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WO2018175327A1 - Système et procédé de traitement de l'onychomycose - Google Patents

Système et procédé de traitement de l'onychomycose Download PDF

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Publication number
WO2018175327A1
WO2018175327A1 PCT/US2018/023154 US2018023154W WO2018175327A1 WO 2018175327 A1 WO2018175327 A1 WO 2018175327A1 US 2018023154 W US2018023154 W US 2018023154W WO 2018175327 A1 WO2018175327 A1 WO 2018175327A1
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WO
WIPO (PCT)
Prior art keywords
body part
chamber
plasma
gas
treatment
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
Application number
PCT/US2018/023154
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English (en)
Inventor
Jeffrey N. Roe
Timothy C. GRAMMER
Raul Ignacio BARRERA-BARRAZA
Eric Tridas
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Devicefarm Inc
Original Assignee
Devicefarm Inc
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Filing date
Publication date
Priority claimed from US15/464,761 external-priority patent/US10039723B2/en
Application filed by Devicefarm Inc filed Critical Devicefarm Inc
Publication of WO2018175327A1 publication Critical patent/WO2018175327A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/40—Peroxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M35/00—Devices for applying media, e.g. remedies, on the human body
    • A61M35/003—Portable hand-held applicators having means for dispensing or spreading integral media
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M35/00—Devices for applying media, e.g. remedies, on the human body
    • A61M35/30—Gas therapy for therapeutic treatment of the skin

Definitions

  • the invention in one aspect relates generally to a system and method for the treatment of onychomycosis.
  • Onychomycosis also known as “dermatophyte onychomycosis,” or
  • tinea unguium is a fungal infection of the nail. It is the most common disease of the nails and constitutes about half of all nail abnormalities. This condition may affect toenails or fingernails, but toenail infections are particularly common. It occurs in about 10% of the adult population. [0005] The most common symptom of a fungal nail infection is the nail becoming thickened and discolored. As the infection progresses the nail can become brittle, with pieces breaking off or coming away from the toe or finger completely. If left untreated, the skin can become inflamed and painful underneath and around the nail. There may also be white or yellow patches on the nail bed or scaly skin next to the nail, and an odor may result. There is usually no pain or other bodily symptoms, unless the disease is severe. People with onychomycosis may experience significant psychosocial problems due to the appearance of the nail, particularly when fingers - which usually are always visible - rather than toenails are affected.
  • Dermatophytids are fungus-free skin lesions that sometimes form as a result of a fungus infection in another part of the body. This could take the form of a rash or itch in an area of the body that is not infected with the fungus. Dermatophytids can be thought of as an allergic reaction to the fungus.
  • the causative pathogens of onychomycosis include dermatophytes, Candida, and non-dermatophytic molds. Dermatophytes are the fungi most commonly responsible for onychomycosis in the temperate western countries; while Candida and nondermatophytic molds are more frequently involved in the tropics and subtropics with a hot and humid climate.
  • Trichophyton rubrum is the most common dermatophyte involved in onychomycosis. Other dermatophytes that may be involved are T. inter -digitate, Epidermophyton floccosum, T. violaceum, Microsporum gypseum, T. tonsurans, and T. soudanense. A common outdated name that may still be reported by is Trichophyton mentagrophytes for T. inter digitate . The name T mentagrophytes is now restricted to the agent of favus skin infection of the mouse; though this fungus may be transmitted from mice and their danders to humans, it generally infects skin and not nails.
  • Candida and nondermatophytic molds in particular members of the mold generation Scytalidium (name recently changed to Neoscytalidium), Scopulariopsis, and Aspergillus.
  • Candida mainly causes fingernail onychomycosis in people whose hands are often submerged in water.
  • Scytalidium mainly affects people in the tropics, though it persists if they later move to areas of temperate climate.
  • the present disclosure provides a system and method that includes delivery of a redox gas solution to treat onychomycosis, wherein the redox gas solution comprises a reactive species dissolved in a perfluorocarbon liquid.
  • the reactive species may include, alone or in combination, one or more of reactive oxygen, reactive nitrogen, reactive chlorine, or reactive bromine species.
  • the perfluorocarbon liquid may include perfluorodecalin.
  • a system may include a housing with a chamber disposed therein.
  • the chamber may include an opening through which a foot to be treated may be at least partially inserted.
  • One or more reactive species generators may be disposed within the chamber.
  • the toes of the inserted foot may be positioned a desired distance from the one or more reactive species generators.
  • a disposable tray may be used to help prevent contact between the foot and the sides (i.e., bottom, walls) of the housing chamber.
  • the disposable tray may include a curtain that closes the opening about the inserted foot, e.g., to help prevent the escape of reactive species through the opening.
  • the generators provide for a desired period of time reactive species to the chamber including the inserted foot.
  • FIG. 1 is an illustration by flowchart of an exemplary method in accordance with the disclosure.
