Medical treatment device, method for using a medical treatment device, and method for spraying active gas

Abstract

A medical treatment device 100 is designed to generate plasma and eject active gas generated by the generated plasma from an ejection port, wherein the active gas has a temperature of 40°C or less at an ejection surface located at a distance of 1 mm or more and 10 mm or less from the ejection port, and a radical concentration of 0.1 to 300 μmol / L is obtained by the following measurement method of hydroxyl radical concentration. The radical concentration is obtained in the following manner. The distance from the ejection port to the liquid surface is set to 5.0 mm, 0.4 mL of a 0.2 mol / L solution of DMPO (5,5-dimethyl-1-pyrroline-N-oxide) is ejected with active gas for 30 seconds, and then the solution after the active gas ejection is measured for the hydroxyl radical concentration by electron spin resonance (ESR) method, and the result is taken as the radical concentration.

Description

[0001] This application is a divisional application of Chinese patent application No. 201880018071.0, entitled "Medical Treatment Device, Method of Using Medical Treatment Device and Method of Injecting Active Gas", filed on June 15, 2018. Technical Field

[0002] This invention relates to a medical treatment device, a method of using the medical treatment device, and a method of injecting active gas.

[0003] This application claims priority based on Japanese Patent Application No. 2017-119152, filed in Japan on June 16, 2017, the contents of which are incorporated herein by reference. Background Technology

[0004] There are existing devices that use plasma jets, typically used in dental treatments and other medical applications, to treat wounds and heal the affected area.

[0005] For example, Patent Document 1 discloses a dental treatment device that has a plasma jetting device mounted on the instrument used for dental treatment, which can jet plasma onto the treated area.

[0006] According to the invention described in Patent Document 1, wounds are healed by directly spraying the generated plasma onto the affected area.

[0007] Existing technical documents

[0008] Patent documents

[0009] Patent Document 1: Japanese Patent No. 5441066 Summary of the Invention

[0010] Technical problem solved by the present invention

[0011] As so-called plasma jetting devices, there are plasma jetting devices and reactive gas jetting devices.

[0012] The plasma jetting device generates plasma and reacts the generated plasma with gases in or around the plasma to produce reactive oxygen species such as hydroxyl radicals, singlet oxygen, ozone, hydrogen peroxide, and superoxide anion radicals, as well as reactive nitrogen species such as nitric oxide, nitrogen dioxide, peroxynitrite, nitrous oxide, and dinitrogen trioxide, which are directly sprayed onto the object being jetted.

[0013] The active gas injection device generates plasma and injects active gases containing reactive oxygen species such as hydroxyl radicals, singlet oxygen, ozone, hydrogen peroxide, and superoxide anion radicals, as well as reactive nitrogen species such as nitric oxide, nitrogen dioxide, peroxynitrite, nitrous oxide, and dinitrogen trioxide, generated by reactions with gases in or around the generated plasma and moisture contained in the target material, into the target material.

[0014] The composition of the active gas varies depending on the gas that generates the plasma or the surrounding gas.

[0015] Furthermore, the effects of plasma jetting vary depending on the composition of the reactive gas.

[0016] However, regarding plasma jetting devices for generating cryogenic plasma in medical applications, the plasma-generating gas is generally limited to rare gases.

[0017] Therefore, the object of the present invention is to provide a medical treatment device that can generate plasma using a wide range of plasma generating gases and spray active gases.

[0018] Technical means to solve the problem

[0019] [1] A medical treatment device that generates plasma and ejects an active gas generated by the plasma through a nozzle, wherein...

[0020] The temperature of the active gas at the sprayed surface located at a distance of 1 mm to 10 mm from the nozzle is below 40°C, and the free radical concentration determined by the following method for determining the concentration of hydroxyl free radicals is 0.1 to 300 μmol / L.

[0021] <Methods for determining the concentration of hydroxyl radicals>

[0022] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL solution of DMPO (5,5-dimethyl-1-pyrrolidone-N-oxide) at a concentration of 0.2 mol / L for 30 seconds. Then, the concentration of hydroxyl radicals in the solution after the active gas spray was determined by electron spin resonance (ESR) and used as the free radical concentration.

[0023] [2] A medical treatment device that generates plasma and ejects an active gas generated by the plasma through a nozzle, wherein...

[0024] The temperature of the active gas at the sprayed surface located at a distance of 1 mm to 10 mm from the nozzle is below 40°C, and the singlet oxygen concentration determined by the singlet oxygen concentration determination method described below is 0.1 to 300 μmol / L.

[0025] <Methods for determining singlet oxygen concentration>

[0026] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL TPC (2,2,5,5-tetramethyl-3-pyrrolino-3-carboxamide) 0.1 mol / L solution for 30 seconds. Then, the singlet oxygen concentration of the solution after the active gas spray was determined by electron spin resonance (ESR) method and taken as the singlet oxygen concentration.

[0027] [3] A medical treatment device that generates plasma and ejects an active gas generated by the plasma through a nozzle, wherein...

[0028] The temperature of the active gas at the sprayed surface located at a distance of 1 mm to 10 mm from the nozzle is 40°C or less, the free radical concentration determined by the following method for determining hydroxyl free radical concentration is 0.1 to 300 μmol / L, and the singlet oxygen concentration determined by the following method for determining singlet oxygen concentration is 0.1 to 300 μmol / L.

[0029] <Methods for determining the concentration of hydroxyl radicals>

[0030] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL solution of DMPO (5,5-dimethyl-1-pyrrolidone-N-oxide) at a concentration of 0.2 mol / L for 30 seconds. Then, the concentration of hydroxyl radicals in the solution after the active gas spray was determined by electron spin resonance (ESR) and used as the free radical concentration.

