Apparatus for treating allergic dermatitis and method for treating allergic dermatitis

Abstract

Provided is a method for treating allergic dermatitis (excluding practices on humans), the method including one or more cycles of an irradiation step in which a plasma generation gas is supplied to a plasma generation unit provided with electrodes to generate plasma and a biological tissue is irradiated with an irradiation gas containing at least one of the plasma and an active gas generated by means of the plasma, wherein the irradiation step includes irradiating the biological tissue with the irradiation gas for 1-300 seconds per cm2.

Description

Allergic dermatitis treatment device and allergic dermatitis treatment method

[0001] The present invention relates to an apparatus and method for treating allergic dermatitis. This application claims priority to Japanese Patent Application No. 2024-035704 filed on March 8, 2024, and Japanese Patent Application No. 2024-232862 filed on December 27, 2024, the contents of which are incorporated herein by reference.

[0002] Plasma generators are known that use plasma or activated species generated by plasma to perform treatment, sterilization, etc. In the plasma generators, for example, an irradiation gas containing plasma or activated species is irradiated onto an affected area to promote healing of a wound, etc. For example, Patent Document 1 proposes a cell activator having a hydroxyl radical concentration within a specific range.

[0003] Japanese Patent Application Laid-Open No. 2020-172498

[0004] Various treatment methods for allergic dermatitis such as atopic dermatitis have been reported. Further enhancement of the therapeutic effect for allergic dermatitis is desired. The present invention aims to provide a new device for treating allergic dermatitis.

[0005] The present invention has the following aspects: <1> A method for treating a living body tissue comprising one or more irradiation steps of supplying a plasma generating gas to a plasma generating unit having an electrode to generate plasma, and irradiating a living body tissue with an irradiation gas containing at least one of the generated plasma and an active gas generated by the plasma, wherein the irradiation step is performed by supplying the irradiation gas to the living body tissue for 1 to 300 seconds / cm ２ <2> The method for treating allergic dermatitis according to <1>, wherein the irradiation step irradiates the irradiation gas at a velocity of 6 to 650 m / s (or irradiates for 1 to 600 seconds).

[0006] <3> A plasma generating unit having an electrode, a gas supply unit that supplies a plasma generating gas to the plasma generating unit, an irradiation device having a nozzle that ejects an irradiation gas containing at least one of the plasma generated in the plasma generating unit and an activated gas generated by the plasma, and an irradiation time of the irradiation gas of 1 to 300 seconds / cm ２ and a control unit that sets the irradiation gas at a speed of 6 to 650 m / s.

[0007] <5> A plasma generating gas is supplied to a plasma generating unit having an electrode to generate plasma, and an irradiation gas containing at least one of the generated plasma and an activated gas generated by the plasma is applied at a rate of 1 to 300 seconds / cm ２ <6> A method for producing a therapeutic agent for allergic dermatitis according to <5>, wherein the irradiation step comprises ejecting the irradiation gas at a speed of 6 to 650 m / s (or ejecting the irradiation gas for 1 to 600 seconds).

[0008] <7> A method for treating a living tissue comprising one or more irradiation steps of supplying a plasma generating gas to a plasma generating unit having an electrode to generate plasma, and irradiating a living tissue with an irradiation gas containing at least one of the generated plasma and an active gas generated by the plasma, wherein the irradiation step is performed by supplying the irradiation gas to the living tissue for 1 to 300 seconds / cm ２ <8> The pain relief method, pain treatment method, or pain prevention method according to <7>, wherein the irradiation step irradiates the irradiation gas at a speed of 6 to 650 m / s (or irradiates for 1 to 600 seconds).

[0009] <9> A plasma generating unit having an electrode; a gas supply unit that supplies a plasma generating gas to the plasma generating unit; an irradiation device having a nozzle that ejects an irradiation gas containing at least one of the plasma generated in the plasma generating unit and an activated gas generated by the plasma; and an irradiation time of the irradiation gas of 1 to 300 seconds / cm ２<10> The pain relief device, pain treatment device, or pain prevention device according to <9>, wherein the irradiation instrument ejects the irradiation gas at a speed of 6 to 650 m / s.

[0010] <11> A method for treating a skin cancer, comprising one or more irradiation steps of supplying a plasma generating gas to a plasma generating unit having an electrode to generate plasma, and irradiating biological tissue with an irradiation gas containing at least one of the generated plasma and an active gas generated by the plasma, wherein the irradiation step is performed by supplying the irradiation gas to the biological tissue for 1 to 300 seconds / cm ２ <12> The method for alleviating, treating, or preventing itch according to <11>, wherein the irradiation step involves irradiating the irradiation gas at a speed of 6 to 650 m / s.

[0011] <13> A plasma generating unit having an electrode; a gas supply unit that supplies a plasma generating gas to the plasma generating unit; an irradiation device having a nozzle that ejects an irradiation gas containing at least one of the plasma generated in the plasma generating unit and an activated gas generated by the plasma; and an irradiation time of the irradiation gas of 1 to 300 seconds / cm ２ <14> The device for alleviating pruritus, treating pruritus, or preventing pruritus according to <13>, wherein the irradiation instrument ejects the irradiation gas at a speed of 6 to 650 m / s.

[0012] <15> A method for treating a skin cancer, comprising one or more irradiation steps of supplying a plasma generating gas to a plasma generating unit having an electrode to generate plasma, and irradiating biological tissue with an irradiation gas containing at least one of the generated plasma and an active gas generated by the plasma, wherein the irradiation step is performed by supplying the irradiation gas to the biological tissue for 1 to 300 seconds / cm ２<16> The method for alleviating redness, the method for treating redness, or the method for preventing redness according to <15>, wherein the irradiation step irradiates the irradiation gas at a speed of 6 to 650 m / s.

[0013] <17> A plasma generating unit having an electrode; a gas supply unit that supplies a plasma generating gas to the plasma generating unit; an irradiation device having a nozzle that ejects an irradiation gas containing at least one of the plasma generated in the plasma generating unit and an activated gas generated by the plasma; and an irradiation time of the irradiation gas of 1 to 300 seconds / cm ２ <18> The redness alleviation device, redness treatment device, or redness prevention device according to <17>, wherein the irradiation instrument ejects the irradiation gas at a speed of 6 to 650 m / s.

[0014] <19> The method or device for treating allergic dermatitis according to any one of <1> to <4>, which alleviates or treats at least one symptom selected from the group consisting of redness, pain, and itching. <20> The amount of active species in one irradiation step (unit amount of active species) is 0.1 to 300 μmol / cm ２ and 0.1 to 100 μmol / cm ２ is preferred, and 0.1 to 50 μmol / cm ２ The method for treating allergic dermatitis, the device for treating allergic dermatitis, or the method for producing a therapeutic drug for allergic dermatitis according to any one of <1> to <6> and <19> is more preferably: <21> The time for irradiating the irradiation gas in one irradiation step (irradiation time) is 1 to 300 seconds / cm ２ and 3 to 60 seconds / cm ２<22> The method for treating allergic dermatitis, the device for treating allergic dermatitis, or the method for manufacturing a therapeutic drug for allergic dermatitis according to any one of <1> to <6>, <19>, and <20>, wherein the distance from the irradiation port through which the irradiation gas is discharged to the irradiated surface (irradiation distance) is 1.0 to 10 mm, and preferably 1 to 5 mm. <23> The method for treating allergic dermatitis, the device for treating allergic dermatitis, or the method for manufacturing a therapeutic drug for allergic dermatitis according to any one of <1> to <6>, <19> to <22>, wherein the flow rate of the irradiation gas is 0.3 to 30 L / min, and preferably 3 to 30 L / min. <24> The method for treating allergic dermatitis, the device for treating allergic dermatitis, or the method for producing a therapeutic agent for allergic dermatitis according to any one of <1> to <6> and <19> to <23>, wherein the flow velocity of the irradiation gas is 6 to 650 m / s.

[0015] According to the allergic dermatitis treatment device of the present invention, the treatment effect of allergic dermatitis can be enhanced.

[0016] 1 is a schematic diagram of a treatment device according to a first embodiment of the present invention; FIG. 2 is a partial cross-sectional view of an irradiation device of the treatment device according to the first embodiment of the present invention; FIG. 3 is a block diagram of a treatment device according to a first embodiment of the present invention; FIG. 4 is a graph showing the results of Experimental Example 1; FIG. 5 is a graph showing the results of Experimental Example 2; FIG. 6 is a graph showing the results of Experimental Example 3; FIG. 7 is a graph showing the results of Experimental Example 4; FIG. 8 is a graph showing the results of Experimental Example 4; FIG. 9 is a graph showing the results of Experimental Example 4; FIG. 10 is a graph showing the results of Experimental Example 4; FIG. 11 is a photograph of skin before the onset of allergic dermatitis; FIG. 12 is a photograph of skin after the onset of allergic dermatitis; FIG. 13 is a photograph of skin after the onset of allergic dermatitis; FIG. 14 is a photograph of skin after the onset of allergic dermatitis; FIG. 15 is a photograph of skin after the onset of allergic dermatitis; FIG. 16 is a photograph of skin after the onset of allergic dermatitis; FIG. 17 is a photograph of skin after the onset of allergic dermatitis; FIG. 18 is a photograph of skin after the onset of allergic dermatitis; FIG. 19 is a cross-sectional photograph showing the thickness of the back skin before the onset of allergic dermatitis; FIG. 19 is a cross-sectional photograph showing the thickness of the back skin after the onset of allergic dermatitis; 10 is a graph showing the results of Experimental Example 5. 11 is a graph showing the results of Experimental Example 6. 12 is a graph showing the results of Experimental Example 7. 13 is a graph showing the results of Experimental Example 8. 14 is a graph showing the results of Experimental Example 9. 15 is a graph showing the results of Experimental Example 10.