  • FIG. 2 is a cross-sectional view of a portion of an exemplary system in accordance with the disclosure.
  • FIG. 3A is a cross-sectional view of a container including an exemplary perfluorocarbon liquid in accordance with the disclosure.
  • FIG. 3B is a cross-sectional view of a cap for the container shown in FIG. 3 A, the cap including an applicator for providing perfluorocarbon liquid to a nail/tissue.
  • FIG. 3C is a perspective view of an exemplary application of perfluorocarbon liquid to nail/tissue using the applicator shown in FIG. 3B.
  • FIG. 4 is a partial schematic view of an exemplary plasma generating device proximate nail/tissue to which a perfluorocarbon liquid has been applied in accordance with the disclosure.
  • FIG. 5A is a perspective view of an exemplary toe-clip applicator in accordance with the disclosure.
  • FIG. 5B is a partial cross-sectional view of the exemplary toe-clip applicator shown in FIG. 5 A.
  • FIG. 6 is a perspective view of an alternate exemplary treatment system embodiment in accordance with the disclosure.
  • FIG. 7 is a perspective view of another alternate exemplary treatment system embodiment in accordance with the disclosure.
  • FIG. 8 is an assembly view of the exemplary treatment system shown in Figure
  • FIG. 9 is an assembly view of the chamber housing of the exemplary treatment system shown in Figure 8.
  • FIG. 10 is an assembly view of the exhaust duct of the exemplary treatment system shown in Figure 8.
  • FIG. 11 is an assembly view of the power supply housing of the exemplary treatment system shown in Figure 8.
  • FIG. 12A is a perspective view of a disposable tray of the exemplary treatment system shown in Figures 7 and 9.
  • FIG. 12B is a perspective view of a disposable tray in a folded configuration for use in the exemplary treatment system shown in Figures 7 and 9.
  • the figures show an exemplary treatment system and method.
  • the system provides delivery of a redox gas solution to treat onychomycosis, wherein the redox gas solution comprises a reactive species dissolved in a perfluorocarbon liquid.
  • the perfluorocarbon liquid is applied at step 10 to the nail/tissue.
  • a plasma gas is generated proximate the nail/tissue.
  • the plasma gas forms reactive species that dissolve in the perfluorocarbon liquid to form a redox gas solution.
  • the process may repeat or continue until sufficient redox gas solution is produced to eradicate nail/tissue fungus. See step 30.
  • the reactive species may include, alone or in combination, one or more of reactive oxygen, reactive nitrogen, reactive chlorine, or reactive bromine species.
  • the reactive species may be formed through use of a nonthermal plasma device, or otherwise be provided.
  • a plasma 40 may be formed proximate a ground electrode 50.
  • the plasma forms reactive species 60, 70.
  • the reactive species 60, 70 dissolve in a perfluorocarbon liquid 80 applied to the surface 90 of nail/tissue 100.
  • the redox gas solution including reactive species 60, 70 diffuses into the nail/tissue bed to eradicate fungus located therein.
  • the plasma generating device includes a ground electrode 50.
  • the device generates a sufficiently high voltage signal applied between two electrodes, one of which is the ground electrode 50, where at least one of the electrodes is insulated for plasma generation (not shown for clarity in Figure 2).
  • the perfluorocarbon liquid may include perfluorodecalin.
  • Perfluorodecalin and other suitable perfluorocarbon liquids have desirable wetting, gas absorption and diffusion properties.
  • Perfluorocarbons PFCs
  • fluorocarbons fluorocarbons
  • perfluorochemicals liquids are formally derived from liquid hydrocarbons by replacing all the hydrogen atoms with fluorine atoms.
  • This class of chemical compounds is characterized by its property to be extremely inert - chemically, biologically, and physiologically - due to the remarkable stability of the C-F bonds.
  • the C-F bond is the strongest bond encountered in organic chemistry, and its strength is further increased when several fluorine atoms are present on the same carbon atom. The presence of fluorine even reinforces the strength of the C-C bonds.
  • PFC liquids generally are clear, colorless, odorless, electrically nonconducting, and nonflammable. They are approximately twice as dense as water, and generally are capable of dissolving large amounts of physiologically important gases. For their gas uptake function, PFCs act only as a carrier of the gasses and do not react with the gas or produce the gases. PFCs are generally very chemically stable compounds that are not metabolized in body tissues. They are physiologically inert as there is no enzyme system capable of modifying liquid PFCs, neither metabolically nor catabolically. Liquid PFCs are both hydrophobic and lipophobic, i.e., they are immiscible both with water and lipophilic liquids and generally form emulsions with them.
  • PFCs are used in a variety of industries. They were first synthesized in the
  • PFCs are currently being used in retinal detachment surgery, liquid ventilation therapy for the lungs, as a blood substitute and as ultrasound and radiological imaging agents. They are used in both cosmetics and paints to facilitate easier product spreading and in textile manufacturing as a fabric protector.
