Classifications

• • 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
  • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
  • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
  • A61L2/18—Liquid substances or solutions comprising solids or dissolved gases
• • A—HUMAN NECESSITIES
  • A45—HAND OR TRAVELLING ARTICLES
  • A45C—PURSES; LUGGAGE; HAND CARRIED BAGS
  • A45C11/00—Receptacles for purposes not provided for in groups A45C1/00-A45C9/00
  • A45C11/005—Contact lens cases
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
  • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
  • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
  • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
  • A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• • 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
  • A61L12/086—Container, accessories or devices therefor
• • 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
  • A61L12/14—Organic compounds not covered by groups A61L12/10 or A61L12/12
• • 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
  • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
• • 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
  • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
  • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
  • A61L2/04—Heat
  • A61L2/06—Hot gas
  • A61L2/07—Steam
• • 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
  • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
  • A61L2/26—Accessories or devices or components used for biocidal treatment
  • A61L2/28—Devices for testing the effectiveness or completeness of sterilisation, e.g. indicators which change colour
• • 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
  • A61L9/00—Disinfection, sterilisation or deodorisation of air
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
  • B29D—PRODUCING PARTICULAR ARTICLES FROM PLASTICS OR FROM SUBSTANCES IN A PLASTIC STATE
  • B29D11/00—Producing optical elements, e.g. lenses or prisms
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
  • B29D—PRODUCING PARTICULAR ARTICLES FROM PLASTICS OR FROM SUBSTANCES IN A PLASTIC STATE
  • B29D11/00—Producing optical elements, e.g. lenses or prisms
  • B29D11/00605—Production of reflex reflectors
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
  • B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
  • B65B25/00—Packaging other articles presenting special problems
  • B65B25/008—Packaging other articles presenting special problems packaging of contact lenses
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
  • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
  • B65D81/00—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents
  • B65D81/18—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient
  • B65D81/22—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient in moist conditions or immersed in liquids
• • C—CHEMISTRY; METALLURGY
  • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
  • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
  • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
  • C11D3/0005—Other compounding ingredients characterised by their effect
  • C11D3/0078—Compositions for cleaning contact lenses, spectacles or lenses
• • C—CHEMISTRY; METALLURGY
  • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
  • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
  • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
  • C11D3/16—Organic compounds
  • C11D3/37—Polymers
  • C11D3/3703—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
  • C11D3/3719—Polyamides or polyimides
• • G—PHYSICS
  • G02—OPTICS
  • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
  • G02B5/00—Optical elements other than lenses
  • G02B5/12—Reflex reflectors
  • G02B5/122—Reflex reflectors cube corner, trihedral or triple reflector type
  • G02B5/124—Reflex reflectors cube corner, trihedral or triple reflector type plural reflecting elements forming part of a unitary plate or sheet

Definitions

• the field of the invention is contact lenses packages.
• Microbial contamination of contact lenses is a serious public health concern due to its implications in ocular infiltrates, infections and microbial keratitis.
• Studies have demonstrated that lens handling greatly increases the incidence of microbial contamination of lenses see e.g. Szczotka-Flynn et al., Eye Contact Lens (2010) 36(2):116-29).
• Daily disposable contact lens wearers can be particularly at risk for contamination due to the non-compliant storage of contact lenses after use in their original packaging solution and subsequent reuse (Boost et al., Optom Vis Sci (2011) 88(12:1409-13).
• ⁇ -polylysine is a homopolymer of about 25-35 residues of L-lysine in which the epsilon-amino and carboxyl groups of L-Lysine are linked. It is a naturally-occurring polymer produced by Streptomyces species. It has broad-spectrum antimicrobial activity and has been widely used as a food preservative in Japan and as an additive in a variety of consumer products. The use of ⁇ -polylysine in contact lens care solutions has been described (see e.g. U.S. Pat. No. 6,187,264, and U.S. Pat. Publ. No. 2005/0074467). Antimicrobial hydrogels made from epsilon-poly-L-lysine-graft-methacrylamide have been reported (Zhou et al., Biomaterials 32 (2011) 2704-2712).