[0017] In this specification and claims, the use of "to" indicating a range of values ​​means that the range of values ​​includes the values ​​before and after it as the lower and upper limits. In this specification and claims, the term "treatment" also includes palliative care.

[0018] (Allergic dermatitis treatment device) The allergic dermatitis treatment device of the present invention comprises a plasma generation unit, a gas supply unit, an irradiation device having a nozzle for discharging irradiation gas, and a control unit for controlling the irradiation time of the irradiation gas. An example of the allergic dermatitis treatment device of the present invention (hereinafter, sometimes simply referred to as "treatment device") will be described below with reference to the drawings.

[0019] 1 to 3 includes an irradiation device 10, a supply 20, and a connecting cable 30. The connecting cable 30 houses an electric supply line 32, a grounding line 34, and a gas line 36.

[0020] 2 is a cross-sectional view (longitudinal cross-section) of a plane along the axis of the irradiation device 10. As shown in FIG.

[0021] The irradiation device 10 comprises a long cowling 2, a nozzle 1 protruding from the tip of the cowling 2, and a plasma generating unit 12 located within the cowling 2. The cowling 2 comprises a cylindrical body 2b and a head 2a that closes the tip of the body 2b. The body 2b is not limited to a cylindrical shape, and may be a polygonal cylinder such as a square, hexagonal, or octagonal cylinder.

[0022] The head portion 2a gradually narrows toward the tip. That is, the head portion 2a in this embodiment is conical. The head portion 2a is not limited to a conical shape, and may be a polygonal pyramid such as a square pyramid, a hexagonal pyramid, or an octagonal pyramid. The head portion 2a has a fitting hole 2c at its tip. The fitting hole 2c is a hole that receives the nozzle 1. The nozzle 1 is detachably attached to the head portion 2a. The head portion 2a has a first active gas flow path 7 therein that extends in the direction of the tube axis O1. The tube axis O1 is the tube axis of the body portion 2b.

[0023] The plasma generating unit 12 includes a tubular dielectric 3 (dielectric), an internal electrode 4, and an external electrode 5. The tubular dielectric 3 is a cylindrical member extending in the direction of the tube axis O1. The tubular dielectric 3 has a gas flow path 6 extending in the direction of the tube axis O1 inside. In this embodiment, the plasma generating gas flows through the gas flow path 6 in the direction of the tube axis O1. The first active gas flow path 7 and the gas flow path 6 are connected. The tube axis O1 is the same as the tube axis of the tubular dielectric 3. The tubular dielectric 3 includes an internal internal electrode 4. The internal electrode 4 is a substantially cylindrical member extending in the direction of the tube axis O1. The internal electrode 4 is spaced apart from the inner surface of the tubular dielectric 3. The tubular dielectric 3 includes an external electrode 5 on a part of its outer peripheral surface, along the internal electrode 4. The external electrode 5 is an annular electrode that surrounds the outer peripheral surface of the tubular dielectric 3. The tubular dielectric 3, the internal electrode 4, and the external electrode 5 are positioned concentrically around the tube axis O1. In this embodiment, the outer peripheral surface of the internal electrode 4 and the inner peripheral surface of the external electrode 5 face each other across the tubular dielectric 3. The internal electrode 4 is connected to an electric supply line 32. The external electrode 5 is connected to a grounding line 34 and is electrically grounded. Note that, although the plasma generating unit 12 of this embodiment has electrodes facing each other in a direction perpendicular to the flow direction of the plasma generation gas, the present invention is not limited thereto. The plasma generating unit 12 may be configured with two electrodes facing each other along the flow direction of the plasma generation gas (see Japanese Patent No. 5441066), or may have only one electrode to which a voltage is applied (see Japanese Patent Publication No. 2018-504202).

[0024] The nozzle 1 comprises a base 1b that fits into the fitting hole 2c and an irradiation tube 1c that protrudes from the base 1b. The base 1b and the irradiation tube 1c are integrated. The nozzle 1 has a second active gas flow path 8 therein. The nozzle 1 has an irradiation port 1a at its tip. The second active gas flow path 8 and the first active gas flow path 7 are in communication with each other.

[0025] The material of the body portion 2b is not particularly limited, but an insulating material is preferable. Examples of insulating materials include thermoplastic resins and thermosetting resins. Examples of thermoplastic resins include polyethylene, polypropylene, polyvinyl chloride, polystyrene, and acrylonitrile-butadiene-styrene resin (ABS resin). Examples of thermosetting resins include phenolic resin, melamine resin, urea resin, epoxy resin, unsaturated polyester resin, and silicone resin. There are no particular limitations on the size of the body portion 2b, and it can be a size that is easy to grip with the fingers.

[0026] The material of the head portion 2a is not particularly limited, and may or may not have insulating properties. The material of the head portion 2a is preferably a material with excellent abrasion resistance and corrosion resistance. An example of a material with excellent abrasion resistance and corrosion resistance is metal such as stainless steel. The materials of the head portion 2a and the body portion 2b may be the same or different. The size of the head portion 2a can be determined taking into consideration the intended use of the treatment device 100, etc.

[0027] Dielectric materials used in known plasma generating devices can be used as the material of the tubular dielectric 3. Examples of the material of the tubular dielectric 3 include glass, ceramics, synthetic resin, etc. The lower the dielectric constant of the tubular dielectric 3, the more preferable it is.

[0028] The inner diameter R of the tubular dielectric 3 can be appropriately determined in consideration of the outer diameter d of the internal electrode 4. The inner diameter R is determined so that the distance s, which will be described later, falls within a desired range.

[0029] The internal electrode 4 is not particularly limited in shape as long as it extends in the tube axis O1 direction. The internal electrode 4 may be, for example, a member having a smooth peripheral surface, or a member having irregularities such as threads on the peripheral surface.

[0030] The outer diameter d of the internal electrode 4 can be determined appropriately taking into consideration the use of the treatment device 100 (i.e., the size of the irradiation instrument 10), etc. The outer diameter d is preferably 0.5 to 20 mm, for example, and more preferably 1 to 10 mm. When the internal electrode is a member having irregularities such as threads on its periphery, the largest diameter among the outer diameters of the internal electrode is taken as the outer diameter d.

[0031] The material of the internal electrode 4 is not particularly limited as long as it is a conductive material, and any metal that can be used for electrodes of known plasma generators can be used. Examples of materials for the internal electrode 4 include metals such as stainless steel, copper, and tungsten, and carbon.

[0032] The material of the internal electrode 4 is not particularly limited as long as it is a conductive material, and any metal that can be used for electrodes of known plasma generators can be used. Examples of materials for the internal electrode 4 include metals such as stainless steel, copper, and tungsten, and carbon.

[0033] The distance s between the outer surface of the internal electrode 4 and the inner surface of the tubular dielectric 3 is preferably 0.05 to 5 mm, more preferably 0.1 to 1 mm. When the distance s is equal to or greater than the lower limit, a desired amount of plasma generation gas can be easily passed through. When the distance s is equal to or less than the upper limit, plasma can be generated more efficiently and the temperature of the irradiation gas can be lowered.

[0034] The material of the external electrode 5 is not particularly limited as long as it is a conductive material, and may be a metal used in electrodes of known plasma generators. Examples of the material of the external electrode 5 include metals such as stainless steel, copper, and tungsten, and carbon.

[0035] The material of the nozzle 1 is not particularly limited and may be insulating or conductive. A material having excellent wear resistance and corrosion resistance is preferred as the material of the nozzle 1. Examples of materials having excellent wear resistance and corrosion resistance include metals such as stainless steel.

[0036] The length of the flow path in the irradiation tube 1c in the nozzle 1 (i.e., distance L2) can be appropriately determined taking into consideration the use of the treatment device 100, etc. The opening diameter of the irradiation port 1a is preferably 0.5 to 5 mm, for example. When the opening diameter is equal to or greater than the above-mentioned lower limit, the pressure loss of the irradiation gas can be suppressed. When the opening diameter is equal to or less than the above-mentioned upper limit, the flow rate of the irradiated irradiation gas can be increased, thereby promoting the therapeutic effect. The irradiation tube 1c is bent with respect to the tube axis O1. The angle θ formed between the tube axis O2 and the tube axis O1 of the irradiation tube 1c can be determined taking into consideration the use of the treatment device 100, etc. The irradiation tube 1c may be straight from the base end to the tip, or may be bent along the way.