  • perfluorocarbon liquid or "PFC liquid” as used herein may include organic compounds in which all (or essentially all) of the hydrogen atoms are replaced with fluorine atoms.
  • Representative perfluorinated liquids include cyclic and non- cyclic perfluoroalkanes, cyclic and non-cyclic perfluoroamines, cyclic and noncyclic perfluoroethers, cyclic and non-cyclic perfluoroaminoethers, and any mixtures thereof.
  • perfluorinated liquids include the following: perfluoropentane, perfluorohexane, perfluoroheptane, perfluorooctane, perfluorodecalin, perfluoromethylcyclohexane, perfluorotributyl amine, perfluorotriamyl amine, perfluoro-N-methylmocpholine, perfluoro-Nethylmocpholine, perfluoroisopropyl mocpholine, perfluoro-N- methyl pyrrolidine, perfluoro- 1,2 is(trifluoromethyl)hexafluorocyclobutane, perfluoro-2- butyltetrahydrofuran, perfluorotriethylamine, perfluorodibutyl ether, and mixtures of these and other perfluorinated liquids.
  • Perfluorocarbons in general improve gas exchange and are a desirable medium to carry redox gases.
  • PFC at one atmosphere of pressure can carry 20 times more oxygen than saline will hold.
  • PFCs are low viscosity surfactants that may lower the surface tension on the nail, so the PFC may spread uniformly and quickly over the nail structure. The low surface tension contributes to improved wetting of the surfaces.
  • the surface tensions of PFCs are generally less than 20 dynes/cm and usually between 10 to 20 dynes/cm when measured at 25°C. When used in lung injury for ARDS patients, surface tension in the lung is noted to be 67 to 75 dynes/cm. In a lung with PFC, the surface tension is only 18 dynes/cm, which helps prevent alveolar collapse and reduces alveolar opening pressures.
  • PFCs may displace water and circulate to those areas where gas exchange is diminished. PFCs also may wash out debris if the debris is lighter than the PFC used. PFCs are not taken up by the body and do not break down into toxic metabolites.
  • Perfluorocarbon liquids may be compounds containing a high level of carbon- bound fluorine that are liquid at or below 106 °F at atmospheric pressure. These fluorinated fluids may be capable of dissolving a substantial amount of a redox gas at operating conditions, typically in a temperature range from about 0 °C to about 50 °C.
  • the perfluorocarbon liquid may be converted in whole or in part to a redox gas solution before topical application by dissolving the reactive gaseous species into perfluorocarbon liquid at the manufacturing facility and delivering the topical composition to the customer in a usable form such that the customer can apply the solution to the infected area as a treatment.
  • PFC fluids may dissolve at least 500 mL of gaseous chlorine per 100 mL of fluid at 1 atm and 25 °C. In another exemplary embodiment, the PFC fluids may dissolve at least 1200 mL of gaseous chlorine at 1 atm and 25 °C.
  • the oxidizing gas solutions used in the described methods may be saturated with a desired oxidizing gas. In another example, the concentration of ozone in the PFC may be greater than 1 ppm but less than 500 ppm.
  • perfluorocarbons include, by way of example, perfluorocarbons such as fluoroheptanes, fluorocycloheptanes, fluoromethylcycloheptanes, fluorohexanes, fluorocyclohexanes, fluoropentanes, fluorocyclopentanes, fluoromethylcyclopentanes, fluorodimethylcyclopentanes, fluoromethylcyclobutanes, fluorodimethylcyclobutanes, fluorotrimethylcyclobutanes, fluorobutanes, fluorocyclobutanes, fluoropropanes, fluoroethers, fluoropolyethers, fluorotributylamines, fluorotriethylamines, perfluorohexanes, perfluoropentanes, perfluorobutanes, perfluoropropanes, sulfur hexafluoride, Methylperfluorobuty
  • Other liquids may fulfill the mechanism of penetration enhancer / gas carrier and could concentrate the antifungal species from the plasma.
  • alternative molecules that both concentrate and promote gas exchange may be used and include, but are not limited to, neuroglobin, apomyoglobin, hemoglobin, myoglobin, and synthetic blood or blood substitutes such as respirocytes.
  • the perfluorocarbon or other liquid may include a co-solvent to improve as desired specific physical properties of the fluid.
  • a semifluorinated alkane (SFA) that has a non-fluorinated hydrocarbon segment may be added to a PFC liquid.
  • the liquid composition may comprise the combination of more than one PFC and/or more than one SFA. It may be useful to combine PFCs and SFAs, for example, to achieve a particular desired target property, such as a certain density, viscosity, lipophilicity or soluble capacity for a particular active ingredient such as a dye.
  • the SFA may be essentially non-reactive with the redox gas.
  • the SFA also may not reduce the solubility of the redox gas in the PFC.
