WO2018175327A1 - Onychomycosis treatment system and method - Google Patents

Abstract

A system and method includes delivery of a redox gas solution to treat onychomycosis, wherein the redox gas solution comprises a reactive species dissolved in a perfluorocarbon liquid, and wherein the reactive species may include, alone or in combination, one or more of reactive oxygen, reactive nitrogen, reactive chlorine, or reactive bromine species, and the perfluorocarbon liquid may include perfluorodecalin.

Description

TITLE

ONYCHOMYCOSIS TREATMENT SYSTEM AND

METHOD

RELATED APPLICATIONS

[0001] This application claims priority to pending US patent application 15/464,761, filed March 21, 2017 and is a continuation-in-part of, and is related to and claims priority from, pending US patent application serial number 14/963,552, filed December 9, 2015, which is related to and claims priority from US provisional patent application serial number 62/089,945, filed December 10, 2014, entitled Onychomycosis Treatment Apparatus and Method, each of which is hereby incorporated by reference herein for all purposes.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] This invention was made with government support under NSF Award ID

1343994 and NIH Award ID 1R43GM112196-01 awarded by the National Science Foundation and the National Institute of Health. The government has certain rights in the invention.

FIELD OF THE DISCLOSURE

[0003] The invention in one aspect relates generally to a system and method for the treatment of onychomycosis.

BACKGROUND

[0004] 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.

[0006] 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.

[0007] 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.

[0008] 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.

[0009] Other causative pathogens include 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.

[0010] All causative pathogens are susceptible to certain toxic gasses, such as ozone, oxides of nitrogen, and similar reactive materials. It is understood that fluid and solid materials may also have similar beneficial anti-pathogenic properties. However, there are a number of problems associated with the use of such anti-pathogenic substances to treat onychomycosis. The nail bed itself can act as a barrier to curative gasses and beneficial anti-pathogenic substances. Thus, there remains a need for a system and method for the treatment of onychomycosis that permits substances to traverse, surround and/or enter the nail bed and similar physiological structures for a beneficial effect.

[0011] There also remains an unmet medical need for a topical treatment device and treatment method for onychomycosis that is effective, requiring short treatment times and without the undesirable side effects of the prior art. Many chemical compounds exhibit antifungal (fungistatic or fungicidal) properties, and can be incorporated into creams, lotions, gels, solutions and the like. However, antifungal compounds applied topically (i.e., directly to the nail) do not adequately and consistently penetrate the nail bed to kill the fungus at its source, and thus are not consistently effective.

[0012] Thus, an additional or improved apparatus and method for treating onychomycosis is desirable.

SUMMARY

[0013] 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.

[0014] In one exemplary embodiment, 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.

[0015] In one exemplary embodiment, a system is provided that 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. In one embodiment, 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. In one embodiment, 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. During treatment, the generators provide for a desired period of time reactive species to the chamber including the inserted foot.

[0016] Other benefits and advantages of the present disclosure will be appreciated from the following detailed description.

DESCRIPTION OF THE DRAWINGS

[0017] Exemplary embodiments of a system and method are shown in the accompanying drawings.

[0018] FIG. 1 is an illustration by flowchart of an exemplary method in accordance with the disclosure.

[0019] FIG. 2 is a cross-sectional view of a portion of an exemplary system in accordance with the disclosure.

[0020] FIG. 3A is a cross-sectional view of a container including an exemplary perfluorocarbon liquid in accordance with the disclosure.

[0021] 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.

[0022] FIG. 3C is a perspective view of an exemplary application of perfluorocarbon liquid to nail/tissue using the applicator shown in FIG. 3B.

[0023] 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.

[0024] FIG. 5A is a perspective view of an exemplary toe-clip applicator in accordance with the disclosure.

[0025] FIG. 5B is a partial cross-sectional view of the exemplary toe-clip applicator shown in FIG. 5 A.

[0026] FIG. 6 is a perspective view of an alternate exemplary treatment system embodiment in accordance with the disclosure.

[0027] FIG. 7 is a perspective view of another alternate exemplary treatment system embodiment in accordance with the disclosure.

[0028] FIG. 8 is an assembly view of the exemplary treatment system shown in Figure

7.

[0029] FIG. 9 is an assembly view of the chamber housing of the exemplary treatment system shown in Figure 8.

