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WO2024134382A1 - Compositions pour dispositifs ophtalmologiques - Google Patents

Compositions pour dispositifs ophtalmologiques Download PDF

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Publication number
WO2024134382A1
WO2024134382A1 PCT/IB2023/062629 IB2023062629W WO2024134382A1 WO 2024134382 A1 WO2024134382 A1 WO 2024134382A1 IB 2023062629 W IB2023062629 W IB 2023062629W WO 2024134382 A1 WO2024134382 A1 WO 2024134382A1
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WO
WIPO (PCT)
Prior art keywords
composition
kit
product
chlorous acid
acid compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
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PCT/IB2023/062629
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English (en)
Inventor
Frank Neely
Donald E. Riederer
Justin Scott Jacobs
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Johnson and Johnson Vision Care Inc
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Johnson and Johnson Vision Care Inc
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Publication of WO2024134382A1 publication Critical patent/WO2024134382A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
    • A61L12/02—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using physical phenomena, e.g. electricity, ultrasonics or ultrafiltration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
    • A61L12/08—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
    • A61L12/10—Halogens or compounds thereof

Definitions

  • the present invention relates to ophthalmic device packaging compositions containing chlorous acid compound and a reductant for storing and/or packaging vinylpyrrolidone containing polymeric ophthalmic device in the compositions. Methods of using the compositions of the present invention are also disclosed. Methods of using the compositions of the present invention are also disclosed. BACKGROUND OF THE INVENTION Contact lenses are generally provided to consumers as individually packaged products.
  • the single unit containers which package such contact lenses typically use buffered saline as storage or packaging solutions.
  • packaging solutions should provide for, at least in some cases, a short-term period – e.g., between solution preparation and sterilization of the end-staged packaged product - an environment that does not facilitate the growth of harmful or undesirable microorganisms.
  • undersirable microorganisms include Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Bacillus subtilis and Aspergillus brasiliensis.
  • the packaging solutions should be gentle to the eye since at least some of the packaging solution will, most likely, remain on a contact lens once it is removed from the packaging solution and placed directly on (i.e., by direct application to) the eye.
  • the contact lens (or other ophthalmic device) packaging/storage solution should also be compatible with the materials forming the contact lens (or other ophthalmic device) and the packaging in which the solution and ophthalmic device are stored.
  • a challenge in preparing chlorous acid containing packaging/storage solutions for ophthalmic devices is formulating solutions which do not negatively affect eye comfort or the solution’s compatibility with the polymeric material(s) forming the ophthalmic device.
  • chlorous acid compounds e.g., chlorites
  • long term exposure e.g., through storage or packaging
  • chlorous acid compound in such compositions results in adverse changes in certain contact lens - such as potential increase in the advancing dynamic contact angle of the contact lenses.
  • This is especially the case in contact lenses formed from polymer materials containing polyvinyl pyrrolidone.
  • reductants by incorporating reductants into chlorous acid compound containing contact lens storage/packaging compositions, the concentration of the chlorous acid compounds is reduced in the storage/packaging, reducing the effect of the chlorous acid compound on the advancing dynamic contact angle of the contact lens, as detailed below.
  • the present invention relates to ophthalmic products or kits, comprising: a) a composition comprising an admixture or mixture of: i. a chlorous acid compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. a buffer compound; iii. a reductant for neutralizing the chlorous acid compound, provided that, after the reductant’s admixture to the composition, the chlorous acid compound remains effective to inhibit the growth of microorganisms in the composition for a period of time; and iv. an ophthalmologically acceptable carrier 2 Docket No.
  • the present invention also relates methods of reducing or preventing the reaction between chlorous acid compounds and a high molecular weight polyvinylpyrrolidone polymer containing polymeric ophthalmic device, comprising the steps of: a. mixing a composition comprising: i. a chlorous acid compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. a buffer compound; and iii.
  • a reductant for neutralizing the chlorous acid compound provided that, after the reductant’s admixture to the composition, the chlorous acid compound remains effective to inhibit the growth of microorganisms in the composition for a period of time; b. placing the composition in a container with the high molecular weight polyvinylpyrrolidone polymer containing polymeric ophthalmic device.
  • the present invention also relates to methods of making and using the disclosed compositions.
  • FIGURES Figures 1-3 are graphs showing the inhibition of growth of the fungi Candida albicans and Aspergillus brasiliensis and the bacteria Bacillus subtilis – subspecies spizizenii, respectively, when each microorganism was spiked into the compositions of Table 9 comprising a microbial growth inhibiting compound at various concentrations.
  • 3 Docket No. VTN6139WOPCT1 DETAILED DESCRIPTION OF THE INVENTION As indicated above, the present invention relates to compositions comprising one or more chlorous acid compounds and one or more phosphate compound as an ophthalmologically acceptable carrier.
  • the compositions may be useful for storing or as a packaging solution for ophthalmic devices.
  • the present invention provides ophthalmic solutions comprising a transient microbial growth inhibiting compound that is bacteriostatic from the formulation of the composition through heat sterilization, such as autoclaving, but substantially or entirely neutralized during sterilization providing a non-preserved ophthalmic solution after sterilization.
  • the present invention further provided hermetically sealed contact lens packages comprising a contact lens and an ophthalmic solution of the present invention.
  • the compositions may be useful for direct application to the eyes for an eye care benefit such as relieving eye discomfort.
  • the compositions and methods of the present invention can comprise, consist of, or consist essentially of the steps, essential elements and limitations of the invention described herein, as well any of the additional or optional ingredients, components, or limitations described herein.
  • VTN6139WOPCT1 The term “pharmaceutically acceptable”, as used herein, means biologically tolerable, and otherwise biologically suitable for application or exposure to the eyes and surrounding tissues of the eyes without undue adverse effects such as toxicity, incompatibility, irritation, allergic response and the like.
  • ophthalmically acceptable and/or compatible means the composition or component(s) is pharmaceutically acceptable and is not or substantially is not, detrimental, negative, or harmful to any part of the eye (or surrounding tissues) or the other ingredients (including actives) in the composition itself.
  • water soluble means that the components, either alone or in combination with other components, do not form precipitates or gel particles visible to the human eye at the concentrations selected and across the temperatures and pH regimes common for manufacturing, sterilizing and storing the ophthalmic solution or ophthalmic product.
  • cationic preservatives means net positively charged compounds having antimicrobial properties and include, without limitation thereto, one or more of 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 are positively charged surface active agents (i.e., cationic surfactants ) which act to compromise the cell walls and membranes, and examples include BUSAN 77, ONAMERM, MIRAPOLA15, IONENES A, POLYQUATERNIUM 11, POLYQUATERNIUM 7, BRADOSOL, AND POLYQUAT D-17- 1742.
  • the term “lidstock”, as used herein means, a flexible film or sheet which is heat sealed to the concave side of the plastic blister packaging to form a sealed cavity. Lidstock is generally multilayered and comprises a support layer and a peelable seal layer. The lidstock may further comprise additional layers including print layers, lamination layers, foil layers and combinations thereof and the like.
  • advancing dynamic contact angle means the angle measured where the test liquid-air interface meets the surface of a contact lens as the lens is raised and lowered 5 Docket No. VTN6139WOPCT1 relative to the surface of a test solution and is determined by lowering the test article (e.g., a contact lens) into a test solution.
  • the advancing dynamic contact angles provide information on the wettability, topography, and homogeneity of the surface and are influenced by experimental variables, such as the speed of movement of the article within the test solution.
  • the term “effective to inhibit”, as used herein means an amount which causes an inhibition in the growth of microorganisms.
  • the term “inhibition of in the growth of microorganisms” in the composition occurs where, and means that, there is a less than a 0.5 log, or less than 0.3, 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 date of preparation of the compositions of the present invention.
  • hydrophilic monomers with at least one hydroxyl group means an ethylenically unsaturated compound comprising at least one hydroxyl alkyl group selected from C2-C4 mono or dihydroxy substituted alkyl, and poly(ethylene glycol) having 1-10 repeating units; or is selected from 2-hydroxyethyl, 2,3-dihydroxypropyl, or 2- hydroxypropyl, and combinations thereof.
  • hydroxyalkyl monomers examples include 2-hydroxyethyl (meth)acrylate, 3- hydroxypropyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2,3-dihydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, 1-hydroxypropyl 2-(meth)acrylate, 2-hydroxy-2-methyl-propyl (meth)acrylate, 3-hydroxy-2,2-dimethyl-propyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, 2-hydroxyethyl (meth)acrylamide, N-(2- hydroxypropyl) (meth)acrylamide, N,N-bis(2-hydroxyethyl) (meth)acrylamide, N,N-bis(2- hydroxypropyl) (meth)acrylamide, N-(3-hydroxypropyl) (meth)acrylamide, 2,3-dihydroxypropyl (meth)acrylamide, glyce
  • the hydroxyalkyl monomer may also be selected from the group consisting of 2- hydroxyethyl methacrylate, glycerol methacrylate, 2-hydroxypropyl methacrylate, hydroxybutyl methacrylate, 3-hydroxy-2,2-dimethyl-propyl methacrylate, and mixtures thereof. 6 Docket No. VTN6139WOPCT1
  • the hydroxyalkyl monomer may comprise 2-hydroxyethyl methacrylate, 3-hydroxy-2,2- dimethyl-propyl methacrylate, hydroxybutyl methacrylate or glycerol methacrylate.
  • hydrophilic vinyl-containing monomers means ethylenically unsaturated compounds comprising a vinyl reactive group such as hydrophilic N-vinyl lactam and N-vinyl amide monomers including: N-vinyl pyrrolidone (NVP), N-vinyl-2-piperidone, N-vinyl-2- caprolactam, N-vinyl-3-methyl-2-caprolactam, N-vinyl-3-methyl-2-piperidone, N-vinyl-4- methyl-2-piperidone, N-vinyl-4-methyl-2-caprolactam, N-vinyl-3-ethyl-2- pyrrolidone, N-vinyl- 4,5-dimethyl-2-pyrrolidone, N-vinyl acetamide (NVA), N-vinyl-N-methylacetamide (VMA), N- vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl
  • hydrophilic O-vinyl carbamates and O-vinyl carbonates monomers mean ethylenically unsaturated compounds including O-vinyl carbamate or O-vinyl carbonates groups including N-2-hydroxyethyl vinyl carbamate and N-carboxy-ß-alanine N-vinyl ester.
  • hydrophilic vinyl carbonate or vinyl carbamate monomers are disclosed in U.S. Patent No.5,070,215, and the hydrophilic oxazolone monomers are disclosed in U.S. Patent No. 4,910,277.
  • vinyl carbamates and carbonates include: N-2-hydroxyethyl vinyl carbamate, N-carboxy-ß-alanine N-vinyl ester, other hydrophilic vinyl monomers, including vinylimidazole, ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, 2-ethyl oxazoline, vinyl acetate, acrylonitrile, and mixtures thereof.
  • EGVE ethylene glycol vinyl ether
  • DEGVE di(ethylene glycol) vinyl ether
  • allyl alcohol 2-ethyl oxazoline
  • vinyl acetate acrylonitrile
  • acrylonitrile and mixtures thereof.
  • (meth)acrylamide monomers means hydrophilic ethylenically unsaturated compounds comprising a (meth)acrylamide group.
  • ophthalmic device refers to an object that resides in or on the eye. These devices can provide optical correction, cosmetic enhancement, light blocking (including UV, HEV, visible light and combinations thereof) glare reduction, therapeutic effect, including preventing the progression of myopia, wound healing, delivery of drugs or neutraceuticals, diagnostic evaluation or monitoring, or any combination thereof.
  • Ophthalmic devices include (selected from or selected from the group consisting of), but are not limited to, soft contact lenses, intraocular lenses, overlay lenses, ocular inserts, punctual plugs, and optical inserts.
  • the ophthalmic device may be a contact lens.
  • Contact lenses (or “contacts”) are placed directly on the surface of the eyes (e.g., placed on the film of tears that covers the surface of the eyes).
  • Contact lenses include soft contact lens (e.g., conventional or silicone hydrogel), rigid contact lenses or hybrid contact lenses (e.g., with soft skirt or shell).
  • Soft contact lenses may be formed from hydrogels. Contact lenses useful with the compositions can be manufactured employing various conventional techniques, to yield a shaped article having the desired posterior and anterior lens surfaces.
  • Hydrogels are polymeric networks that swell in water or aqueous solutions, typically absorbing at least 10 weight percent water.
  • Silicone hydrogels are hydrogels that are made from at least one silicone-containing component with at least one hydrophilic component. Hydrophilic components may also include non-reactive polymers.
  • Conventional hydrogels refer to polymeric networks made from components without any siloxy, siloxane or carbosiloxane groups.
  • Conventional hydrogels are prepared from reactive mixtures comprising hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate (“HEMA”), N-vinyl pyrrolidone (“NVP”), N, N-dimethylacrylamide (“DMA”) or vinyl acetate.