  • one or more useful SFAs may be selected from a group of SFAs including F4H5, F4H6, F4H8, F 6 H6 and FeHs.
  • the perfluorocarbon liquid absorbs anti- pathogenic substances generated by a plasma-generating device. See, e.g., Figure 2.
  • onychomycosis treatment is enhanced using a solution containing gaseous reactive oxygen or reactive nitrogen or reactive chlorine/bromine species that are dissolved in a perfluorocarbon liquid.
  • redox gas solution a solution containing gaseous reactive oxygen or reactive nitrogen or reactive chlorine/bromine species dissolved in a perfluorocarbon liquid shall be referred to herein as a "redox gas solution.”
  • an onychomycosis treatment system and method includes a topical composition to overcome one or more disadvantages of current topical fungal treatments.
  • the topical composition may include a redox gas solution.
  • a further exemplary embodiment provides a method of treating fungal infections like onychomycosis comprising contacting a skin or nail surface with a perfluorocarbon liquid, and converting at least a portion of the perfluorocarbon liquid into a redox gas solution.
  • such method includes the step of dissolving a redox gas in a perfluorocarbon liquid proximate the site of a fungal infection like onychomycosis to be treated.
  • the redox gas is formed during a non-thermal plasma treatment step.
  • first and second treatment vectors for a fungal infection like onychomycosis are provided, wherein the first vector includes a redox gas formed as a result of a non-thermal plasma treatment step, and the second vector includes a redox gas solution.
  • a plasma-generating device may create antimicrobial plasma species proximate a nail or skin area to be treated.
  • antibacterial means tending to destroy microbes, prevent their development, or inhibit their pathogenic action, and includes reference to, without limitation, antibacterial and antifungal properties.
  • Plasma is a gas-like phase of matter that typically contains many more reactive chemistry species than gas.
  • a plasma-generating device turns electrical energy and a preselected gas (typically air, argon or helium) into electric fields, energetic electrons and favorable chemistry for antimicrobial therapy.
  • a preselected gas typically air, argon or helium
  • Non-thermal plasma gas at atmospheric pressure have been generated by microwave-induced plasma systems, dielectric barrier discharge (DBD), corona discharge, gliding arc discharge, and atmospheric pressure plasma jet.
  • DBD dielectric barrier discharge
  • corona discharge corona discharge
  • gliding arc discharge and atmospheric pressure plasma jet.
  • U.S. Patent No. 7,572,998 is hereby expressly incorporated by reference herein in its entirety for all purposes. The '998 patent describes some representative, but not exclusive, plasma generators that may be useful.
  • the plasma-generating device 110 is electrically connected to both a power supply 120 and electrical control circuit to control both the duration and intensity of the plasma gas effluent 150.
  • the electrical system may generate a high-voltage alternating current, typically between 2 to 20 kV at a frequency between 1 to 60 kHz.
  • the power consumption may range from 0.05 W to 10.0 W.
  • the high voltage electrode 130 may include a cylindrical copper block covered by a thin quartz plate 135 (e.g., approximately 1 mm in thickness).
  • a stainless-steel woven wire mesh may be positioned next to the quartz plate 135 and used as the ground electrode 140.
  • a wire diameter of 0.5 mm and mesh density of 8 ⁇ 8 meshes per cm 2 for example, may be used.
  • a variation of the dielectric barrier discharge (DBD), the surface micro- discharge (SMD) may prove advantageous as the plasma-generating device in applications for igniting a stable plasma at ambient conditions.
  • a SMD is a configuration of a DBD where the high voltage electrode is separated from a grounded electrode by a dielectric layer.
  • the term dielectric barrier discharges may be used because a high electric field is generated through an electrical insulator (e.g., glass) to create a plasma.
  • the charged particles may be confined to a plasma generation region around the grounded metal electrode.
  • a SMD may be a desirable source of reactive chemical species for several reasons: the treated body part is electrically isolated from high-voltage electrode due to ground electrode; the discharges are non- thermal, increasing adjacent gas temperature slightly, e.g., by only a few degrees; devices can be scaled simply, e.g., by changing electrode size and input power; and the discharges may operate in ambient air, e.g., without requiring a noble gas mixture.
  • SMD devices have been further described in a series of articles by Graves et al. and Morfill et al.
  • ROS reactive oxygen species
  • RNS reactive nitrogen species
  • the active content of the plasma effluent at the treatment surface may include, for example, singlet oxygen (102), hydroxide (OH), hydrogen peroxide (H2O2), ozone (O3), nitrous oxide (N2O), nitrogen dioxide (NO2) and other excited molecules of air constituents that includes other reactive nitrogen and reactive oxygen species such as HNO2, NO3, HNO3 and N2O5 .
  • Side reactions with these chemistries also may generate beneficial liquids and solids as the nail keratin and water in the nail can maintain antifungal properties long after the treatment is complete. Charged particles, electric fields and UV light also may be generated by plasma.
