preceding and subsequent embodiments, wherein the organic acid buffer is citric acid, its salts, and mixtures thereof. 15. A composition as described in any of the preceding and subsequent embodiments, wherein the organic acid buffer is selected from citric acid, its sodium or potassium salt, and mixtures thereof. 16. A composition as described in any of the preceding and subsequent embodiments, wherein the organic acid buffer is selected from citric acid, its sodium or potassium salt, and mixtures thereof. 17. A composition as described in any of the preceding and subsequent embodiments, wherein the organic acid buffer comprises a salt of a dibasic organic acid anion (e.g., dibasic sodium citric acid monohydrate) and a salt of a monobasic organic acid anion (monobasic sodium citric acid). 18. A composition as described in any of the preceding and subsequent embodiments, 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 sterilization. 19. A composition as described in any of the preceding and subsequent embodiments, wherein the composition is free of boric acid and borate. 20. A composition as described in 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. 21. The composition as described in any of the preceding and subsequent embodiments, wherein when formulated, the organic acid buffer is present in the composition at a concentration 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. 22. The composition as described in any of the preceding and subsequent embodiments, further comprising a reducing agent. 23. The composition 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, manganese metal, aluminum metal, magnesium metal, dithiothreitol, NADH ₂ , ascorbate, ferricyanide, hydroquinone, tyrosine, aldehyde, N-acetylcysteine, butylhydroxymethoxybenzene, dibutylhydroxytoluene, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ophthalmically compatible salts thereof, cellulose disaccharide, glucose (L and D isomers), phenol, polymeric aldehyde, polyacryltyrosine methyl ester co-N,N-dimethylacrylamide, polynoblock (2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2-hydroxyethyl)phenol) co-N,N-dimethylacrylamide, polymeric phenol, or mixtures thereof. 24. A composition as described in any of the preceding and subsequent embodiments, wherein the reducing agent is selected from ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ophthalmically compatible salts thereof, cellulose disaccharides, glucose (L and D isomers), phenol, or a mixture thereof, or comprises EDTA. 25. A composition as described in any of the preceding and subsequent embodiments, wherein the composition further comprises a modifier polymer. 26. A composition as described in any of the preceding and subsequent embodiments, wherein the buffering agent 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. 27. A composition as described in any of the preceding and subsequent embodiments, wherein the buffering agent polymer is selected from polyvinyl pyrrolidone, methyl ethyl cellulose, polyvinyl alcohol, polymethacrylic acid, carboxymethyl cellulose, propylene glycol, 1,3-propylene glycol, polyethylene glycol, and mixtures thereof. 28. A composition as described in any of the preceding and subsequent embodiments, wherein the modifier polymer is methyl ethyl cellulose. 29. A composition as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least one day. 30. A composition as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least two days. 31. A composition as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least three days. 32. The composition of any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least seven days. 33. The composition of any of the preceding and subsequent embodiments, wherein the osmotic pressure is 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. 34. A composition as described in any of the preceding and subsequent embodiments, wherein the composition is free of or substantially free of one or more of boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural gums, glycerol, polyoxyethylene-castor oil, and derivatives thereof. 35. A composition as described in any of the preceding and subsequent embodiments, wherein the composition is free of boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural gums, glycerol, polyoxyethylene-castor oil, and derivatives thereof. 36. A composition as described in any of the preceding and subsequent method embodiments, wherein the composition is manufactured under sterile conditions or is sterilized during and/or after the time period. 37. The composition 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. 38. The composition 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. 39. The composition of 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. 40. A method for inhibiting the growth of microorganisms in a composition during the period from preparation of the composition to sterilization of the composition in a sealed container, comprising the steps of: a. mixing a composition comprising: i. a microorganism growth inhibiting compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. an organic acid compound buffer; and iii. optionally, a reducing agent for neutralizing the microorganism growth inhibiting compound after admixture with the composition; b. storing the composition for the period during which there is inhibition of microorganism growth; c. placing the composition in a container; d. sealing the container of step c; e. sterilizing the container of step d; Optionally, the composition contains no or substantially no boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural rubber, glycerol, polyoxyethylene-castor oil and derivatives thereof. 