  • HEMA 2-hydroxyethyl methacrylate
  • NDP N-vinyl pyrrolidone
  • DMA N-dimethylacrylamide
  • 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 conventional hydrogels.
  • VTN6139WOPCT1 hydrogels include, but are not limited to, etafilcon, genfilcon, hilafilcon, lenefilcon, nelficlon, nesofilcon, ocufilcon, omafilcon, polymacon, and vifilcon, including all of their variants.
  • Sililicone hydrogels refer to polymeric networks made from at least one hydrophilic component and at least one silicone-containing component.
  • hydrophilic components examples include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N-vinyl amides, N-vinyl imides, N- vinyl ureas, O-vinyl carbamates, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof.
  • Non-limiting examples of hydrophilic components include N,N-dimethyl acrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), N-vinyl pyrrolidone (NVP), N-vinyl acetamide (NVA), N-vinyl-N-methylacetamide (VMA), and mixtures thereof. Silicone- containing components are well known and have been extensively described in the patent literature.
  • the silicone-containing component may comprise at least one polymerizable group (e.g., a (meth)acrylate, a styryl, a vinyl ether, a (meth)acrylamide, an N- vinyl lactam, an N-vinylamide, an O-vinylcarbamate, an O-vinylcarbonate, a vinyl group, or mixtures of the foregoing), at least one siloxane group, and one or more linking groups (which may be a bond) connecting the polymerizable group(s) to the siloxane group(s).
  • a polymerizable group e.g., a (meth)acrylate, a styryl, a vinyl ether, a (meth)acrylamide, an N- vinyl lactam, an N-vinylamide, an O-vinylcarbamate, an O-vinylcarbonate, a vinyl group, or mixtures of the foregoing
  • siloxane group e.g.,
  • the silicone- containing components may, for instance, contain from 1 to 220 siloxane repeat units from 3 to 100, from 3 to 40, or from 3 to 20 siloxane repeat units.
  • the silicone-containing component may also contain at least one fluorine atom.
  • the silicone hydrogel formulation may also include a polymeric wetting agent, which are non-polymerizable and become entrapped in the silicone hydrogel upon polymerization forming a semi-interpenetrating network.
  • the polymeric wetting agent may be polymerizable, for example as polyamide macromers or prepolymers, and in this case, are covalently incorporated into the silicone hydrogels. Mixtures of polymerizable and non-polymerizable polyamides may also be used.
  • Suitable wetting agents include cyclic and linear polyamides, and specific examples include polyvinylpyrrolidone (PVP), polyvinylmethyacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof.
  • PVP polyvinylpyrrolidone
  • PVMA polyvinylmethyacetamide
  • PDMA polydimethylacrylamide
  • PNVA polyvinylacetamide
  • the polymeric wetting agent may be PVP, a mixture of PVP (e.g., PVP K90) and PVMA (e.g., having a Mw of about 570 KDa).
  • the polyamides 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 to about 2,000,000 daltons; between about 300,000 to 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 formulations may also contain additional components such as, but not limited to, diluents, initiators, light absorbing compounds, including UV, visible light absorbers, photochromic compounds, pharmaceuticals, nutraceuticals, antimicrobial substances, tints, pigments, copolymerizable dyes, nonpolymerizable dyes, release agents, and combinations thereof.
  • photochromic compounds tints or dyes are preferably stable in the presence of the chlorous acid compound at the selected chlorous acid compound concentrations.
  • An example of a UV absorber which is stable in the presence of chlorous acid compound is Norbloc.
  • Silicone hydrogel lenses may contain a coating, and the coating may be the same or different material from the substrate.
  • silicone hydrogels examples include acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon, including all of their variants, as well as silicone hydrogels as prepared in US 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, 7,249,848, 7,553,880, 7,666,921, 7,786,185, 7,956,131, 8,022,158, 8,27
  • An "interpenetrating polymeric network” comprises two or more networks which are at least partially interlaced on the molecular scale but not covalently bonded to each other and which cannot be separated without braking chemical bonds.
  • a "semi-interpenetrating polymeric network” comprises one or more networks and one or more polymers characterized by some mixing on the molecular level between at least one network and at least one polymer. A mixture of different polymers is a "polymer blend.”
  • a semi-interpenetrating network is technically a polymer blend, but in some cases, the polymers are so entangled that they cannot be readily removed.
  • compositions of the present invention at the time of mixing, comprise one or more chlorous acid compounds or salts thereof.
  • the chlorous acid compounds and salts thereof are ophthalmically compatible with the eyes and surrounding tissue and are compatible with the ingredients in compositions of the present invention. Upon degradation (e.g., sterilization or storage conditions), the chlorous acid compounds and salts degrade to ophthalmically compatible degradants.
  • the degradants of chlorous acid compounds and salts thereof do not interact with the contact lens stored or packaged therewith nor the storage/packaging containers (including the lidstock).
  • the chlorous acid compound may be an anhydride or a hydrate.
  • the salts of chlorous acid may be a mono or a double salt.
  • chlorous acid compounds suitable for use in the compositions or methods of the present invention include (selected from or selected from the group consisting of), but are not limited to, chlorous acid; an alkali metal salt of chlorous acid including lithium chlorite, sodium chlorite, sodium chlorite trihydrate, or potassium chlorite and the like; an alkali earth metal salt of chlorous acid including magnesium chlorite, magnesium chlorite trihydrate, calcium chlorite, calcium chlorite trihydrate, barium chlorite, or barium chlorite dihydrate and 11 Docket No.
  • VTN6139WOPCT1 the like; an earth metal salt of chlorous acid such as aluminum chlorite; a zinc-family salt of chlorous acid such as zinc chlorite dihydrate; a transitional metal salt of chlorous acid such as copper chlorite (II), copper chlorite (III), silver chlorite, nickel chlorite dihydrate or manganese chlorite; ammonium chlorite; a quaternary ammonium salt of chlorous acid such as tetramethylammonium chlorite; a quaternary phosphonium salt of chlorous acid such as (2,4- dinitrophenyl) triethylphosphonium chlorite; an amine salt of chlorous acid such as a methyl amine salt of chlorous acid, a tripropyl amine salt of chlorous acid, a hydrazine salt of chlorous acid, a pyridine salt of chlorous acid, a 4-methyl pyridine salt of chlorous acid, a 2,4-dimethyl pyridine salt of chlorous
  • compositions of the present invention are sources of chlorous acid compounds such as stabilized oxychloro complex, (Purite, Bio-Cide International Inc., Ok, USA) and/or stabilized chlorite peroxide (SOC - Oxyd Tubilux.). Mixtures of any the above-mentioned chlorous acid compounds or sources of chlorous acid compounds may also be used.
  • sources of chlorous acid compounds such as stabilized oxychloro complex, (Purite, Bio-Cide International Inc., Ok, USA) and/or stabilized chlorite peroxide (SOC - Oxyd Tubilux.).
  • Salts of chlorous acid compounds which are particularly preferred for use herein are ophthalmically compatible salts including, but not limited to, lithium chlorite, sodium chlorite, sodium chlorite trihydrate, or potassium chlorite and the like; an alkali earth metal salt of chlorous acid including magnesium chlorite, magnesium chlorite trihydrate, calcium chlorite, calcium chlorite trihydrate, aluminum chlorite, ammonium chlorite; a quaternary ammonium salt of chlorous acid such as tetramethylammonium chlorite; a quaternary phosphonium salt of chlorous acid such as (2,4-dinitrophenyl) triethylphosphonium chlorite; an amine salt of chlorous acid such as a methyl amine salt of chlorous acid, a tripropyl amine salt of chlorous acid, a pyridine salt of chlorous acid, a 4-methyl pyridine salt of chlorous acid, a 2,4-dimethyl pyridine salt of chlorous acid or a quino
  • Chlorite compounds suitable for use in the present invention include (selected from or selected from the group consisting of), but are not limited to, water soluble alkali metal chlorites, water soluble alkaline metal chlorites and mixtures thereof.
  • Specific examples of chlorite compounds include (selected from or selected from the group 12 Docket No. VTN6139WOPCT1 consisting of) potassium chlorite, sodium chlorite, calcium chlorite, magnesium chlorite and mixtures thereof.
  • the chlorite compound may comprise sodium chlorite.
  • the chlorous acid compound is incorporated into the compositions of the present invention to provide bacteriostatic properties for inhibiting microbial growth in the compositions.
  • the bacteriostatic properties for inhibiting microbial growth may occur for and are in effect during a period of time which may be from the preparation or manufacture of the compositions of the present invention up to the time of performing at least one sterilization method on the composition, which may be sterilization of the composition in a sealed package with at least one contact lens as described below. In practice, this time period may be as long as two weeks, during which the solution is stored in a sealed container at ambient temperature.
  • the chlorous acid compound concentration is substantially or entirely neutralized.
  • the concentration of the microbial growth inhibiting compound may be reduced by at least about 50%, about 70%, about 80%, about 90% or 100%.
  • concentrations for the chlorous acid compound include concentrations from 0.0020% (or about 0.0020%) to 0.2000% (or about 0.2000%), or from 0.0020% (or about 0.0020%) to 0.1000% (or about 0.1000%), or from 0.0050% (or about 0.0050%) to 0.1000% (or about 0.1000%), or from 0.0075% (or about 0.0075%) to 0.1000% (or about 0.1000%), or from 0.0080% (or about 0.0080%) to 0.0500% (or about 0.0500%), or from 0.0090% (or about 0.0090%) to 0.0200%.
  • the chlorous acid compound provides chlorite anion concentrations of from 0.0015% (or about 0.0015%) to 0.1500% (or about 0.1500%), or from 0.0015% (or about 0.0015%) to 0.0750% (or about 0.0750%), or from 0.0037% (or about 0.0037%) to 0.0750% (or about 0.0750%), or from 0.0056% (or about 0.0056%) to 0.0750% (or about 0.0750%), or from 0.0060% (or about 0.0060%) to 0.0370% (or about 0.0370%), or from 0.0067% (or about 13 Docket No.
  • VTN6139WOPCT1 0.0067%) to 0.0150%. (or about 0.0150%), or from 0.0071% (or about 0.0071%) to 0.0110%. (or about 0.0110%), based on the total weight of the composition upon formulation.
  • period of time as used in association with the bacteriostatic properties of the chlorous acid compound, it is meant up to or at least one day, two days, three days, four days, five days, six days, seven days, eight days, ten days, twelve days, fourteen days, fifteen days, 18 days, 20 days, 21 days or 22 days from date of preparation of the compositions of the present invention.
  • the period of time may be up two weeks, during which the solution is stored in a sealed container at ambient temperature.
  • the compositions of the present invention comprise a buffer compound.
  • Suitable buffer compounds include, but are not limited to, phosphate compounds, organic buffers and mixtures thereof.
  • phosphate or “phosphate compound” (used interchangeably herein) shall refer to phosphoric acid, salts of phosphoric acid and other pharmaceutically acceptable phosphates (e.g., inorganic or organic pharmaceutically acceptable salts), or combinations thereof.
  • examples of phosphate compounds useful in the compositions are those selected from pharmaceutically acceptable organic or inorganic phosphate salts of alkali and/or alkaline earth metals. Suitable phosphates may be incorporated as one or more monobasic phosphates, dibasic phosphates and the like.
  • the phosphate compound may include one or more of organic phosphates such as phytic acid (or salts thereof such as their potassium or sodium salts), or one or more inorganic phosphates such as sodium dibasic phosphate (Na2HPO4), sodium monobasic phosphate (NaH2PO4), and potassium monobasic phosphate (KH2PO4) or mixtures of any above the above-mentioned phosphate compounds.
  • organic phosphates such as phytic acid (or salts thereof such as their potassium or sodium salts)
  • inorganic phosphates such as sodium dibasic phosphate (Na2HPO4), sodium monobasic phosphate (NaH2PO4), and potassium monobasic phosphate (KH2PO4) or mixtures of any above the above-mentioned phosphate compounds.
  • the inorganic phosphate compound can be present in the compositions at concentrations of from 0.3% (or about 0.3%) w/v to 0.9% (or about 0.9%) w/v, or from 0.4% (or about 0.4%) w/v to 0.85% (or about 0.85%) w/v, or from 0.5% (or about 0.5%) w/v to 0.8% (or about 0.8%) w/v or from 0.6% (or about 0.6%) w/v to 0.75% (or about 0.75%) w/v of the total composition upon formulation. 14 Docket No.
  • the organic phosphate compound can be present in the compositions at concentrations of from 0.05% (or about 0.05%) w/v to 1.0% (or about 1.0%) w/v, or from 0.10% (or about 0.10%) w/v to 0.50% (or about 0.50%) w/v, or from 0.15% (or about 0.15%) w/v to 0.30% (or about 0.30%) w/v or from 0.17% (or about 0.17%) w/v to 0.25% (or about 0.25%) w/v of the total composition upon formulation.