  • the ionized gases generally last for very short periods of time (e.g., less than a second), but free radicals and reactive oxygen and nitrogen species that are electrically neutral may last long enough to be effective - perhaps up to many meters away from the source - in destroying fungus, bacteria and their spores. These free radicals denature critical lipid, protein and nucleic acid contents of the microbes, ultimately causing cell death. Research has demonstrated the effectiveness of plasma gas as well as nitrogen and oxygen free radicals such as ozone or hydrogen peroxide vapor or a combination of these in causing retarded fungal growth and fungal death.
  • the byproduct of the plasma process is water (H 2 0) and carbon dioxide (CO2).
  • the non-thermal plasma gas effluent may be directed to a treatment site in two ways: direct mode or indirect mode.
  • Direct mode puts the treatment area within the visible plasma region discharge or plume, which may be between about 0.0 mm and about 5.0 mm for most devices.
  • direct mode UV light, some charged particles and electric fields, in addition to reactive neutral species, may directly reach the treatment surface 160, to which a perfluorocarbon 170 may be applied.
  • Indirect mode may have the treatment surface between about 5.0 mm and about 1.0 meter away. Thus, charged particles and electric field may have dissipated or decayed and may not reach the treatment surface.
  • the indirect mode may benefit from a gas delivery system, wherein the plasma gas effluent may be directed to the treatment surface with tubing, inline fans, connectors, ports, etc. for input, delivery and output of antimicrobial agent to the treatment surface. That is, simple diffusion or forced air flow may promote delivery of reactive species to the nail bed, where the non-thermal plasma effluent or gas composition acts as an antimicrobial agent.
  • Treatment may occur for a predetermined or desired period of time.
  • the antimicrobial agent may be applied for a sufficient time to achieve an effective killing of all or a portion of the fungus within the nail structure.
  • a sufficient time for application may be a time from about 10 seconds to about 4 hours.
  • antimicrobial agent may be applied for a time from about 1 minute to about 15 minutes.
  • antimicrobial agent may be applied for a time from about 5 minutes to about 20 minutes.
  • antimicrobial agent may be applied for a time from about 30 minutes to about 1 hour.
  • the application of antimicrobial agent may be cyclical in nature, wherein an electrical control circuit cycles the device on and off, e.g., for a predetermined period of time (for example a 50% duty cycle (1 minute on l ⁇ minute off) for a 30 minute to 1 hour treatment period).
  • a predetermined period of time for example a 50% duty cycle (1 minute on l ⁇ minute off) for a 30 minute to 1 hour treatment period.
  • Other reactive gases not created by a non-thermal plasma generator may be useful in making redox gas solutions.
  • Such other reactive gases may include any gas capable of directly causing or actively triggering a reaction that eradicates pathogens within or on the surface of a material (e.g., skin or nail) where the gas is also readily soluble in a perfluorocarbon fluid.
  • gases include, for example, methanethiol, bromine, chlorine, nitric oxide, ozone, chlorine dioxide, and/or sulfur dioxide.
  • Reactive oxygen and reactive nitrogen species play a central role in oxidation-reduction biochemistry (also called redox biology) and are active in the immune response of both animals and plants.
  • the reactive oxygen/nitrogen/chlorine/bromine or sulfur species listed in Table 1 may be useful in making redox gas solutions.
  • Redox gases can be purchased in their gaseous form but, due to their relatively high vapor pressure, require expensive sealed and pressurized tanks for storage. To provide handling convenience and cost-effectiveness, redox reagents are often created in an aqueous solution such as hypochlorous acid (generated from sodium hypochlorite), hydrogen peroxide, or nitric acid. These aqueous solutions are, however, less reactive than their gaseous counterparts, often requiring elevated temperatures and significant time to complete the redox reaction in situ.
  • hypochlorous acid generated from sodium hypochlorite
  • hydrogen peroxide or nitric acid
  • a redox gas may be added to a perfluorocarbon liquid by any conventional technique (e.g., sparging or gas injection or simple diffusion) to create a redox gas solution.
  • redox gas solutions provide a means for delivering a stable solution of an oxidation or reduction gas in its most active, non- hydrolyzed state that also allows handling convenience and cost-effectiveness.
  • Effective treatment of fungal nail infection may come from combining a redox gas with a perfluorocarbon liquid, then applying the redox gas solution topically, so that it penetrates the nail plate and inactivates pathogens residing in the nail bed.
  • a method for treating nail fungus may comprise the steps of: preparing a redox gas solution and applying the redox gas solution to the infected nails.
  • An applicator may be used to coat the infected nail.
  • a redox gas solution 180 may include chlorine dioxide gas dissolved in perfluorodecalin to saturation and may be provided in a container 190 as a topical treatment for onychomycosis.
  • the solution may have a minimum of 80 ppm chlorine dioxide as the treating agent.