41. The method as described in any of the above 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 above 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 above method embodiments and any of the following method embodiments, wherein the time period is at least 1 day. 44. The method as described in any of the preceding method embodiments and any of the following method embodiments, wherein the time period is at least 3 days. 45. The method as described in any of the preceding method embodiments and any of the following method embodiments, wherein the time period is at least 7 days. 46. A method for packaging and sterilizing a composition in a sealed container, comprising the following steps: a. mixing a composition comprising: i. a microbial growth inhibiting compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. an organic acid compound buffer; and iii. optionally, a reducing agent for neutralizing the microbial growth inhibiting compound after blending with the composition; b. placing the composition in a container; c. sealing the container of step b; d. sterilizing the container of step c; optionally, wherein the composition does not contain or substantially does not contain one or more of boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural gums, glycerin, polyoxyethylene-castor oil and derivatives thereof. 47. The method of any of the preceding method embodiments and any of the following embodiments, wherein the composition is stored for a period of time during which there is inhibition of microbial growth prior to placing the composition in the container. 48. 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 period of time. 49. The method of any of the preceding method embodiments and any of the following embodiments, wherein the composition is sterilized after the period of time by a sterilization process selected from autoclave sterilization, UV sterilization, and gamma electron beam sterilization. 50. The method as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibiting compound is selected from peroxides, peroxide sources, chlorous acid compounds, salts thereof, and/or mixtures thereof. 51. The method as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibiting compound is a chlorous acid compound. 52. The method as described in claim 49, wherein the chlorous acid compound is a chlorite selected from water-soluble alkali metal chlorites, water-soluble alkaline metal chlorites, and mixtures thereof. 53. 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. 54. The composition of any of the preceding and subsequent embodiments, wherein the chlorous acid compound is present at a concentration of about 0.002% to about 0.200% by weight of the total composition when formulated. 55. The method of any of the preceding and subsequent embodiments, wherein the microbial growth inhibiting compound is a peroxide or a peroxide source. 56. The method of embodiment 53, wherein the peroxide or the peroxide source is selected from benzoyl peroxide, hydrogen peroxide, and mixtures thereof. 57. The method of embodiments 53 and 54, wherein the peroxide or the peroxide source is present at a concentration of about 0.0001% to about 0.02% by weight of the total composition when formulated. 58. The method as described in any of the preceding and subsequent embodiments, wherein the organic acid buffer is selected from mellitic acid, citric acid and its salts, and mixtures thereof. 59. The method as described in any of the preceding and subsequent embodiments, wherein the organic acid buffer is citric acid, its salts, and mixtures thereof. 60. The method as described in any of the preceding and subsequent embodiments, wherein the organic acid buffer is present in the composition at a concentration of about 0.10% to about 0.4% by weight of the total composition. 61. The method as described in any of the preceding and subsequent embodiments, further comprising a reducing agent. 62. The method of embodiment 61, 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, manganese metal, aluminum metal, magnesium metal, dithiothreitol, NADH ₂ , ascorbate, ferricyanide, hydroquinone, tyrosine, aldehyde, N-acetylcysteine, butylhydroxymethoxyphenyl, dibutylhydroxytoluene, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ophthalmically compatible salts thereof, cellulose disaccharides, glucose (L and D isomers), phenol, polymeric aldehydes, polyacryloyltyrosine methyl ester co-N,N-dimethylacrylamide, polynoblock (2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2-hydroxyethyl)phenol) co-N,N-dimethylacrylamide, polymeric phenol, or mixtures thereof. 63. The method as described in any of the preceding and subsequent embodiments, wherein the composition further comprises a buffer polymer. 64. The method of Example 63, wherein the buffering agent 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. 65. The method of Example 63, wherein the buffering agent polymer is selected from polyvinyl pyrrolidone, methyl ethyl cellulose, polyvinyl alcohol, polymethacrylic acid, carboxymethyl cellulose, propylene glycol, 1,3-propylene glycol, polyethylene glycol, and mixtures thereof. 66. The method of Example 63, wherein the buffering agent polymer is methyl ethyl cellulose. 67. The method as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least one day. 68. The method as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least two days. 69. The method as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least three days. 70. The method as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least seven days. 71. The method of any of the preceding and subsequent embodiments, wherein the osmotic pressure is 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. 72. The method as described in any of the preceding and subsequent embodiments, wherein the composition is free of or substantially free of one or more of boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural gums, glycerol, polyoxyethylene-castor oil, and derivatives thereof. 