[0037] The sum of the distance L1 from the tip Q1 of the external electrode 5 to the tip Q2 of the head portion 2a and the distance L2 from the tip Q2 to the irradiation port 1a (i.e., the distance from the plasma generation area to the irradiation port 1a) is determined appropriately taking into consideration the size required for the treatment device 100 and the temperature of the surface (irradiated surface) on which the irradiated irradiation gas hits. If the sum of the distances L1 and L2 is long, the temperature of the irradiated surface can be lowered. If the sum of the distances L1 and L2 is short, the concentration of activated species in the irradiation gas can be further increased, further improving the treatment effect at the affected area. The tip Q2 is the intersection of the tube axis O1 and the tube axis O2.

[0038] The supply device 20 includes a power supply unit 50, a gas supply unit 60, a gas supply source 70, a control unit 90, and a housing 21 that accommodates these components. The supply device 20 also includes an irradiation operation unit 9 and a timer 80.

[0039] In this embodiment, the irradiation operation unit 9 is provided on the top surface of the housing 21. Examples of the irradiation operation unit 9 include switches such as buttons and touch panels. The irradiation operation unit 9 does not have to be provided on the top surface of the housing 21. The irradiation operation unit 9 may be, for example, a foot pedal provided below the supply device 20, or a switch provided on the irradiation device 10.

[0040] The housing 21 detachably houses the gas supply source 70. This allows the gas supply source 70 to be replaced when the gas inside the gas supply source 70 housed in the housing 21 runs out.

[0041] The power supply unit 50 is connected to a power source such as a 100 V household power source. The power supply unit 50 is connected to the internal electrode 4 of the irradiation device 10 via an electric supply line 32.

[0042] The power supply unit 50 switches on and off the supply of electricity to the electrodes of the plasma generation unit 12. In addition, the power supply unit 50 adjusts the voltage and frequency applied to the electrodes. An example of the power supply unit 50 is a circuit including an inverter.

[0043] The timer 80 displays the irradiation time or manages the irradiation time, for example. Note that the treatment device 100 does not necessarily have to include the timer 80.

[0044] The gas supply unit 60 includes a gas pipe 65 that connects a gas supply source 70 and the gas pipeline 36. The gas pipe 65 is provided with a solenoid valve 61, a pressure regulator 63, and a flow rate controller 64 (flow rate adjustment unit). The flow rate controller 64 and the solenoid valve 61 are connected to a control unit 90. In this embodiment, the gas supply unit is composed of the gas supply source 70 and the gas pipeline 36.

[0045] The solenoid valve 61 switches between opening and closing to start and stop the supply of plasma generation gas from the gas supply source 70 to the irradiation instrument 10. In the illustrated example, the solenoid valve 61 is not configured to be adjustable in valve opening degree, but is configured to be only switchable between opening and closing. Note that the solenoid valve 61 may be configured to be adjustable in valve opening degree.

[0046] The pressure regulator 63 is disposed between the solenoid valve 61 and the gas supply source 70. The pressure regulator 63 reduces the pressure of the plasma generation gas flowing from the gas supply source 70 to the solenoid valve 61 (depressurizes the plasma generation gas).

[0047] The flow rate controller 64 is disposed between the solenoid valve 61 and the gas pipe 36. The flow rate controller 64 adjusts the flow rate (amount supplied per unit time) of the plasma generation gas that has passed through the solenoid valve 61. The flow rate controller 64 adjusts the flow rate of the plasma generation gas to, for example, 0.3 to 30 L / min.

[0048] A joint 66 is provided at the end of the gas pipe 65 on the gas supply source 70 side. The gas supply source 70 is detachably attached to the joint 66. By attaching and detaching the gas supply source 70 to and from the joint 66, the gas supply source 70 can be replaced while the gas supply unit 60 remains fixed to the housing 21. In this case, a common gas supply unit 60 can be used for both the old gas supply source 70 and the new gas supply source 70. Note that the gas supply unit 60 may be fixed to the gas supply source 70 and be detachable from the housing 21 together with the gas supply source 70.

[0049] The gas supply source 70 supplies plasma generation gas to the plasma generation unit 12. The gas supply source 70 is a pressure-resistant container or the like that contains plasma generation gas. The gas supply source 70 is detachably attached to the gas supply unit 60 arranged in the housing 21. Note that the gas supply source 70 may be located outside the housing 21 or may be a device independent of the treatment device 100.

[0050] The control unit 90 is configured using an information processing device. That is, the control unit 90 includes a CPU (Central Processor Unit), a memory, and an auxiliary storage device, which are connected via a bus. The control unit 90 operates by executing a program.

[0051] The gas pipeline 36 is a path for supplying plasma generating gas from the supply device 20 to the irradiation device 10. The gas pipeline 36 is connected to the tubular dielectric 3 of the irradiation device 10. There are no particular restrictions on the material of the gas pipeline 36, and any known material used for gas pipes can be used. Examples of materials for the gas pipeline 36 include resin piping and rubber tubing, and flexible materials are preferred.

[0052] The electric supply line 32 includes wiring that supplies electricity from a power source to the plasma generating unit 12 of the irradiation instrument 10. There are no particular limitations on the material of the electric supply line 32, and any known material used for electric wiring can be used. Examples of the material of the electric supply line 32 include a metal conductor coated with an insulating material.

[0053] The treatment device 100 has an alarm unit 22. The alarm unit 22 may be a component having a visual notification function or a component having an auditory notification function. An example of a component having a visual notification function is a light-emitting element such as an LED. An example of a component having an auditory notification function is a sound element such as a buzzer or an alarm. The alarm unit 22 may be provided in the supplier 20, or in the irradiation instrument 10, or may be provided independently of the supplier 20 and the irradiation instrument 10. Furthermore, the treatment device 100 does not need to have the alarm unit 22. The alarm unit 22 is preferably configured to cooperate with the control unit 90 to notify that a predetermined irradiation of the irradiation gas onto the surface of the irradiated object (affected area) has been completed. For example, the control unit 90 may determine an appropriate irradiation time (seconds / cm) from the flow rate (m / s) of the irradiation gas. ２ ) and notify the user when the time has elapsed. The appropriate irradiation time can be calculated using the following formulas 1 and 2. ２ ) × flow rate of irradiation gas (m / s) = flow rate of irradiation gas (L / min) (Formula 1) (1 / flow rate of irradiation gas) (L / min) × (flow rate of gas effective for treatment) (L / min) = appropriate irradiation time (Formula 2)

[0054] (Method for treating allergic dermatitis) The method for treating allergic dermatitis of the present invention includes one or more irradiation steps of irradiating biological tissue (subject to be irradiated) with an irradiation gas (i.e., a therapeutic drug for allergic dermatitis). The method for treating allergic dermatitis of the present invention will be described below based on one embodiment. The method for treating allergic dermatitis of the present invention is particularly suitable for mammals including humans. Furthermore, the method for treating allergic dermatitis of the present invention may exclude actions on humans. Examples of mammals other than humans include animals of the Bovidae family, Equidae family, Caprinae family, Suidae family, Canidae family, Felidae family, Rodents, and non-human primates, preferably cats, dogs, and pigs.

[0055] A method for treating allergic dermatitis according to this embodiment (hereinafter sometimes simply referred to as the "treatment method") using the treatment device 100 will be described. For example, a user such as a doctor turns on the main power of the supply device 20. At this time, if the timer 80 has a function for managing the irradiation time, the timer 80 sets the irradiation time of the irradiation gas. When the user operates the irradiation operation unit 9, the control unit 90 activates the timer 80, supplies plasma generating gas from the gas supply source 70 to the plasma generation unit 12 of the irradiation instrument 10 via the gas supply unit 60 and the gas pipeline 36, adjusts the supply voltage to the plasma generation unit 12, and applies voltage to the electrodes.

[0056] The plasma generating gas supplied to the plasma generating section 12 flows from the rear of the tubular dielectric 3 into the hollow space of the tubular dielectric 3. The plasma generating gas is ionized at the position where the internal electrode 4 and the external electrode 5, to which a voltage is applied, face each other, and becomes plasma.

[0057] In this embodiment, the internal electrode 4 and the external electrode 5 face each other in a direction perpendicular to the flow direction of the plasma generation gas. The plasma generated at the position where the outer peripheral surface of the internal electrode 4 faces the inner peripheral surface of the external electrode 5 flows through the gas flow path 6, the first activated gas flow path 7, and the second activated gas flow path 8, in that order. During this time, the plasma changes its gas composition as it flows, becoming an irradiation gas containing activated species such as radicals. The generated irradiation gas is discharged from the irradiation port 1a of the nozzle 1. The discharged irradiation gas further activates a portion of the gas near the irradiation port 1a to generate activated species. The irradiation gas containing these activated species is irradiated onto the object to be irradiated (irradiation process). When a desired irradiation time (the time set by the timer 80) has elapsed in the irradiation process, the control unit 90 stops at least one of the supply of plasma generation gas to the plasma generating unit 12 and the supply of electricity to the plasma generating unit 12, thereby ending the discharge of the irradiation gas. At this time, it is preferable to stop the supply of electricity to the plasma generating unit 12 (i.e., application of voltage to the electrodes) and the supply of plasma generating gas to the plasma generating unit 12, and to stop the instruction from the irradiation operation unit 9.