  • Treating an infected nail with the solution comprises using an applicator 200 (for example coupled to the cap 210 of container 190) to spread a coating 220 on and around the nail 230.
  • an applicator 200 for example coupled to the cap 210 of container 190
  • such application includes a series of successive treatments to improve the aesthetic appearance of the nail, destroy the fungal infection and promote healthy nail growth.
  • the solution may be applied once a day for a minimum of sixty days to inactivate the fungus.
  • the solution may be applied once a week to prevent fungus or fungal spores from reinfecting the nail matrix.
  • a redox gas solution alternately may be generated at the skin or nail site by applying a perfluorocarbon liquid topically to the treatment area then treating the site with a redox gas, such as a gas created by a plasma-generating device. See Figures 2 and 4.
  • a perfluorocarbon liquid may be administered immediately prior to treatment with a non-thermal plasma device in an amount sufficient to enhance the permeation of antifungal gas through and around the nail.
  • the non-thermal plasma device allows the in-situ generation of gaseous reactive oxygen species and reactive nitrogen species that have antifungal properties.
  • perfluorodecalin is pre-applied to the infected nail to act as a redox gas facilitator substance.
  • a toe-clip 300 incorporating a plasma-generating device 320 is then attached to the infected toe and a 30- minute treatment protocol is initiated which generates antifungal gases 310 using electrical energy and air.
  • This treatment may be performed as a series of successive treatments to improve the aesthetic appearance of the nail, destroy the fungal infection and promote healthy nail growth.
  • the perfluorodecalin enhances the gas exchange between the nail bed and the plasma-generating device and allows the antifungal gas to more effectively penetrate the dense nail plate.
  • a pre-made redox gas solution may be applied to a treatment area and additional treatment can be applied through the use of a non-thermal plasma treatment, thus replenishing or adding additional species of redox gas to the treatment area.
  • a plasma-generating device 400 may include a chamber 410 having a lid or door 420, within which chamber a foot 430 may be placed for treatment proximate a plasma source 440.
  • the plasma may be provided for a predetermined amount of time using a control circuit including a timer 450 that is activated by pressing a start/stop button or switch 460.
  • the method includes coating the affected nail(s) along with the entire foot, in order to destroy pathogens thereon and help prevent reinfection of the nail by pathogens residing elsewhere on the foot.
  • the redox gas solutions used during treatment may provide a means for delivering a stable solution of an oxidation or reduction gas in its most active, non- hydrolyzed state.
  • the redox gas solutions may offer the advantage of providing a very low surface tension medium (generally on the order of approximately 15 dynes/cm), thereby enabling the oxidizing gas solution to efficiently contact and thoroughly penetrate a nail or skin infection.
  • the PFC can act as a gas facilitator by providing an improvement in gas exchange between a non-thermal plasma device that creates in situ an antimicrobial gas and the nail barrier where the microbe resides.
  • the PFC enhances the capacity of an active fungicidal gas to effectively penetrate the keratin matrix of fingernails and toenails such as to produce therapeutically relevant concentrations even in deeper regions of the matrix.
  • a main body housing 500 includes a chamber assembly 510, a power supply assembly 520, a shield assembly 530, an electronics panel assembly 540, and a rear cover assembly 550.
  • the main body housing 500 further may include an on/off button 560 for overall control of system operation.
  • a display 570 disposed on the top of the main body housing 500 may provide desired information related to system operation.
  • the display 570 may show a countdown timer reflecting the time remaining in a treatment session.
  • the main body housing 500 may include a handle 580 to help promote positioning of the system for a treatment session.
  • a chamber assembly housing 600 includes a chamber 610 disposed therein.
  • a plasma head holder 620 disposed within the chamber generally positions a pair of plasma head assemblies 630 in the upper portion of the chamber 610.
  • a plasma head assembly 630 may have a UV plasma filter 640 disposed proximate the holder 620.
  • the housing 600 includes an opening 650 at the lower front portion of the housing 600.
  • a chamber hatch cover 660 may be hingedly attached to the housing 600 above the opening 650, so that the cover 660 may be rotatable downwardly to a lower position covering at least a portion of the periphery of opening 650.
  • a foot ramp 670 may be hingedly attached to the housing 600 below the opening 650, so that during system non-use the ramp 670 may be rotatable upwardly to an upper position covering the cover 660 and opening 650.
  • the system includes use of a disposable liner 680. See Figures 9 and 12A and 12B.
  • the liner 680 includes a tray portion 690 including a base 700, a back wall 710, and two side walls 720, 730.
  • the liner 680 may be provided in a flat configuration (see Figure 12 A) and then be folded into a final configuration for use (see Figure 12B).
  • the base 700 proximately corresponds in size and shape to the size and shape of the bottom of chamber 610.
  • the front of tray portion 690 includes a perimeter support 740 and a membrane 750.