[0031] <Methods for determining singlet oxygen concentration>

[0032] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL TPC (2,2,5,5-tetramethyl-3-pyrrolino-3-carboxamide) 0.1 mol / L solution for 30 seconds. Then, the singlet oxygen concentration of the solution after the active gas spray was determined by electron spin resonance (ESR) method and taken as the singlet oxygen concentration.

[0033] [4] Any medical treatment instrument described in any of [1] to [3] is for dental use.

[0034] [5] A method of using a medical treatment device, wherein the active gas is sprayed onto a target object using any of the medical treatment devices described in [1] to [4].

[0035] [6] A method for injecting an active gas, comprising: applying a voltage to a gas that generates plasma to generate plasma, and injecting the active gas generated by the plasma onto a subject selected from cells, living tissues, and biological individuals, thereby promoting the purification, activation, or healing of abnormalities in the subject.

[0036] In the method of injecting an active gas (excluding medical procedures on humans), the temperature of the active gas at the sprayed surface located at a distance of 1 mm to 10 mm from the injection port is 40°C or less, and the free radical concentration determined by the following method for determining the concentration of hydroxyl free radicals is 0.1 to 300 μmol / L.

[0037] <Methods for determining the concentration of hydroxyl radicals>

[0038] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL solution of DMPO (5,5-dimethyl-1-pyrrolidone-N-oxide) at a concentration of 0.2 mol / L for 30 seconds. Then, the concentration of hydroxyl radicals in the solution after the active gas spray was determined by electron spin resonance (ESR) and used as the free radical concentration.

[0039] [7] A method for injecting an active gas, comprising: applying a voltage to a gas that generates plasma to generate plasma, and injecting the active gas generated by the plasma onto a subject selected from cells, living tissues, and biological individuals, thereby promoting the purification, activation, or healing of abnormalities in the subject.

[0040] A method for injecting an active gas (excluding medical procedures on humans), wherein the temperature of the active gas at the surface to which it is injected, located at a distance of 1 mm to 10 mm from the injection port, is 40°C or less, and the singlet oxygen concentration determined by the method described below is 0.1 to 300 μmol / L.

[0041] <Methods for determining singlet oxygen concentration>

[0042] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL TPC (2,2,5,5-tetramethyl-3-pyrrolino-3-carboxamide) 0.1 mol / L solution for 30 seconds. Then, the singlet oxygen concentration of the solution after the active gas spray was determined by electron spin resonance (ESR) method and taken as the singlet oxygen concentration.

[0043] [8] A method for injecting an active gas, comprising: applying a voltage to a gas that generates plasma to generate plasma, and injecting the active gas generated by the plasma onto a subject selected from cells, living tissues, and biological individuals to promote the purification, activation, or healing of abnormalities in the subject.

[0044] In the method of injecting reactive gas (excluding medical procedures on humans), the temperature of the surface on which the reactive gas is injected at a distance of 1 mm to 10 mm from the injection port is 40°C or less, and the free radical concentration determined by the following method for determining the concentration of hydroxyl free radicals is 0.1 to 300 μmol / L, and the singlet oxygen concentration determined by the following method for determining the concentration of singlet oxygen is 0.1 to 300 μmol / L.

[0045] <Methods for determining free radical concentration>

[0046] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL solution of DMPO (5,5-dimethyl-1-pyrrolidone-N-oxide) at a concentration of 0.2 mol / L for 30 seconds. Then, the concentration of hydroxyl radicals in the solution after the active gas spray was determined by electron spin resonance (ESR) and used as the radical concentration.

[0047] <Methods for determining singlet oxygen concentration>

[0048] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL TPC (2,2,5,5-tetramethyl-3-pyrrolino-3-carboxamide) 0.1 mol / L solution for 30 seconds. Then, the singlet oxygen concentration of the solution after the active gas spray was determined by electron spin resonance (ESR) method and taken as the singlet oxygen concentration.

[0049] [9] The method for injecting an active gas according to any one of [6] to [8], wherein the plasma generating gas is mainly composed of nitrogen.

[0050]

[10] The method for injecting an active gas according to any one of [6] to [9], wherein the oxygen concentration of the plasma-generating gas is 1% by volume or less.

[0051]

[11] A treatment method comprising applying a voltage to a plasma-generating gas to generate plasma, and spraying an active gas generated by the plasma onto a subject selected from human cells, living tissues, and biological individuals.

[0052] The temperature of the active gas at the sprayed surface located at a distance of 1 mm to 10 mm from the nozzle is below 40°C, and the free radical concentration determined by the following method for determining the concentration of hydroxyl free radicals is 0.1 to 300 μmol / L.

[0053] <Methods for determining the concentration of hydroxyl radicals>

[0054] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL solution of DMPO (5,5-dimethyl-1-pyrrolidone-N-oxide) at a concentration of 0.2 mol / L for 30 seconds. Then, the concentration of hydroxyl radicals in the solution after the active gas spray was determined by electron spin resonance (ESR) and used as the free radical concentration.

[0055]

[12] A treatment method wherein a voltage is applied to a plasma-generating gas to generate plasma, and an active gas generated by the plasma is sprayed onto a subject selected from human cells, living tissues, and biological individuals.

[0056] The temperature of the active gas at the sprayed surface located at a distance of 1 mm to 10 mm from the nozzle is below 40°C, and the singlet oxygen concentration determined by the singlet oxygen concentration determination method described below is 0.1 to 300 μmol / L.

[0057] <Methods for determining singlet oxygen concentration>

[0058] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL TPC (2,2,5,5-tetramethyl-3-pyrrolino-3-carboxamide) 0.1 mol / L solution for 30 seconds. Then, the singlet oxygen concentration of the solution after the active gas spray was determined by electron spin resonance (ESR) method and taken as the singlet oxygen concentration.

