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WO1996020736A1 - Desinfection de verres de contact avec du superoxyde - Google Patents

Desinfection de verres de contact avec du superoxyde Download PDF

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Publication number
WO1996020736A1
WO1996020736A1 PCT/US1995/015989 US9515989W WO9620736A1 WO 1996020736 A1 WO1996020736 A1 WO 1996020736A1 US 9515989 W US9515989 W US 9515989W WO 9620736 A1 WO9620736 A1 WO 9620736A1
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WO
WIPO (PCT)
Prior art keywords
superoxide
solution
kit
peroxidase
hydrogen peroxide
Prior art date
Application number
PCT/US1995/015989
Other languages
English (en)
Inventor
Terrence J. Hunt
Original Assignee
Allergan
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Allergan filed Critical Allergan
Priority to AU45124/96A priority Critical patent/AU4512496A/en
Publication of WO1996020736A1 publication Critical patent/WO1996020736A1/fr

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Classifications

    • 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
    • C11D3/39—Organic or inorganic per-compounds
    • C11D3/3942—Inorganic per-compounds
    • 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
    • A61L12/12—Non-macromolecular oxygen-containing compounds, e.g. hydrogen peroxide or ozone
    • A61L12/124—Hydrogen peroxide; Peroxy compounds
    • A61L12/126—Hydrogen peroxide; Peroxy compounds neutralised with catalase or peroxidase
    • 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
    • B65D81/32—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 for packaging two or more different materials which must be maintained separate prior to use in admixture
    • B65D81/3216—Rigid containers disposed one within the other
    • B65D81/3227—Rigid containers disposed one within the other arranged parallel or concentrically and permitting simultaneous dispensing of the two materials without prior mixing
    • 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
    • C11D3/38—Products with no well-defined composition, e.g. natural products
    • C11D3/386—Preparations containing enzymes, e.g. protease or amylase
    • C11D3/38654—Preparations containing enzymes, e.g. protease or amylase containing oxidase or reductase

Definitions

  • the present invention relates to an improved method for disinfecting contact lenses using superoxide.
  • the present invention also relates to kits and devices for carrying out the inventive method.
  • 4,407,791 and 4,525,346 show the polyguaternary ammonium contact lens disinfecting agent 1-tris (2-hydroxyethyl) ammonium-2- butenyl-4-poly [1-dimethyl ammonium-2-butenyl] - ⁇ -tris (2- hydroxyethyl) ammonium chloride salt.
  • European patent application 89810477.3 discloses the disinfecting agent dodecyl-dimethyl- (2-phenoxyethyl) -ammonium bromide.
  • U.S. Patent No. 4,029,817, assigned to Allergan, Inc. shows the contact lens disinfecting agent tallow triethanol ammonium chloride.
  • U.S. Patent No. 4,758,595 describes the hexamethylene biguanide contact lens disinfecting agent.
  • U.S. Patent No. 4,588,586, to Kessler et al . discloses a method for disinfecting a contact lens involving the use of peroxidases to generate free radicals in a solution.
  • a peroxidase such as horseradish peroxidase, is used to oxidize substrates, or "donor molecules," such as phenols, aryl and alkyl amines, hydroquinones, NADH, NADPH, palmitate, halogens, glutathione, ferrocytochrome C and ascorbate to produce anti-bacterial free radicals.
  • donor molecules such as phenols, aryl and alkyl amines, hydroquinones, NADH, NADPH, palmitate, halogens, glutathione, ferrocytochrome C and ascorbate to produce anti-bacterial free radicals.
  • a method of disinfecting a contact lens comprising the steps of generating superoxide in a solution, and exposing a contact lens to the superoxide in the solution for a time effective to disinfect the lens.
  • superoxide is generated enzymatically.
  • the superoxide generating step comprises oxidizing a peroxidase with a first hydrogen peroxide molecule in a solution to generate an oxidized peroxidase, oxidizing a substrate in the solution with the oxidized peroxidase to generate a cationic radical, and oxidizing a second hydrogen peroxide molecule in the solution with the cationic radical to generate superoxide.
  • superoxide is generated electrochemically.