  • the support 740 and membrane 750 are slightly larger in peripheral size and shape as compared to the peripheral size and shape of the opening 650. In that way, the front of tray portion 690 may be held in place over the opening 650 and between the cover 660 and the front of housing 600 when the cover 660 is rotated into its lower position.
  • the base 700 covers the bottom of chamber 610, and the back wall 710 and side walls 720, 730 cover at least part of the lower ends of the back and side walls of chamber 610; and a seal is provided to help prevent during treatment the escape of gases from the chamber 610 at the periphery of opening 650.
  • the liner 680 may include a sheet 760 extending forward from the base of the front of tray portion 690.
  • the sheet 760 proximately corresponds in size and shape to the foot ramp 670.
  • the sheet 760 may help to prevent contact between the treatment system and the foot 780 of a patient undergoing treatment. See Figure 7.
  • the membrane 750 includes a port
  • the port 800 may be sized and shaped so that a foot 780 may be inserted in part therethrough. In that way, the membrane 750 acts as a seal about the foot 780 to help prevent the escape of gases from the chamber 610 during treatment.
  • a wedge 810 may be removably placed at the bottom of chamber 610 below the tray portion 690.
  • a 4.5 degree wedge may be used.
  • 18 mm high toes an 8.5 degree wedge may be used.
  • the distance between the top of the toes and a plasma head assembly 630 may be approximately 15 mm.
  • the wedge 810 may be separate from the tray portion 690.
  • the wedge 810 may be formed with the tray portion 690, e.g., at the base 700.
  • the wedge 810 may be formed by folding material to provide a wedge 810 of a desired size and shape.
  • the rear wall of the housing 600 may include an exhaust port 820.
  • an exhaust fan 830 Mounted to the outside of housing 600 at exhaust port 820 may be an exhaust fan 830.
  • the exhaust fan 830 turns on automatically to help empty the chamber 610 of any active gases.
  • Activated gases may be directed by the fan 830 from chamber 610 through a carbon filter disposed in exhaust duct 840 of shield assembly 530. See Figure 10. Deactivated gases then may exit the exhaust duct 840 at exit port 850 of rear cover assembly 550.
  • the plasma head assemblies 630 transfer their energy onto a patient's nail through diffusion of the plasma constituents. These constituents flow like a gas within the chamber 650. This action provides a controlled bathing of the nail in plasma energy at a low thermal profile.
  • the typical temperature in the treatment chamber 650 may be 31-26 °C (89-79 °F) after a 45-minute treatment.
  • the disposable liner 680 may be single use only and help prevent cross contamination between patients by covering areas of the system that may come in contact with a patient's foot.
  • the liner 680 includes a box-like tray portion 690 that may be made of medical grade APET plastic (polyester).
  • the membrane 750 and sheet 760 may be made of medical grade linear low density polyethylene, and may be latex free to avoid biocompatibility or allergy issues.
  • the disposable liner 680 may be locked in place in the system prior to insertion of a patient's foot through the opening or port 800 in membrane 750.
  • a doctor topically applies perfluorodecalin to the toe nail to be treated just before plasma treatment.
  • the perfluorodecalin forms a thin, transparent layer between the plasma and the nail and actively exchanges plasma species through purely mechanical means.
  • the in vitro test model uses a bovine hoof disk, a surrogate nail model established in the literature. It is used along with a modified Franz-type diffusion cell to isolate the fungal contaminated side of the hoof in an enclosed chamber that ensures the treatment path is through the hoof barrier. An equal amount of T. rubrum is pipetted onto each hoof disc consisting of a lOOul suspension. Each hoof disk is then placed fungus side down into the modified Franz cell and sealed with an O-ring. Each hoof is then plasma treated for 45 minutes where the average thickness of hoof disks is 0.35mm. Eight hoof disks were treated as:
  • each hoof went through a fungal collection protocol consisting of washing, dilution, plating and incubation.
  • the results after seven days of incubation was a colony count of about 24,000,000 from the control hoof plate.
  • the two hoofs that were treated with PFD-only had colony reductions of 7% and 28% compared to control.
  • the two hoofs that were treated with 45 minutes of plasma only had colony reductions of 84% and 88% when compared to control and quite unexpectedly the three hoofs that were treated with both PFD and 45 minutes of plasma treatment showed a colony reduction of 94% for one hoof and no colonies or 100% and 100% reductions for the other two hoofs.
  • the contacting of the infected area with the perfluorocarbon can occur by various means.
  • the perfluorocarbon can be applied with a dropper, foam tip swab, a cotton tip swab or a sponge applicator. It may be sprayed or squeezed on in a foam or gel formulation.
  • a further apparatus for contacting the infected area with a perfluorocarbon consist of a gas-permeable membrane that includes perfluorocarbon liquid in its composition and allows for the rapid, enhanced and uniform transfer of plasma reactive species between the plasma device and the infection.
  • the contacting of the infection with the perfluorocarbon membrane may define the treatment site.