  • the concentration of the phosphate compound may be at least 1.5 (or about 1.5), or at least 2.0 (or about 2.0), and or at least 2.5 (or about 2.5), but up to 4, or up to 3, times the amount of the borate compound on a weight basis.
  • organic acid buffer means a non-phosphate containing organic acid having two or more carboxylic acid groups.
  • the organic acid also has a buffer capacity over the range of pH values consistent with ophthalmic compositions (e.g., eye drops and eye washes) and packaging solutions for eye care devices (e.g., contact lens) and may buffer the compositions of the present invention to a pH of from about 6.0 to a pH of about 8.0, or a pH of from about 6.5 to a pH of about 8.0, or a pH of from about 6.5 to a pH of about 7.5, or a pH of about 7.0 to a pH of about 7.5, or a pH of greater than 7.2 (or about 7.2) to a pH of 7.5 (or about 7.5).
  • ophthalmic compositions e.g., eye drops and eye washes
  • packaging solutions for eye care devices e.g., contact lens
  • Preferred organic acid buffers for use in the compositions of the present invention have a pK value in the range of 6 (or about 6) to 8 (or about 8), or 6 (or about 6) to 7 (or about 7).
  • Also useful herein is phytic acid (or salts thereof such as their potassium or sodium salts).
  • Phytic acid has 12 replaceable protons, whereby six are strongly acidic (pKa approximately 1.5), three are weaker acidic (pKa between 5.7 and 7.6), and three are very weakly acidic (pKa >10.0) (Costello, A. J. R.; Glonek, T.; Myers, T. C., 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. 15 Docket No.
  • the organic acid buffer may be selected from phytic acid, mellitic acid, maleic acid and ophthalmically compatible salts thereof (such the sodium or potassium salts of the organic acids) and mixtures thereof.
  • the organic acid buffer may be selected from maleic acid, its sodium or potassium salts and mixtures thereof.
  • the organic acid buffer may be selected from mellitic acid, its sodium or potassium salts and mixtures thereof.
  • the organic acid buffer content of the present compositions is in the range of about 0.10% to about 0.4%, or about 0.18% to about 0.30%, or about 0.20% to about 0.28%, by weight the total weight of the composition upon formulation.
  • the organic acid buffer is preferably a combination of salts of the dibasic organic acid anion (e.g., dibasic sodium maleate monohydrate) and salts of the monobasic organic acid anion (monobasic sodium maleate) where the concentration, prior to sterilization of the composition, of the dibasic organic acid anion is from about 0.1% to about 0.3% and the concentration, prior to sterilization of the composition, of the monobasic organic acid anion is from 0.005% to about 0.002%, by weight of the composition, when present as the metal (e.g., sodium) monohydrate in the case of the dibasic organic acid.
  • the concentration, prior to sterilization of the composition of the dibasic organic acid anion is from about 0.1% to about 0.3%
  • the concentration, prior to sterilization of the composition, of the monobasic organic acid anion is from 0.005% to about 0.002%, by weight of the composition, when present as the metal (e.g., sodium) monohydrate in the case of the dibasic organic acid.
  • compositions of the present invention optionally, comprise a reductant for quenching (or reducing) the chlorous acid compound so as to neutralize it from the composition.
  • reductants include, but are not limited to, the following salts or (metal ions thereof): iron (II), bisulfite such as sodium metabisulfite, tin metal, formate, phosphite, hypophosphite, sulfur, thiosulfate (such as sodium thiosulfate), zinc metal, dithionite, manganese metal, aluminum metal, magnesium metal, dithiothreitol, NADH2, ascorbate, ferricyanide, hydroquinone, tyrosine, aldehydes (such as cinnamic aldehyde), N-acetylcysteine, butylated hydroxyanisole, butylated hydroxytoluene, ethylenediaminetetraacetic acid (EDTA), diethylenetriamine pen
  • VTN6139WOPCT1 reducing carbohydrates capable of reacting with oxidants (such as L isomers of glucose, fructose, ribose, xylose, galactose, lactose, maltose and the like and mixtures thereof), phenols (such as butylated hydroxyanisole, butylated hydroxytoluene, tertbutylhydroquinone and propyl gallate), polymeric aldehydes (such as polyvinylpyrrolidone (PVP) K-60 and K-90) and polymeric phenols such as lignans and copolymers of tyrosine acrylamide and N, N-dimethyl acrylamide (such as poly methyl acryloyltyrosinate co N, N-dimethylacrylamide), copolymers of NORBLOC and N,N-dimethyl acrylamide (such as Poly Norbloc (2-(2H-benzo[d][1,2,3]triazol- 2-
  • the reductant may comprise from 15:85 or 10:90 polymethyl acryloyltyrosinate co- N,N- dimethylacrylamide, L-glucose, 4-nitrophenol, vanillin, hydroquinone, ethylenediaminetetraacetic acid (EDTA), Cellobiose, PVP and mixtures thereof.
  • the reductant may comprise 15:85 or 10:90 polymethyl acryloyltyrosinate co N,N- dimethylacrylamide, L-glucose, ethylenediaminetetraacetic acid (EDTA), Cellobiose, PVP and mixtures thereof.
  • the reductant may comprise EDTA.
  • the EDTA may be used in a molar excess compared to the chlorous acid compound.
  • the EDTA may be used in concentrations of about 0.01 to about 0.075 wt% EDTA, or about 0.05 to about 0.075 wt% EDTA.
  • the reductant comprises PVP
  • the PVP reductant has a weight average molecular weight of greater than 100,000 (or about 100,000) Daltons, or greater than 100,000 (or about 100,000) Daltons to 1,500,000 (or about 1,500,000) Daltons, or from 300,000 (or about 300,00) Daltons to 1,000,000 (or about 1,000,000) Daltons, or from 300,000 (or, about 300, 000) Daltons to 750,000 (or about 750, 000) Daltons, or from 320,000 (or about 320,000) Daltons to 500,000 (or about 500,000) Daltons.
  • the molecular weight of PVP reductant of the invention can be also expressed by the K-value, based on kinematic viscosity measurements, as described in N-Vinyl Amide Polymers by E.S. Barabas in Encyclopedia of Polymer Science and Engineering, Second edition, Vol 17, pgs.198-257, John Wiley & Sons Inc. When expressed in this manner, PVP reductants having K-values of 46-100 are preferred. 17 Docket No. VTN6139WOPCT1 Preferred reductants for use herein include PVP, ethylenediaminetetraacetic acid, polymeric phenols, reducing carbohydrates and mixtures thereof. Preferably the reductant is a PVP.
  • the PVP used as reductant is PVP K-60, PVP K-90, PVP-120 or mixtures thereof.
  • the PVP used as reductant is PVP K-60, PVP K-90 or mixtures thereof.
  • the reductant and the chlorous acid compound may be present such that the ratio in molar equivalents upon formulation of the chlorous acid compound to the reductant is from 1:1 to 1:20, or 1:1 to 1:15, preferably 1:1 to 1:10, or 1:1 to 1:5, or greater than 1:1 to 1:1.5.
  • the reductant is EDTA
  • the molar equivalents of chlorous acid compound to EDTA may be 1:2 to 1:5, or 1:3 to 1:5 or 1:4.
  • the molar equivalents 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.
  • the composition comprising the chlorous acid compound and reductant remains colorless or lightly colored, even after autoclaving, which can be determined visually or measured via known methods such as APHA color technique.
  • the solution after autoclaving may have a APHA color value of less than about 180, or less than about 40.
  • the products of the present invention comprise a hydrogel or silicone hydrogel ophthalmic device comprising one or more high molecular weight vinylpyrrolidone polymers, such as those disclosed in US6,367,929, WO03/22321, WO03/22322, US10,935,695, US8,053,539, US10,371,865, US10,370,476 US7,431,152, US7,841,716 and US7,262,232.
  • “high molecular weight” means weight average molecular weight of no less than about 100,000 Daltons.
  • high molecular weight preferably refers to a weight average molecular weight of greater than about 150,000 Daltons; between about 150,000 Daltons 18 Docket No. VTN6139WOPCT1 to about 2,000,000 Daltons, preferably between about 300,000 Daltons to about 1,800,000 Daltons, or about 500,000 to about 1,500,000 Daltons.
  • the high molecular weight vinylpyrrolidone polymer may be poly-N-vinylpyrrolidone (PVP) homopolymer or a copolymer, including graft copolymers of PVP.
  • PVP copolymers may comprise 50 mol%, 30 mol% or 20 mol% of additional repeating units (or comonomers) selected from hydroxyalkyl(meth)acrylates, alkyl(meth)acrylates or other hydrophilic monomers and siloxane substituted acrylates or methacrylates.
  • Suitable comonomers include hydrophilic monomers with at least one hydroxyl group (hydroxyalkyl monomer), hydrophilic vinyl-containing monomers, hydrophilic O-vinyl carbamates and O-vinyl carbonates monomers, (meth)acrylamide monomers and combinations thereof.
  • additional monomers which may be used to form PVP copolymers include 2-hydroxyethylmethacrylate, vinyl acetate, acrylonitrile, hydroxypropyl methacrylate, 2- hydroxyethyl acrylate, methyl methacrylate and hydroxybutyl methacrylate, glycerol monomethacrylate, polyethylene glycols, and the like and mixtures thereof. Ionic monomers may also be included.
  • ionic monomers include acrylic acid, methacrylic acid, 2- methacryloyloxyethyl phosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1- sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS), methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).
  • DMVBAPS 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1- sulfonate
  • the PVP homopolymers and vinylpyrrolidone copolymers may also comprise N- vinylpyrrolidone substituted with hydrophilic substituents such as phosphoryl choline.
  • Further examples of high molecular weight vinylpyrrolidone polymers include, but are not limited to, poly-N-vinylpyrrolidone, poly-N-vinyl-3-ethyl-2-pyrrolidone, and poly-N-vinyl-4,5-dimethyl-2- pyrrolidone and/or mixtures thereof.
  • the high molecular weight vinylpyrrolidone polymer When the high molecular weight vinylpyrrolidone polymer is added in the hydrogel or silicone hydrogel reactive mixture it may be included in a concentration of from about 1% to about 20%, from about 2% to about 15%, from about 2% to about 12%, from about 4% to about 15%, or about 4 to about 12% based on total composition weight excluding solvent, such as, for example as disclosed in US6,367,929, US6,822,016, US7,052,131, US7,666,921, US7,691,916, 19 Docket No. VTN6139WOPCT1 US8,450,387, US2021/0163650, and US10,370,476.
  • solvent such as, for example as disclosed in US6,367,929, US6,822,016, US7,052,131, US7,666,921, US7,691,916, 19 Docket No. VTN6139WOPCT1 US8,450,387, US2021/0163650,
  • Formulations cured thermally may comprise lower amounts of PVP (for example about 5% or less), but still display the desired properties, such as disclosed in US2020/0399429.
  • PVP for example about 5% or less
  • Formulations cured thermally may comprise lower amounts of PVP (for example about 5% or less), but still display the desired properties, such as disclosed in US2020/0399429.
  • the high molecular weight vinylpyrrolidone polymer when the high molecular weight vinylpyrrolidone polymer is added to the silicone hydrogel reactive mixture, the high molecular weight vinylpyrrolidone polymer functions as an internal wetting agent.
  • the high molecular weight vinylpyrrolidone polymer of the present invention may be non-polymerizable, and in this case, is incorporated into the silicone hydrogels as a semi-interpenetrating network.
  • the high molecular weight vinylpyrrolidone polymer is entrapped or physically retained within the silicone hydrogel.
  • the high molecular weight vinylpyrrolidone polymer may be polymerizable, for example as high molecular weight vinylpyrrolidone macromers or prepolymers, and in this case, are covalently incorporated into the silicone hydrogels. Mixtures of polymerizable and non-polymerizable high molecular weight vinylpyrrolidone polymer may also be used. Also useful are ophthalmic device (e.g., contact lens) polymers where vinylpyrrolidone monomer is included in the contact lens reactive mixture and polymerizes mostly at the end of polymerization to form relatively long chains of vinylpyrrolidone. Examples of such silicone hydrogels include somofilcon, stenfilcon and samfilcon.
  • the vinylpyrrolidone may be included in a concentration of from about 20%, about 25%, about 30%, about 25 to about 75%, about 20% to about 70%, about 20% to about 60%, about 30 to about 70 %, about 30 to about 60% or about 37 to about 60% vinylpyrrolidone, based on total composition weight excluding solvent.
  • Examples include US2010/0048847, US8,937,110, US7,915,323, US7,994,356, US8,420,711, US8,827,447, and US9,039,174.
  • the high molecular weight vinylpyrrolidone polymer may also be incorporated into the packaging composition and become entrapped in the finished contact lens, as disclosed in US9,395,559.