  • the superoxide generating step comprises applying an electrical potential to a solution comprising a compound capable of forming a cationic radical upon application thereof, thereby forming a cationic radical, and oxidizing a hydrogen peroxide molecule in the solution with the cationic radical to generate superoxide.
  • Another more specific aspect of the present invention is directed to generation of superoxide chemically.
  • the superoxide generating step comprises the step of dissolving in the solution a superoxide salt.
  • An additional more specific aspect of the present invention relates to generation of superoxide in an aqueous solution under conditions permitting the disproportionation of superoxide to hydrogen peroxide.
  • a contact lens is exposed to the aqueous solution for a time effective to disinfect the lens.
  • the superoxide is generated by dissolution of a superoxide salt, such as potassium superoxide, in the aqueous solution.
  • a kit for disinfecting a contact lens comprising a system for generating an effective contact lens disinfecting amount of superoxide in a solution, and preferably a container adapted to hold a contact lens and a solution.
  • the kit further includes a solution, such as a saline solution, for the system for generating superoxide.
  • a solution such as a saline solution
  • the kit includes an enzymatic system for generating superoxide.
  • the enzymatic system includes a peroxidase, a substrate for the peroxidase which is capable of being oxidized to generate a cationic radical, and a source of hydrogen peroxide.
  • the kit includes an electrochemical system for generating superoxide.
  • the electrochemical system includes an apparatus for applying an electrical potential to the solution, a compound capable of forming a cationic radical in the solution upon application of the electrical potential thereto, and a source of hydrogen peroxide.
  • the kit includes a chemical system for generating superoxide.
  • the chemical system includes a superoxide salt.
  • an article of manufacture for use in disinfecting a contact lens which comprises a surface upon which a peroxidase is immobilized in reactive form.
  • the amount of the peroxidase is sufficient to initiate a series of reactions, in the presence of a solution comprising hydrogen peroxide and a substrate for an oxidized form of the peroxidase, which generates an amount of superoxide sufficient to disinfect the contact lens.
  • the article is a container adapted to hold a contact lens and a solution, or a dipstick.
  • a dispenser for a system for generating superoxide which comprises an outer container, a plurality of inner bladders, in particular two inner bladders, disposed within the container, and a cap to which the outer container and plurality of inner bladders are removably affixed.
  • the cap has defined therein a manifold which is in fluid communication with each of the plurality of inner bladders, and an external opening which is in fluid communication with the manifold.
  • Each bladder of the dispenser can be at least partially filled with a different solution, such that the solutions combine within the manifold to form the system for generating superoxide.
  • FIG. 1 depicts an exemplary enzymatic reaction sequence for generating superoxide
  • FIG. 2 is a graph showing the dependence of superoxide half-life on solution pH
  • FIG. 3 depicts a container for use with an embodiment of the inventive method using an enzymatic system for generating superoxide
  • FIG. 4 depicts a dipstick for use in an embodiment of the inventive method using an enzymatic system for generating superoxide
  • FIG. 5 depicts an apparatus for use with an electrochemical disinfection method according to the invention.
  • FIGS. 6-8 depict an article useful for dispensing a system for generating superoxide, wherein
  • FIG. 6 is a perspective view of the article showing the disposition of two inner bladders within an outer container
  • FIG. 7 is a sectional view along line A-A' in FIG. 6 showing the disposition of the two inner bladders within the outer container, with the large arrows indicating the application of external pressure, such as by squeezing, and the small arrows indicating the action on the inner bladders of air within the article compressed as a result of the external pressure, and
  • FIG. 8 is a sectional view along line B-B' in FIG. 6 showing the attachment of the outer container and inner bladders to a cap within which is defined a manifold for mixing solutions which are dispensed from the inner bladders.
  • the present invention can be used with all contact lenses such as conventional hard, soft, rigid, gas permeable, and silicone lenses but is preferably employed with soft lenses such as those commonly referred to as hydrogel lenses prepared from monomers such as hydroxyethyl methacrylate, hydroxyethylmethyl methacrylate, vinylpyrrolidone, glycerol methacrylate, methacrylic acid or acid esters and the like. Hydrogel lenses typically absorb significant amounts of water such as from 38 to 80 percent by weight. Care should be exercised when using the present invention with tinted contact lenses, as tinted lenses may be bleached to a slight extent by compositions of the invention.