  • the gas permeable membrane composition comprises at least one material selected from ceramics, polymers, woven substrates, non-woven substrates, polyamide, polyester, polyurethane, fluorocarbon polymers, polyethylene, polypropylene, polyvinyl alcohol, polystyrene, vinyl, plastics, metals, alloys, minerals, non-metallic minerals, wood, fibers, cloth, glass, and hydrogels.
  • the membrane barrier is a silicone composition that contains an effective amount of perfluorocarbon and acts as a dressing.
  • the membrane may be manufactured in a toe or finger cot shape that may be slipped easily over the infected digit.
  • a PFC may be loaded with antifungal gas in a manufacturing facility.
  • a home-use device may be provided so that a patient may "load" the PFC at their home, then apply it to their toenails.
  • the loading can be done with a plasma device, and/or a pure gas canister (NO, ozone, H2O2, etc.), etc. before treatment application by the patient at home.
  • a pure gas canister NO, ozone, H2O2, etc.
  • a secondary chemical reaction may create the gas.
  • Redox gases can be purchased in their gaseous form but have relatively high vapor pressure, require expensive sealed and pressurized tanks for storage.
  • redox reagents are often created in an aqueous solution such as hypochlorous acid (generated from sodium hypochlorite), hydrogen peroxide, or nitric acid.
  • hypochlorous acid generated from sodium hypochlorite
  • hydrogen peroxide or nitric acid.
  • a redox gas may be added to a perfluorocarbon liquid by any means.
  • redox gas solutions provide a means for delivering a stable solution of an oxidation or reduction gas in its most active, non- hydrolyzed state that also allows handling convenience and cost- effectiveness.
  • Use of the described system and method also may promote wound sterilization and healing, may treat ear infections, may improve the sterilization of medical devices, may treat dental infections, may treat acne and various other dermatological infections, may promote bleeding cessation, may improve hand disinfection hygiene, or may treat skin, esophagus or colon cancer. It can also be used in veterinarian animal health for all such described applications.
  • a method of sterilizing or decontaminating an item comprises the steps of: (a) coating the item to be sterilized with a perfluorocarbon liquid layer to allow the perfluorocarbon liquid to come in close proximity with the item; (b) generating a gaseous plasma around the item, such that both the liquid perfluorocarbon and the exterior of item is exposed to reactive components of said plasma; and (c) maintaining the item in said plasma for a time period sufficient to allow the active sterilizing species generated from the plasma to effect sterilization and destroy any microorganisms present.
  • decontamination of a liquid or gas may occur using a PFC including a reactive species.
  • PFC including a reactive species. Examples include, without limitation, using the PFC/reactive species solution to eliminate microbes in blood with the aid of a dialysis machine, and to improve the sterilization of air using conventional methods.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Apparatus For Disinfection Or Sterilisation (AREA)

Abstract

La présente invention concerne un système et un procédé consistant à utiliser une solution de gaz redox pour traiter une onychomycose, la solution de gaz redox comprenant une espèce réactive dissoute dans un liquide perfluorocarboné, et l'espèce réactive pouvant comprendre, seuls ou en combinaison, un ou plusieurs éléments parmi une espèce d'oxygène réactif, d'azote réactif, de chlore réactif ou de brome réactif, le liquide perfluorocarboné pouvant comprendre de la perfluorodécaline.
PCT/US2018/023154 2017-03-21 2018-03-19 Système et procédé de traitement de l'onychomycose Ceased WO2018175327A1 (fr)

Applications Claiming Priority (2)

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US15/464,761 US10039723B2 (en) 2014-12-10 2017-03-21 Onychomycosis treatment system and method
US15/464,761 2017-03-21

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109731226A (zh) * 2019-03-07 2019-05-10 华中科技大学 一种等离子体灰指甲治疗装置
WO2025017299A1 (fr) 2023-07-18 2025-01-23 King's College London Sulfure d'hydrogène pour le traitement topique d'une infection des ongles

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090143842A1 (en) * 2007-11-02 2009-06-04 Cumbie William E Phototherapy Treatment and Device for Infections, Diseases, and Disorders
US20160166607A1 (en) * 2014-12-10 2016-06-16 DeviceFarm Inc. Onychomycosis Treatment Apparatus and Method

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090143842A1 (en) * 2007-11-02 2009-06-04 Cumbie William E Phototherapy Treatment and Device for Infections, Diseases, and Disorders
US20160166607A1 (en) * 2014-12-10 2016-06-16 DeviceFarm Inc. Onychomycosis Treatment Apparatus and Method

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109731226A (zh) * 2019-03-07 2019-05-10 华中科技大学 一种等离子体灰指甲治疗装置
WO2025017299A1 (fr) 2023-07-18 2025-01-23 King's College London Sulfure d'hydrogène pour le traitement topique d'une infection des ongles

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