[0030] FIG. 10 is an assembly view of the exhaust duct of the exemplary treatment system shown in Figure 8.

[0031] FIG. 11 is an assembly view of the power supply housing of the exemplary treatment system shown in Figure 8.

[0032] FIG. 12A is a perspective view of a disposable tray of the exemplary treatment system shown in Figures 7 and 9.

[0033] 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.

DETAILED DESCRIPTION

[0034] Embodiments of the invention and various alternatives are described. Those skilled in the art will recognize, given the teachings herein, that numerous alternatives and equivalents exist which do not depart from the invention. It is therefore intended that the invention not be limited by the description set forth herein or below.

[0035] One or more specific embodiments of the system and method will be described below. These described embodiments are only exemplary of the present disclosure. Additionally, in an effort to provide a concise description of these exemplary embodiments, all features of an actual implementation may not be described in the specification. It should be appreciated that in the development of any such actual implementation, as in any engineering or design project, numerous implementation- specific decisions must be made to achieve the developers' specific goals, such as compliance with system-related and business-related constraints, which may vary from one implementation to another. Moreover, it should be appreciated that such a development effort might be complex and time consuming, but would nevertheless be a routine undertaking of design, fabrication, and manufacture for those of ordinary skill having the benefit of this disclosure.

[0036] Further, for clarity and convenience only, and without limitation, the disclosure (including the drawings) sets forth exemplary representations of only certain aspects of events and/or circumstances related to this disclosure. Those skilled in the art will recognize, given the teachings herein, additional such aspects, events and/or circumstances related to this disclosure, e.g., additional elements of the devices described; events occurring related to onychomycosis treatment; etc. Such aspects related to this disclosure do not depart from the invention, and it is therefore intended that the invention not be limited by the certain aspects set forth of the events and circumstances related to this disclosure.

[0037] Turning now to the drawings, the figures show an exemplary treatment system and method. As described in Figure 1, 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. Then, at step 20, 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.

[0038] In one exemplary embodiment, 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.

[0039] As shown in Figure 2, 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. As shown in Figure 2, the plasma generating device includes a ground electrode 50. In addition, 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).

Perfluorocarbon Liquids (PFCsVOther Facilitators

[0040] The perfluorocarbon liquid may include perfluorodecalin. Perfluorodecalin and other suitable perfluorocarbon liquids have desirable wetting, gas absorption and diffusion properties.

[0041] Perfluorocarbons (PFCs), fluorocarbons, or perfluorochemicals (terms which may be used interchangeably) 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.

[0042] 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.

[0043] PFCs are used in a variety of industries. They were first synthesized in the

1920s and developed for industry in the 1940s. 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.

[0044] The term "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.

[0045] Specific examples of 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.

[0046] 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.

[0047] 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.

[0048] 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. In one exemplary embodiment, 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. Fluorinert™ Fluids, product bulletin 98- 0211-8301- 1(65.05)R, issued 5/95, available from 3M Co., St. Paul, Minn., provides the solubility of many oxidizing gases in Fluorinert™ Electronic Fluids.

[0049] Other perfluorocarbons that may be used 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, Methylperfluorobutylether (GransilSiW 7100) or Perfluoro(tert-butylcyclohexane). Also mixtures of perfluorocarbons could also be utilized in this invention that combine different perfluorocarbons and perfluorocarbon compositions such as PFC emulsions or PFC gels.

[0050] Other liquids may fulfill the mechanism of penetration enhancer / gas carrier and could concentrate the antifungal species from the plasma. In addition to PFCs, 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.

[0051] In another exemplary embodiment, 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. In another exemplary embodiment, 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. In one exemplary embodiment, one or more useful SFAs may be selected from a group of SFAs including F4H5, F4H6, F4H8, F₆H6 and FeHs.

Redox Gas Solutions

[0052] In one exemplary embodiment, the perfluorocarbon liquid absorbs anti- pathogenic substances generated by a plasma-generating device. See, e.g., Figure 2. In one exemplary aspect, 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.

[0053] For convenience only, and without limitation, 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."

[0054] In accordance with another exemplary embodiment, an onychomycosis treatment system and method includes a topical composition to overcome one or more disadvantages of current topical fungal treatments. In one aspect, the topical composition may include a redox gas solution.