  • the present invention in its broadest aspect affords disinfection of a contact lens through exposure of the contact lens to a solution comprising superoxide.
  • a solution comprising superoxide.
  • system denotes any element or combination of elements, whether enzymatic, electrochemical, chemical or otherwise, which singly or together are capable of producing superoxide in a solution (preferably a saline solution or other aqueous solution) .
  • enzymatic system denotes a system including an enzyme or combination of enzymes which participates in a reaction or sequence of reactions leading to the generation of superoxide.
  • An “electrochemical system” as used herein is a system in which an electrical potential is applied to at least one chemical species in a solution to generate superoxide.
  • An electrochemical system can also include means for applying the electrical potential to the chemical agent.
  • a “chemical system” as used herein is a system in which at least one non-enzymatic chemical species, but no enzyme, participates in a reaction or sequence of reactions leading to the generation of superoxide.
  • an effective disinfecting amount of superoxide is generated in the solution in which the contact lens to be treated is disposed.
  • An effective disinfecting amount of superoxide is an amount which will at least partially reduce the microorganism population in the solutions employed.
  • an effective disinfecting amount is that amount which will reduce the microbial burden by two log orders in four hours and more preferably by one log order in one hour for all organisms with the exception of A . fumigatus .
  • an effective disinfecting amount is an amount which will eliminate the microbial burden on a contact lens when used in a contact lens care regimen which includes a recommended soaking time (FDA Chemical Disinfection Efficacy Test-July, 1985 Contact Lens Solution Draft Guidelines, incorporated herein by reference) .
  • a first aspect of the invention comprises enzymatic generation of superoxide in a solution.
  • An exemplary enzymatic generation process is depicted in Figure 1.
  • a molecule of hydrogen peroxide in a solution for example saline solution, activates (i.e., oxidizes) a peroxidase.
  • the activated enzyme subsequently oxidizes a substrate to produce a cationic radical.
  • the cationic radical so formed oxidizes another molecule of hydrogen peroxide to form superoxide.
  • the superoxide so formed is then available for disinfection of the contact lens.
  • the hydrogen peroxide molecules can be provided in stabilized form in the solution according to well-known methods. Alternatively, the hydrogen peroxide molecules can be generated chemically or enzymatically in the solution.
  • Chemical sources of hydrogen peroxide can include, for example, sodium perborate and sodium peroxide.
  • Enzymatic sources include the glucose/glucose oxidase system. Other chemical and enzymatic systems known to those skilled in the art can also be employed to generated hydrogen peroxide.
  • an amount of hydrogen peroxide is provided which is sufficient for generation of an amount of superoxide capable of disinfecting the contact lens.
  • the enzyme or combination of enzymes useful according to the invention is capable of oxidizing a substrate to produce a cationic radical, which subsequently oxidizes a second hydrogen peroxide molecule to produce superoxide.
  • Any enzyme or enzyme combination capable of producing a cationic radical as described herein is contemplated as being within the scope of the instant invention.
  • Exemplary enzymes include ferric peroxidases, horseradish peroxidase and lactoperoxidase.
  • a preferred ferric peroxidase is lignin peroxidase.
  • Other peroxidases can also be employed.
  • the enzymatic generation of superoxide be carried out at room temperature.
  • the pH of the solution preferably ranges from about 7 to 12, more particularly from about 8 to 11.
  • the particular pH for a given system will be determined by balancing the desired disinfection efficacy against enzyme activity.
  • Superoxide half-life is strongly dependent on pH, as shown in Figure 2 (data from J. Rabini et al., J. Phys . Chem. , vol. 7, p. 3736 (1969); S. Marklund, J. Biol . Chem. , vol. 251, p. 7505 (1976)).
  • superoxide half-life is significantly increased.
  • the increased half-life in turn tends to increase microbial kill.
  • high pH may also reduce peroxidase activity.
  • a peroxidase which is active at high pH should be employed.
  • the enzyme can be provided in a variety of forms, for example in liquid or solid form, and can be provided in combination with a reducing agent and optional additional components.
  • a superoxide salt such as K0 2 is preferably provided in solid form, such as tablets or powders, together with optional additional agents.
  • the solid compositions are dissolved in a suitable solution for use in the inventive method.