[0059]

[13] A treatment method wherein a voltage is applied to a plasma-generating gas to generate plasma, and the plasma generated is sprayed through the plasma onto a subject selected from human cells, living tissues, and biological individuals.

[0060] The temperature of the active gas at the sprayed surface located at a distance of 1 mm to 10 mm from the nozzle is 40°C or less, the free radical concentration determined by the following method for determining the concentration of hydroxyl free radicals is 0.1 to 300 μmol / L, and the singlet oxygen concentration determined by the following method for determining the concentration of singlet oxygen is 0.1 to 300 μmol / L.

[0061] <Methods for determining the concentration of hydroxyl radicals>

[0062] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL solution of DMPO (5,5-dimethyl-1-pyrrolidone-N-oxide) at a concentration of 0.2 mol / L for 30 seconds. Then, the concentration of hydroxyl radicals in the solution after the active gas spray was determined by electron spin resonance (ESR) and used as the free radical concentration.

[0063] <Methods for determining singlet oxygen concentration>

[0064] The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL TPC (2,2,5,5-tetramethyl-3-pyrrolino-3-carboxamide) 0.1 mol / L solution for 30 seconds. Then, the singlet oxygen concentration of the solution after the active gas spray was determined by electron spin resonance (ESR) method and taken as the singlet oxygen concentration.

[0065]

[14] The treatment method described in any one of

[11] to

[13] , wherein the plasma generating gas is mainly composed of nitrogen.

[0066]

[15] The treatment method described in any one of

[11] to

[14] , wherein the oxygen concentration of the plasma-generating gas is less than 1% by volume.

[0067] The effects of the invention

[0068] According to the medical treatment device of the present invention, a wide range of plasma-generating gases can be used to generate plasma and to spray active gases. Attached Figure Description

[0069] Figure 1 This is a schematic diagram of a medical treatment device according to one embodiment of the present invention.

[0070] Figure 2 This is a partial cross-sectional view of a medical treatment device according to one embodiment of the present invention.

[0071] Figure 3 It is along Figure 2 A cross-sectional view of the cut line xx.

[0072] Figure 4 This is an early photograph of the trauma in Example 7.

[0073] Figure 5 This is a photograph taken 14 days after the trauma in Example 7.

[0074] Figure 6 This is an early photograph of the trauma in Example 8.

[0075] Figure 7This is a photograph taken 14 days after the injury in Example 8.

[0076] Figure 8 This is an early photograph of the trauma in Example 13.

[0077] Figure 9 This is a photograph taken 14 days after the injury in Example 13.

[0078] Figure 10 This is an early photograph of the trauma in Example 14.

[0079] Figure 11 This is a photograph taken 14 days after the trauma in Example 14.

[0080] Figure 12 This is a photograph of the initial stage of trauma in Comparative Example 2.

[0081] Figure 13 This is a photograph of the patient in Comparative Example 2 14 days after the trauma.

[0082] Figure 14 These are photographs of the initial stage of trauma in Comparative Example 3.

[0083] Figure 15 This is a photograph of the patient in Comparative Case 3 14 days after the trauma.

[0084] Figure 16 These are optical microscope images of the traumatic tissue taken 14 days after Example 10.

[0085] Figure 17 These are optical microscope images of the wounded tissue taken 14 days after Example 11.

[0086] Figure 18 These are optical microscope images of the traumatic tissue taken 14 days after Example 12.

[0087] Figure 19 These are optical micrographs of the traumatic tissue taken 14 days after Comparative Example 1.

[0088] Figure 20 These are optical micrographs of the traumatic tissue taken 14 days after Comparative Example 4. Detailed Implementation

[0089] The medical treatment device of the present invention generates plasma and ejects active gas generated by the plasma through the injection port.

[0090] It should be noted that, in this specification, "reactive gas" refers to a gas containing any of the following with high chemical reactivity: free radicals or other active species, excited atoms, excited molecules, or ions.

[0091] Hereinafter, the present invention will be described with reference to preferred embodiments.

[0092] Medical Therapeutic Devices

[0093] A schematic diagram of a medical treatment device 100 according to one embodiment of the present invention is shown in [the diagram]. Figure 1 .

[0094] The medical treatment device 100 includes an instrument 10, a power supply unit 20, a gas line 30, and an electrical wiring 40. The instrument 10 is connected to the power supply unit 20 via the gas line 30 and the electrical wiring 40. Preferably, the gas line 30 and the electrical wiring 40 are bundled together and connected to the instrument 10.

[0095] Device 10 is a jetting device that ejects active gas generated by plasma from a jet nozzle.

[0096] like Figure 2 As shown, the device 10 includes a nozzle 1 and a cylindrical cover 2. The nozzle 1 includes a base portion 1b and a spray pipe 1c extending from the base portion 1b.

[0097] The cover 2 consists of a head 2a and a main body 2b. The front end of the head 2a is conical, and a nozzle 1 is provided at its top. The base 1b of the nozzle 1 is detachably fitted into the head 2a of the cover 2. A switch 9 is provided on the outer surface of the main body 2b.

[0098] A flow path 7 is formed inside the head 2a and base 1b of the cover 2.

[0099] A flow path 8 is formed inside the injection tube 1c of the nozzle 1. An injection port 1a is formed at the front end of the injection tube 1c to inject the active gas generated by the plasma.