[0058] In the irradiation process, when the irradiation operation unit 9 transmits an electrical signal only once per operation, the control unit 90 controls the solenoid valve 61, the flow rate controller 64, the timer 80, and the power supply unit 50, for example, as follows. When the control unit 90 receives an electrical signal from the irradiation operation unit 9, the control unit 90 opens the solenoid valve 61 and causes the flow rate controller 64 to adjust the flow rate of the plasma generation gas passing through the solenoid valve 61. The control unit 90 also controls the power supply unit 50 to apply a voltage to the electrodes of the plasma generation unit 12. The control unit 90 also starts the timer 80. When the timer 80 reaches a predetermined time, the control unit 90 receives a signal from the timer 80 and closes the solenoid valve 61 or stops applying a voltage to the electrodes of the plasma generation unit 12. Alternatively, the notification unit 22 notifies the user that irradiation has been completed for a predetermined time. As a result, when the user operates the irradiation operation unit 9 once, a predetermined amount of irradiation gas containing activated species is discharged from the irradiation port 1a.

[0059] In the irradiation process, if the irradiation operation unit 9 continues to transmit an electrical signal while it is being operated, the control unit 90 controls the solenoid valve 61, the flow rate controller 64, the timer 80, and the power supply unit 50, for example, as follows. While the control unit 90 receives an electrical signal from the irradiation operation unit 9, the control unit 90 opens the solenoid valve 61 and causes the flow rate controller 64 to adjust the flow rate of the plasma generation gas passing through the solenoid valve 61. The control unit 90 also controls the power supply unit 50 to apply a voltage to the electrodes of the plasma generation unit 12. The control unit 90 also activates the timer 80. When the operation of the irradiation operation unit 9 is stopped, the control unit 90 closes the solenoid valve 61 or stops applying a voltage to the electrodes of the plasma generation unit 12. Alternatively, the notification unit 22 notifies the user that a predetermined time has elapsed. As a result, the irradiation gas is discharged from the irradiation port 1a while the user is operating the irradiation operation unit 9.

[0060] Examples of plasma generating gases include rare gases (helium, neon, argon, krypton, etc.), nitrogen, oxygen, air, etc. These gases may be used alone or in combination of two or more. The plasma generating gas preferably contains nitrogen as the main component. Here, "containing nitrogen as the main component" means that the nitrogen content in the plasma generating gas is more than 50% by volume. That is, the nitrogen content in the plasma generating gas is preferably more than 50% by volume, more preferably 70% by volume or more, still more preferably 80 to 100% by volume, and particularly preferably 90 to 100% by volume. Examples of gas components other than nitrogen in the plasma generating gas include oxygen, rare gases, etc. When the plasma generating gas contains nitrogen, more NO ｘ The oxygen concentration of the plasma generating gas is preferably 1% by volume or less. When the oxygen concentration is equal to or less than the upper limit, the generation of ozone can be reduced.

[0061] The flow rate of the plasma generating gas introduced into the tubular dielectric 3 in the irradiation step is preferably 0.3 to 30 L / min, more preferably 3 to 10 L / min. When the flow rate of the plasma generating gas introduced into the tubular dielectric 3 is equal to or higher than the above-mentioned lower limit, the amount of active species generated can be increased, and the therapeutic effect can be further enhanced. When the flow rate of the plasma generating gas introduced into the tubular dielectric 3 is equal to or lower than the above-mentioned upper limit, the surface of the irradiated object (affected area) can be prevented from drying, and the therapeutic effect can be further enhanced.

[0062] The AC voltage applied between the internal electrode 4 and the external electrode 5 in the irradiation step is preferably 1 kVpp or more and 20 kVpp or less, more preferably 5 kVpp or more and 20 kVpp or less. Here, the unit "Vpp (Volt peak to peak)" representing the AC voltage is the potential difference between the maximum and minimum values ​​of the AC voltage waveform. When the applied AC voltage is equal to or less than the upper limit, the temperature of the generated plasma can be kept low. When the applied AC voltage is equal to or more than the lower limit, plasma can be generated more efficiently.

[0063] The frequency of the AC current applied between the internal electrode 4 and the external electrode 5 in the irradiation step is preferably 0.1 kHz to 30 kHz, more preferably 1 kHz to 30 kHz, and even more preferably 5 kHz to 30 kHz. When the frequency of the AC current is equal to or less than the upper limit, the temperature of the generated plasma can be kept low. When the frequency of the AC current is equal to or greater than the lower limit, the plasma can be generated more efficiently.

[0064] The time for irradiating the irradiation gas in one irradiation step (irradiation time) is 1 to 300 seconds / cm ２ is preferred, and 2 to 100 seconds / cm ２ More preferably, 3 to 60 seconds / cm ２is more preferable. This irradiation time is the irradiation time of the irradiation gas per unit area of ​​the irradiation target (affected area) (hereinafter, sometimes referred to as "irradiation time per unit area"). The area of ​​the affected area can be determined by a known method. For example, an image of the skin including the affected area can be processed to identify areas where abnormalities (redness, swelling, blisters, rash, epidermal peeling, lichenification, etc.) have occurred, a boundary line can be drawn surrounding the area including such areas, and the area of ​​the area can be measured as the affected area. Furthermore, even when the irradiation gas is irradiated while moving the nozzle, the area irradiated in one irradiation step is defined as the affected area. Note that, when the irradiation gas is irradiated while moving the nozzle, it is preferable to move the nozzle so that the irradiation gas is uniformly irradiated over the entire affected area of ​​the target. When the irradiation time per unit area is equal to or greater than the above lower limit, the irradiation amount of the active species can be increased, thereby further improving the therapeutic effect. When the irradiation time per unit area is equal to or less than the above upper limit, dryness of the affected area can be suppressed, thereby further improving the therapeutic effect. Furthermore, by controlling the irradiation time per unit area within the above range, an appropriate irradiation dose can be achieved depending on the area to be treated (affected area). The irradiation time per unit area may be set for each irradiation step, or the control unit 90 may stop at least one of the supply of electricity and the supply of plasma generation gas to the plasma generator 12 based on a preset time. Furthermore, the actual time for irradiating the irradiation gas in one irradiation step (the actual irradiation time not taking into account the area of ​​the irradiation target, hereinafter also referred to as the "actual irradiation time") is preferably 1 to 600 seconds, more preferably 5 to 300 seconds, and even more preferably 10 to 120 seconds. When the actual irradiation time is equal to or greater than the above lower limit, the irradiation dose of the activated species can be increased, thereby further enhancing the therapeutic effect. When the irradiation time per unit area is equal to or less than the above upper limit, drying of the affected area can be suppressed, thereby further enhancing the therapeutic effect. The actual irradiation time may be set for each irradiation step, or the control unit 90 may stop at least one of the supply of electricity and the supply of plasma generation gas to the plasma generator 12 based on a preset time.

[0065] Amount of active species in one irradiation step (unit amount of active species): 0.1 to 300 μmol / cm ２is preferred, and 0.1 to 100 μmol / cm ２ More preferably, 0.1 to 50 μmol / cm ２ is more preferable. When the unit amount of active species is equal to or greater than the lower limit, the therapeutic effect can be further enhanced. When the unit amount of active species is equal to or less than the upper limit, the irritation to the irradiated surface can be further reduced. The amount of active species can be measured by electron spin resonance (ESR) spectroscopy.

[0066] The temperature of the irradiation gas irradiated from the irradiation port 1a of the nozzle 1 is preferably 100°C or less, more preferably 80°C or less, and even more preferably 60°C or less. When the temperature of the irradiation gas irradiated from the irradiation port 1a of the nozzle 1 is equal to or less than the above upper limit value, it is easy to make the temperature of the irradiated surface equal to or less than 60°C. By making the temperature of the irradiated surface equal to or less than 60°C, irritation to the irradiated surface can be further reduced. There is no particular restriction on the lower limit of the temperature of the irradiation gas irradiated from the irradiation port 1a of the nozzle 1, and it is, for example, 10°C. The temperature of the irradiation gas is a value obtained by measuring the temperature of the irradiation gas at the irradiation port 1a with a thermocouple.

[0067] The distance from the irradiation port 1a to the irradiated surface (irradiation distance) is, for example, preferably 1.0 to 10 mm, more preferably 1 to 5 mm, and even more preferably 1 to 3 mm. If the irradiation distance is equal to or greater than the above-mentioned lower limit, the temperature of the irradiated surface can be lowered, and the stimulation to the irradiated surface can be further alleviated. If the irradiation distance is equal to or less than the above-mentioned upper limit, the therapeutic effect can be further improved.

[0068] The temperature of the irradiated surface at a distance of 1 mm to 10 mm from the irradiation port 1a is preferably 60°C or less. If the temperature of the irradiated surface is 40°C or less, the irritation to the irradiated surface can be reduced. The lower limit of the temperature of the irradiated surface is not particularly limited, but is, for example, 10°C. The temperature of the irradiated surface can be adjusted by combining the AC voltage applied between the internal electrode 4 and the external electrode 5, the discharge amount of the irradiated irradiation gas, the distance from the tip Q1 of the region where the internal electrode 4 and the external electrode 5 face each other to the irradiation port 1a, etc. The temperature of the irradiated surface can be measured using a thermocouple.