• the invention provides a sealed contact lens package comprising a sterile, unworn contact lens and a contact lens packaging solution, said contact lens packaging solution comprising epsilon polylysine ( ⁇ PLL), wherein the unworn contact lens exhibits reduced contamination from at least one microbe, wherein said reduced contamination is determined by a test where Pseudomonas aeruginosa (PA) introduced to the lens during removal from the contact lens packaging solution compared to a control contact lens packaged in an identical contact lens packaging solution but without said ⁇ PLL.
• PA Pseudomonas aeruginosa
• the unworn contact less results in less than a two log kill of PA compared to the control contact lens when tested after 24 hours incubation with 104 CFU PA using an in vitro bioactivity assay.
• the contact lens package comprises (a) a plastic base member comprising a cavity which retains a sterile, unworn contact lens and a contact lens packaging solution comprising epsilon polylysine ( ⁇ PLL); and (b) a resealable cover that forms a liquid-tight seal with the plastic base member.
• a plastic base member comprising a cavity which retains a sterile, unworn contact lens and a contact lens packaging solution comprising epsilon polylysine ( ⁇ PLL); and (b) a resealable cover that forms a liquid-tight seal with the plastic base member.
• ⁇ PLL epsilon polylysine
• a sealed contact lens package comprising a sterile, unworn contact lens and a contact lens packaging solution comprising epsilon polylysine ( ⁇ PLL) in an amount effective to reduce or completely eliminate microbial contamination introduced to the lens during its removal from the package.
• unworn means that the contact lens has never been placed on an eye
• sealed means having a water-tight seal.
• a sealed contact lens package comprising a sterile, unworn contact lens and a contact lens packaging solution comprising epsilon polylysine ( ⁇ PLL) are provided.
• the unworn contact lens exhibits reduced contamination from at least one microbe.
• the reduced contamination can be determined by a test where Pseudomonas aeruginosa (PA) introduced to the lens during removal from the contact lens packaging solution compared to a control contact lens packaged in an identical contact lens packaging solution but without said ⁇ PLL.
• PA Pseudomonas aeruginosa
• At least one microbe can comprise, consists of, consists essentially of, or include Pseudomonas aeruginosa and/or Staphylococcus aureus , and/or the at least one microbe is a microbe(s) found in microbial keratitis and/or at least one microbe causing at least in part or entirely ocular infiltrates and/or infections.
• the contact lens sealed in the contact lens package of the present disclosure may be made from any contact lens material, including but not limited to conventional hydrogels and silicone hydrogels.
• a “conventional hydrogel” refers to a material formed from polymerization of one or more hydrophilic monomers such as 2-hydroxyethyl methacrylate (HEMA) or vinyl alcohol, optionally in combination with other monomers, and contains no siloxane (i.e. a molecule comprising at least one Si—O group).
• HEMA 2-hydroxyethyl methacrylate
• vinyl alcohol optionally in combination with other monomers, and contains no siloxane (i.e. a molecule comprising at least one Si—O group).
• siloxane i.e. a molecule comprising at least one Si—O group
• Examples of conventional hydrogels include etafilcon A, nelfilcon A, ocufilcon B, ocufilcon D, omafilcon A, omafilcon D and
• Silicone hydrogel materials are typically formed from polymerization of one or more monomers or prepolymers comprising at least one Si—O group with one or more hydrophilic monomers.
• silicone hydrogels include balafilcon A, comfilcon A, enfilcon A, somofilcon A, narafilcon A, narafilcon B, lotrafilcon A, stenfilcon A, and senofilcon A.
• the sealed contact lens package comprises a sterile, unworn silicone hydrogel contact lens.