[0100] The interior space of the housing 2 contains a tubular dielectric 3, an internal electrode 4, and an external electrode 5. The tubular dielectric 3 extends in the longitudinal direction and contacts the inner surface of the housing 2. The tube axis O1 of the tubular dielectric 3 is aligned with the tube axis of the housing 2. A cylindrical internal electrode 4 is disposed in the hollow portion inside the tubular dielectric 3. The tube axis of the internal electrode 4 is aligned with the tube axis O1 of the tubular dielectric 3. The inner surface of the tubular dielectric 3 is separated from the internal electrode 4, thereby forming a flow path 6. The flow path 6 serves as the flow path for plasma-generating gas. Flow paths 6, 7, and 8 are connected to the injection port 1a. A tubular external electrode 5 is disposed on a portion of the outer periphery of the tubular dielectric 3, on the outer side where the internal electrode 4 is disposed. The tube axis of the external electrode 5 is aligned with the tube axis O1 of the tubular dielectric 3.

[0101] Figure 3 The middle indicates along Figure 2 A cross-sectional view cut off by line xx. For example... Figure 3As shown, the cylindrical cover 2, the cylindrical external electrode 5, the tubular dielectric 3, and the internal electrode 4 are arranged in concentric circles from the outside towards the center (tube axis O1). The external electrode 5 is disposed in close contact with the outer peripheral surface of the tubular dielectric 3. The external electrode 5 is disposed in close contact with the inner peripheral surface of the main body 2b of the cover 2.

[0102] The internal electrode 4 is positioned at the center of the concentric circles and is separated from the inner circumferential surface of the tubular dielectric 3. A flow path 6 is formed between the internal electrode 4 and the tubular dielectric 3, through which plasma-generating gas flows.

[0103] The tube axis O2 of nozzle 1 intersects the tube axis O1 of tubular dielectric 3 at point Q, forming an angle θ. The angle θ between tube axis O1 and tube axis O2 can be appropriately determined considering the purpose of medical treatment device 100, etc.

[0104] The opening diameter of the injection port 1a is preferably 0.5 to 5 mm, for example. If the opening diameter is above the lower limit, the pressure loss of the active gas can be suppressed. If the opening diameter is below the upper limit, the flow rate of the injected active gas can be increased, thereby further promoting healing, etc.

[0105] The length of the flow path 8 (i.e., distance L2) within the jet pipe 1c can be appropriately determined taking into account the purpose of the medical treatment device 100, etc.

[0106] The material of nozzle 1 is not particularly limited; it may or may not be insulating. Preferably, the material of nozzle 1 is one with excellent wear resistance and corrosion resistance. Metals such as stainless steel are examples of materials with excellent wear resistance and corrosion resistance.

[0107] The flow path 7 formed in the head 2a of the cover 2 is located on the extension line of the tube axis O1. The distance L1 from the center point P of the front end of the external electrode 5 to the intersection point Q of the tube axis O1 and the tube axis O2 can be appropriately determined by taking into account the size required for the medical treatment device 100, or the temperature of the active gas on the surface (the sprayed surface) after spraying.

[0108] The shape of the cover 2 is not particularly limited, but it is preferably a shape that can accommodate both the external electrode 5 and the internal electrode 4 within the internal space. It is also preferable that the tubular dielectric 3 is similarly accommodated within the internal space. The cover 2 is preferably cylindrical, but it can also be shaped for easy handling.

[0109] If the head 2a of the cover 2 and the nozzle 1 are of a size that can be inserted into a person's mouth, the instrument 10 can be easily applied to dental treatment instruments, which is therefore preferred.

[0110] From the viewpoint of preventing electric shock, the main body 2b of the cover 2 is preferably made of an electrically insulating material. For example, the main body 2b may be formed using only an electrically insulating material, or it may be a multi-layer structure consisting of an electrically insulating material and a layer of metal material on its surface.

[0111] Materials that provide electrical insulation include: thermoplastic resins such as polyethylene, polypropylene, polyvinyl chloride, and polystyrene; phenolic resins; melamine resins; urea-formaldehyde resins; epoxy resins; and thermosetting resins such as unsaturated polyester resins.

[0112] Examples of metallic materials include stainless steel, titanium, and aluminum.

[0113] The material of the head 2a of the cover 2 is not particularly limited; in addition to the electrically insulating material, a metallic material can be used. The preferred material for the head 2a is one with excellent wear resistance and corrosion resistance. Examples of materials with excellent wear resistance and corrosion resistance include stainless steel. The materials of the head 2a and the main body 2b can be the same or different.

[0114] The material of the tubular dielectric 3 is not particularly limited, and any dielectric material known for use in plasma generating devices can be used. Examples of materials for the tubular dielectric 3 include glass, ceramics, and synthetic resins. The lower the dielectric constant of the tubular dielectric 3, the better. Glass with a low dielectric constant is preferred as the material for the tubular dielectric 3.

[0115] The cross-sectional shape of the tubular dielectric 3 is not particularly limited; for example, it can be a circle, an ellipse, a quadrilateral, a hexagon, etc.

[0116] A threaded groove (i.e., a spiral groove) is provided on the outer peripheral surface of the internal electrode 4. That is, a spiral protrusion is provided on the outer peripheral surface of the internal electrode 4. Figure 2 In this configuration, the outer peripheral surface of the inner electrode 4 faces and clamps the inner peripheral surface of the outer electrode 5. A thread on the outer peripheral surface of the inner electrode 4 is located close to the inner peripheral surface of the outer electrode 5. A threaded groove (threaded groove) on the outer peripheral surface of the inner electrode 4 is positioned away from the inner peripheral surface of the outer electrode 5.

[0117] With this configuration, the electric field at the front end of the thread is locally strengthened, and the discharge initiation voltage is lowered, thus enabling the generation and maintenance of plasma with low power.

[0118] In the region where the inner electrode 4 and the outer electrode 5 face each other, the distance between the apex of the thread on the outer peripheral surface of the inner electrode 4 and the inner peripheral surface of the outer electrode 5 can be all the same or different. Preferably, the inner peripheral surface of the outer electrode 5 is approached at two or more points on the thread at a distance that allows plasma to be generated. For example, a distance of 0.01 to 2.0 mm can be used to generate low-temperature plasma at atmospheric pressure.