[0069] The flow rate of the irradiation gas discharged from the irradiation port 1a is preferably 0.3 to 30 L / min, more preferably 1 to 30 L / min, and even more preferably 3 to 30 L / min. When the flow rate of the irradiation gas is equal to or higher than the lower limit, the therapeutic effect can be further enhanced. When the flow rate of the irradiation gas is equal to or lower than the upper limit, the affected area can be prevented from drying out, and the therapeutic effect can be further enhanced. In the treatment device 100, the flow rate of the irradiation gas discharged from the irradiation port 1a can be adjusted by the amount of plasma generation gas supplied to the plasma generation unit 12.

[0070] The flow velocity of the irradiation gas discharged from the irradiation port 1a is preferably 6 to 650 m / s, more preferably 20 to 650 m / s, and even more preferably 50 to 650 m / s. When the flow velocity of the irradiation gas is equal to or greater than the lower limit, the amount of activated species per unit can be increased, and the therapeutic effect can be further enhanced. When the flow velocity of the irradiation gas is equal to or less than the upper limit, the affected area can be prevented from drying out, and the therapeutic effect can be further enhanced.

[0071] The number of irradiation steps in the treatment method may be at least once per year, preferably at least three times per year, and more preferably at least five times per year. If the number of irradiation steps is equal to or greater than the above-mentioned lower limit, the therapeutic effect can be further improved. The upper limit of the number of irradiation steps is not particularly limited, but is preferably 100 times per year or less.

[0072] When the treatment method includes two or more irradiation steps, the interval between the irradiation steps is, for example, preferably 4 to 336 hours, more preferably 6 to 168 hours, and even more preferably 8 to 72 hours. When the interval between the irradiation steps is equal to or greater than the above-mentioned lower limit, irritation to the affected area can be further reduced. When the interval between the irradiation steps is equal to or less than the above-mentioned upper limit, the therapeutic effect can be further improved.

[0073] When multiple irradiation steps are performed, the number of irradiation steps per day is preferably 1 to 3. When the number of irradiation steps per day is equal to or greater than the above-mentioned lower limit, the therapeutic effect can be further enhanced. When the number of irradiation steps per day is equal to or less than the above-mentioned upper limit, irritation to the affected area can be further reduced.

[0074] (Irradiation Gas) The irradiation gas of the present invention contains active species, such as singlet oxygen, hydroxyl radical, ozone, hydrogen peroxide, superoxide anion radical, NOｘ Examples include nitrogen monoxide, nitrogen dioxide, peroxynitrite, peroxynitrite, dinitrogen trioxide, etc. The type of active species contained in the irradiation gas can be adjusted, for example, by the type of plasma generating gas.

[0075] The concentration of the active species in the irradiation gas is, for example, preferably 0.1 to 300 μmol / L, more preferably 0.1 to 100 μmol / L, and even more preferably 0.1 to 50 μmol / L. When the concentration of the active species in the irradiation gas is equal to or higher than the above-mentioned lower limit, the therapeutic effect can be further enhanced. When the concentration of the active species in the irradiation gas is equal to or lower than the above-mentioned upper limit, irritation to the irradiated surface can be further reduced. The concentration of the active species in the irradiation gas can be adjusted by a combination of the applied voltage of the supply current to the electrodes of the plasma generating unit 12, the type of plasma generating gas, and the amount of plasma generating gas supplied to the plasma generating unit 12, etc.

[0076] An example of a method for measuring the concentration of active species in an irradiation gas will be described. The cumulative singlet oxygen concentration in the irradiation gas is measured by irradiating 0.8 mL of a 0.1 mol / L solution of TPC (2,2,5,5-tetramethyl-3-pyrroline-3-carboxamide) with the irradiation gas for an arbitrary time and at an arbitrary distance, and then measuring the singlet oxygen concentration of the solution irradiated with the irradiation gas by electron spin resonance (ESR). This is defined herein as the cumulative singlet oxygen concentration for an arbitrary time and at an arbitrary distance.

[0077] The 0.1 mol / L TPC solution (hereinafter sometimes simply referred to as "TPC solution") is an aqueous solution.

[0078] The distance when the irradiation gas is irradiated to the TPC solution (the distance from the irradiation port of the plasma irradiator to the water surface of the TPC solution) is the same as the irradiation distance in the irradiation step of the treatment method, and is, for example, 10 mm.

[0079] The time for irradiating the TPC solution with the irradiation gas (irradiation time per unit area of ​​the liquid surface) is the same as the irradiation time per unit area in the irradiation step. That is, the cumulative singlet oxygen concentration in the irradiation gas is correlated with the total amount of activated species in one irradiation step.

[0080] NO in the irradiation gas ｘ The concentration of NO is determined by colorimetry using an NO measurement kit manufactured by BioAssay Systems.

[0081] As described above, the treatment method of this embodiment can enhance the therapeutic effect of allergic dermatitis.

[0082] (Other Embodiments) The above-described method for treating allergic dermatitis may involve a combination of irradiating the affected area with an irradiating gas and administering another drug. Examples of the administration of another drug include transdermal administration of a steroid. By combining irradiation with an irradiating gas and transdermal administration of a steroid, the healing of allergic dermatitis can be promoted. Furthermore, compared to conventional treatments using only transdermal administration of a steroid, combining irradiation with an irradiating gas and transdermal administration of a steroid can reduce the dose (per dose or total dose) and the number of doses (per day or total number of doses) of the steroid, or lengthen the interval between doses.

[0083] Examples of steroids include Dermovate ointment and Rinderon ointment. The dosage of the drug in transdermal administration is determined appropriately depending on the type of steroid. The frequency of administration of the drug in transdermal administration is determined appropriately depending on the type of steroid.

[0084] The order of irradiating the affected area with the irradiation gas (irradiation step) and administering the drug (administration step) is not particularly limited.

[0085] The above-mentioned allergic dermatitis treatment device can also be applied to a pain relief device, a pain treatment device, a pain prevention device, an itch relief device, an itch treatment device, an itch prevention device, a redness relief device, a redness treatment device, or a redness prevention device. The configurations of the pain relief device, pain treatment device, pain prevention device, itch relief device, itch treatment device, or itch prevention device are the same as those of the above-mentioned allergic dermatitis treatment device. Furthermore, the above-mentioned allergic dermatitis treatment method can also be applied to a pain relief method, pain treatment method, pain prevention method, itch relief method, itch treatment method, itch prevention method, redness relief method, redness treatment method, or redness prevention method. Note that the pain relief method, pain treatment method, pain prevention method, itch relief method, itch treatment method, or itch prevention method may or may not include an action on a human being.

[0086] In this specification, the term "pain" is a concept that includes not only pain associated with skin diseases such as allergic diseases, but also pain caused by other diseases. However, the pain relief method, pain treatment method, and pain prevention method are suitable for sites to which irradiation gas can be applied, such as the skin, gums, nostrils, and outer ear. The irradiation conditions (irradiation step) of the irradiation gas in the pain relief method, pain treatment method, and pain prevention method are the same as the irradiation conditions in the treatment method for allergic dermatitis. The administration step in the pain relief method, pain treatment method, and pain prevention method is the same as the administration step in the treatment method for allergic dermatitis.

[0087] In this specification, the term "pruritus" refers to a concept that includes not only pain associated with skin diseases such as allergic diseases, but also pruritus caused by other diseases. However, the method for alleviating pruritus, the method for treating pruritus, and the method for preventing pruritus are suitable for sites to which irradiated gas can be applied, such as the skin, gums, nostrils, and outer ear. The irradiation conditions (irradiation step) of the irradiated gas in the method for alleviating pruritus, the method for treating pruritus, and the method for preventing pruritus are the same as the irradiation conditions in the method for treating allergic dermatitis. The administration step in the method for alleviating pruritus, the method for treating pruritus, and the method for preventing pruritus is the same as the administration step in the method for treating allergic dermatitis.

[0088] In this specification, the term "redness" refers not only to redness associated with skin diseases such as allergic diseases, but also to itching caused by other diseases. However, the redness alleviation method, redness treatment method, and redness prevention method are suitable for areas to which the irradiated gas can be applied, such as the skin, gums, nostrils, and external ear. The irradiation conditions (irradiation step) of the irradiated gas in the redness alleviation method, redness treatment method, and redness prevention method are the same as those in the allergic dermatitis treatment method. The administration step in the redness alleviation method, redness treatment method, and redness prevention method is the same as the administration step in the allergic dermatitis treatment method. It should be noted that, with regard to the treatment methods and treatment devices according to various aspects of the present invention, the activated gas generated by the plasma promotes the activation of normal cells, and therefore it can be assumed that they are effective not only in alleviating and treating the onset of allergic dermatitis (i.e., pain, itching, and redness associated with allergic dermatitis), but also in preventing it.

[0089] The treatment targets using the above-described device and method of the present invention include, for example, affected areas with an AD score (Atopic Dermatitis Score) of 1 or more, 1.5 or more, or 2 or more, and areas with a transepidermal water loss of 8 g / h / m ２ Above, 10g / h / m ２ or more than 15 g / h / m ２ The above affected areas include:

[0090] The present invention will be described in more detail below using examples, but the present invention is not limited to these examples.