• the silicone hydrogel contact lens is non-ionic, meaning it that it contains no anionic groups that bind to the cationic amine groups present in the ⁇ PLL via ionic interaction.
• the silicone hydrogel contact lens is made from a material selected from comfilcon A or stenfilcon A.
• the sealed contact lens package comprises an unworn conventional hydrogel contact lens made from a material selected from ocufilcon B, ocufilcon D, or omafilcon A.
• the contact lens sealed in the contact lens package of the present disclosure may be of any lens wear modality.
• Lens wear modality refers to the how many days and nights in a row the lens can be worn without removal.
• the contact lens sealed in the contact lens package of the present disclosure is a daily disposable lens. Daily disposable lenses are indicated for single use, up to about 12 or 16 hours of continuous wear, and should be discarded after the single use.
• the contact lens sealed in the contact lens package of the present disclosure is a daily wear lens. Daily wear lenses are worn during the waking hours, typically up to about 12 to 16 hours, and are removed before sleep. Daily wear lenses are typically stored in a contact lens case containing a contact lens care solution for cleaning and disinfecting the lens during the hours of non-use. Daily wear lenses are typically discarded after a maximum of 30 days wear.
• the contact lens is an extended wear lens. Extended wear lenses are typically worn continuously for up to 6, 14 or 30 consecutive days and nights.
• the packaging solution sealed within the contact lens package of the present disclosure may be any contact-lens compatible solution comprising an effective amount of ⁇ PLL.
• the packaging solution comprises, consists, or consists essentially, of an aqueous solution of a buffer, and/or a tonicity agent, and ⁇ PLL.
• the packaging solution contains additional agents such as one or more additional antimicrobial agents, and/or a comfort agent, and/or a hydrophilic polymer, and/or a surfactant and/or other additive that prevents the lens from sticking to the package.
• the packaging solution can have a pH in the range of about 6.8 or 7.0 up to about 7.8 or 8.0.
• the packaging solution comprises phosphate buffer or borate buffer.
• the packaging solution comprises a tonicity agent selected from sodium chloride or sorbitol in an amount to maintain osmolality in the range of about 200 to 400 mOsm/kg, and typically from about 270 mOsm/kg up to about 310 mOsm/kg.
• a reference to “examples”, “an example”, “one example”, or similar phrase is intended to introduce a feature or features of the contact lens package, unworn contact lens, or packaging solution, as the case may be (depending on context) that can be combined with any combination of previously-described or subsequently-described examples (i.e. features), unless a particular combination of features is mutually exclusive, or if context indicates otherwise.
• An effective amount of ⁇ PLL is an amount that reduces microbial contamination introduced to the lens during its removal from the contact lens package (e.g., as compared to no ⁇ PLL present).
• the ability of ⁇ PLL to reduce microbial contamination introduced to a lens during its removal from a package can be demonstrated using methodology substantially as described in Example 1 or Example 2 below.
• Example 1 demonstrates that microbial contamination of contact lenses caused by normal, non-pathogenic skin flora can be significantly reduced by inclusion of ⁇ PLL in the contact lens packaging solution.
• Example 2 demonstrates that microbial contamination of contact lenses caused by Pseudomonas aeruginosa (PA), one of the most common pathogens implicated in microbial keratitis, can also be significantly reduced by inclusion of ⁇ PLL in the contact lens packaging solution.
• PA Pseudomonas aeruginosa
• the unworn contact lens exhibits reduced contamination from PA introduced to the lens during removal from the packaging solution compared to a control contact lens in the same packaging comprising a contact lens packaging solution without ⁇ PLL but otherwise identical, as determined using a lens handling assay as described or substantially as described in Example 2.
• the packaging solution comprises ⁇ PLL in amounts of at least 5 ppm, 10 ppm, 25 ppm, 50 ppm, 100 ppm, 150 ppm, 200 ppm, 250 ppm, or 500 ppm.