[0119] The length L3 of the region of the inner electrode 4 opposite the outer electrode 5 is preferably 1 to 100 mm, more preferably 2 to 50 mm. If the length L3 is above the lower limit, the plasma generation area can be increased, and plasma can be generated more efficiently. If the length L3 is below the upper limit, the temperature rise of the plasma gas can be suppressed, and the temperature of the active gas on the sprayed surface can be kept low. In this embodiment, the length L3 is equal to the length of the outer electrode 5.

[0120] It should be noted that the external electrode 5 can be divided into two or more parts in the direction of the tube axis O1. When the external electrodes 5 are separated in the direction of the tube axis O1, the length L3 is the length from the rear end to the front end of the two external electrodes, and includes the distance between the two external electrodes.

[0121] The shape of the internal electrode 4 of the device 10 is not limited to a shape with a threaded groove; it can also be a shape with uneven surfaces on the electrode surface opposite to the external electrode 5. For example, a coil-shaped shape can be used; or a shape with multiple protrusions, holes, or through holes formed on the outer peripheral surface of the rod-shaped or cylindrical internal electrode 4. The cross-sectional shape of the internal electrode 4 perpendicular to the tube axis O1 is not particularly limited; for example, a circle, ellipse, quadrilateral, hexagon, etc., can be used.

[0122] The material of the internal electrode 4 can be any conductive material; there are no special restrictions, and the metals used in known plasma generating devices can be used.

[0123] The shape of the external electrode 5 is not particularly limited as long as it can be arranged along the internal electrode 4; for example, cylindrical, rod-shaped, and plate-shaped shapes are possible. The shape of the external electrode 5 is preferably cylindrical, and more preferably cylindrical with an inner diameter that can be tightly fitted to the outer peripheral surface of the tubular dielectric 3. By using such a cylindrical shape, the external electrode 5 can be arranged, and the inner peripheral surface of the external electrode 5 can be reliably opposed to the outer peripheral surface of the internal electrode 4.

[0124] When the external electrode 5 is rod-shaped or plate-shaped, the number of external electrodes 5 is not particularly limited; it can be one or more. When two or more are provided, if they are arranged at equal intervals around the outer periphery of the tubular dielectric 3, the ionization of the plasma-generating gas is dispersed, which is preferable.

[0125] The material of the external electrode 5 can be any conductive material; there are no particular limitations, and metals commonly used in plasma generating devices can be used. The materials of the external electrode 5 and the internal electrode 4 can be the same or different.

[0126] The power supply unit 20 is a device for supplying power to the apparatus 10. A known power supply device can be used as the power supply unit 20.

[0127] The power supply unit 20 preferably has the function of controlling the voltage and frequency applied between the external electrode 5 and the internal electrode 4.

[0128] The power supply unit 20 is a device for supplying power to the instrument 10. In this embodiment, the power supply unit 20 includes a pump that supplies plasma-generating gas to the instrument 10 via a gas line 30. The power supply unit 20 can adjust the voltage and frequency applied between the external electrode 5 and the internal electrode 4.

[0129] It should be noted that the power supply unit 20 may not have a pump. In this case, a pump can be provided independently of the power supply unit 20. Alternatively, the plasma generating gas can be supplied to the device 10 by the pressure of the plasma generating gas supply source.

[0130] The gas line 30 is the path for supplying plasma-generating gas from the power supply unit 20 to the device 10. The gas line 30 is connected to the rear end of the tubular dielectric 3 of the device 10. The material of the gas line 30 is not particularly limited, and known materials used for gas lines can be used. Examples of materials for the gas line 30 include resin tubing and rubber tubing, and a flexible material is preferred.

[0131] Electrical wiring 40 is a wiring that supplies power from power supply unit 20 to device 10. Electrical wiring 40 is connected to internal electrode 4, external electrode 5, and switch 9 of device 10. The material of electrical wiring 40 is not particularly limited, and commonly known materials used for electrical wiring can be used. Examples of materials for electrical wiring 40 include metal wires covered with insulating material.

[0132] Instructions for Use of Medical Therapy Instruments

[0133] based on Figure 1 as well as Figure 2 The method of using the medical treatment device 100 is explained below. Plasma generating gas is supplied to the device 10 from the power supply unit 20. The plasma generating gas supplied to the device 10 is introduced into the hollow part of the tubular dielectric 3 from the rear end of the tubular dielectric 3.

[0134] Then, power is supplied to the device 10 from the power supply unit 20, and the switch 9 is turned on to apply a voltage between the internal electrode 4 and the external electrode 5. The plasma introduced into the hollow part of the tubular dielectric 3 generates gas, which is ionized at the position where the internal electrode 4 and the external electrode 5 are opposite, becoming plasma.

[0135] In this invention, the internal electrode 4 and the external electrode 5 are positioned opposite each other in a direction perpendicular to the flow direction of the plasma-generating gas. Therefore, 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 is guided to the ejector port 1a via flow paths 6, 7, and 8. The plasma is an active gas containing active species based on ions, electrons, excited molecules and atoms, and the type of plasma-generating gas. As the plasma generation unit moves away, the composition of the active gas changes; at the point of guidance to the ejector port 1a, ionized ions and electrons recombine, and active species become the main constituent elements. Furthermore, sometimes the gas present near the ejector port 1a reacts with the ejected active gas to generate other types of active gases. As a result, plasma-generating gas or active gas corresponding to the gas present near the ejector port 1a is ejected from the ejector port 1a.

[0136] Therefore, the fluid ejected from nozzle 1 does not contain plasma itself, but rather active gases of active species generated by the plasma. In this respect, the medical treatment device 100 of the present invention differs from existing plasma jetting devices.