  • the high molecular weight vinylpyrrolidone polymer is added 20 Docket No. VTN6139WOPCT1 to the packaging solution in a concentration of from about 100 ppm to about 3,000ppm, about 200 ppm to about 1000 ppm or less than 500ppm, such as disclosed in US9,395,559.
  • the present inventors have discovered that the advancing dynamic contact angle of contact lenses comprising polymeric material comprising vinylpyrrolidone polymers may increase over time in the presence of chlorous acid compounds to beyond an angle of greater than 100°.
  • the high molecular weight vinylpyrrolidone polymers in the polymeric material of the hydrogel or silicone hydrogel contact lens reacts with the chlorous acid compound resulting in chain scission of the high molecular weight vinylpyrrolidone polymer which leads to depletion of high molecular weight vinylpyrrolidone polymer at and near the surface of the lens causing an undesirable increase in advancing dynamic contact angle.
  • the present inventors have found that by incorporating reductants with chlorous acid compounds to decrease the concentration of the chlorous acid compounds in the packaging/storage composition ( e.g., by consuming the chlorous acid compound) to below 0.001% (or about 0.001%), by weight, of the total packaging/storage composition, the advancing dynamic contact angle of contact lens comprising a polymer comprising a high molecular weight vinylpyrrolidone can be maintained at an advancing dynamic contact angle of from about 40 o to about 80 o , from about 40 o to about 70 o , from about 40 o to about 60 o , or from about 45 o to about 55 o .
  • the advancing dynamic contact angle of contact lens comprising a polymer comprising a high molecular weight vinylpyrrolidone can be maintained at an advancing dynamic contact angle of within about 20%, or about 15%, or about 10%, of the originally measured advancing dynamic contact angle value for such contact lens.
  • the PVP added to the packaging solution composition when a PVP containing contact lens is packaged therein “protects” the PVP in and at the surface of the lens by acting in a sacrificial manner.
  • EDTA may also function as a reductant of chlorite during the autoclave sterilization cycle, thereby reducing the concentration of chlorite to a level that exhibits no deleterious effect on the wettability of the PVP-containing lens.
  • 21 Docket No. VTN6139WOPCT1 Silicone Hydrogel Formulations Contact lenses of the invention may comprise a free radical reaction product of a reactive mixture containing one or more monomers suitable for making the desired lens (also referred to herein as device forming monomers or hydrogel forming monomers), and optional components. When polymerized, the reactive mixture results in formation of a polymeric network of which the lens may be comprised.
  • the polymeric network may, for instance, be a hydrogel (e.g., a conventional hydrogel or a silicone hydrogel).
  • a polymeric network may be made from a reactive mixture comprising one or more of: hydrophilic components, hydrophobic components, silicone- containing components, high molecular weight vinylpyrrolidone polymer wetting agents, crosslinking agents, and further components such as diluents and initiators.
  • Hydrophilic Components include hydrophilic monomers, macromers and polymers.
  • hydrophilic monomers examples include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyl lactams, N- vinyl amides, N-vinyl imides, N-vinyl ureas, O-vinyl carbamates, O-vinyl carbonates, other hydrophilic vinyl compounds, and mixtures thereof.
  • Non-limiting examples of hydrophilic (meth)acrylate and (meth)acrylamide monomers include: acrylamide, N-isopropyl acrylamide, N,N-dimethylaminopropyl (meth)acrylamide, N,N- dimethyl acrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2,3-dihydroxypropyl (meth)acrylate, 2- hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, N- (2-hydroxyethyl) (meth)acrylamide, N,N-bis(2-hydroxyethyl) (meth)acrylamide, N-(2- hydroxypropyl) (meth)acrylamide, N,N-bis(2-hydroxypropyl) (meth)acrylamide, N-(3- hydroxypropyl) (meth)acrylamide
  • VTN6139WOPCT1 (meth)acrylamide, glycerol methacrylate, polyethyleneglycol monomethacrylate, (meth)acrylic acid, vinyl acetate, acrylonitrile, and mixtures thereof.
  • Hydrophilic monomers may also be ionic, including anionic, cationic, zwitterions, betaines, and mixtures thereof.
  • Non-limiting examples of such charged monomers include (meth)acrylic acid, N-[(ethenyloxy)carbonyl]- ⁇ -alanine (VINAL), 3-acrylamidopropanoic acid (ACA1), 5-acrylamidopentanoic acid (ACA2), 3-acrylamido-3-methylbutanoic acid (AMBA), 2- (methacryloyloxy)ethyl trimethylammonium chloride (Q Salt or METAC), 2-acrylamido-2- methylpropane sulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)-N,N-dimethyl-3- [(1-oxo-2-propen-1-yl)amino]-, inner salt (CBT), 1-propanaminium, N,N-dimethyl-N-[3-[(1- oxo-2-propen-1-yl)amino]propyl]-3-sulfo-, inner salt (S
  • Non-limiting examples of hydrophilic N-vinyl lactam and N-vinyl amide monomers include: N-vinyl pyrrolidone (NVP), N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3- methyl-2-caprolactam, N-vinyl-3-methyl-2-piperidone, N-vinyl-4-methyl-2-piperidone, N-vinyl- 4-methyl-2-caprolactam, N-vinyl-3-ethyl-2- pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone, N- vinyl acetamide (NVA), N-vinyl-N-methylacetamide (VMA), N-vinyl-N-ethyl acetamide, N- vinyl-N-ethyl formamide, N-vinyl formamide, N-vinyl-N-methylpropionamide, N-vinyl-N- methyl-2-
  • Non-limiting examples of hydrophilic O-vinyl carbamates and O-vinyl carbonates monomers include N-2-hydroxyethyl vinyl carbamate and N-carboxy-ß-alanine N-vinyl ester. Further examples of hydrophilic vinyl carbonate or vinyl carbamate monomers are disclosed in U.S. Patent No.5,070,215. Hydrophilic oxazolone monomers are disclosed in U.S. Patent No. 4,910,277.
  • Other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, and 2-ethyl oxazoline.
  • the hydrophilic monomers may also be macromers or prepolymers of linear or branched poly(ethylene glycol), poly(propylene glycol), or statistically random or block copolymers of ethylene oxide and propylene oxide, having polymerizable moieties such as (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinylamides, and the like.
  • the macromers of these polyethers have one polymerizable group; the prepolymers may have two or more polymerizable groups.
  • the hydrophilic monomers include DMA, NVP, HEMA, VMA, NVA, and mixtures thereof.
  • the hydrophilic monomers include NVP, DMA, HEMA and combinations thereof.
  • hydrophilic monomers may be selected based upon the desired characteristics of the resulting hydrogel, including water content, clarity, wettability, protein uptake, and the like. Wettability may be measured by contact angle, and desirable contact angles are less than about 100 ⁇ , less than about 80 ⁇ , and less than about 60 ⁇ .
  • the hydrophilic monomer may be present in an amount in the range of, for instance, about 0.1 to about 100 weight percent, alternatively in the range of about 1 to about 80 weight percent, alternatively about 5 to about 65 weight percent, alternatively in the range of about 40 to about 60 weight percent, or alternatively about 55 to about 60 weight percent, based on the total weight of the reactive components in the reactive monomer mixture.
  • Silicone-Containing Components suitable for use in lenses comprise one or more polymerizable compounds, where each compound independently comprises at least one 24 Docket No. VTN6139WOPCT1 polymerizable group, at least one siloxane group, and one or more linking groups connecting the polymerizable group(s) to the siloxane group(s).
  • the silicone-containing components may, for instance, contain from 1 to 220 siloxane repeat units, such as the groups defined below.
  • the silicone-containing component may also contain at least one fluorine atom.
  • the silicone-containing component may comprise: one or more polymerizable groups as defined above; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.
  • the silicone-containing component may comprise: one or more polymerizable groups that are independently a (meth)acrylate, a styryl, a vinyl ether, a (meth)acrylamide, an N-vinyl lactam, an N-vinylamide, an O- vinylcarbamate, an O-vinylcarbonate, a vinyl group, or mixtures of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.
  • the silicone-containing component may comprise: one or more polymerizable groups that are independently a (meth)acrylate, a (meth)acrylamide, an N-vinyl lactam, an N- vinylamide, a styryl, or mixtures of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.
  • the silicone-containing component may comprise: one or more polymerizable groups that are independently a (meth)acrylate, a (meth)acrylamide, or mixtures of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups connecting the polymerizable groups to the siloxane units.
  • the silicone-containing component may comprise one or more polymerizable compounds of Formula A: Docket No. VTN6139WOPCT1 at least one R A is a group of formula Rg-L- wherein Rg is a polymerizable group and L is a linking group, and the remaining R A are each independently: (a) R g -L-, (b) C1-C16 alkyl optionally substituted with one or more hydroxy, amino, amido, oxa, carboxy, alkyl carboxy, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof, (c) C 3 -C 12 cycloalkyl optionally substituted with one or more alkyl, hydroxy, amino, amido, oxa, carbonyl, alkoxy, amido, carbamate, carbonate, halo, phenyl, benzyl, or combinations thereof, (d) a C 6 -C 14 ary
  • the SiO units may carry the same or different R A substituents and if different R A substituents are present, the n groups may be in random or block configuration.
  • three R A may each comprise a polymerizable group, alternatively two R A may each comprise a polymerizable group, or alternatively one R A may comprise a polymerizable group.
  • the number of SiO repeat units in such compounds is preferably from 3 to 100, more preferably from 3 to 40, or still more preferably from 3 to 20.
  • Table A mono-methacryloxypropyl terminated mono-n-butyl terminated 1 polydimethylsiloxanes (mPDMS) (preferably containing from 3 to 15 SiO repeating units) 2 mono-acryloxypropyl terminated mono-n-butyl terminated p olydimethylsiloxane 3 mono(meth)acryloxypropyl terminated mono-n-methyl terminated p olydimethylsiloxane 4 mono(meth)acryloxypropyl terminated mono-n-butyl terminated p olydiethylsiloxane 5 mono(meth)acryloxypropyl terminated mono-n-methyl terminated p olydiethylsiloxane 6 mono(meth)acrylamidoalky
  • VTN6139WOPCT1 2 hydroxy-3-methacryloxypropyloxypropyl- tris(trimethylsiloxy)silane mono-(2-hydroxy-3-methacryloxypropyloxy)-propyl terminated mono-n-butyl terminated polydimethylsiloxanes (OH-mPDMS) (containing from 4 to 30, or from 4 to 20, or from 4 to 15 SiO repeat units)
  • j2 where applicable is preferably from 1 to 100, more preferably from 3 to 40, or still more preferably from 3 to 15. In compounds containing j1 and j2, the sum of j1 and j2 is preferably from 2 to 100, more preferably from 3 to 40, or still more preferably from 3 to 15.
  • Table C 25 26 p is 1 to 10 29 Docket No.
  • VTN6139WOPCT1 p is 5-10 1,3-bis[4-(vinyloxycarbonyloxy)but-1-yl]tetramethyl-disiloxane 3-(vinyloxycarbonylthio) propyl-[tris (trimethylsiloxy)silane] 3-[tris(trimethylsiloxy)silyl] propyl allyl carbamate 3-[tris(trimethylsiloxy)silyl] propyl vinyl carbamate tris(trimethylsiloxy)silylstyrene (Styryl-TRIS)
  • the silicone-containing component may include one or more mono-methacryloxypropyl terminated mono-n-butyl terminated polydimethylsiloxanes (mPDMS) (preferably containing from 3 to 15 SiO repeating units), mono(meth)acryloxypropyl terminated mono-n-methyl terminated polydimethylsiloxane (preferably containing from 3 to 15 SiO repeating units), a silicone based crosslinker, such as bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (ac- PDMS); 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA), and mixtures thereof either alone or with additional silicone-containing components.
  • mPDMS mono-methacryloxypropyl terminated mono-n-butyl terminated polydimethylsiloxanes
  • a silicone based crosslinker such as bis-3-acryloxy-2-hydroxyprop
  • the silicone containing component(s) may be present in amounts up to about 95 weight %, or from about 10 to about 80 weight %, or from about 20 to about 70 weight %, based upon all reactive components of the reactive mixture (excluding diluents). Where concentrations of high molecular weight vinylpyrrolidone polymer greater than about 3% or about 5% are desired to be included in the reactive mixture, the reactive mixture 31 Docket No. VTN6139WOPCT1 may also include a compatibilizing component, such as the hydroxyl functionalized silicones including compounds 13,15,16,17 and 36 in Tables B and C, those disclosed in US6,822,016 or non-silicone compatibilizing components such as disclosed in US2021/063650.
  • a compatibilizing component such as the hydroxyl functionalized silicones including compounds 13,15,16,17 and 36 in Tables B and C, those disclosed in US6,822,016 or non-silicone compatibilizing components such as disclosed in US2021/063650.