[0091] (Experimental Example 1) Six-week-old female NC / Nga mice (Japan SLC Co., Ltd.) were percutaneously sensitized to 5% toluene diisocyanate dissolved in acetone on the abdominal area (sensitization period: 3 days). One week later, hair was removed from the back skin and percutaneously challenged with 0.5% toluene diisocyanate to induce atopic dermatitis-like symptoms (inflammation and itching). The day percutaneous challenge began was designated as test day 0. Using a treatment device similar to treatment device 100, the affected area was irradiated with irradiation gas once per day (irradiation process). The first irradiation process was performed on test day 0, and continued until day 16. Immediately after the irradiation processes on days 1, 4, 7, 10, and 16, skin findings were evaluated as AD scores for the auricle and back skin, respectively. The values ​​are shown in Figure 4. Figure 4 is a graph showing the AD score on the vertical axis and the irradiation date after the first irradiation on the horizontal axis. In FIG. 4, AD Control is an example where no treatment was performed (no irradiation gas was applied), Placebo is an example where only nitrogen gas was applied, and Plasma gas is an example where irradiation gas was applied (irradiation conditions described below).

[0092] <Irradiation conditions> Applied voltage: 13 kHz, 7 kVpp AC current. Flow rate of plasma generating gas: 3 L / min. Irradiation time per unit area: 3 seconds / cm ２ Actual irradiation time: 60 seconds. Irradiation distance: 5 mm. Plasma generating gas: 100% by volume of nitrogen. Irradiation gas flow rate: 60 m / s.

[0093] <Method of measuring AD score> Skin findings were scored for crust / ulcer formation and redness on the auricle and back skin (AD score: severity of symptoms scored on a scale of 0 to 6), and the cumulative value was evaluated as a cumulative score.

[0094] As shown in FIG. 4, the AD score was reduced by irradiating the irradiation gas, and a significant therapeutic effect was observed.

[0095] (Experimental Example 2) Six-week-old female NC / Nga mice (Japan SLC Co., Ltd.) were percutaneously sensitized on the abdominal area with 5% toluene diisocyanate dissolved in acetone (sensitization period: 3 days), and one week later, hair was removed from the back skin and percutaneously challenged with 0.5% toluene diisocyanate to induce atopic dermatitis-like symptoms (inflammation and itching). The day percutaneous challenge began was designated as test day 0. Using a treatment device similar to treatment device 100, the affected area was irradiated with irradiation gas once per day (irradiation step). The first irradiation step was performed on test day 0, and irradiation steps were continued until day 16. Immediately after the irradiation steps on days 1, 4, 7, 10, and 16, the transepidermal water loss (Trans Epidermal Water Loss, g / h / m ２ ) was measured, and the values ​​are shown in Figure 5. Figure 5 is a graph in which the vertical axis represents transepidermal water loss (Trans Epidermal Water Loss) and the horizontal axis represents the irradiation day after the first irradiation. In Figure 5, AD Control is an example in which no treatment was performed (no irradiation with irradiation gas), Placebo is an example in which only nitrogen gas was irradiated, and Plasma gas is an example in which irradiation gas was irradiated (irradiation conditions described below).

[0096] <Irradiation conditions> Applied voltage: 7 kHz, 13 kVpp AC current. Flow rate of plasma generating gas: 3 L / min. Irradiation time per unit area: 3 seconds / cm ２ Actual irradiation time: 60 seconds. Irradiation distance: 5 mm. Plasma generating gas: 100% by volume of nitrogen. Irradiation gas flow rate: 60 m / s.

[0097] <Method for measuring transepidermal water loss> Transepidermal water loss of the dorsal skin was measured twice using a VAPO SCAN (AS-VT100RS, ASCH JAPAN Co., Ltd.), and the average value was evaluated as the individual value.

[0098] As shown in FIG. 5, the amount of transepidermal water loss was reduced by irradiating the irradiation gas.

[0099] (Experimental Example 3) Six-week-old female NC / Nga mice (Japan SLC Co., Ltd.) were percutaneously sensitized to 5% toluene diisocyanate dissolved in acetone on the abdominal area (sensitization period: 3 days). One week later, hair was removed from the back skin and percutaneously challenged with 0.5% toluene diisocyanate to induce atopic dermatitis-like symptoms (inflammation and itching). The day percutaneous challenge began was designated test day 0. Using a treatment device similar to treatment device 100, the affected area was irradiated with irradiation gas once per day (irradiation process). The first irradiation process was performed on test day 0, and irradiation processes were continued until day 16. Immediately after the irradiation processes on days 1, 4, 7, 10, and 16, the thicknesses (mm) of the auricle and dorsal skin were measured, and the values ​​are shown in Figure 6. Figure 6(a) is a graph showing ear thickness on the vertical axis and the number of days after the first irradiation on the horizontal axis. 6(b) is a graph in which the vertical axis represents back skin thickness and the horizontal axis represents the number of days after the first irradiation. In FIG. 6, AD Control is an example of no treatment (no irradiation with irradiation gas), Placebo is an example of irradiation with nitrogen gas only, and Plasma gas is an example of irradiation with irradiation gas (irradiation conditions described below).

[0100] <Irradiation conditions> Applied voltage: 7 kHz, 13 kVpp AC current. Flow rate of plasma generating gas: 3 L / min. Irradiation time per unit area: 3 seconds / cm ２ Actual irradiation time: 60 seconds. Irradiation distance: 5 mm. Plasma generating gas: 100% by volume of nitrogen. Irradiation gas flow rate: 60 m / s.

[0101] <Method for measuring ear thickness and back skin thickness> The thickness of the ear and back skin was measured using a dedicated micrometer (Quick Mini PK-1012APX, Mitutoyo Corporation).

[0102] As shown in Figures 6(a) and (b), the ear thickness and back skin thickness were reduced by irradiating the irradiation gas, and a significant therapeutic effect was observed.

[0103] (Experimental Example 4) Six-week-old female NC / Nga mice (Japan SLC Co., Ltd.) were percutaneously sensitized to 5% toluene diisocyanate dissolved in acetone on the abdominal area (sensitization period: 3 days). One week later, 0.5% toluene diisocyanate was percutaneously challenged on the dorsal skin after hair removal to induce atopic dermatitis-like symptoms (inflammation and itching). The day percutaneous challenge began was designated as test day 0. Using a treatment device similar to treatment device 100, the affected area was irradiated with irradiation gas once per day (irradiation step). The first irradiation step was performed on test day 0, and irradiation steps were continued until day 16. Immediately after the irradiation steps on days 1, 4, 7, 10, and 16, the mice were euthanized, and auricular lymph nodes and auricular skin samples were collected. The auricular lymph nodes were isolated into single cells and then analyzed using CellDrop. ＴＭ The total cell number was measured using a Cell Counting System (DeNovix Inc., DE, USA), and then analyzed using a BD FACSAria. ＴＭCells were isolated based on cell surface antigens using a 3D Cell Sorter (BD Biosciences, Tokyo, Japan). Among the resulting cells, T cells were cultured in the presence of anti-CD3 and anti-CD28 antibodies (Veritas Corporation) for 24 hours, after which cytokine (IL-5, IL-13) production in the culture supernatant was measured by ELISA. The collected ear and dorsal skin were fixed in formalin, paraffin sections were prepared using standard methods, and histological evaluation was performed using hematoxylin-eosin staining. Cell hyperplasia, inflammatory cell infiltration, ulcers, etc. were evaluated for the epidermis and dermis of each skin tissue on a scale of 0 to 3 (3 being the most severe). The results are shown in Figures 7 to 11. Figure 7 is a graph with the vertical axis representing the total cell count (total cells in LN) and the horizontal axis representing the test group. (LN means lymph node. The same applies to Figures 8 to 10.) Figures 8(a) to (e) are graphs with the number of T cells on the vertical axis and the test group on the horizontal axis. Figures 9(a) to (b) are graphs with the number of B cells on the vertical axis and the test group on the horizontal axis. Figures 10(a) to (c) are graphs with the number of dendritic cells on the vertical axis and the test group on the horizontal axis. Figure 11(a) is a graph with the amount of IL5 on the vertical axis and the test group on the horizontal axis. Figure 11(b) is a graph with the amount of IL3 on the vertical axis and the test group on the horizontal axis. In Figures 7 to 11, "Intact" refers to untreated mice (no allergic dermatitis-like symptoms), "AD Control" refers to mice with allergic dermatitis symptoms that were not irradiated with irradiation gas, "Placebo gas" refers to mice with allergic dermatitis symptoms that were irradiated with nitrogen gas only, and "Plasma gas" refers to mice with allergic dermatitis symptoms that were irradiated with irradiation gas (irradiation conditions described below).

[0104] <Irradiation conditions> Applied voltage: 7 kHz, 13 kVpp AC current. Flow rate of plasma generating gas: 3 L / min. Irradiation time per unit area: 3 seconds / cm ２ Actual irradiation time: 60 seconds. Irradiation distance: 5 mm. Plasma generating gas: 100% by volume of nitrogen. Irradiation gas flow rate: 60 m / s.

[0105] As shown in Figures 7 to 11, a significant therapeutic effect was observed by irradiating the irradiation gas.

[0106] 12 to 15 show photographs of the skin before the onset of allergic dermatitis (FIG. 12), without treatment (FIG. 13), after irradiation with nitrogen gas only (day 16, FIG. 14), and after irradiation with the irradiating gas (day 16, FIG. 15) in Experimental Example 1. In FIG. 12, where the irradiating gas was irradiated, the condition of the skin surface was the same as in FIG. 12 (before the onset of allergic dermatitis).