  • Enzymatic systems for generating superoxide preferably are provided in liquid form.
  • the enzyme or combination of enzymes and their substrates are provided in a plurality of separate solutions, which are combined at the time of use.
  • the amount of enzyme provided typically is about 10-200 ⁇ g, preferably about 50-100 ⁇ g.
  • Reducing agents useful according to the instant invention are generally any non-toxic reducing agent, either dry or liquid, depending in part upon whether the delivery system is tablet or solution.
  • exemplary reducing agents include thiols, such as N-acetylcysteine.
  • Additional components that may be added to or incorporated into the enzyme tablets or the disinfecting solution include effervescing agents, stabilizers, buffering agents, chelating and/or sequestering agents, coloring agents, tonicity adjusting agents, surfactants and the like.
  • binders, lubricants, carriers, and other excipients normally used in producing tablets may be incorporated into the enzyme tablet when enzyme tablets are employed.
  • Neutralizing agents for neutralization of residual hydrogen peroxide can also be included, or can be supplied separately. Such additives and their use are well known to those skilled in the art . Other additives can also be employed to provide desired characteristics.
  • Radical scavengers e.g., mannitol
  • Radical scavengers can reduce or eliminate adverse effects due to side reactions of radicals, such as the hydroxyl radical, with lens hydrogel materials, tints, etc.
  • Additional enzymes such as superoxide dismutase, can be employed for system neutralization.
  • Useful additives include chelating agents such as EDTA, surfactants membrane permeabilizers, etc.
  • Additional preferred enzymes include cleaning enzymes, in particular proteases such as subtilisin A. Proteases which are active at high pH, e.g., pH of 8 or above, are preferred.
  • substrates for producing the cationic radical are useful in the inventive method, depending on the enzyme employed.
  • exemplary substrates include phenolic lignins, non-phenolic lignins, methoxybenzene derivatives, 2, 2-azino-bis- (3-ethylbenzthiazoline) -6-sulfonic acid (ABTS) , chlorpazamine, benzyl alcohols and polyphenols.
  • ABTS 2-azino-bis- (3-ethylbenzthiazoline) -6-sulfonic acid
  • chlorpazamine benzyl alcohols
  • polyphenols include phenolic lignins, non-phenolic lignins, methoxybenzene derivatives, 2, 2-azino-bis- (3-ethylbenzthiazoline) -6-sulfonic acid (ABTS) , chlorpazamine, benzyl alcohols and polyphenols.
  • Such substrates may be chosen based on molecular weight. Higher molecular weights tend to reduce
  • Particularly preferred substrates are ABTS and veratryl alcohol. Any other substrate which is capable of being oxidized by an enzyme to yield a cationic radical is contemplated as being within the scope of the instant invention.
  • the substrates can also be provided in a variety of solid or liquid forms for use in the inventive method.
  • a color indication of the reaction process may be provided.
  • ABTS is oxidized to a stable green cation radical having absorption maxima at 414 and 660 nm.
  • Other oxidative indicators or pH indicators which are ophthalmologically acceptable may also be employed.
  • the enzymatic embodiment of the disinfection process can be carried out in a number of ways.
  • solutions including the enzyme, hydrogen peroxide or peroxide generator, and substrate can be combined in a container into which the contact lens to be disinfected is placed.
  • Such solutions can be produced, as noted above, by dissolving a solid composition including the particular ingredient in an appropriate solution.
  • one of the enzyme or substrate can be immobilized in reactive form on the surface of the container, and solutions including the other of the enzyme and substrate, and hydrogen peroxide or peroxide generator, can then be combined within the container.
  • the former option immobilization of the enzyme
  • the latter option is appropriate, for example, when the substrate is not ophthalmologically acceptable, or when disposable containers are desired.
  • container 10 has inner surface 12 upon at least a portion of which is immobilized in reactive form an enzyme 14 as described herein.
  • Saline solution 16 containing a substrate for enzyme 14, and solution 18, containing a source of hydrogen peroxide, are added to container 10. If desired, the same solution can include both the substrate and the source of hydrogen peroxide.
  • Contact lens 20 is placed within container 10 and is disinfected with the superoxide generated by the reaction sequence involving the enzyme, substrate and hydrogen peroxide.