  • the high molecular weight vinylpyrrolidone polymer may introduced into the lens by adding it as a component to the reaction mixture, forming the lens first and then polymerizing the high molecular weight vinylpyrrolidone polymer in a separate step as disclosed in US7,262,232 adding it to the packaging solution as disclosed in US7,841,716.
  • the reactive mixture may contain additional components such as, but not limited to, crosslinkers, diluents, initiators, UV absorbers, HEV absorbers, visible light absorbers, photochromic compounds which reversibly darken when exposed to specific wavelengths of light, pharmaceuticals, nutraceuticals, antimicrobial substances, tints, pigments, copolymerizable dyes, nonpolymerizable dyes, release agents, and combinations thereof.
  • the reactive mixture may comprise: and a hydrophilic component selected from DMA, NVP, HEMA, VMA, NVA, methacrylic acid, and mixtures thereof.
  • the reactive mixture may comprise: a hydrophilic component selected from NVP, DMA, VMA, HEMA and mixtures thereof; a silicone-containing component selected from 2-hydroxy- 3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA), mono- methacryloxypropyl terminated mono-n-butyl terminated polydimethylsiloxane (mPDMS), mono-methacryloxypropyl terminated mono-n-methyl terminated polydimethylsiloxane (methyl -mPDMS), mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether terminated mono-n-butyl terminated polydimethylsiloxane (OH-mPDMS), and mixtures thereof; and optionally high molecular weight vinylpyrrolidone polymer.
  • a hydrophilic component selected from NVP, DMA, VMA, HEMA and mixtures thereof
  • silicone-containing component selected from 2-hydroxy-
  • the reactive mixture may comprise: between 20-70 wt%, 25 to 65wt% or 30-60wt% at least one silicone-containing component; about 30-80, 35-75 wt% or 40-70% of at least one hydrophilic monomer; optionally at least one high molecular weight vinylpyrrolidone polymer.
  • the reactive mixture may comprise: between 20-70 wt%, 25 to 65wt% or 30-60wt% at least one silicone-containing component; about 35-70 wt% or 40-60% of at least one hydrophilic monomer selected from NVP, VMA or combinations thereof; optionally additional hydrophilic monomers, and optionally at least one high molecular weight vinylpyrrolidone polymer.
  • VTN6139WOPCT1 foregoing reactive mixtures may contain optional ingredients such as, but not limited to, one or more initiators, reactive or non-reactive wetting agents, crosslinkers, other UV or HEV absorbers, pigments, polymeric, polymerizable non-polymerizable dyes and nonphotochromic compounds capable of reversibly change color, darken or reflect light when exposed to various wavelengths of light, release agents, diluents and the like.
  • UV, HEV absorbers, visible light absorbers, photochromic compounds tints or dyes (polymerizable or non-polymerizable) are used they are preferably stable in the presence of the chlorous acid compound at the selected chlorous acid compound concentrations.
  • Silicon hydrogel formulations comprising at least one high molecular weight polyvinylpyrrolidone polymer as an internal wetting agent include all variations of aquafilcon, galyfilcon, senofilcon, narafilcon and the formulations disclosed in US6,367,929, WO03/22321, WO03/22322, US10,935,695, US8,053,539, US10,371,865, and US10,370,476.
  • Silicone hydrogel formulations including substantial quantities of NVP, which may polymerize into PVP blocks include comfilcon, formofilcon, riofilcon, somofilcon, kalifilcon, verofilcon, those disclosed in US9,588,258, US9,156,934, US8,937,110, US8,937,111 and the like.
  • the present invention may also be used with conventional lenses comprising at least one high molecular weight polyvinylpyrrolidone polymer as an internal wetting agent, such as those disclosed in US7,431,152, US7,841,716 and either conventional or silicone hydrogel lenses as disclosed in US7,262,232.
  • compositions of the present invention comprise an ophthalmologically acceptable carrier.
  • the ophthalmologically acceptable carrier may be water or an aqueous excipient solution.
  • aqueous typically denotes a formulation wherein the excipient is at least about 50%, at least about 75%, at least about 90%, up about 95% about 99%, by weight, water.
  • the compositions of the present invention may be free or substantially free of oils or oily substances (e.g., medium-chain triglycerides, castor oil, flaxseed oil and the like or mixtures thereof).
  • compositions contain less than about 0.05%, less than about 0.025% less than about 0.01%, less than about 0.005%, of such oils or oily components, by weight, based on the total 33 Docket No. VTN6139WOPCT1 composition.
  • the compositions are not multiphasic compositions such as oil in water emulsions.
  • the water is preferably distilled water.
  • the carrier is preferably free of C 1-4 alcohols such as methanol, ethanol, propanol, isopropanol, butanol, and the like which can sting, irritate, or otherwise cause discomfort to the eye.
  • the water may be present in the ophthalmologically acceptable carrier at concentrations of from about 96% to about 99.9%, from about 98% to about 99.5%, or from about 99.0% to about 99.5% by weight of the total composition.
  • the ophthalmologically acceptable carrier may be present at concentrations of from about 96% to about 99.5%, from about 98% to about 99.5%, or from about 98.5% to about 99.2% by weight of the total composition.
  • the compositions may be sterile, namely such that the absence of microbial contaminants in the product prior to release or use is statistically demonstrated to the degree necessary for such products.
  • the compositions may be selected to have no or substantially no detrimental, negative, harmful effect on the contact lens or on the eye (or on the region around the eye).
  • compositions according to the present invention are physiologically compatible with the eye and ophthalmic devices.
  • the composition should be “ophthalmically safe” for use with an ophthalmic device such as a contact lens, meaning that a contact lens treated with the solution is generally suitable and safe for direct placement on or direct application to the eye without rinsing, that is, the solution is safe and comfortable for ophthalmic devices, soaked in, rinsed or wetted with the solution, including contact lenses of any wear frequency.
  • An ophthalmologically safe composition has a tonicity and pH that is compatible with the eye and includes materials, and amounts thereof, that are ophthalmologically compatible and non- cytotoxic according to ISO standards and U.S. Food & Drug Administration (FDA) regulations.
  • FDA Food & Drug Administration
  • compositions of the present invention may be adjusted with tonicity agents, to approximate the osmotic pressure of normal lacrimal fluids, which is equivalent to a 0.9 percent solution of sodium chloride.
  • the compositions may be made substantially isotonic with physiological saline used alone or in combination with other tonicity agents such as dextrose, otherwise if simply blended with sterile water and made hypotonic or made hypertonic the 34 Docket No. VTN6139WOPCT1 ophthalmic devices such as contact lenses may lose their desirable optical parameters.
  • excess saline may result in the formation of a hypertonic composition, which will cause stinging, and eye irritation.
  • the osmolality of the composition may be at least about 200 mOsm/kg to less than 500 mOsm/kg, preferably from about 200 to about 450 mOsm/kg, preferably from about 205 to about 380 mOsm/kg, preferably from about 210 to about 360 milliosmoles per kilogram (mOsm/kg), preferably from about 250 to about 350 mOsm/kg, or preferably, from about 270 to about 330 mOsm/kg, as measured using osmolality measurement method USP ⁇ 785> (current as of November, 2022).
  • the ophthalmic compositions will generally be formulated as sterile aqueous compositions or as non-sterile compositions which are subsequently sterilized.
  • suitable tonicity adjusting agents include (selected from or selected from the group consisting of), but are not limited to, sodium, potassium, calcium, zinc and magnesium chloride, alkali metal halides, dextrose, and the like and mixtures thereof. These agents may be used individually in amounts ranging from about 0.01 to about 2.5% w/v and preferably from about 0.2 to about 1.5% w/v.
  • the tonicity adjusting agent may be sodium chloride which can be incorporated at concentrations of from about 0.4 to about 0.9% w/v, preferably, from about 0.4 to about 0.7% w/v, or preferably, from about 0.5% to about 0.6% w/v.
  • the ophthalmically acceptable carrier can contain one or more of the above-mentioned tonicity adjusting agents.
  • the compositions of the present invention may have a pH of from about 6.0 to about 8.0, from about 6.5 to about 8.0, from about 6.5 to about 7.5, or about 7.0 to about 7.5, or a pH of about 7.2 to a pH of about 7.4.
  • compositions may have a pH matching the physiological pH of the human tissue to which the composition will contact or be directly applied.
  • the pH of the ophthalmic composition may be adjusted using acids and bases, such as mineral acids, such as, but not limited to hydrochloric acid and bases such as sodium hydroxide.
  • acids and bases such as mineral acids, such as, but not limited to hydrochloric acid and bases such as sodium hydroxide.
  • the compositions of the present invention are also useful as packaging solutions for packaging of ophthalmic devices and for storing such ophthalmic devices.
  • the packaging solutions of the present invention may have a viscosity of less than about 5.2 cP at 25oC.
  • compositions may also be useful for direct application to eye as a wetting or rewetting eye drop for providing relief to eye discomfort (e.g., burning sensations relating to the eye or general eye irritation) during contact lens wear.
  • eye discomfort e.g., burning sensations relating to the eye or general eye irritation
  • the compositions of the present invention are not further mixed with another or separate composition(s) prior to direct application to the eye or for storing of (or as packaging solution for) ophthalmic devices (e.g., contacts) – namely the compositions of the present invention (or products thereof) are not in the form of 2- or multi-composition or products.
  • Suitable borates include, but are not limited to, boric acid; pharmaceutically acceptable salts, such as alkaline metal salts such as sodium borate, potassium borate; alkaline earth metal salts such as calcium borate, magnesium borate; transition metal salts such as manganese borate; and mixtures thereof.
  • pharmaceutically acceptable salts such as alkaline metal salts such as sodium borate, potassium borate; alkaline earth metal salts such as calcium borate, magnesium borate; transition metal salts such as manganese borate; and mixtures thereof.
  • alkaline metal salts such as sodium borate, potassium borate
  • alkaline earth metal salts such as calcium borate, magnesium borate
  • transition metal salts such as manganese borate
  • non-chlorous acid preservative means compounds, which are not chlorous acid compounds, 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, 36 Docket No.
  • VTN6139WOPCT1 methylparaben, phenols 0.5%, phenoxyethanol, sorbate, propionic acid, propylparaben, sodium benzoate, sorbic acid, thimerosol, polyquaternium compounds (such as polyquarternium-42 and polyquarternium-1), biguanide compounds (e.g., polyhexamethylene biguanide or polyaminopropyl biguanide).
  • Non-chlorous acid preservatives, especially cationic preservatives can be irritating to eye and/or cause allergic reactions, undesirably affecting consumers’ use of the eye care compositions or contact lens which contain (on its surface) such non-chlorous acid preservative due to the storage of the contact lens with such compounds.
  • the term “sources of peroxides”, as used herein, means a compound or material that releases (or can release peroxide or hydrogen peroxide) in aqueous solution and includes, but are not limited to, barium peroxide, sodium peroxide, zinc peroxide, magnesium peroxide, calcium peroxide, strontium peroxide, lithium peroxide, butanone peroxide, cyclohexanone peroxide, benzoyl peroxide, urea hydrogen peroxide (carbamide peroxide, carbamide perhydrate, or percarbamide), percarbonates such as calcium percarbonate or magnesium percarbonate, tert-butylhydroperoxide, perborate salts such as sodium perborate, peroxy acids such as methyl ethyl ketone peroxide, mixtures thereof and derivatives.
  • Peroxides e.g., hydrogen peroxide
  • sources of peroxides can be harsh and irritating to eye and can undesirably affect consumers’ use of contact lens which contain (on its surface) the peroxides 37 Docket No. VTN6139WOPCT1 (e.g., hydrogen peroxide) and/or sources of peroxides due to the storage of the contact lens with such compounds.
  • the term "persulfates”, as used herein, means persulfate anions or salts of such persulfates and other pharmaceutically acceptable persulfates, or combinations thereof.
  • Suitable persulfates include, but are not limited to, sodium peroxymonosulfate, potassium peroxymonosulfate, sodium persulfate , ammonium persulfate potassium persulfate and mixtures thereof.
  • Persulfates can be harsh and irritating to eye and can undesirably affect consumers’ use of contact lens which contain (on its surface) the persulfates due to the storage of the contact lens with such compounds.
  • Humectants and/or demulcents such as carboxy vinyl polymers (e.g., carbomers), natural gums (e.g., guar gum, gum tragacanth), glycerin, polyoxyethylene-castor oil and/or derivatives thereof are well known thickening agents which, when present on surface of contact lenses, can undesirably affect consumers’ vision through contact lens, causing blurring or otherwise reducing vision clarity by either interacting with the surface of the contact lens or slowly diffusing from the tear fluid trapped between the eye-facing side of the contact lens and the corneal surface. Though the latter effect is generally temporary, dissipating within several minutes post insertion with trapped fluid being cleared by repetitive blinking, such visual impairing effects may be undesirable.