[0107] 16 to 19 show cross-sectional photographs of back skin before the onset of allergic dermatitis (FIG. 16), without treatment (FIG. 17), after irradiation with nitrogen gas only (day 16, FIG. 18), and after irradiation with irradiated gas (day 16, FIG. 19) in Experimental Example 3. In FIG. 19, after irradiation with irradiated gas, the thickness of the skin was the same as in FIG. 16 (before the onset of allergic dermatitis).

[0108] Example 5: The neck and back of 7-week-old female NC / Nga mice (Japan SLC Co., Ltd.) were depilated with hair removal cream, and 100 mg of Biosta AD (trade name, manufactured by Biosta Co., Ltd.) was applied transdermally to perform the initial induction. From the second time onwards, 150 μL of 4% SDS (sodium dodecyl sulfate) aqueous solution was added to the back and auricles, dried to a certain extent with a hair dryer, returned to the cage, and left to air dry for 2-3 hours. 100 mg of Biosta AD (trade name) was applied to the back and auricles. This procedure was repeated a total of five times from the second time onwards to create chronic AD model mice. Hair removal was performed using a shaver as appropriate. For chronic AD model mice that underwent each treatment for 9 days, skin findings were evaluated as AD scores for the auricles and dorsal skin. The values ​​are shown in Figure 20. Figure 20 is a graph with the AD score on the vertical axis and the test group on the horizontal axis. The treatments for the test groups in Figure 20 are described below.

[0109] <Onset of Allergy> After preparing the chronic AD model mice, the mice were left untreated for 9 days (no treatment) as a test group. N (number of tests) = 3.

[0110] <Plasma alone (daily)> A test group in which the same device as the treatment device 100 was used to irradiate the affected area with irradiation gas once per day (irradiation step). The irradiation conditions were as follows: N=7.

[0111] <Irradiation conditions> Applied voltage: 7 kHz, 13 kVpp AC current. Flow rate of plasma generating gas: 3 L / min. Irradiation time per unit area: 3 seconds / cm ２ Actual irradiation time: 60 seconds. Irradiation distance: 5 mm. Plasma generating gas: 100% by volume of nitrogen. Irradiation gas flow rate: 60 m / s.

[0112] <Steroid only> Test group in which Dermovate ointment (containing 0.1% Clobetasol Propionate (CP) as an active ingredient) was applied to the affected area once a day. N=7.

[0113] <Steroid 1 / 3 (applied once every three days) + plasma (once every three days)> This test group applied Dermovate ointment to the affected area, and then irradiated the area with irradiated gas. This treatment was performed three times every three days. N=6.

[0114] As shown in Figure 20, irradiation with irradiated gas produced an effect equivalent to that of steroid administration. In addition, a significant decrease in AD score was observed by combining steroid administration with irradiated gas irradiation. In addition, the combination of steroid administration with irradiated gas irradiation allowed for a reduction in the amount and frequency of steroid administration.

[0115] (Experimental Example 6) Chronic AD model mice were obtained in the same manner as in Experimental Example 5. The chronic AD model mice were subjected to each treatment for 9 days and then euthanized, and auricular lymph nodes were collected. The collected auricular lymph nodes were mashed on a 70 μm cell strainer (manufactured by AS ONE Corporation) using RPMI-1640 (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) to obtain a cell suspension. The cell suspension was centrifuged (1500 rpm, 5 minutes), the supernatant was removed, and 1 mL of RPMI-1640 was added and the number of cells in the cell suspension was determined using CellDrop. ＴＭ The isolated lymphocytes were counted using a Cell Counting System (DeNovix Inc., DE, USA). ＴＭ III (manufactured by Nippon Becton Dickinson Co., Ltd.) to identify T cells (CD3 ＋ CD4 ＋ ) and IgE B cells (CD19 ＋ IgE＋ The proportion of each cell type was analyzed. The number of each cell type was calculated by multiplying the proportion of each cell type by the total cell number. The above-mentioned cell suspension was co-cultured with Dynabeads (registered trademark) Mouse T-Activator CD3 / CD28 for 24 hours, and cytokines produced by T cells were measured by ELISA (R&D Systems). Statistical analysis of the measurement results was performed using GraphPad Prism 10. For each test item, statistical significance was analyzed at the 5% and 1% risk levels. Significant differences were determined using Sidak's multiple comparisons test. These results are shown in Figures 21(a) to (g). Figure 21(a) is a graph with the vertical axis representing the number of dendritic cells and the horizontal axis representing the test group. Figure 21(b) is a graph with the number of CD4+ T cells on the vertical axis and the test group on the horizontal axis. Figure 21(c) is a graph with the number of B cells on the vertical axis and the test group on the horizontal axis. Figure 21(d) is a graph with the amount of IL-5 on the vertical axis and the test group on the horizontal axis. Figure 21(e) is a graph with the amount of INFγ on the vertical axis and the test group on the horizontal axis. Figure 21(f) is a graph with the amount of TNFα on the vertical axis and the test group on the horizontal axis. Figure 21(g) is a graph with the amount of total IgE on the vertical axis and the test group on the horizontal axis. The treatments for the test groups in Figure 21 are described below.

[0116] <Untreated> A test group of untreated mice without allergic dermatitis-like symptoms. N=3.

[0117] <AD Control> A test group in which chronic AD model mice were not treated. N=7.

[0118] <N ２ -CAP> A test group in which chronic AD model mice were irradiated with irradiation gas once a day for 9 days (irradiation conditions described below). N=7.

[0119] <Irradiation conditions> Applied voltage: 7 kHz, 13 kVpp AC current. Flow rate of plasma generating gas: 3 L / min. Irradiation time per unit area: 3 seconds / cm ２ Actual irradiation time: 60 seconds. Irradiation distance: 5 mm. Plasma generating gas: 100% by volume of nitrogen. Irradiation gas flow rate: 60 m / s.

[0120] 21, the amount of IL-5 and the amount of total IgE were significantly reduced by irradiation with the irradiation gas, which indicates that atopic dermatitis was significantly improved by irradiation with the irradiation gas.

[0121] (Experimental Example 7) Chronic AD model mice were obtained in the same manner as in Experimental Example 5. Chronic AD model mice were subjected to each treatment for 9 days and then euthanized, and auricular lymph nodes were collected. A cell suspension was prepared from the obtained auricular lymph nodes in the same manner as in Experimental Example 6, and the cells were co-cultured. Cytokines produced by T cells were measured. The measurement results were evaluated for significance in the same manner as in Experimental Example 6. These results are shown in Figures 22(a) to (g). Figure 22(a) is a graph with the number of dendritic cells on the vertical axis and the test group on the horizontal axis. Figure 22(b) is a graph with the number of CD4+ T cells on the vertical axis and the test group on the horizontal axis. Figure 22(c) is a graph with the number of B cells on the vertical axis and the test group on the horizontal axis. Figure 22(d) is a graph with the amount of IL-5 on the vertical axis and the test group on the horizontal axis. Figure 22(e) is a graph with the amount of INFγ on the vertical axis and the test group on the horizontal axis. Figure 22(f) is a graph with the amount of TNFα on the vertical axis and the test group on the horizontal axis. Figure 22(g) is a graph with the amount of total IgE on the vertical axis and the test group on the horizontal axis. The treatments for the test groups in Figure 22 are described below.

[0122] <Untreated> Untreated mice without allergic dermatitis-like symptoms. N=3.

[0123] <AD Control> A test group in which chronic AD model mice were not treated. N=7.

[0124] <Clobetasol Propionate (CP)> A test group in which Dermovate ointment was applied once a day to chronic AD model mice (hereinafter sometimes referred to as "CP group"), N=7.

[0125] <CP+N ２ -CAP> A test group in which Dermovate ointment was applied once a day to chronic AD model mice and irradiation gas was applied once a day. N=5.

[0126] <CP ｌｏｗ +N ２ -CAP> A test group in which chronic AD model mice were treated with Dermovate ointment and irradiated with irradiating gas three times every three days. N=6.

[0127] As shown in FIG. 22, the combined use of CP administration and irradiation with the irradiation gas significantly reduced each of the measurement targets.

[0128] (Experimental Example 8) Human epidermal keratinocyte cell line (HaCaT) maintained in DMEM medium (Dulbecco's modified Eagle's medium) supplemented with 10% fetal bovine serum and penicillin-streptomycin was seeded onto a 12-well plate until the cells reached 70% confluence. Plasma medium was prepared by irradiating untreated DMEM solution with irradiation gas for 60 seconds (irradiation conditions described below). After exposing the cells to the plasma medium for 24 hours, total RNA was extracted from the cells, and gene expression of TRPV (Transient Receptor Potential Vanilloid) 1, TRPV4, and histamine H4 receptor (H4R) was confirmed by qPCR using housekeeping gene (Actβ) correction. Furthermore, total RNA was similarly extracted from HaCaT cells stimulated with capsaicin or histamine for 1 hour, and gene expression of TRPV1, TRPV4, and histamine H4 receptor (H4R) was confirmed by qPCR using housekeeping gene (Actβ) correction ("N" in the figure). ２ -CAP", N=8). These results are shown in Figures 23(a) to (c). Figure 23(a) is a graph with the expression level of TRPV1 upon stimulation with capsaicin on the vertical axis and the test group on the horizontal axis. Figure 23(b) is a graph with the expression level of TRPV4 upon stimulation with capsaicin on the vertical axis and the test group on the horizontal axis. Figure 23(c) is a graph with the expression level of H4R upon stimulation with histamine on the vertical axis and the test group on the horizontal axis. Capsaicin is a substance that stimulates pain-sensing nerves, and if the expression level of TRPV1 or TRPV4 upon stimulation with capsaicin is low, pain can be suppressed. Histamine is a substance that causes itching, and if the expression level of H4R upon stimulation with histamine is low, it can suppress itching. The other test groups in Figure 23 are described below.