  • Container 10 can be, for example, a vial for holding a contact lens in a solution, a contact lens case, or any other type of container useful for holding a contact lens.
  • an article of manufacture such as a dipstick, has immobilized in reactive form on a least a portion of its surface one of the enzyme and substrate described above. The article is subsequently contacted with a solution or combination of solutions containing the other of the enzyme and substrate and a hydrogen peroxide source. The contact lens to be disinfected is exposed to the resulting solution and disinfected by the superoxide so generated.
  • Dipstick 22 has a surface 24 upon at least a portion of which is immobilized in reactive form an enzyme 14 as described herein. Dipstick 22 is contacted with solution 26 including a substrate for enzyme 14 and a hydrogen peroxide source within container 28, resulting in generation of superoxide. Contact lens 20 is disinfected by the superoxide so generated.
  • the contact lens to be disinfected is exposed to the solution containing superoxide for a time effective to disinfect the lens. Exposure time will depend on a number of factors, such as speed of kill, impact on the lens to be treated, pH neutralization considerations, the presence of other active agents such as proteases, etc., all of which can readily be evaluated by those skilled in the art.
  • the contact lens is exposed to the solution for a time ranging from about 5 minutes to 12 hr, or overnight, depending on the particular embodiment selected.
  • a tablet including a superoxide salt such as K0 2 will achieve relatively rapid kill, requiring treatment times from about 15 minutes to 1 hour.
  • a second aspect of the invention comprises electrochemical generation of superoxide in a solution.
  • superoxide is generated by applying an electrical potential to a solution which includes a compound capable of forming a cationic radical upon application of the potential.
  • the cationic radical so formed subsequently oxidizes a hydrogen peroxide molecule present in the solution.
  • this oxidation step generates superoxide in the solution, which then is available to disinfect a contact lens immersed within the solution.
  • Container 30 contains a solution 32 including a compound capable of forming a cationic radical upon application of a potential thereto.
  • Electrodes 34 and 36 extend into the solution.
  • the electrodes can, for example, be affixed to a cap 38 which fits over container 30.
  • An electrical potential is applied via electrodes 34 and 36 to the compound in the solution, thereby producing the cationic radical.
  • the cationic radical then oxidizes a hydrogen peroxide molecule to produce superoxide for disinfection of contact lens 20 immersed within the solution.
  • ABTS ABTS
  • Hydrogen peroxide can be supplied in the same manner as with the enzymatic aspect of the inventive method, either as stabilized hydrogen peroxide or as the product of a chemical or enzymatic system for generating hydrogen peroxide.
  • a third aspect of the invention comprises chemical generation of superoxide in a solution.
  • superoxide is generated by dissolution of a superoxide salt in a solution.
  • salts such as potassium superoxide or sodium superoxide can be dissolved in a solution, such as a buffered saline solution, boric acid
  • the superoxide salts can be provided in tableted form, powdered form or another form which is readily dissolved in the selected solution.
  • tablets containing superoxide salts can also contain other conventional additives such as effervescing agents, stabilizers, reducing agents and buffering agents, along with radical scavengers, additional enzymes such as superoxide dismutase, etc.
  • additional neutralizing agents for neutralization of residual hydrogen peroxide can also be included, or can be supplied separately.
  • the superoxide salt such as potassium superoxide
  • the superoxide salt is employed in the solution in an effective amount, typically about 5 to 200 mg/10 ml, preferably about 50 to 100 mg/10 ml.
  • a variation of the foregoing methods includes the steps of generating superoxide, by any desired means, in an aqueous solution under conditions permitting the disproportionation of superoxide to hydrogen peroxide.
  • the contact lens to be disinfected is exposed to the aqueous solution for a time effective to disinfect the lens.
  • the resulting solution contains superoxide, hydrogen peroxide, hydrogen and oxygen. Further reaction involving the target microorganisms may generate additional radicals, for example hydroxyl. Disinfection occurs through the action of one or more of these species.
  • the superoxide is preferably generated in a solution at room temperature and at approximately physiological pH (e.g., tap water, distilled water, buffered saline solution) ; however, it is advantageous to allow the pH of the solution to rise during the disinfection process. Hydroxide generated in the disproportionation reactions results in a solution pH in the range of about 8-13, depending on the initial quantity of superoxide salt, the buffering capacity of the solution, etc. Preferably, the pH is allowed to rise to about 12, then is reduced the pH to approximately neutral, over a cycle time of about 1 hour.