[0137] Examples of active species (free radicals, etc.) contained in reactive gases include: hydroxyl radicals, singlet oxygen, ozone, hydrogen peroxide, superoxide anion radicals, nitric oxide, nitrogen dioxide, peroxynitrite, nitrous oxide, and dinitrogen trioxide.

[0138] Within the hollow portion of the tubular dielectric 3, the outer peripheral surface of the inner electrode 4 and the inner peripheral surface of the outer electrode 5 are arranged opposite each other, clamping the tubular dielectric 3. The electric field at the threaded tip of the inner electrode 4 is locally strengthened, and the discharge initiation voltage is lowered, thus enabling the generation and maintenance of plasma with low power.

[0139] It is not limited to the case where the outer peripheral surface of the internal electrode 4 is threaded. As long as the internal electrode has multiple protrusions and depressions formed on the surface of the outer peripheral surface, plasma can be generated and maintained with low power in the same way.

[0140] It should be noted that the internal electrode 4 may not have threads or other irregularities on its outer peripheral surface. That is, the internal electrode 4 may also be a cylindrical component without irregularities on its outer peripheral surface.

[0141] The temperature of the active gas on the sprayed surface, located at a distance of 1 mm to 10 mm from the nozzle 1a, is below 40°C. By setting the temperature of the active gas on the sprayed surface to below 40°C, the irritation to the sprayed surface can be reduced.

[0142] The temperature of the active gas on the sprayed surface is measured by placing the tip of a rod-shaped thermocouple on the sprayed surface. As described below, the temperature of the active gas on the sprayed surface can be adjusted by controlling the temperature of the active gas at the injection port 1a of nozzle 1.

[0143] The temperature of the active gas at the injection port 1a of nozzle 1 is preferably below 50°C, more preferably below 45°C, and even more preferably below 40°C.

[0144] If the temperature of the active gas at the injection port 1a of nozzle 1 is below the upper limit value, it is easy to control the temperature of the active gas on the sprayed surface to below 40°C.

[0145] There is no particular limitation on the lower limit of the temperature of the active gas at the injection port 1a of nozzle 1, for example, it is above 0°C.

[0146] The temperature of the active gas ejected from the injection port 1a of nozzle 1 can be determined by the flow rate of the gas and the path traveled by the plasma introduced into the tubular dielectric 3. Figure 2 The total distance between L1 and L2), the plasma gas temperature at the plasma generation location, and combinations thereof are adjusted.

[0147] The flow rate of the plasma-generating gas introduced into the tubular dielectric 3 is preferably 1 L / min to 10 L / min.

[0148] If the flow rate of the plasma-generating gas introduced into the tubular dielectric 3 is above the lower limit, it easily promotes the purification, activation, or healing of abnormalities in the sprayed material selected from cells, living tissues, and biological individuals. Below the upper limit, it is easy to control the temperature of the active gas at the injection port 1a of the nozzle 1 to below 50°C.

[0149] It should be noted that in the medical treatment device 100, the flow rate ratio (introduced flow rate) of the plasma-generating gas introduced into the tubular dielectric 3 to the flow rate of the active gas ejected from the ejector port 1a (ejected flow rate) is preferably 0.8 to 1.2, more preferably 0.9 to 1, and even more preferably 1:1. By adjusting the introduced flow rate and the ejected flow rate to fall within the aforementioned range, the ejected flow rate can be easily controlled. The introduced flow rate and the ejected flow rate can be adjusted to fall within the aforementioned range by appropriately adjusting the shape of the tubular dielectric 3 or the opening diameter of the ejector port 1a.

[0150] The temperature of the active gas at the injection port 1a of nozzle 1 can be adjusted by the total distance between L1 and L2. The total distance between L1 and L2 is appropriately determined by taking into account the required size of the medical treatment device 100 or the temperature of the active gas on the sprayed surface.

[0151] If the total distance between L1 and L2 is longer, the temperature of the active gas on the sprayed surface can be lower. If the total distance between L1 and L2 is shorter, the concentration of free radicals in the active gas can be further increased, thereby further enhancing the purification, activation, and healing effects on the sprayed surface.

[0152] The total distance between L1 and L2 can be adjusted by the length of the injection pipe 1c and the positions of the internal electrode 4 and the external electrode 5.

[0153] The temperature of the active gas ejected from the injection port 1a of nozzle 1 can be adjusted by the plasma gas temperature at the plasma generation location.

[0154] By lowering the plasma gas temperature at the plasma generation location, the temperature of the active gas ejected from the nozzle 1a can be reduced. The plasma gas temperature at the plasma generation location is appropriately determined based on the magnitude and frequency of the voltage applied between the internal electrode 4 and the external electrode 5.

[0155] The concentration of free radicals in the reactive gas generated by plasma is 0.1–300 μmol / L. Preferably, the concentration of free radicals in the reactive gas generated by plasma is 0.1–100 μmol / L, more preferably 0.1–50 μmol / L.

[0156] If the concentration of free radicals in the reactive gas generated by the plasma is above the lower limit, it easily promotes the purification, activation, or healing of abnormalities in the sprayed material selected from cells, living tissues, and biological individuals. If it is below the upper limit, it easily reduces irritation to the sprayed surface.

[0157] The concentration of free radicals in the reactive gas generated by plasma can be adjusted by the flow rate of the plasma-generating gas introduced into the tubular dielectric 3, the total distance between L1 and L2, the plasma gas temperature at the plasma generation location, and combinations thereof.

[0158] The flow rate of the plasma-generating gas introduced into the tubular dielectric 3 is preferably 1 L / min to 10 L / min, more preferably 1 to 5 L / min, and even more preferably 1 to 3 L / min.