[0055] In another aspect, 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. In another aspect, 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. In another exemplary embodiment, the redox gas is formed during a non-thermal plasma treatment step.

[0056] In accordance with another exemplary embodiment, 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.

Plasma-generating Devices

[0057] In accordance with one exemplary embodiment, a plasma-generating device may create antimicrobial plasma species proximate a nail or skin area to be treated.

[0058] As used herein, the term "antimicrobial" means tending to destroy microbes, prevent their development, or inhibit their pathogenic action, and includes reference to, without limitation, antibacterial and antifungal properties.

[0059] 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.

[0060] There are multiple technologies that have been used for plasma- generating devices at atmospheric pressure and temperatures. 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. 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.

[0061] As shown in Figure 4, 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 ^χ 8 meshes per cm², for example, may be used.

[0062] 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. In a SMD, 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.

[0063] Multiple reactive oxygen species (ROS) and reactive nitrogen species (RNS) may be generated in a non-thermal plasma. 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 (H₂0) and carbon dioxide (CO2). Kogelschatz and co-workers have performed early studies on the discharge characteristics and chemistry of air DBDs. More recently Y. Sakiyama et al. created a plasma chemistry model of a SMD device to determine the dynamics of the reactive neutral species it produces.

[0064] The non-thermal plasma gas effluent may be directed to a treatment site in two ways: direct mode or indirect mode. Direct mode (see Figure 4) 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. In 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.

[0065] 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. For example, a sufficient time for application may be a time from about 10 seconds to about 4 hours. In one exemplary embodiment, antimicrobial agent may be applied for a time from about 1 minute to about 15 minutes. In yet another exemplary embodiment, antimicrobial agent may be applied for a time from about 5 minutes to about 20 minutes. In a further exemplary embodiment, antimicrobial agent may be applied for a time from about 30 minutes to about 1 hour. In other exemplary embodiments, 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).

Gaseous Species

66] 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. Such 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.

[0067] 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.

[0068] 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. Such 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.

[0069] 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.

[0070] 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.

[0071] As shown in Figures 3A-3C, in one exemplary embodiment, 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. In one embodiment, 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. In another embodiment, the solution may be applied once a day for a minimum of sixty days to inactivate the fungus. In another embodiment, the solution may be applied once a week to prevent fungus or fungal spores from reinfecting the nail matrix.

[0072] 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. As an example, 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.

[0073] In one embodiment, perfluorodecalin is pre-applied to the infected nail to act as a redox gas facilitator substance. As shown in Figures 5A and 5B, 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.

[0074] In another exemplary embodiment, 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. As shown in Figure 6, 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.

[0075] In another exemplary embodiment, 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.

[0076] 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. In addition, 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.

[0077] Additionally, 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.

[0078] As shown in Figures 7-12, an exemplary embodiment of a system for treating onychomycosis is described. 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.

[0079] 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. By way of example only, and without limitation, the display 570 may show a countdown timer reflecting the time remaining in a treatment session. Further, the main body housing 500 may include a handle 580 to help promote positioning of the system for a treatment session.

[0080] The chamber assembly 510 is shown in greater detail in Figure 9. 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.

[0081] In operation, 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).

[0082] 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. In this 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.

[0083] The liner 680 may include a sheet 760 extending forward from the base of the front of tray portion 690. In one embodiment, 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.

[0084] As illustrated in Figures 7, 12A and 12B, the membrane 750 includes a port

800 therein. 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.

[0085] To help position the foot within the chamber 610, a wedge 810 may be removably placed at the bottom of chamber 610 below the tray portion 690. For 24 mm high toes a 4.5 degree wedge may be used. For 18 mm high toes an 8.5 degree wedge may be used. In one embodiment, during treatment the distance between the top of the toes and a plasma head assembly 630 may be approximately 15 mm. In one embodiment, the wedge 810 may be separate from the tray portion 690. In another embodiment, the wedge 810 may be formed with the tray portion 690, e.g., at the base 700. In yet another embodiment, the wedge 810 may be formed by folding material to provide a wedge 810 of a desired size and shape.

[0086] The rear wall of the housing 600 may include an exhaust port 820.