  • physiological pH e.g., tap water, distilled water, buffered saline solution
  • the foregoing disinfection method can be employed alone or in combination with other methods which require generation of hydrogen peroxide as part of the disinfection regimen.
  • One advantage of such a combination is the elimination of the need for stabilized solutions of hydrogen peroxide.
  • a coating preferably is employed to control the release and dissolution of individual components (e.g., superoxide salts, buffers, peroxide neutralizers, etc.), and thereby control disinfection solution conditions such as pH, peroxide concentration, etc.
  • individual components e.g., superoxide salts, buffers, peroxide neutralizers, etc.
  • disinfection solution conditions such as pH, peroxide concentration, etc.
  • particles are formed by separately coating a superoxide salt, such as K0 2 , and an additive, such as citric acid, with a polyvinylpyrrolidone such as VA-64 (commercially available from BASF) . The coated particles are then compressed together to form a tablet.
  • kits for disinfecting contact lens according to the foregoing methods.
  • the kits in general include a system for generating an effective contact lens disinfecting amount of superoxide in a solution, in particular a system as described herein, and a container adapted to hold a contact lens and a solution.
  • the inventive kit includes a system for the enzymatic generation of superoxide as described herein.
  • the selected peroxidase, substrate and hydrogen peroxide source are included in tablet, powder, liquid or other desired forms and packaged in pre-measured amounts effective to disinfect a contact lens. Multiple packaged units of the tablet, powder, liquid, etc., can be included in the kit for user convenience.
  • the inventive kit optionally can further include a solution for the superoxide generating system.
  • the solution can be, for example, a prepackaged spray canister of a saline or other buffered solution which the user squirts into the container.
  • additives such as radical scavengers or superoxide dismutase
  • inventive kit can also be provided with the inventive kit, either in separately packaged form or in admixture with one or more of the other elements of the superoxide generating system.
  • a kit according to the invention can include, as the container, a container having immobilized in reactive form therein one of the peroxidase and substrate, as described herein.
  • the kit can include a dipstick or other article of manufacture having immobilized in reactive form thereon one of the peroxidase and substrate. The dipstick or other article would be used in conjunction with the container and other elements of the kit as described herein.
  • kits for generating superoxide.
  • a kit can include, for example, an apparatus for applying an electrical potential to a solution such as shown in Figure 5, together with appropriate pre-packaged amounts of a compound capable of forming a cationic radical in the solution upon application of the electrical potential thereto, and of a source of hydrogen peroxide.
  • a compound capable of forming a cationic radical in the solution upon application of the electrical potential thereto and of a source of hydrogen peroxide.
  • These materials can be in solid or liquid form as described herein.
  • kits within the scope of the present invention includes a chemical system for generating superoxide.
  • a superoxide salt such as potassium superoxide
  • appropriate pre-packaged amounts of a superoxide salt such as potassium superoxide can be provided in tablet or powder form, optionally together with a supply of a solution such as saline solution.
  • Dispenser 40 includes outer container 42. Juxtaposed within space 44 within outer container 42, without contacting outer container 42, are first inner bladder 46, having outer exterior surface 48 and inner exterior surface 50, and second inner bladder 52 having outer exterior surface 54 and inner exterior surface 56. Inner exterior surfaces 50 and 56 of first and second inner bladders 46 and 52, respectively, preferably are separated by a plurality of contact points 58, one or more of which are disposed on each of said inner exterior surfaces 50 and 56.
  • Outer container 42 and first and second inner bladders 46 and 52 are joined to cap 60, within which is defined manifold 62.
  • First and second inner bladders 46 and 52 are in fluid communication with manifold 62 by attachment to necks 64 in the underside of cap 60.
  • Manifold 62 in turn is in fluid communication with opening 66 defined in cap 60.
  • inner bladders 46 and 52 are filled with separate solutions which form a system for generating superoxide when combined.
  • one of inner bladders 46 and 52 can filled with a first aqueous solution comprising a peroxidase, and the other inner bladder can be filled with a second solution comprising hydrogen peroxide and a substrate for the peroxidase which is capable of being oxidized to generate a cationic radical.