• the packaging solution comprises 10-50 ppm ⁇ PLL, 25-75 ppm ⁇ PLL, 50-150 ppm ⁇ PLL, or 100-500 ppm ⁇ PLL.
• the concentration of ⁇ PLL in a packaging solution is determined prior to its contact with the unworn contact lens.
• ⁇ PLL is commercially available typically as a homopolymer ranging from about 25 to about 35 lysine (LYS) residues (CAS no. 28211-04-3). All fractions of the naturally-occurring homopolymer of ⁇ PLL may be used. Alternatively, a select fraction of the ⁇ PLL may be used (e.g. a homopolymer of 30-35 LYS residues) with the remaining fractions removed and not used in this option. As an alternative to naturally-occurring ⁇ PLL, the ⁇ PLL used in the packaging solution may be obtained from synthetic peptide methods.
• LYS lysine residues
• the amount of ⁇ PLL included in the contact lens packaging solution results in less than a two log kill of PA compared to a control contact lens when tested after 24 hours incubation with 10 4 CFU (colony-forming units) PA as determined using an in vitro bioactivity assay substantially as described in Example 4 below.
• the contact lens package remains effective against microbial contamination introduced from initial handling of the lens during its removal from its original packaging, and thus is particularly suitable for a daily disposable contact lens.
• the contact lens package described herein can provide protection against microbial contamination that might arise from a non-compliant daily lens wearer who stores a worn lens overnight in its original package and remaining packaging solution for a second day of wear.
• the contact lens package comprises a plastic base member comprising a cavity configured to retain the contact lens and packaging solution and a flange region extending outwardly around the cavity. A removable foil is attached to the flange region to provide a sealed contact lens package.
• the contact lens package comprises a contact lens indicated for daily wear for at least 2 days, wherein the package is configured to allow resealing after its initial opening for subsequent replacement of the lens for overnight storage after it has been worn.
• the contact lens package may comprise a plastic base member comprising a cavity configured to retain the contact lens and packaging solution and a resealable cover.
• a “resealable cover” is one that is configured to form a liquid-tight or spill-proof seal with the base member after the contact lens package is opened.
• the plastic base member may comprise a plurality of threads for engagement with a compatible set of threads on a cap which serves as the resealable cover.
• Such configurations are commonly used in contact lens care cases (see e.g. U.S. Pat. No. 3,977,517).
• an advantage of the contact lens package disclosed herein is that it can serve a dual purpose, i.e. both as a contact lens package for a sterile, unworn contact lens and as a subsequent contact lens carrying case for a worn lens.
• a method of manufacturing a contact lens package including the step of placing an unworn contact lens and a contact lens packaging solution comprising ⁇ PLL in a receptacle, placing a cover on the receptacle, and sealing the cover on the receptacle.
• the receptacle is configured to receive a single contact lens and an amount of packaging solution sufficient to completely cover the contact lens, typically about 0.5-1.5 ml.
• the receptacle may be made from any suitable material, such as glass or plastic.
• the receptacle comprises a plastic base member comprising a cavity configured to retain the contact lens and packaging solution and a flange region extending outwardly around the cavity, and the cover comprises a removable foil attached to the flange region to provide the sealed contact lens package.
• the removable foil may be sealed by any conventional means such as heat sealing or gluing.
• the receptacle is in the form of a plastic base member comprising a plurality of threads and the cover comprises a plastic cap member comprising a compatible set of thread for engagement with the threads of the base member thereby providing a resealable cover.
• the contact lens package may comprise a plastic cover comprising features that engage with compatible features of the receptacle to form an interference fit.
• the method of manufacturing the sealed contact lens package may further comprise sterilizing the unworn contact lens by autoclaving the sealed contact lens package.
• balafilcon A contact lenses in their original blister packaging were used in this lens-handling study.
• Five individuals washed their hands with soap and water and dried their hands using paper towels.