73. The method as described in any of the preceding and subsequent embodiments, wherein the composition is free of boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural gums, glycerol, polyoxyethylene-castor oil, and derivatives thereof. 74. The method as described in any of the preceding and subsequent embodiments, wherein the product is manufactured under aseptic conditions or is sterilized during and/or after the time period. 75. The method of embodiment 72, wherein the product is sterilized after the time period by a sterilization process selected from autoclave sterilization, UV sterilization, and gamma electron beam sterilization. 76. A sealed ophthalmic product comprising: a) a composition for storing contact lenses as an admixture or mixture: i. a microbial growth inhibiting compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. an organic acid compound buffer; iii. optionally, a reducing agent for neutralizing the microbial growth inhibiting compound, with the proviso that after the reducing agent is admixed with the composition, the microbial growth inhibiting compound remains effective to inhibit the growth of the microorganisms in the composition for a period of time; and iv. an ophthalmically acceptable carrier comprising one or more tonicity agents and b) a container comprising a sealed compartment, the sealed compartment containing at least one contact lens in the presence of the composition. 77. The product 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. 78. The product 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. 79. The product of any of the preceding method embodiments and any of the following method embodiments, wherein the microbial growth inhibitory compound is selected from peroxides, peroxide sources, chlorous acid compounds, salts thereof, and/or mixtures thereof. 80. The product of any of the preceding method embodiments and any of the following method embodiments, wherein the microbial growth inhibitory compound is a chlorous acid compound. 81. The product of Example 80, wherein the chlorous acid compound is a chlorite selected from the group consisting of water-soluble alkali metal chlorites, water-soluble alkaline metal chlorites, and mixtures thereof. 82. The product of Example 81, wherein the chlorite is selected from the group consisting of potassium chlorite, sodium chlorite, calcium chlorite, magnesium chlorite, and mixtures thereof. 83. The product of Examples 80 to 82, wherein upon formulation, the chlorous acid compound is present at a concentration of about 0.002% to about 0.200% by weight of the total composition. 84. The product of any of the preceding and following examples, wherein the microbial growth inhibiting compound is a peroxide or a source of a peroxide. 85. The product of Example 84, wherein the peroxide or the peroxide source is selected from benzoyl peroxide, hydrogen peroxide, and mixtures thereof. 86. The product of Examples 84 and 85, wherein the peroxide or the peroxide source is present at a concentration of about 0.0001% to about 0.02% by weight of the total composition. 87. The product of any of the preceding and subsequent examples, wherein the organic acid buffer is selected from mellitic acid, citric acid and its salts, and mixtures thereof. 88. The product of any of the preceding and subsequent examples, wherein the organic acid buffer is citric acid, its salts, and mixtures thereof. 89. The product as described in any of the preceding and subsequent embodiments, wherein the organic acid buffer is present in the composition at a concentration of about 0.10% to about 0.4% by weight of the total composition. 90. The product as described in any of the preceding and subsequent embodiments, further comprising a reducing agent. 91. The product of Example 90, 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, manganese metal, aluminum metal, magnesium metal, dithiothreitol, NADH ₂ , ascorbate, ferricyanide, hydroquinone, tyrosine, aldehyde, N-acetylcysteine, butylhydroxymethoxyphenyl, dibutylhydroxytoluene, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ophthalmically compatible salts thereof, cellulose disaccharides, glucose (L and D isomers), phenol, polymeric aldehyde, polyacryloyl tyrosine methyl ester co-N,N-dimethylacrylamide, polynoblock (2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2-hydroxyethyl)phenol) co-N,N-dimethylacrylamide, polymeric phenol, or a mixture thereof. 92. The product as described in any of the preceding embodiments and any of the following embodiments, wherein the composition further comprises a buffer polymer. 93. The product as described in Example 90, 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; non-cyclic polyamides, and mixtures thereof. 94. The product as described in Example 90, wherein the softener polymer is selected from polyvinyl pyrrolidone, methyl ethyl cellulose, polyvinyl alcohol, polymethacrylic acid, carboxymethyl cellulose, propylene glycol, 1,3-propylene glycol, polyethylene glycol, and mixtures thereof. 95. The product as described in Example 90, wherein the softener polymer is methyl ethyl cellulose. 96. The product as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least one day. 97. The product as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least two days. 98. The product as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least three days. 99. The product as described in any of the preceding and subsequent embodiments, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least seven days. 100. The product 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. 