  • carboxy vinyl polymers e.g., carbomers
  • natural gums e.g., guar gum, gum tragacanth
  • glycerin polyoxyethylene-castor oil and/or derivatives thereof
  • substantially free as related to compounds selected from boric acid, borates, non-chlorous acid preservatives, peroxides (e.g., hydrogen peroxide) or sources of peroxides, persulfates, carboxy vinyl polymers (e.g., carbomers), natural gums (e.g., guar gum, gum tragacanth), glycerin, polyoxyethylene-castor oil and/or derivatives means that such compounds are present in the compositions of the present invention as impurities which are not intentionally added or are at a concentration of less than 2% (or about 2%), less than 1.5% (or about 1.5%), less than 1% (or about 1%), less than 0.5% (or about 0.5%), less than 0.1% (or about 0.1%), less than 0.05% (or about 0.05%), less than 0.01% (or about 0.01%), less than 0.005% (or about 0.005%) by weight of the total composition.
  • peroxides e.g., hydrogen peroxide
  • compositions of the present invention may be free of such compounds.
  • contact lenses can be immersed in a composition of the present invention and stored in a suitable packaging container, in certain embodiments, a packaging 38 Docket No. VTN6139WOPCT1 container for single contact lens unit.
  • a packaging container for the storage of a contact lens includes at least a sealing layer sealing the container containing an unused contact lens immersed in the composition of the present invention.
  • the sealed container may be hermetically sealed packaging container and may have any form that creates a sealed space to contain the composition and contact lens.
  • the hermetically sealed packaging container may have any suitable form include sealed packets formed from two sheets of plastic, metal or multilayer structures or a blister pack in which a base with a concave well containing a contact lens is covered by a metal, plastic or laminate sheet adapted for peeling in order to open the blister-pack.
  • the sealed container may be formed from any suitable, generally inert packaging material providing a reasonable degree of protection to the lens.
  • the packaging material may be formed of plastic material such as polypropylene, polysulfone (PSU), polyethersulfone (PESU), polycarbonate (PC), polyetherimide (PEI), polyamides, including nylons, polyolefins including polypropylene, polymethylpentene, (PMP), and olefin co-polymers, including COPs (Cyclic Olefin Polymer) and COCs,(Cyclic Olefin Co-polymers), acrylics, rubbers, urethanes, fluorocarbons, polyoxymethylene, polyvinylchloride (PVC), polyphenylsulfide (PPS), polycarbonate copolymers, polyvinylidene fluoride (PVDF), and the like and copolymers and blends of the foregoing.
  • plastic material such as polypropylene, polysulfone (PSU), polyethersulfone (PESU), polycarbonate (PC), polyetherimide (PE
  • Blends include polybutylene terephthalate polyester blends, including PBT and PC blends, PC/polyester blends, and polypropylene blended with COPs or COCs.
  • the plastic material may be selected from polypropylene, COPs (Cyclic Olefin Polymer) and COCs, (Cyclic Olefin Co-polymers) and blends thereof.
  • any water soluble, demulcent (or demulcent like – e.g., having demulcent properties such as viscosity increasing capabilities) polymer may also be employed in the composition of this invention provided that it has no (or no substantial) detrimental effect on the contact lens being stored or on the wearer of the contact lens (e.g., blurring or otherwise reducing vision clarity) at the concentrations used in the composition of the present invention or on the eye (or on the region around the eye).
  • Particularly useful components are those, which are water soluble, for example, soluble at the concentrations used in the presently useful liquid aqueous media.
  • Suitable water-soluble demulcent polymers include, but are not limited to, demulcent polymers, such as block copolymer surfactants (e.g., block copolymers of polyethyleneoxide (PEO) and polypropyleneoxide (PPO)); polyvinyl alcohol, polyvinyl pyrrolidone; polyacrylic acid; polyethers such as polyethylene glycols (e.g., 39 Docket No.
  • demulcent polymers such as block copolymer surfactants (e.g., block copolymers of polyethyleneoxide (PEO) and polypropyleneoxide (PPO)); polyvinyl alcohol, polyvinyl pyrrolidone; polyacrylic acid; polyethers such as polyethylene glycols (e.g., 39 Docket No.
  • block copolymer surfactants e.g., block copolymers of polyethyleneoxide (PEO) and polypropyleneoxide (PPO)
  • PEO polyethyleneoxide
  • VTN6139WOPCT1 polyethylene glycol 300, polyethylene glycol 400) and polyethylene oxides; hyaluronic acid, and hyaluronic acid derivatives such as sodium hyaluronate) ; chitosan; polysorbates such as polysorbate 80, polysorbate 60 and polysorbate 40); dextrans such as dextran 70; cellulosic derivatives such as carboxy methyl cellulose methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and methyl ethyl cellulose; acyclic polyamides such as those having a weight average molecular weight of 2,500 to 1,800,000 Daltons as disclosed in US7,786,185 herein incorporated by reference in its entirety; salts of any of the above and mixtures of any of the above.
  • the block copolymers of PEO and PPO include poloxamers and poloxamines, including those disclosed in US6,440,366, herein incorporated by reference in its entirety.
  • the water-soluble demulcent polymer is selected from polyvinyl pyrrolidone, methyl ethyl cellulose, polymethacrylic acid, carboxymethyl cellulose, propylene glycol, 1,3- propanediol, polyethylene glycols, and mixtures thereof.
  • Water-soluble demulcent polymers may have molecular weights in excess of 100,000. When propylene glycol and/or 1,3-propanediol are used as water-soluble demulcent polymers, they may have molecular weights lower than 100,000.
  • any water-soluble polymer when used in the packing solutions of the present invention, it may be included and present in amounts up to about 0.5, about 1 or about 2 weight %, preferably between about 0.001 and about 2%, between about 0.005 and about 1%, between about 0.01 and about 0.5 weight %, or between about 100 ppm and about 0.5 weight %, all based upon the weight of total composition.
  • any water soluble polymer when used in the direct application eye care formulation, such as an eye drop of the present invention, it may be included and present in amounts up to about 2, about 5 or about 10 weight %, between about 0.001 and about 10%, between about 0.005 and about 2% , between about 0.01 and about 0.5 weight %, or between about 100 ppm and about 2 weight%, all based upon the weight of total composition.
  • the water-soluble demulcent polymer aids in preventing the ophthalmic device from sticking to the packaging container and may enhance the initial (and/or extended) comfort of the contact lens, packaged in the composition, when placed on the eye after removal from the packaging container.
  • the water-soluble demulcent polymer may be a cellulosic derivative.
  • the cellulosic derivative may be present at concentrations of from about 0.002 to about 0.01, or preferably, from about 0.004 to about 0.006 by weight of the total composition of the present invention.
  • Various other materials may be included with the compositions described herein. In the case of compositions of the present invention for direct application to the eye, surfactants may be included.
  • Surfactants suitable for such use include, but are not limited to, ionic and nonionic surfactants (though nonionic surfactants are preferred), RLM 100, POE 20 cetylstearyl ethers such as Procol® CS20, poloxamer block copolymers (such as Pluronic® F68, and block copolymers such as poly(oxyethylene)-poly(oxybutylene) compounds set forth in US2008/0138310 (which publication is herein incorporated 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 having an average value of 10 to 1000 and n is an integer having an average value of 5 to 1000, as disclosed in US8,318,144; m may also be 10 and n may be 5.
  • Surfactants may be present at concentrations of from about 0.01 to about 3%, preferably from about 0.01 to about 1%, preferably, from about 0.02 to about 0.5%, or preferably, from about 0.02 to about 0.1% by weight of the total composition of the present invention.
  • the components may perform more than one function, for example, some demulcents may also function as surfactants (e.g., PEO-PPO and PEO-PBO block copolymers).
  • surfactants e.g., PEO-PPO and PEO-PBO block copolymers.
  • one or more additional components may be, optionally, included in the composition. Such optional component(s) are chosen to impart or provide at least one beneficial or desired property to the composition.
  • Such additional, but optional, components may be selected from components that are conventionally used in ophthalmic device care compositions
  • optional components include (or, are selected from or selected from the group consisting of) cleaning agents (for example in direct application eye drops or cleaning [or eye care solution]), wetting agents, nutrient agents, therapeutic agent, sequestering agents, viscosity builders, contact lens conditioning agents, antioxidants, and the like and mixtures thereof.
  • cleaning agents for example in direct application eye drops or cleaning [or eye care solution]
  • wetting agents for example in direct application eye drops or cleaning [or eye care solution]
  • nutrient agents for example in direct application eye drops or cleaning [or eye care solution]
  • wetting agents for example in direct application eye drops or cleaning [or eye care solution]
  • nutrient agents for example in direct application eye drops or cleaning [or eye care solution]
  • wetting agents for example in direct application eye drops or cleaning [or eye care solution]
  • nutrient agents for example in direct application eye drops or cleaning [or eye care solution]
  • wetting agents for example
  • the ophthalmic solution comprises about 0.01 to about 0.02 wt% sodium chlorite, a phosphate buffer, about 0.01 to about 0.075 wt% EDTA, or about 0.05 to about 0.075wt% EDTA, up to about 1, 1.5 or 2 wt% PVP K60 or K90 and optionally about 0.005 to about 0.01 wt% methyl ethyl cellulose, all based on the ophthalmic solution as formulated, prior to autoclaving.
  • the ranges may be combined in any permutation.
  • the ophthalmic solution may be used as a packaging solution with contact lenses, including silicone hydrogel contact lenses, comprising PVP. All components in the ophthalmic solution of the present invention should be water- soluble.
  • One or more therapeutic agent may also be incorporated into the ophthalmic solution.
  • a wide variety of therapeutic agents may be used, so long as the selected active agent is inert in the presence of chlorous acid compounds (e.g., chlorites) or oxidating agents generally.
  • Suitable therapeutic agents include those that treat or target any part of the ocular environment, including the anterior and posterior sections of the eye and include pharmaceutical agents, vitamins, nutraceuticals combinations thereof and the like.
  • Suitable classes of active agents include antihistamines, antibiotics, glaucoma medication, carbonic anhydrase inhibitors, anti-viral agents, anti-inflammatory agents, non-steroid anti-inflammatory drugs, antifungal drugs, anesthetic agents, miotics, mydriatics, immunosuppressive agents, antiparasitic drugs, anti- protozoal drugs, combinations thereof and the like.
  • active agents When active agents are included, they are included in an amount sufficient to produce the desired therapeutic result (a “therapeutically effective amount”).
  • Useful optional sequestering agents include, but are not limited to, citric acid, sodium citrate and the like and mixtures thereof.
  • the method of packaging and storing a contact lens comprises immersing the device in the compositions described above in a suitable container.
  • the method may include immersing the device in the composition prior to delivery to the 42 Docket No. VTN6139WOPCT1 customer/wearer, directly following manufacture of the contact lens.
  • the incorporation and storing of the device in the compositions may occur at an intermediate point before delivery to the ultimate customer (wearer) but following manufacture and transportation of the device in a dry state, wherein the dry device is hydrated by immersing the device in the compositions.
  • a package for delivery to a customer may comprise a hermetically sealed container containing one or more unused devices (e.g., contact lenses) immersed in the compositions.
  • the steps for packaging the ophthalmic device in the composition of the present invention may include: (1) molding an ophthalmic device (e.g., contact lens) in a mold comprising at least a first and second mold portion, (2) removing the device from the mold portions and removal of unreacted monomer and processing agents, (3) introducing the composition and the device into the packaging (or container), and (4) sealing the packaging.
  • the method may also include the step of sterilizing the contents of the packaging.
  • Sterilization may take place prior to, or most conveniently after, sealing of the container and may be performed by any suitable method known in the art, e.g., by autoclaving of the sealed container at temperatures of about 120° C. or higher (autoclave or steam sterilization method), or by using ultraviolet (UV) sterilization or gamma electron beam sterilization methods.
  • the compositions of the present invention are sterilized by autoclave sterilization.
  • the packaging may be a plastic blister packaging (or package), including a recess for receiving an ophthalmic device and the composition, where the recess is hermetically sealed with lidstock prior to sterilization.
  • the experiment was performed by dipping the contact lens test strip into the borate buffer while measuring the force, in each case exerted on the contact lens sample due to wetting by the probe solution using a sensitive balance (i.e., as in the case of the Kruss K100).
  • the advancing dynamic contact angle of the contact lens sample was determined from the force data collected during sample dipping.
  • the receding contact angle is determined from force data while withdrawing the contact lens sample (in the form of a test strip) from the test liquid.
  • the contact lens test strip was cut from the central area of the sample contact lens.
  • Each strip was approximately 5 mm in width and 14 mm in length, attached to a metallic clip using plastic tweezers, pierced with a metallic wire hook, and equilibrated in packing solution for at least 3 hours. Then, each sample was cycled four times, and the results were averaged to obtain the advancing and receding contact angles of the lens. Typical measuring speeds were 12 mm/min.