[0129] <Con> A test group in which the cells were exposed to a medium not subjected to plasma irradiation instead of the plasma medium, and gene expression levels were measured in the same manner as for N2-CAP, except that they were not stimulated with capsaicin or histamine. N=10.

[0130] <Irradiation conditions> Applied voltage: 7 kHz, 13 kVpp AC current. Flow rate of plasma generating gas: 3 L / min. Irradiation time per unit area: 3 seconds / cm ２ Actual irradiation time: 60 seconds. Irradiation distance: 5 mm. Plasma generating gas: 100% by volume of nitrogen. Irradiation gas flow rate: 60 m / s.

[0131] 23, in the test group that had been previously irradiated with the irradiation gas, the expression levels of TRV1, TRV4, and H4R after capsaicin irradiation were reduced. This result demonstrated that irradiation with the irradiation gas prevented pain and itching.

[0132] (Experimental Example 9) Human epidermal keratinocyte cell line (HaCaT) maintained in DMEM medium supplemented with 10% fetal bovine serum and penicillin / streptomycin was seeded on a glass-bottom dish to allow the cells to reach 70% confluence. Plasma medium was prepared by irradiating untreated DMEM solution with irradiation gas for 60 seconds (irradiation conditions described below). After exposing the cells to the plasma medium for 24 hours, the medium was immediately removed, and the cells were stained for 30 minutes with Fura2-AM, a reagent for measuring intracellular calcium ions. The glass-bottom dish was then placed on an inverted microscope equipped with a fluorescent light source capable of excitation at wavelengths of 340 nm and 380 nm, and the cells were stained with a buffer solution (1 L of ultrapure water containing 115 mM NaCl, 5.4 mM KCl, and 1.8 mM CaCl) to observe the Ca influx in the cells. ２ , 0.8mM-MgCl ２ The mixture was refluxed in a 1000-well plate containing 20 mM HEPE and 13.8 mM glucose (pH adjusted to 7.4) while heating to 37°C. Capsaicin (0.1 nmol), a TRPV1 agonist, or histamine (1 μmol), an H4R agonist, was added while refluxing, and the ratio of the fluorescence intensity at 340 nm (Fura2 bound to intracellular Ca) to that at 380 nm (free Fura2) was calculated (see "N" in the figure). ２-CAP", N=24). These results are shown in Figures 24(a) and 24(b). Figure 24(a) is a graph in which the vertical axis represents the ratio of fluorescence intensity at 340 nm to 380 nm when stimulated with capsaicin, and the horizontal axis represents the test group. Figure 24(b) is a graph in which the vertical axis represents the ratio of fluorescence intensity at 340 nm to 380 nm when stimulated with histamine, and the horizontal axis represents the test group. The other test groups in Figure 24 are explained below.

[0133] <Con1> Test group except that cells were exposed to a medium not subjected to plasma irradiation instead of the plasma medium, and the fluorescence intensity was measured without adding capsaicin or histamine. N=10.

[0134] <Con2> Test group in which cells were exposed to a medium not subjected to plasma irradiation instead of the plasma medium, and the fluorescence intensity was measured after adding capsaicin or histamine. N=38.

[0135] <Irradiation conditions> Applied voltage: 7 kHz, 13 kVpp AC current. Flow rate of plasma generating gas: 3 L / min. Irradiation time per unit area: 3 seconds / cm ２ Actual irradiation time: 60 seconds. Irradiation distance: 5 mm. Plasma generating gas: 100% by volume of nitrogen. Irradiation gas flow rate: 60 m / s.

[0136] As shown in FIG. 24, it was confirmed that the influx of intracellular Ca ions induced by capsaicin and the influx of intracellular Ca ions induced by histamine were suppressed by pre-irradiation with the irradiation gas.

[0137] (Experimental Example 10) A canine epidermal keratinocyte cell line (CPEC) was maintained in EMEM medium supplemented with 10% fetal bovine serum and penicillin-streptomycin. CPEC cells were seeded on a glass-bottom dish and allowed to reach 70% confluence. The cell medium was irradiated with irradiation gas for 60 seconds to form a plasma medium (irradiation conditions described below). After exposing the cells to the plasma medium for 24 hours, the medium was immediately removed, and the cells were stained with Fura2-AM, a reagent for measuring intracellular calcium ions. The glass-bottom dish was then placed on an inverted microscope equipped with a fluorescent light source capable of excitation at wavelengths of 340 nm and 380 nm, and the cells were stained with a buffer solution (1 L of ultrapure water containing 115 mM NaCl, 5.4 mM KCl, and 1.8 mM CaCl) to observe the Ca influx in the cells. ２ , 0.8mM-MgCl ２ The mixture was refluxed in a buffer containing 20 mM HEPE and 13.8 mM glucose (adjusted to pH 7.4) while heating to 37°C. Capsaicin (0.1 nmol), a TRPV1 agonist, histamine (1 μmol), an H4R agonist, and AITC (Allyl isotyiocyanate) were added while refluxing, and the ratio of the fluorescence intensity at 340 nm (Fura2 bound to intracellular Ca) to that at 380 nm (free Fura2) was calculated (see "N" in the figure). ２ -CAP", N=11). AITC is a component found in wasabi and mustard, and is a substance that causes itching and numbness. These results are shown in Figures 25(a) to (c). Figure 25(a) is a graph showing the ratio of fluorescence intensity at 340 nm to 380 nm when stimulated with histamine on the vertical axis and the test group on the horizontal axis. Figure 25(b) is a graph showing the ratio of fluorescence intensity at 340 nm to 380 nm when stimulated with capsaicin on the vertical axis and the test group on the horizontal axis. Figure 25(c) is a graph showing the ratio of fluorescence intensity at 340 nm to 380 nm when stimulated with AITC on the vertical axis and the test group on the horizontal axis. The other test groups in Figure 25 are described below. <Con1> This test group consisted of cells exposed to a medium not subjected to plasma irradiation instead of plasma medium, and fluorescence intensity was measured without the addition of capsaicin or histamine. N=10.

[0138] <Con2> Test group in which cells were exposed to a medium not subjected to plasma irradiation instead of the plasma medium, and the fluorescence intensity was measured after adding capsaicin or histamine. N=13.

[0139] <Irradiation conditions> Applied voltage: 7 kHz, 13 kVpp AC current. Flow rate of plasma generating gas: 3 L / min. Irradiation time per unit area: 3 seconds / cm ２ Actual irradiation time: 60 seconds. Irradiation distance: 5 mm. Plasma generating gas: 100% by volume of nitrogen. Irradiation gas flow rate: 60 m / s.

[0140] As shown in FIG. 25, it was confirmed that the intracellular Ca influx induced by histamine and the intracellular Ca influx induced by AITC were suppressed by pre-irradiation with the irradiation gas.

[0141] REFERENCE SIGNS LIST 1 nozzle 4 internal electrode 5 external electrode 10 irradiation device 12 plasma generating unit 36 ​​gas pipeline 70 gas supply source 90 control unit 100 allergic dermatitis treatment device

Claims

1. The method includes one or more irradiation steps of supplying a plasma generating gas to a plasma generating unit having an electrode to generate plasma, and irradiating biological tissue with an irradiation gas containing at least one of the generated plasma and an activated gas generated by the plasma, wherein the irradiation step is performed by supplying the irradiation gas to the biological tissue for 1 to 300 seconds / cm. ２ A method for treating allergic dermatitis by irradiating with ultraviolet light (excluding treatment on humans).

2. The method for treating allergic dermatitis according to claim 1, wherein the irradiation step irradiates the irradiation gas at a velocity of 6 to 650 m / s.

3. The method for treating allergic dermatitis according to claim 1, which alleviates or treats at least one symptom selected from the group consisting of redness, pain, and itching.

4. A plasma generating unit having an electrode, a gas supply unit that supplies a plasma generating gas to the plasma generating unit, an irradiation device having a nozzle that discharges an irradiation gas containing at least one of the plasma generated in the plasma generating unit and an activated gas generated by the plasma, and an irradiation time of the irradiation gas of 1 to 300 seconds / cm ２ and a control unit configured to:

5. The allergic dermatitis treatment device according to claim 4, wherein the irradiation device discharges the irradiation gas at a velocity of 6 to 650 m / s.

6. The device for treating allergic dermatitis according to claim 4, which relieves or treats at least one symptom selected from the group consisting of redness, pain, and itching.

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