  • External pressure is applied to outer container 42, for example by squeezing. Air within space 44 is compressed, resulting in application of pressure to inner bladders 46 and 52.
  • the solutions within each of the two inner bladders are forced to flow out of the bladders and into manifold 62, where the two solutions mix and subsequently flow through opening 66 into an appropriate container (not shown) which preferably is provided in combination with dispenser 40, and within which superoxide is generated. A contact lens is then disinfected within the container.
  • the flowrate of solution from each of the first and second inner bladders can be controlled by conventional means, such as by the use of appropriately sized orifices within necks 64.
  • one-way valves can be disposed within necks 64 to prevent cross-contamination of the solutions within the two inner bladders.
  • Opening 66 in cap 60 preferably is reclosable to prevent contamination of the solutions within the two inner bladders.
  • Exemplary closing means include outer cap 68 attached to cap 60 via flexible tab 70.
  • Example 1 Disinfecting tablet combination
  • a first tablet is produced by combining K0 2 (100 mg) with NaCl (100 mg) and compressing the resulting mixture.
  • a second tablet is produced as follows: Citric acid (105 mg) is pan coated with polyvinylpyrrolidone VA-64 (20% in acetone) to form coated particles. The coated particles are combined with polyvinylpyrrolidone PVP-15 (105 mg) , PEG-3350 (10 mg) as a lubricant, and pan coated ascorbic acid (50 mg) as a neutralizer, and compressed into a tablet. The tablets are dissolved in 10 ml of a saline solution for use in disinfecting a contact lens.
  • Example 2 Cleaning and disinfecting tablet combination
  • a first tablet is prepared by combining K0 2 (100 mg) and NaCl (100 mg) as described in Example 1.
  • a second tablet is prepared by combining the following ingredients:
  • the tablets are dissolved in 10 ml of a saline solution for use in disinfecting a contact lens.
  • Example 3 Cleaning and disinfecting tablet combination
  • a first tablet is prepared by combining K0 2 (50 mg) and NaCl (50 mg) as described in Example 1.
  • a second tablet is prepared by combining the following ingredients:
  • the tablets are dissolved in 10 ml of a saline solution for use in disinfecting a contact lens.
  • test solution 10 ml volumes of test solution were dispensed into glass centrifuge tubes. The solutions were inoculated to contain a selected number of viable colony forming units (CFU) per milliliter, after which inoculation each tube was immediately vortexed. A tablet was then added to each tube, and the tubes were stored at room temperature. At various time intervals, 0.5 ml from each tube was transferred to a test tube containing 4.5 ml of fluid thioglycolate broth containing 400 units of catalase per milliliter. The tubes were processed for aerobic plate count according to a standard protocol.
  • CFU colony forming units
  • KQ 2 powders were weighed directly into glass centrifuge tubes or lens cases. Test solutions were inoculated to contain a selected number of viable colony forming units (CFU) per milliliter, after which inoculation 10 ml volumes of the inoculated test solution were dispensed into glass centrifuge tubes or lens cases containing the weighed K0 2 powder. Each tube was immediately vortexed, and the tubes were stored at room temperature. At various time intervals, 0.5 ml from each tube was transferred to a test tube containing 4.5 ml of fluid thioglycolate broth containing 400 units of catalase per milliliter. The tubes were processed for aerobic plate count according to a standard protocol.
  • CFU colony forming units
  • Example 1 The test solutions of Example 1 were evaluated for antimicrobial efficiency against S. marcescens (ATCC).
  • Example 4 The test solutions of Example 4 were evaluated for antimicrobial efficiency against C. albicans (ATCC 10231) .
  • Example 4 The test solutions of Example 4 were evaluated for antimicrobial efficiency against A. fumigatus (ATCC 10894) .
  • NK 8x10 s (NK) 8x10 s (NKI 8x10 s (NK)
  • Example 4 The test solutions of Example 4 were evaluated for antimicrobial efficiency against S. marcescens (ATCC 14041) . An initial inoculum of 2xl0 6 CFU/ml was employed with each solution. Results are given in Table VI. Log kills are indicated in parentheses.