101. The product as described in any of the preceding and subsequent embodiments, wherein the composition does not contain or is substantially free of one or more of boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural gums, glycerol, polyoxyethylene-castor oil, and derivatives thereof. 102. The product as described in any of the preceding and subsequent embodiments, wherein the composition does not contain boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural gums, glycerol, polyoxyethylene-castor oil, and derivatives thereof. 103. The product as described in any of the preceding and subsequent embodiments, wherein the product is manufactured under aseptic conditions or is sterilized during and/or after the time period. 104. The product as described in Example 101, wherein the product is sterilized after the time period by a sterilization process selected from autoclave sterilization, UV sterilization, and gamma electron beam sterilization. 105. The product as described in any of the preceding and subsequent embodiments, wherein the contact lens is a soft contact lens. 106. The product as described in any of the preceding and subsequent embodiments, wherein the contact lens is a conventional hydrogel contact lens or a silicone hydrogel contact lens. 107. The product as described in Example 105 or 106, wherein the contact lens is non-ionic. 108. The product of Example 105, wherein the hydrogel contact lens is a silicone hydrogel contact lens. 109. The product of Example 108, wherein the silicone hydrogel contact lens comprises a polymeric wetting agent. 110. The product of Example 109, wherein the polymeric wetting agent comprises PVP. 111. The product of any of the preceding and subsequent embodiments, wherein the contact lens is a hybrid contact lens. 112. A composition, product, or method as described in any preceding or following embodiment, wherein the reducing agent comprises EDTA at a concentration of about 0.01 to about 0.075 wt % of the total composition when formulated. 113. A composition, product, or method as described in any preceding or following embodiment, wherein the antimicrobial inhibitory compound concentration is reduced by at least about 50%, about 70%, about 80%, or about 90% after autoclaving. 114. A composition, product, or method as described in any following embodiment, wherein the composition inhibits the growth of the microorganism prior to sterilization, and the microorganism growth inhibiting compounds degrade into ophthalmically compatible degradants during and after sterilization. 115. A composition, method, or product as described in any of the preceding embodiments, wherein the microbial growth inhibitory compound is a peroxide, and the molar equivalent of the peroxide to EDTA is greater than 1.1 to 1.5, 1:2 to 1:5, or 1:3 to 1:5, or 1:4.

without

without

Claims (40)

An ophthalmic composition comprising: i. a microbial growth inhibitory compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. an organic acid buffer; iii. optionally, a reducing agent for neutralizing the microbial growth inhibitory compound, with the proviso that after the reducing agent is admixed with the composition, the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganisms in the composition for a period of time; and iv. an ophthalmically acceptable carrier comprising at least one of one or more tonic agents and a contact lens sealed in a container with the composition. The composition of claim 1, wherein the microbial growth inhibitory compound is selected from peroxides, peroxide sources, chlorous acid compounds, salts thereof, and/or mixtures thereof. The composition as described in claim 2, wherein the microbial growth inhibitory compound is a chlorous acid compound. The composition as described in claim 3, wherein the chlorous acid compound is a chlorite selected from water-soluble alkali metal chlorites, water-soluble alkaline metal chlorites, and mixtures thereof. The composition of claim 4, wherein the chlorite is selected from potassium chlorite, sodium chlorite, calcium chlorite, magnesium chlorite, and mixtures thereof. The composition of claim 3, wherein when formulated, the chlorous acid compound is present in a concentration of about 0.002 wt % to about 0.200 wt % of the total composition. The composition as described in claim 2, wherein the microbial growth inhibitory compound is a peroxide or a peroxide source. The composition of claim 7, wherein the peroxide or the peroxide source is selected from urea peroxide, hydrogen peroxide, and mixtures thereof. The composition of claim 8, wherein upon formulation, the peroxide or the peroxide source is present at a concentration of about 0.0001 wt % to about 0.02 wt % of the total composition. The composition as claimed in claim 1, wherein the organic acid buffer is selected from mellitic acid, maleic acid and its salts, and mixtures thereof. The composition as described in claim 10, wherein the organic acid buffer is maleic acid, its salt, and a mixture thereof. The composition of claim 1, wherein the organic acid buffer is present in the composition at a concentration of about 0.10% by weight to about 0.4% by weight of the total composition. The composition as described in claim 1 further comprises a reducing agent. The composition of claim 13, 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, manganese metal, aluminum metal, magnesium metal, dithiothreitol, NADH ₂ , ascorbate, ferricyanide, hydroquinone, tyrosine, aldehyde, N-acetylcysteine, butylhydroxymethoxybenzene, dibutylhydroxytoluene, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ophthalmically compatible salts thereof, cellulose disaccharide, glucose (L and D isomers), phenol, polymeric aldehyde, polyacryltyrosine methyl ester co-N,N-dimethylacrylamide, polynoblock (2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2-hydroxyethyl)phenol) co-N,N-dimethylacrylamide, polymeric phenol, or mixtures thereof. The composition as described in claim 1, wherein the composition further comprises a modifier polymer. The composition as described in claim 15, 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. The composition of claim 16, wherein the modifier polymer is selected from polyvinyl pyrrolidone, methylethyl cellulose, polyvinyl alcohol, polymethacrylic acid, carboxymethyl cellulose, propylene glycol, 1,3-propylene glycol, polyethylene glycol, and mixtures thereof. The composition of claim 17, wherein the softener polymer is methyl ethyl cellulose. The composition of claim 13, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least one day. The composition of claim 19, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least two days. The composition of claim 20, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least three days. The composition of claim 21, wherein the microbial growth inhibitory compound remains effective in inhibiting the growth of the microorganism in the composition for at least seven days. The composition of claim 1, wherein the osmotic pressure is about 205 mOsm/kg to about 450 mOsm/kg. A composition as described in claim 1, wherein the composition does not contain or substantially does not contain one or more of boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural rubber, glycerin, polyoxyethylene castor oil, and derivatives thereof. A composition as described in claim 24, wherein the composition does not contain boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural rubber, glycerin, polyoxyethylene castor oil and its derivatives. A composition as described in claim 1, wherein the product is manufactured under aseptic conditions, or is sterilized during and/or after the time period. The composition of claim 26, wherein the product is sterilized after the time period by a sterilization process selected from autoclave sterilization, UV sterilization, and gamma beam sterilization. A method for inhibiting the growth of microorganisms in a composition during the period from preparation of the composition to sterilization of the composition in a sealed container, comprising the following steps: a.     Mixing a composition comprising: i. A microorganism growth inhibiting compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. An organic acid buffer; and iii. Optionally, a reducing agent for neutralizing the microorganism growth inhibiting compound after blending with the composition; b.     Storing the composition for the period during which inhibition of microorganism growth occurs; c.     Placing the composition in a container; d.     Sealing the container of step c; e.     Sterilizing the container of step d; Optionally, the composition contains no or substantially no one or more of boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural gums, glycerin, polyoxyethylene-castor oil and derivatives thereof. The method of claim 28, wherein the sterilization is selected from autoclave sterilization, UV sterilization, and gamma beam sterilization. The method of claim 29, wherein the sterilization is performed by autoclave sterilization. The method of claim 28, wherein the time period is at least 1 day. The method of claim 31, wherein the time period is at least 3 days. The method of claim 32, wherein the time period is at least 7 days. A method for packaging and sterilizing a composition in a sealed container, comprising the following steps: a.     Mixing a composition comprising: i. A microbial growth inhibitory compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. An organic acid buffer; and iii. Optionally, a reducing agent for neutralizing the microbial growth inhibitory compound after blending with the composition; b.     Placing the composition in a container; c.     Sealing the container of step b; d.     Sterilizing the container of step c. Optionally, the composition contains no or substantially no one or more of boric acid, borates, non-chlorous acid/non-peroxide preservatives, persulfates, carboxyvinyl polymers, natural gums, glycerin, polyoxyethylene-castor oil and derivatives thereof. The method of claim 34, wherein the composition is stored for a period of time during which microbial growth is inhibited prior to placing the composition in the container. A sealed ophthalmic product comprising: a)     a composition for storing contact lenses as an admixture or mixture: i. a microbial growth inhibiting compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. an organic acid buffer; iii. optionally, a reducing agent for neutralizing the microbial growth inhibiting compound, with the proviso that after the reducing agent is admixed with the composition, the microbial growth inhibiting compound remains effective to inhibit the growth of the microorganisms in the composition for a period of time; and iv. an ophthalmically acceptable carrier comprising one or more tonic agents and b)     a container comprising a sealed compartment, the sealed compartment containing at least one contact lens in the presence of the composition. The sealed ophthalmic product of claim 36, 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. A sealed ophthalmic product as described in claim 36 or 37, wherein the reducing agent comprises EDTA, and when the composition is formulated, the EDTA and the microbial growth inhibitory compound are present in a ratio of 1:2 to 1:5 of chlorous acid compound to EDTA in molar equivalents. A sealed ophthalmic product as described in claim 36, wherein the contact lens comprises a silicone hydrogel contact lens. A sealed ophthalmic product as described in claim 36, wherein the composition and the contact lens are hermetically sealed in the container.