• the foil cover of each blister was opened aseptically with a gloved hand by the investigator.
• Each individual removed and gently rubbed the lens for approximately 5 seconds using the same hand used to turn off the faucet.
• Each rubbed lens was then placed into an individual sterile 2 mL microcentrifuge (EppendorfTM) tube with 1 mL PBS-T and capped.
• PBS refers phosphate buffered saline of 0.78 wt. % NaCl, 0.05 wt. % sodium phosphate monobasic, and 0.36 wt. % sodium phosphate dibasic at pH 7.5.
• PBS-T refers to PBS with 0.05% Polysorbate 80.
• the tubes were sonicated for 3 cycles of 30 seconds each with 10 seconds vortexing in between. After the final sonication the tubes were vortexed for 10 minutes at 1000 rpm using a multi-tube vortexer. The entire volume of extract from each tube was plated onto a blood agar plate, allowed to dry in a biochemical hood, and incubated at 37° C. for 48-72 hours. Bacteria were counted and reported as CFU/lens. Each bacterium with a distinct phenotype was identified using a Biotyper.
• Detectable levels of contamination from common skin bacteria were found on all five balafilcon A contact lenses. The range of contamination was from 115-6500 CFU/lens. No lens was sterile. Although the identified bacteria are not commonly found in microbial keratitis, they can cause disease in immune-compromised patients.
• ⁇ PLL in a contact lens packaging solution would be protective immediately against microbes deposited during lens removal from a blister package
• the above lens-handling study was repeated using ocufilcon D, comfilcon A, and omafilcon A contact lenses that had been individually packaged in a contact lens blister package containing a packaging solution of either PBS or PBS with 500 ppm ⁇ PLL, sealed with a foil cover, and autoclaved. All three lenses demonstrated a significant reduction in bioburden when ⁇ PLL was present in the packaging solution, with the following average log kill: ocufilcon D—2.4, comfilcon A—1.4, and omafilcon A—2.2.
• the bacterial adherence onto the surface of comfilcon A lenses removed from autoclaved blister packages containing a packaging solution of PBS with or without ⁇ PLL (10, 25, 100, or 500 ppm) was evaluated using a modification of methods described by Nomachi et al., Eye & Contact Lens (2013) 39:234-238. Briefly, the bacterial adherence onto the surface of comfilcon A contact lenses was evaluated using stock solutions of Pseudomona aeruginosa (PA) and Staphylococcus aureus (SA) prepared substantially as described in Example 3 below. Sterile surgical plastic gloves were put on both hands aseptically.
• PA Pseudomona aeruginosa
• SA Staphylococcus aureus
• the thumb and index finger of a hand gloved were dipped into the bacterial suspension (approximately 10 3 CFU/ml in PBS) and used to remove a lens from a package.
• the bacterial suspension approximately 10 3 CFU/ml in PBS
• Four lenses of each type of packaging solution were tested. Each lens was placed into a microcentrifuge tube with 1 mL PBS-T, sonicated for 1.5 minute and vortexed for 10 minutes at 1000 rpm.
• the entire volume of the extract was plated onto a culture dish with tryptic soy agar (TSA) and grown at 37° C. for 2 days in an incubator.
• TSA tryptic soy agar
• the blister package and remaining packaging solution were left covered with the original blister foil at ambient temperature. After 16 hours, the entire volume of remaining packaging solution ( ⁇ 1 mL) was plated onto a culture dish with TSA and left in an incubator at 37° C. for 2 days to grow.
• the packaging solution without any added ePL had an average of 331 CFU/Lens. None of the ePL-containing packaging solutions exhibited microbial growth, i.e. all had 0 CFU/Lens.