  • Example 4 The test solutions of Example 4 were evaluated for antimicrobial efficiency against C. albicans (ATCC 10231) . An initial inoculum of 6xl0 5 CFU/ml was employed with each solution. Results are given in Table VII. Log kills are indicated in parentheses.
  • Example 4 The test solutions of Example 4 were evaluated for antimicrobial efficiency against A. fumigatus (ATCC).
  • Example 12 The solutions of Example 12 were also evaluated for antimicrobial efficiency against S. aureus (ATCC 6538) .
  • An initial inoculum of 8x10 s CFU/ml was employed with each solution. Results are given in Table X. Log kills are indicated in parentheses. Table X
  • the latter buffer serves to maintain the pH of the solution at neutral pH, while the former buffer does not maintain the pH of the solutions at neutral pH but allowed the pH to rise to 12 and higher, levels at which the half-life of superoxide is significantly longer. No increase in activity was observed when tween was added to the 0.5 M KH 2 P0 4 /K 2 HP0 4 buffer, however.
  • Use of superoxide according to the invention showed unexpectedly increased effectiveness against C. albicans compared to use of hydrogen peroxide when carried out at high pH. As shown in Example 12, 50 mg K0 2 in 10 ml of 0.9% saline (pH 12) achieved up to 5.9 logs at 30 minutes against this microorganism.

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Abstract

Selon un procédé de désinfection de verres de contact, on génère un superoxyde dans une solution et on expose les verres de contact au superoxyde contenu dans la solution pendant une durée suffisante pour désinfecter les verres de contact.
PCT/US1995/015989 1994-12-29 1995-12-11 Desinfection de verres de contact avec du superoxyde WO1996020736A1 (fr)

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AU45124/96A AU4512496A (en) 1994-12-29 1995-12-11 Disinfection of contact lenses using superoxide

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999021950A3 (fr) * 1997-10-29 1999-08-05 Unilever Plc Systemes de blanchiment au peroxynitrite
US6171404B1 (en) 1996-02-26 2001-01-09 Alcon Laboratories, Inc. Use of carbon dioxide and carbonic acid to clean contact lenses

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4475994A (en) * 1983-12-27 1984-10-09 Maxdem Incorporated Method and apparatus for separating oxygen from a gaseous mixture
EP0175801A1 (fr) * 1984-09-24 1986-04-02 Jack Dr. Kessler Composition bactericide de désinfection pour lentilles de contact et d'autres produits similaires dans un milieu aqueux
US4670178A (en) * 1985-09-09 1987-06-02 Allergan Pharmaceuticals, Inc. Method for the simultaneous cleaning and disinfecting of contact lenses
WO1992011042A1 (fr) * 1990-12-19 1992-07-09 Allergan, Inc. Compositions et procedes de desinfection de lentilles de contact
WO1995005984A2 (fr) * 1993-08-20 1995-03-02 Keller Wilhelm A Dispositif de comptage et de dosage proportionnel de plusieurs constituants a cartouche compressible

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4475994A (en) * 1983-12-27 1984-10-09 Maxdem Incorporated Method and apparatus for separating oxygen from a gaseous mixture
EP0175801A1 (fr) * 1984-09-24 1986-04-02 Jack Dr. Kessler Composition bactericide de désinfection pour lentilles de contact et d'autres produits similaires dans un milieu aqueux
US4670178A (en) * 1985-09-09 1987-06-02 Allergan Pharmaceuticals, Inc. Method for the simultaneous cleaning and disinfecting of contact lenses
WO1992011042A1 (fr) * 1990-12-19 1992-07-09 Allergan, Inc. Compositions et procedes de desinfection de lentilles de contact
WO1995005984A2 (fr) * 1993-08-20 1995-03-02 Keller Wilhelm A Dispositif de comptage et de dosage proportionnel de plusieurs constituants a cartouche compressible

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6171404B1 (en) 1996-02-26 2001-01-09 Alcon Laboratories, Inc. Use of carbon dioxide and carbonic acid to clean contact lenses
US6273960B1 (en) 1996-02-26 2001-08-14 Alcon Manufacturing Ltd. Method of cleaning contact lenses using carbon dioxide and carbonic acid
WO1999021950A3 (fr) * 1997-10-29 1999-08-05 Unilever Plc Systemes de blanchiment au peroxynitrite

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