  • the contact lens test samples were kept completely immersed in the packing solution during the data acquisition and analysis without touching the metal clip. Values from five individual contact lens test samples were averaged to obtain the reported advancing (and receding) dynamic contact angles of the sample lenses.
  • Example 1 Effect of Chlorous Acid Compound on Advancing Dynamic Contact Angle of PVP containing Contact Lenses. 45 Docket No.
  • VTN6139WOPCT1 Table 1 shows a comparative composition evaluated for storing (or use packaging solution for) poly(vinylpyrrolidone) polymer-containing polymeric ophthalmic devices (e.g., contact lenses) such as ACUVUE ® OASYS Contact Lenses 1-Day with HydraLuxe ® Technology (“ACUVUE OASYS 1-Day lens”).
  • the comparative solution was prepared using standard mixing technology. 1 ml of the comparative composition of Table 1 was individually packaged with a ACUVUE OASYS 1-Day lens in a sealed polypropylene blister packaging without further sterilization. This comparative contact lens/solution packaging is referenced as “Test” in Table 2.
  • Nominal chlorite content in the composition of Table 1 was about72 ⁇ g/mL
  • a “control” formulation identical to the comparative composition of Table 1, except for the exclusion of sodium chlorite (Control) was also prepared as a testing control and similarly packaged with the with an ACUVUE OASYS 1-Day lens in a sealed polypropylene blister packaging.
  • This contact lens/solution packaging is referenced as “Control” in Tables 1 and 2.
  • Poly(vinylpyrrolidone) polymer-containing contact lens and Example 1 or Control solutions were sealed in polypropylene blister packages and subsequently placed in a stability chamber (ES2000 REACH-IN, supplied by Environmental Specialties) set at temperature of 46 Docket No.
  • VTN6139WOPCT1 55°C and relative humidity of 35% to determine chlorite availability over time and advancing dynamic contact angle measurements.
  • Samples were analyzed via ion chromatography with conductivity detection for chlorite concentration at the time periods shown in Table 2, below. The separation was performed using a Dionex AS9-HC column, 4 mm diameter X 250 mm length with a matching guard column. The mobile phase was 9 mmol.L sodium bicarbonate and the suppressor eluent was 500 mL sulfuric acid.
  • the injection volume and flow rate parameters were generally set at 20 ⁇ L and 1 mL/min, respectively. Standardization was performed using certified chlorite reference standards diluted to the applicable concentration regime, typically 0.1 – 20 ⁇ g/mL. The chlorite peak area of standard solutions were fitted to a least-squares fit with the corresponding chlorite concentrations. The equation of the least-squares regression was used to calculate the chlorite concentration of test solutions. The results are summarized in Table 2. Table 2 Real Analysis Result (std dev) (Actual) Simulated Chlorite ( ⁇ g/mL) Adv.
  • the contact lens has been rendered unacceptably hydrophobic - rather than having the desired hydrophilic property.
  • the data support a mechanism suggesting oxidative cleavage of the PVP internal wetting agent with a resultant depletion of PVP from the lens. No significant changes or deleterious effects were observed to other contact lens properties.
  • Table 2 the exposure of OASYS lenses to a solution containing 0.01% sodium chlorite (or 0.0075% chlorite) resulted in an unacceptable, time-dependent increase in advancing dynamic contact angle.
  • Example 2 shows an inventive composition (containing 1% PVP K90 with the chlorous acid compound as a reductant) evaluated for storing (or use packaging solution for) poly(vinylpyrrolidone) polymer- containing polymeric ophthalmic devices (e.g., contact lenses) such as ACUVUE ® OASYS TM 1-Day lenses (senofilcon A). 1 ml of the inventive composition of Table 3 was individually packaged with an ACUVUE ® OASYS TM 1-Day lens in a sealed polypropylene blister packaging.
  • the sealed polypropylene blister packages containing the composition shown in Table 3, and the ACUVUE ® OASYS 1-Day lens were sterilized in an autoclave model 2540E-B/L from Tuttnauer at a temperature of 121°C for 15 minutes (with a temperature ramp upon initiating autoclaving and terminating autoclaving).
  • 48 Docket No. VTN6139WOPCT1 Table 3 Component Weight % Sodium chloride 0.83 Monobasic sodium phosphate 0.10 Dibasic sodium phosphate 0.62 EDTA 0.01 MEC 0.005 Sodium chlorite 0.013 PVP K-90 Varied Water balance of 100% * Provided as stabilized sodium chlorite 80% with 20% sodium chloride.
  • Nominal chlorite content in the composition of Table 3 was about 78 ⁇ g/mL
  • the contact lenses which had been packaged and sterilized in the inventive composition of Table 3 were tested immediately after autoclave sterilization for advancing dynamic contact angle (using the advancing dynamic contact angle procedure described above) and chlorite concentration and 2 weeks later (from date of autoclave) at room temperature (“RT” - about 25°C).
  • RT room temperature
  • VTN6139WOPCT1 Example 3 Table 5 shows the formulation for a composition useful as a solution for storing (or as packaging for poly(vinylpyrrolidone) polymer containing polymeric ophthalmic devices (e.g., contact lenses) or useful as a direct application eye drop solution, which composition can be prepared using conventional mixing technology.
  • Table 5 Component Weight, g Weight % (the balance is water) Sodium Chloride 2.3355 0.7798% Monobasic sodium 0.0292 maleate 0.0097% Dibasic sodium maleate 0.684 monohydrate 0.2284% Sodium Chlorite 0.0362 (anhydrous)* 0.0121% EDTA 0.031 0.0103% Methyl ethyl cellulose 0.0158 (MEC) 0.0053% PVP K-60 3.006 1.0035% Water 293.38 Balance * Provided as stabilized sodium chlorite 80% with 20% sodium chloride. Nominal chlorite content in the composition of Table 5 was about 72 ⁇ g/mL 50 Docket No.
  • Table 6 shows a formulation for a chlorous acid compound containing composition of the present invention incorporating an organic maleate buffer and useful as a solution for storing (or as packaging) solution for ophthalmic devices (e.g., contact lenses) or direct application eye drop solution, which was prepared using conventional mixing technology.
  • Table 6 Component Weight % (the balance is water) Monobasic sodium maleate 0.01008% Dibasic sodium maleate m onohydrate 0.22653% Sodium Chloride 0.77489% Sodium Chlorite* 0.012% EDTA 0.075% Methyl ethyl cellulose (MEC) 0.005% PVP K-60 1.000% Water Balance * Provided as stabilized sodium chlorite 80% with 20% sodium chloride.
  • Nominal chlorite content in the composition of Table 6 was about 72 ⁇ g/mL Pot Life analysis was performed on the composition of Table 6 to determine the useful life of the composition for inhibiting microbial growth for a period of time - as a function of decreasing chlorite concentration in the composition over time.
  • the chlorite containing composition of Table 6 was sufficient to inhibit microbial growth of the panel organisms for a period of at least 5 days.
  • the Pot Life sample was prepared as follows: 1. About 10 mL of the composition of Table 6 was placed into several 20 mL glass screw cap scintillations vials. 2. The vials of step 1 were sealed with gray butylene caps and stored at room temperature in a light blocking container. 3.
  • the Pot Life study shows in Table 7 that at least 95% of the initial chlorite concentration remained viable in the composition of Table 6 in the presence of the EDTA and PVP reductants for at least 5 days. Such viability for such period time can be useful in situations where the packaging/storage composition may require shelving for a period of time prior to sterilized (e.g., by autoclave).
  • the one (1) OASYS 1-Day lens was added to each vial of step 1; 5.
  • the vials containing the OASYS 1-Day lens and composition of Table 6 were sealed with gray butylene caps and autoclaved for 15 min at 121°C. 6.
  • VTN6139WOPCT1 76 23.3 Did Not Test 50.7 (6.1) on the Arrhenius equation which states that a 10°C increase in temperature doubles the rate of reaction (known as a Q10 factor; a Q10 factor of 2 was used).
  • the advancing dynamic contact angle of the test contact lens i.e., poly(vinylpyrrolidone) polymer containing polymeric contact lenses
  • the reductant containing packaging solution of Table 6 exhibited no increase over time (i.e., indicating that the surface of the contact lens did not lose wettability).
  • Statistical analysis of the contact angle following approximately two years of simulated aging demonstrated no statistically significant change from the initial advancing contact angle.
  • Table 9 shows the formulations for compositions having a range of chlorite concentrations useful as a solution for storing (or as packaging) solution for ophthalmic devices (e.g., contact lenses) or direct application eye drop solution, which composition was prepared using conventional mixing technology.
  • VTN6139WOPCT1 * Provided as stabilized sodium chlorite 80% with 20% sodium chloride.
  • the test microorganisms were resuspended following manufacturers’ instructions and approximately 0.5mL aliquots were spread plated onto two separate tryptic soy agar (TSA) media and Sabouraud dextrose agar (SDA) plates.
  • TSA tryptic soy agar
  • SDA Sabouraud dextrose agar
  • the TSA and SDA plates were incubated at 30-35oC and 20-25oC respectively, for 2-7 days.
  • Sterile filtered deionized (DI) water and inoculating loops were used to resuspend the designated test microorganisms from the plate surfaces and the suspensions were aseptically transferred with a sterile pipette into individual 50mL centrifuge tubes.
  • the test microorganism suspensions were diluted until their population counts could be estimated using a hemocytometer. A population count of approximately 1.0 x 107 cells/mL was targeted for each final test microorganism suspension.
  • each inoculated sample of the compositions of Table 9 containing the designated test microorganism was stored at room temperature and at Day 0, Day 1, Day 2, and Day 3 samples were pour-plated in duplicate (Day 0 only) or triplicate with either molten TSA or SDA containing chloramphenicol as required. 55 Docket No.
  • VTN6139WOPCT1 The aliquot volumes were bracketed to increase the chances of the pour plate count results to be within the 25 CFU – 300 CFU countable range. All pour plate sample volumes were adjusted to 1mL using sterile water for injection (WFI) (i.e., 50 ⁇ L + 950 ⁇ L WFI) to allow for sufficient sample dispersion.
  • WFI sterile water for injection
  • AB was pour-plated with both TSA and SDA + chloramphenicol. When pour plated in parallel, the counts of A. brasiliensis were similar for the TSA and SDA+chloramphenicol. Consequently, TSA enabled the enumeration of A. brasiliensis on plates without interference due to sporulation.
  • the microorganism growth was less than a 0.2 log, or no increase in the count throughout the test period, including after 2, 8, 13 and 22 days from spiking for the yeast Candida albicans, the fungus Aspergillus brasiliensis and the bacteria Bacillus subtilis – subspecies spizizenii, respectively.
  • Candida albicans and the bacteria Bacillus subtilis – subspecies spizizenii decreased over the test period for all chlorite concentrations evaluated, when each microorganism was spiked into the composition of Table 9 containing at least 0.84 ⁇ g/ml of chlorite.
  • the fungus Aspergillus brasiliensis count remained the same (within test limits) at the lowest chlorite concentrations (0.84 and 1.7 ⁇ g/ml) and decreased over the test period at the higher concentrations (about 0.2 to about 0.5 log reduction at 3.7 and 7.6 ⁇ g/ml and 2.5 log reduction at 15 ⁇ g/ml.
  • Examples 5-9 show that a range of chlorite concentration provide 56 Docket No. VTN6139WOPCT1 effective inhibition of the growth of microorganisms across at least 22 days.
  • Examples 5-9 also show that elevated concentration of EDTA, approximately 0.075%, reduces microbial growth in a single autoclave and PVP ensures that the advancing contact angle is not adversely impacted, particularly when used in conjunction with chlorite.
  • An ophthalmic product or kit comprising: a) a composition comprising an admixture or mixture of: i. a chlorous acid compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. a buffer compound; iii. a reductant for neutralizing the chlorous acid compound, provided that, after the reductant’s admixture to the composition, the chlorous acid compound remains effective to inhibit the growth of microorganisms in the composition for a period of time; and iv. an ophthalmologically acceptable carrier and b) a container comprising a sealed compartment comprising, the composition and at least one high molecular weight polyvinylpyrrolidone polymer containing polymeric ophthalmic device.
  • the product or kit of embodiment 1 and any succeeding embodiments, wherein the high molecular weight polyvinylpyrrolidone polymer containing polymeric ophthalmic device is a contact lens. 3.
  • the product or kit of embodiments 1 and 2 and any succeeding embodiments, wherein the high molecular weight polyvinylpyrrolidone polymer containing contact lens retains an advancing dynamic contact angle of from about 40 o to about 80 o . 4.
  • chlorous acid compound is present at a concentration of from about 0.002% to about 0.200%, from about 0.0020% to about 0.1000%, or from 0 about 0.0050% to about 0.1000%, or from about 0.0075% to about 0.1000%), or from about 0.0080% to about 0.0500%, or from about 0.0090% to about 0.0200%, or from about 58 Docket No. VTN6139WOPCT1 0.0095% to 0 about 0.0150%, or about 0.01% by weight based on the total weight of the composition upon formulation. 5.