[0159] If the flow rate of the plasma-generating gas introduced into the tubular dielectric 3 is above the lower limit, it is easy to adjust the free radical concentration to 0.1 μmol / L or higher. If it is below the upper limit, it is easy to adjust the temperature of the active gas on the sprayed surface to 40°C or lower.

[0160] Regarding the concentration of free radicals in the reactive gas generated by plasma, it can be determined using a medical therapeutic device by the following method for measuring the concentration of hydroxyl free radicals.

[0161] <Methods for determining the concentration of hydroxyl radicals>

[0162] For a 0.4 mL solution of 0.2 mol / L DMPO (5,5-dimethyl-1-pyrroline-N-oxide), an active gas was injected for 30 seconds. The distance from the injection nozzle to the liquid surface was set to 5.0 mm. The concentration of hydroxyl radicals in the solution after the active gas injection was determined by electron spin resonance (ESR) and used as the radical concentration.

[0163] The concentration of free radicals in the reactive gas transported to the surface by plasma can be adjusted by the total distance between L1 and L2. The total distance between L1 and L2 is appropriately determined by considering the required size of the medical treatment device 100 or the temperature of the reactive gas on the surface being sprayed.

[0164] The total distance between L1 and L2 can be adjusted by the length of the injection pipe 1c and the positions of the internal electrode 4 and the external electrode 5.

[0165] The concentration of free radicals in the reactive gas transported by the plasma to the surface being sprayed can be adjusted by the temperature of the plasma gas at the plasma generation location.

[0166] The plasma gas temperature at the plasma generation location is appropriately determined based on the magnitude and frequency of the voltage applied between the internal electrode 4 and the external electrode 5.

[0167] If the plasma gas temperature at the plasma generation location is high, the free radical concentration is more likely to increase. If the plasma gas temperature at the plasma generation location is low, the free radical concentration is more likely to decrease.

[0168] The singlet oxygen concentration of the reactive gas generated by plasma is 0.1–300 μmol / L. Preferably, the singlet oxygen concentration of the reactive gas generated by plasma is 0.1–100 μmol / L, more preferably 0.1–50 μmol / L.

[0169] If the concentration of singlet oxygen in the reactive gas generated by the plasma is above the lower limit, it easily promotes the purification, activation, or healing of abnormalities in the sprayed material selected from cells, living tissues, and biological individuals. If it is below the upper limit, it easily reduces irritation to the sprayed surface.

[0170] Regarding the concentration of singlet oxygen in the reactive gas generated by plasma, it can be determined using a medical treatment device and by the method described below for measuring singlet oxygen concentration.

[0171] <Methods for determining singlet oxygen concentration>

[0172] For a 0.4 mL solution of 0.1 mol / L TPC (2,2,5,5-tetramethyl-3-pyrrolino-3-carboxamide), an active gas was injected for 30 seconds. The distance from the injection nozzle to the liquid surface was set to 5.0 mm. The singlet oxygen concentration in the solution after the active gas injection was determined by electron spin resonance (ESR) and recorded as the singlet oxygen concentration.

[0173] The singlet oxygen concentration of the active gas generated by plasma can be adjusted by the flow rate of the plasma-generated gas introduced into the tubular dielectric 3, the total distance between L1 and L2, the plasma gas temperature at the plasma generation location, and combinations thereof.

[0174] The adjustments to the flow rate of the plasma-generating gas, the total distance between L1 and L2, and the plasma gas temperature are the same as those for the free radical concentration.

[0175] The active gas generated by plasma preferably has a free radical concentration of 0.1–300 μmol / L and a singlet oxygen concentration of 0.1–300 μmol / L.

[0176] When the concentration of free radicals and singlet oxygen in the reactive gas generated by plasma is within the aforementioned range, it is easier to promote the purification, activation, or abnormal healing of the sprayed material selected from cells, living tissues, and biological individuals.

[0177] The AC voltage applied between the internal electrode 4 and the external electrode 5 is preferably 5.0 kVpp or higher and less than 20 kVpp. Here, the unit "Vpp (Volt peak to peak)" represents the potential difference between the highest and lowest values ​​of the AC voltage waveform.

[0178] It should be noted that when the inner electrode 4 is a cylindrical component without protrusions or depressions on its outer peripheral surface, the AC voltage applied between the inner electrode 4 and the outer electrode 5 is preferably 10 kVpp or higher. When using an inner electrode 4 without protrusions or depressions on its outer peripheral surface, it is necessary to increase the AC voltage applied between the inner electrode 4 and the outer electrode 5 compared to using an inner electrode 4 with protrusions or depressions on its outer peripheral surface.

[0179] By applying an AC voltage lower than the upper limit, the temperature of the generated plasma gas can be suppressed to a lower level. By applying an AC voltage above the lower limit, plasma is easily generated.

[0180] The frequency of the AC voltage applied between the internal electrode 4 and the external electrode 5 is preferably 0.5 kHz or more and less than 20 kHz, more preferably 1 kHz or more and less than 15 kHz, further preferably 2 kHz or more and less than 10 kHz, especially preferably 3 kHz or more and less than 9 kHz, and most preferably 4 kHz or more and less than 8 kHz.

[0181] By making the frequency of the alternating voltage lower than the upper limit, the temperature of the generated plasma can be suppressed to a lower level. By making the frequency of the alternating voltage higher than the lower limit, plasma is easily generated.

[0182] The flow rate of the active gas injected from the injection port 1a is preferably 1 L / min to 10 L / min.

[0183] When the flow rate of the active gas ejected from nozzle 1a is above the lower limit, the efficiency of the active gas in acting on the sprayed surface can be sufficiently improved. When the flow rate of the active gas ejected from nozzle 1a is below the upper limit, excessive temperature rise of the active gas on the sprayed surface can be prevented. Furthermore, in the case of a wet sprayed surface, rapid drying of the sprayed surface can be prevented. Moreover, when the sprayed surface is a diseased area, pain caused by heat in the patient can be further suppressed.