• Cultures were prepared from growing a single colony of each of the bacterial species shown in Table 3 below in 50 mL. trypticase soy broth (TSB) overnight at 37° C. on a rotary shaker. 1 mL of each culture was centrifuged, and the bacterial pellet resuspended in 1.0 mL of the diluent shown in Table 3. For each bacterial species, a suspension of approximately 10 8 CFU/mL was prepared by diluting the bacterial suspension to achieve the optical density indicated in Table 3. Each suspension is further diluted for use in the handling assay described in Example 2 or the in vitro bioactivity assay described in Example 4.
• TAB trypticase soy broth
• a contact lens is removed from its packaging and rinsed in 2.5 ml sterile PBS for a few seconds to remove residual packaging solution.
• the rinsed lens is then transferred to an individual well of a 24-well plate containing 1.0 mL of 10 4 CFU PA.
• the plate is incubated at 37° C. with gentle shaking for 24 hours.
• the lens is removed from its well and transferred to a well of a 12-well plate containing 2.5 mL of sterile PBS.
• the plate is gently swirled for about 30 seconds. This step is repeated once for each lens.
• Each washed lens is placed in a microcentrifuge tube containing 1 mL of Dey-Engley (DE) neutralizing broth and adhered bacteria are removed by a combination of sonication for about 2 minutes and vortexing for about 10 minutes.
• Serial dilutions are made for each recovered cell suspension using DE neutralizing broth and suitable dilutions are plated onto TSA. Plates are incubated overnight at 37° C. and CFUs are counted.
• DE Dey-Engley
• the CFU for each plate is multiplied by the dilution factor (DF) as well as the plating dilution factor (PDF).
• the total CFUs recovered for a given sample are then converted to the log 10.
• the present invention includes the following aspects/embodiments/features in any order and/or in any combination:
• a sealed contact lens package comprising a sterile, unworn contact lens and a contact lens packaging solution comprising epsilon polylysine ( ⁇ PLL), wherein the unworn contact lens exhibits reduced contamination from Pseudomonas aeruginosa (PA) introduced to the lens during removal from the contact lens packaging solution compared to a control contact lens packaged in a substantially identical contact lens packaging solution without ⁇ PLL.
• PA Pseudomonas aeruginosa
• a sealed contact lens package comprising a sterile, unworn contact lens and a contact lens packaging solution comprising epsilon polylysine ( ⁇ PLL), wherein the unworn contact lens exhibits reduced contamination from at least one microbe, wherein said reduced contamination is determined by a test where Pseudomonas aeruginosa (PA) introduced to the lens during removal from the contact lens packaging solution compared to a control contact lens packaged in an identical contact lens packaging solution but without said ⁇ PLL.
• PA Pseudomonas aeruginosa
• the package of any preceding or following embodiment/feature/aspect wherein, in the test, the unworn contact less results in less than a two log kill of PA compared to the control contact lens when tested after 24 hours incubation with 10 4 CFU PA using an in vitro bioactivity assay. 4. The package of any preceding or following embodiment/feature/aspect, wherein, in the test, the unworn contact less results in less than a one log kill of PA (but more than a zero log kill) compared to the control contact lens when tested after 24 hours incubation with 10 4 CFU PA using an in vitro bioactivity assay. 5. The package of any preceding or following embodiment/feature/aspect, wherein the contact lens is a silicone hydrogel contact lens. 6.
• the package of any preceding or following embodiment/feature/aspect, wherein the contact lens is a non-ionic contact lens. 7. The package of any preceding or following embodiment/feature/aspect, wherein the contact lens is an ionic contact lens. 8. The package of any preceding or following embodiment/feature/aspect, wherein the contact lens is a daily disposable contact lens. 9. The package of any preceding or following embodiment/feature/aspect, wherein the contact lens is a daily wear contact lens. 10. The package of any preceding or following embodiment/feature/aspect, wherein the packaging solution comprises between 5 ppm and 500 ppm ⁇ PLL. 11. The package of any preceding or following embodiment/feature/aspect, wherein the packaging solution comprises between 5 ppm and 50 ppm ⁇ PLL. 12.