Mounted to the outside of housing 600 at exhaust port 820 may be an exhaust fan 830. In one embodiment, during the final 15 seconds of a treatment period 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. [0087] During operation, 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.

[0088] 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.

[0089] During treatment, 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. Once the perfluorodecalin is placed on the patient's toe nail, the foot is placed into the liner 680 that has already been locked into place in the system. After a desired treatment time (e.g., 45 minutes), the patient's foot is removed and the liner 680 is properly discarded.

Examples

[0090] The following examples are offered to aid in a better understanding of the present invention. These examples are not to be construed as an exhaustive compilation of all embodiments of the present invention and are not to be construed as limiting the scope thereof.

Eradication of T. rubrum through a bovine hoof using Perfluorodecalin (PFD) facilitator and an SMD plasma-generating device

[0091] 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:

[0092] a. Control that is placed directly into the wash tube without any treatment.

[0093] b. Two PFD-only hoofs had lOOul PFD pipetted directly onto the hoof opposite side from the fungus. This was allowed to sit for 45 minutes in the hood before placing in the wash tube.

[0094] c. Two Plasma treatment only hoofs get just a 45 minute plasma treatment.

[0095] d. Three Plasma treatment with PFD hoofs had lOOul PFD pipetted directly onto the hoof opposite side from the fungus immediately before applying plasma treatment (i.e., while wet).

[0096] After treatment, 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.

Application of PFC onto the skin/nail

[0097] 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.

[0098] 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 (e.g., a dressing, bandage, patch, etc.) 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. In one embodiment, the membrane barrier is a silicone composition that contains an effective amount of perfluorocarbon and acts as a dressing. For nail treatment, the membrane may be manufactured in a toe or finger cot shape that may be slipped easily over the infected digit.

Loading PFC with antifungal gas

[0099] A PFC may be loaded with antifungal gas in a manufacturing facility. Alternately, 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. As described, there are other ways of loading the PFC with antifungal gas after it is applied to the infections site (e.g., besides a plasma device). In one embodiment, a pure gas canister (NO, ozone, H2O2, etc.) may be used. In another embodiment, 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. 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.

[00100] Again, 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. Such 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. Sterilization and Other Therapies

[00101] 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.

[00102] In one embodiment, 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.

[00103] In another embodiment, decontamination of a liquid or gas may occur using a 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.

[00104] It should be understood that the foregoing description is only illustrative of the invention. Various alternatives and modifications can be devised by those skilled in the art having the benefit of this disclosure, without departing from the invention. Accordingly, the invention is intended to embrace all such alternatives, modifications and variances.

[00105] Certain exemplary embodiments of the disclosure may be described. Of course, the embodiments may be modified in form and content, and are not exhaustive, i.e., additional aspects of the disclosure, as well as additional embodiments, will be understood and may be set forth in view of the description herein. Further, while the invention may be susceptible to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and will be described in detail herein. However, it should be understood that the invention is not intended to be limited to the particular forms disclosed. Rather, the invention is to cover all modifications, equivalents and alternatives falling within the spirit and scope of the invention.

Claims

CLAIMS What is claimed is:

1. An onychomycosis treatment system including:

(a) a chamber assembly housing including a sealed chamber formed therein;

(b) A plasma source disposed within the chamber for delivery of a redox gas; and

(c) perfluorodecalin for forming a coating on a nail or tissue removably inserted within the chamber for treatment, wherein the redox gas dissolves in the coating, and wherein the treatment effectively destroys all or a portion of the onychomycosis.

2. The system of claim 1, including an opening disposed at a lower front portion of the housing.

3. The system of claim 2, including a liner at least partially insertable through the opening.

4. The system of claim 3, wherein the liner comprises a tray portion including a back wall or a side wall.

5. The system of claim 4, wherein the tray further comprises a front portion including a perimeter support and a membrane, the support and membrane being of a peripheral size and shape that is

larger than a peripheral size and shape of the opening.

6. The system of claim 5, further comprising a hatch cover hingedly attached to the chamber assembly housing above the opening and rotatable downwardly to a lower position holding the perimeter support and

membrane at the opening.

7. The system of claim 1, further comprising a UV filter provided

proximate the plasma source assembly.