  • chlorous acid compound is selected from water soluble alkali metal chlorites, water soluble alkaline metal chlorites and mixtures thereof.
  • chlorite is selected from potassium chlorite, sodium chlorite, calcium chlorite, magnesium chlorite and mixtures thereof.
  • chlorite comprises sodium chlorite.
  • the reductant comprises EDTA
  • the chlorous acid compound comprises at least one chlorite compound and the chlorite compound and EDTA are present in molar equivalents of 1:2 to 1:5, or 1:3 to 1:5 or 1:4 upon formulation of the composition. 10.
  • the reductant is selected from iron (II), bisulfite, tin metal, formate, phosphite, hypophosphite, sulfur, thiosulfate, zinc metal, dithionite, manganese metal, aluminum metal, magnesium metal, dithionite, dithiothreitol, NADH 2 , ascorbate, ferricyanide, hydroquinone, tyrosine, aldehydes, N-acetylcysteine, butylated hydroxyanisole, butylated hydroxytoluene, ethylenediaminetetraacetic acid (EDTA), Cellobiose, reducing carbohydrates, phenols, polymeric aldehydes, polymeric phenols, copolymers of
  • the product or kit of embodiment 12 wherein the reductant polyvinylpyrrolidone has a weight average molecular weight of greater than about 100,000 Daltons to about 1,500,000 Daltons, from about 300,000 Daltons to about 1,000,000 Daltons, from about 300,000 Daltons to about 750, 000 Daltons, or from about 320,000 Daltons to about 500,000 Daltons. 14.
  • the product or kit of embodiment 12 wherein the reductant polyvinylpyrrolidone is PVP K-60, PVP K-90, PVP-120 or mixtures thereof.
  • the reductant polyvinylpyrrolidone is selected from polyvinylpyrrolidone K-60, polyvinylpyrrolidone K-90 or mixtures thereof. 16.
  • 60 Docket No. VTN6139WOPCT1 20 The product or kit of any of the preceding embodiments and any succeeding embodiments, wherein the osmolality is from about 200 mOsm/kg to less than about 500 mOsm/kg, from about 200 to about 450 mOsm/kg, from about 205 to about 380 mOsm/kg, from about 210 to about 360 (mOsm/kg), from about 250 to about 350 mOsm/kg, from about 270 to about 330 mOsm/kg, or about 205 mOsm/kg to about 350 mOsm/kg. 21.
  • the buffer compound is a phosphate compound. 24.
  • the product or kit of embodiment 23, wherein the phosphate compound is a combination of salts of the dibasic phosphate anion (HPO 4 ) 2- and salts of the monobasic phosphate anion (H2PO4)-. 25.
  • the product or kit of embodiment 23, wherein the phosphate compound is sodium dibasic phosphate (Na 2 HPO 4 ), sodium monobasic phosphate (NaH 2 PO 4 ) or a mixture thereof.
  • the buffer compound is an organic acid buffer.
  • the product or kit of embodiment 27 wherein the organic acid buffer is a non-phosphate containing organic acid having two or more carboxylic acid groups. 28.
  • the product or kit of embodiment 27 wherein the organic acid buffer is selected from phytic acid, mellitic acid, maleic acid and ophthalmically compatible salts thereof. 29. The product or kit of embodiment 27 wherein the organic acid buffer is selected from maleic acid, its sodium or potassium salts and mixtures thereof. 61 Docket No. VTN6139WOPCT1 30. The product or kit of embodiment 27 wherein the organic acid buffer is selected from mellitic acid, its sodium or potassium salts and mixtures thereof. 31. The product or kit of embodiment 28 wherein the organic acid buffer comprises salts of dibasic organic acid anion (e.g., dibasic sodium maleate monohydrate) and salts of monobasic organic acid anion (monobasic sodium maleate). 32.
  • dibasic organic acid anion e.g., dibasic sodium maleate monohydrate
  • monobasic organic acid anion monobasic sodium maleate
  • 33. The product or kit of any of the preceding embodiments and any succeeding embodiments, wherein the composition is free of boric acid and borates.
  • 34. The product or kit of any of the preceding embodiments and any succeeding embodiments, wherein the composition has a pH of from about 7.0 to about 7.5, or about 7.2 to about 7.4. 35.
  • composition is manufactured under sterile conditions or sterilized during and/or after the period of time.
  • composition is sterilized after the period of time by a sterilization process selected from autoclave sterilization, UV sterilization and gamma electron beam sterilization.
  • a sterilization process selected from autoclave sterilization, UV sterilization and gamma electron beam sterilization.
  • the composition further comprises one or more demulcents. 38.
  • the product or kit of embodiment 38 wherein the demulcent polymer is selected from block copolymer surfactants; polyvinyl alcohol, polyvinyl pyrrolidone; polyacrylic acid; polyethers; hyaluronic acid and hyaluronic acid derivatives; chitosan; polysorbates; dextrans; cellulosic derivatives; acyclic polyamides and mixtures thereof.
  • 62 Docket No. VTN6139WOPCT1 A method of reducing or preventing the reaction between chlorous acid compounds and a high molecular weight polyvinylpyrrolidone polymer containing polymeric ophthalmic device, comprising the steps of: a. mixing a composition comprising: i.
  • a chlorous acid compound in an amount effective to inhibit the growth of microorganisms in the composition; ii. a buffer compound; and iii. a reductant for neutralizing the chlorous acid compound, provided that, after the reductant’s admixture to the composition, the chlorous acid compound remains effective to inhibit the growth of microorganisms in the composition for a period of time; b. placing the composition in a container with the high molecular weight polyvinylpyrrolidone polymer containing polymeric ophthalmic device.
  • the method of any of the preceding method embodiments and any succeeding method embodiments, wherein the sterilization is selected from autoclave sterilization, UV sterilization and gamma electron beam sterilization.
  • the method of any of the preceding method embodiments and any succeeding method embodiments, wherein the sterilization is by autoclave sterilization.
  • the method of any of the preceding method embodiments and any succeeding method embodiments, wherein the high molecular weight polyvinylpyrrolidone polymer containing ophthalmic device is a contact lens.
  • the method of any of the preceding method embodiments and any succeeding method embodiments, wherein the high molecular weight polyvinylpyrrolidone polymer containing contact lens retains an advancing dynamic contact angle of from about 40 o to about 80 o .
  • the chlorous acid compound is present at a concentration of from about 0.002% to about 0.200%, from about 0.0020% to about 0.1000%, or from 0 about 0.0050% to about 0.1000%, or from about 0.0075% to about 0.1000%, or from about 0.0080% to about 0.0500%, or from about 0.0090% to about 0.0200%, or from about 0.0095% to 0 about 0.0150%, or about 0.01% by weight based on the total weight of the composition upon formulation of the composition. 48.
  • the chlorous acid compound is selected from water soluble alkali metal chlorites, water soluble alkaline metal chlorites and mixtures thereof.
  • the chlorite is selected from potassium chlorite, sodium chlorite, calcium chlorite, magnesium chlorite and mixtures thereof.
  • the chlorite comprises sodium chlorite. 51.
  • the reductant is selected from iron (II), bisulfite, tin metal, formate, phosphite, hypophosphite, sulfur, thiosulfate, zinc metal, dithionite, manganese metal, aluminum metal, magnesium metal, dithionite, dithiothreitol, NADH2, ascorbate, ferricyanide, hydroquinone, tyrosine, aldehydes, N-acetylcysteine, butylated hydroxyanisole, butylated hydroxytoluene, ethylenediaminetetraacetic acid (EDTA), diethylenetriamine pentaacetic acid (DTPA) and ophthalmically compatible salts thereof, Cellobiose, reducing carbohydrates, phenols, polymeric aldehydes, polymeric phenols, copolymers of tyrosine acrylamide and N’N-dimethyl acrylamide,
  • the reductant is selected from polymeric aldehydes, ethylenediaminetetraacetic acid, polymeric phenols, reducing carbohydrates and mixtures thereof, or comprises EDTA.
  • the polymeric aldehyde is a polyvinylpyrrolidone.
  • the reductant polyvinylpyrrolidone has a weight average molecular weight of greater than about 100,000 Daltons to about 1,500,000 Daltons, from about 300,000 Daltons to about 1,000,000 Daltons, from about 300,000 Daltons to about 750, 000 Daltons, or from about 320,000 Daltons to about 500,000 Daltons.
  • reductant polyvinylpyrrolidone is PVP K-60, PVP K-90, PVP-120 or mixtures thereof.
  • the total polyvinylpyrrolidone component has a weight average molecular weight of greater than about 100,000 daltons. Docket No. VTN6139WOPCT1 59.
  • the polyvinylpyrrolidone is selected from polyvinylpyrrolidone K-60, polyvinylpyrrolidone K-90 or mixtures thereof. 60.
  • the osmolality is from about 200 mOsm/kg to less than about 500 mOsm/kg, from about 200 to about 450 mOsm/kg, from about 205 to about 380 mOsm/kg, from about 210 to about 360 (mOsm/kg), from about 250 to about 350 mOsm/kg, from about 270 to about 330 mOsm/kg, or about 205 mOsm/kg to about 350 mOsm/kg. 65.
  • the composition has a pH of from about 6.0 to a about 8.0, or a pH of from about 6.5 to about 8.0, or a pH of from about 6.5 to 7.5, or a pH of about 7.0 to about 7.5.
  • the buffer compound is selected from phosphate compound, organic acid buffers, salts thereof or mixtures thereof.
  • the buffer compound is a phosphate compound.
  • the phosphate compound is a combination of salts of the dibasic phosphate anion (HPO4) 2- and salts of the monobasic phosphate anion (H 2 PO 4 ) -. 69.
  • the method of embodiment 67, wherein the phosphate compound is sodium dibasic phosphate (Na2HPO4), sodium monobasic phosphate (NaH2PO4) or a mixture thereof.
  • the buffer compound is an organic acid buffer.
  • the organic acid buffer is a non-phosphate containing organic acid having two or more carboxylic acid groups. 72.
  • the method of embodiment 70 wherein the organic acid buffer is selected from phytic acid, mellitic acid, maleic acid and ophthalmically compatible salts thereof. 73. The method of embodiment 70 wherein the organic acid buffer is selected from maleic acid, its sodium or potassium salts and mixtures thereof. 74. The method of embodiment 70 wherein the organic acid buffer is selected from mellitic acid, its sodium or potassium salts and mixtures thereof. 75. The method of embodiments 70 through 74 wherein the organic acid buffer comprises salts of dibasic organic acid anion (e.g., dibasic sodium maleate monohydrate) and salts of monobasic organic acid anion (monobasic sodium maleate). 76.
  • dibasic organic acid anion e.g., dibasic sodium maleate monohydrate
  • monobasic organic acid anion monobasic sodium maleate
  • the concentration, of the dibasic organic acid anion is from about 0.1% to about 0.3% and the concentration of the monobasic organic acid anion is from 0.005% to about 0.002%, by weight of the composition, when present as the metal (e.g., sodium) monohydrate in the case of the dibasic organic acid.
  • the composition is free of boric acid and borates.
  • VTN6139WOPCT1 The method of any of the preceding embodiments and any succeeding embodiments, wherein the composition has a pH of from about 7.0 to about 7.5, or about 7.2 to about 7.4. 79.
  • composition is manufactured under sterile conditions or sterilized during and/or after the period of time. 80. The method of any of the preceding embodiments and any succeeding 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. 81. The method of any of the preceding embodiments and any succeeding embodiments, wherein the composition further comprises one or more demulcents. 82.
  • the demulcent polymer is selected from block copolymer surfactants; polyvinyl alcohol, polyvinyl pyrrolidone; polyacrylic acid; polyethers; hyaluronic acid and hyaluronic acid derivatives; chitosan; polysorbates; dextrans; cellulosic derivatives; acyclic polyamides and mixtures thereof.
  • the chlorous acid compound concentration is reduced after autoclaving by at least about 50%, about 70%, about 80% or about 90%.
  • the hydrogel contact lens is silicone hydrogel contact lens.
  • the contact lens is a hybrid contact lens. 68 Docket No. VTN6139WOPCT1 The method or product of any of the preceding embodiments wherein the reductant comprises EDTA in a concentration of about 0.01 to about 0.075 wt% based upon the total composition upon formulation.

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Abstract

La présente invention concerne des compositions d'emballage de dispositif ophtalmique contenant un composé d'acide chloreux et un réducteur pour stocker et/ou conditionner un dispositif ophtalmique polymère contenant de la pyrrolidone de vinyle dans les compositions. Sont aussi divulgués des procédés d'utilisation des compositions de la présente invention.
PCT/IB2023/062629 2022-12-21 2023-12-13 Compositions pour dispositifs ophtalmologiques Ceased WO2024134382A1 (fr)

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