• the contact lens package further comprises (a) a plastic base member comprising i) a cavity which retains the unworn contact lens and the contact lens packaging solution, and ii) a flange region extending outwardly around the cavity; and (b) a removable foil attached to the flange region.
• the contact lens package further comprises (a) a plastic base member comprising a cavity which retains the unworn contact lens and the contact lens packaging solution; and (b) a resealable cover that forms a liquid-tight seal with the plastic base member.
• the plastic base member comprises a plurality of threads for engagement with a compatible set of threads on the resealable cover.
• the at least one microbe is Pseudomonas aeruginosa.
• the at least one microbe is Staphylococcus aureus.
• the at least one microbe is a microbe found in microbial keratitis. 18.
• a method of manufacturing the sealed contact lens package comprising placing an unworn contact lens and a contact lens packaging solution comprising ⁇ PLL in a receptacle configured to receive a contact lens and sealing the receptacle with a cover to provide a sealed contact lens package, wherein the unworn contact lens exhibits reduced contamination from Pseudomonas aeruginosa (PA) introduced to the lens during removal from the contact lens packaging solution compared to a control contact lens packaged in a substantially identical contact lens packaging solution without ⁇ PLL, and wherein the unworn contact less results in less than a two log kill of PA compared to the control contact lens when tested after 24 hours incubation with 10 4 CFU PA using an in vitro bioactivity assay.
• PA Pseudomonas aeruginosa
• a method of manufacturing the sealed contact lens package comprising placing an unworn contact lens and a contact lens packaging solution comprising ⁇ PLL in a receptacle configured to receive a contact lens and sealing the receptacle with a cover to provide a sealed contact lens package, wherein the unworn contact lens exhibits reduced contamination from at least one microbe, wherein said reduced contamination is determined by a test where Pseudomonas aeruginosa (PA) introduced to the lens during removal from the contact lens packaging solution compared to a control contact lens packaged in an identical contact lens packaging solution but without said ⁇ PLL, and wherein the unworn contact less results in less than a two log kill of PA compared to the control contact lens when tested after 24 hours incubation with 10 4 CFU PA using an in vitro bioactivity assay.
• PA Pseudomonas aeruginosa
• a method of manufacturing the sealed contact lens package comprising placing an unworn contact lens and a contact lens packaging solution comprising ⁇ PLL in a receptacle configured to receive a contact lens and sealing the receptacle with a cover to provide a sealed contact lens package, wherein the unworn contact lens exhibits reduced contamination from Pseudomonas aeruginosa (PA) introduced to the lens during removal from the contact lens packaging solution compared to a control contact lens packaged in a substantially identical contact lens packaging solution without ⁇ PLL, and wherein the contact lens package comprises a resealable cover.
• PA Pseudomonas aeruginosa
• a method of manufacturing the sealed contact lens package comprising placing an unworn contact lens and a contact lens packaging solution comprising ⁇ PLL in a receptacle configured to receive a contact lens and sealing the receptacle with a cover to provide a sealed contact lens package, wherein the unworn contact lens exhibits reduced contamination from at least one microbe, wherein said reduced contamination is determined by a test where Pseudomonas aeruginosa (PA) introduced to the lens during removal from the contact lens packaging solution compared to a control contact lens packaged in an identical contact lens packaging solution but without said ⁇ PLL, and wherein the contact lens package comprises a resealable cover.
• PA Pseudomonas aeruginosa
• any preceding or following embodiment/feature/aspect wherein the contact lens package is any one of 1 through 17. 25. The method of any preceding or following embodiment/feature/aspect, further comprising sterilizing the unworn contact lens by autoclaving the sealed contact lens package.
• the present invention can include any combination of these various features or embodiments above and/or below as set forth in sentences and/or paragraphs. Any combination of disclosed features herein is considered part of the present invention and no limitation is intended with respect to combinable features.

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• 2015
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