8. The system of claim 1, further comprising a disposable liner comprising:

(a) tray portion including a base foldably attached to:

(i) a back wall,

(ii) a first side wall,

(iii) a second sidewall disposed opposite the first side wall, and

(iv) a front portion disposed opposite the back wall, the front portion including a perimeter support and a membrane, and

(b) a sheet extending forward from the front portion of the tray.

9. The system of claim 8, wherein the membrane includes a port therein through which a body part may be partially inserted, sealing the body part within the chamber.

10. The system of claim 1, wherein the plasma source further comprises a

plasma head assembly.

11. An onychomycosis treatment system for treating an infection on a body

part comprising:

(a) a chamber assembly housing including a sealed chamber formed therein for removably inserting said body part within said sealed chamber for treatment, said chamber assembly housing further comprising an exhaust duct and a gas filter disposed in said exhaust duct of said assembly housing chamber,

(b) a tray for supporting said body part, said tray comprising a liner to support said body part,

(c) a plasma head assembly disposed within the sealed chamber; said plasma head assembly comprising an electrical control circuit, a high voltage electrode, a dielectric, and a ground electrode,

(d) an opening formed in said assembly housing chamber, said opening further comprising a removable door fitted to said assembly housing chamber opening allowing said body part to be position in said sealed chamber such that said body part is proximal to said plasma head assembly, (e) a UV filter disposed proximate to said plasma head assembly, wherein said plasma head assembly is capable of forming a plasma reactive species gas proximate to said ground electrode, and

(f) a perfluorodecalin liquid coating in communication with said infection on the body part, wherein said coating transfers said plasma reactive species gas located between said plasma head assembly and said infection on the body part.

12. The system of claim 11, wherein said opening is disposed at a lower

front portion of the chamber assembly housing and in direct communication with the sealed chamber.

13. The system of claim 12, where said liner is at least partially insertable

through the chamber assembly housing opening.

14. The system of claim 13, wherein the front portion of the tray comprises

a perimeter support and a membrane, the support and membrane being of a

peripheral size and shape that is larger than a peripheral size and shape of the chamber assembly housing opening replacing said door.

15. The system of claim 11, further comprising a hatch cover replacing said

door hingedly attached to the chamber assembly housing above the opening and rotatable downwardly to a lower position holding the perimeter support and membrane at the opening.

16. The system of claim 11, where said liner is a disposable liner.

17. The system of claim 11, wherein the body part is selected from the

group consisting of a nail, foot, a toe, a hand, a finger and a tissue.

18. The system of claim 17, wherein the membrane includes a port therein

through which the body part may be inserted.

19. A method of treating an infection on a body part comprising of the steps:

(a) placing a body part on a tray, said tray having a liner to support said body part,

(b) placing a perfluorodecalin liquid on an infected body part for transfer of a plasma reactive species gas, said gas originating in a sealed chamber comprising a plasma head assembly, said gas being located between the said plasma head assembly and in communication with the infection,

(c) inserting said tray containing said body part into a chamber assembly housing including the sealed chamber formed therein for removably inserting said body part within said sealed chamber for treatment, said sealed chamber having a plasma head assembly disposed within the sealed chamber; said plasma head assembly comprising an electrical control circuit, a high voltage electrode, a dielectric, and a ground electrode and a gas filter disposed in an exhaust duct of the chamber assembly housing,

(d) placing the body part within the liner, wherein the liner surrounds the body part,

(e) forming a seal between the chamber assembly housing and said liner surrounding the body part upon insertion of the tray, to prevent escape of reactive species gas from the chamber,

(f) setting a timer to a treatment time for treatment of said infection,

(g) energizing said plasma head assembly having a UV plasma filter disposed proximate to said plasma head assembly to form a plasma reactive species gas proximate to said ground electrode,

(h) generating said plasma reactive species gas within the sealed chamber for a time sufficient to and in direct line with the body part to permit penetration of reactive species gas through the perfluorodecalin coating and into a nail or a tissue of the treated body part,

(i) deenergizing said plasma head assembly at the end of the said treatment time, and (j) exhausting the gases within the chamber assembly housing after said timer has finished through said exhaust duct and said filter, wherein pathogens residing in the nail or tissue of the treated body part are effectively destroyed.

20. The system of claim 19, wherein said body part is selected from the

group consisting of a nail, foot, toe, hand, finger or tissue.