[0184] There is no particular limitation on the type of plasma-generating gas introduced into the tubular dielectric 3. For example, known plasma-generating gases such as oxygen, helium, argon, nitrogen, carbon dioxide, and air can be used.

[0185] As described above, the instrument 10 of the medical treatment device 100 can generate and maintain plasma with low power through the effect of the threads provided on the outer peripheral surface of the internal electrode 4.

[0186] Therefore, in this invention, not limited to existing rare gases, a wide variety of plasma-generated gases can be used.

[0187] The plasma-generating gas introduced into the tubular dielectric 3 can be a single gas or a mixture of two or more gases.

[0188] The plasma generating gas introduced into the tubular dielectric 3 is preferably composed mainly of nitrogen. Here, "composed mainly of nitrogen" means that the volume of nitrogen contained in the plasma generating gas exceeds 50% by volume. That is, the volume of nitrogen contained in the plasma generating gas is preferably more than 50% by volume, more preferably 70% by volume or more, and even more preferably 90 to 100% by volume. If the main component of the plasma generating gas is nitrogen, the metastable nitrogen molecules in the plasma have a longer lifetime, thus making it easier to maintain the activity of the gas and to increase the concentration of free radicals of the active gas reaching the ejected material.

[0189] There are no particular limitations on the types of residual gas components in the plasma-generating gas; air can be listed as an example. Air can be mixed with nitrogen to create nitrogen plasma.

[0190] The plasma-generating gas, with nitrogen as its main component, can further promote the purification, activation, or healing of the sprayed object. Furthermore, by using nitrogen as the main component, oxygen in the plasma-generating gas is reduced, as is ozone in the active gas. When the active gas spraying device 10 is used for intraoral treatment, reducing ozone in the active gas is preferable.

[0191] In existing plasma generation units, it is difficult to generate plasma if a plasma generating gas containing nitrogen is used. In this embodiment, plasma can be easily generated because an internal electrode with helical protrusions (threads) on its outer peripheral surface (i.e., with helical grooves) is used.

[0192] The oxygen concentration of the plasma-generating gas introduced into the tubular dielectric 3 is preferably 1% by volume or less. If the oxygen concentration is below the upper limit, the generation of excessive ozone can be further suppressed.

[0193] Methods for Injecting Reactive Gases

[0194] The active gas generated by the medical treatment device 100 is preferably used for spraying living organisms such as cells, living tissues, and biological individuals. By spraying the active gas onto a living organism, it can be used for treatment or activation. For example, by spraying the active gas onto a wound or other abnormality such as a cut, abrasion, burn, or scald, bacteria on the wound or abnormal surface can be inactivated, thereby promoting healing.

[0195] When spraying reactive gas onto a wounded or abnormal area, it is sometimes necessary to reduce the spray volume in order to suppress irritation to the wound. In this case, the amount of reactive gas sprayed from the nozzle 1a can be reduced by reducing the amount of plasma-generating gas introduced from the rear end of the tubular dielectric 3 of the medical treatment device 100.

[0196] Sometimes it is desirable to further promote the healing by increasing the concentration of active species contained in the active gas. In this case, when spraying the active gas, the nozzle 1a is brought close to the part being sprayed and the distance is 0.01 mm or more and 10 mm or less, thereby spraying an active gas containing a higher concentration of active species.

[0197] The medical treatment device 100 allows the temperature of the injected active gas to be set to below 50°C. Therefore, even when the nozzle 1a is brought close to the part being sprayed, there is no need to worry about the temperature of the sprayed part becoming excessively high. Thus, when the part being sprayed is a affected area, the active gas can be sprayed onto the affected area without causing excessive stimulation.

[0198] The active gas generated by utilizing the plasma produced by the medical treatment device 100 has the effect of promoting the healing of injuries or abnormalities. As shown in the following examples, by spraying cells, living tissues, or biological individuals with the active gas generated by the plasma, the sprayed part can be cleansed or activated, or the injury or abnormality located on the sprayed part can be healed.

[0199] Examples of living tissues include internal organs, epithelial tissues covering the inner surface of the body or body cavity, periodontal tissues such as gingiva, alveolar bone, root ligament, and cementum, teeth, and bones.

[0200] Diseases and symptoms that can be treated by spraying active gases include, for example, oral diseases such as gingivitis and periodontitis, and skin trauma.

[0201] When spraying reactive gas generated by plasma for the purpose of promoting the healing of injuries or abnormalities, there are no particular limitations on the spraying frequency, number of sprays, or spraying time. For example, when spraying the affected area with reactive gas generated by plasma at a spraying rate of 0.5L or more but less than 5.0L per minute, the number of sprays per day is preferably 1 to 5. Furthermore, when the spraying rate is 0.5L or more but less than 5.0L per minute, the spraying time for each session is preferably 10 seconds to 10 minutes. When the spraying rate is 0.5L or more but less than 5.0L per minute, the spraying period is preferably 1 to 30 days. Under these conditions, further promotion of healing can be achieved.

[0202] As described above, the medical treatment device of this embodiment can generate low-temperature plasma more stably, and spray the affected area with active gas generated by the plasma. The sprayed active gas can be sprayed onto the tissue of the target without damage, thereby promoting tissue repair. Therefore, the medical treatment device of this embodiment is also useful as a cosmetic device for the skin, etc.

[0203] The medical treatment apparatus of the present invention is particularly suitable for use as an intraoral treatment apparatus and a dental treatment apparatus.

[0204] Furthermore, the medical treatment device of the present invention is also preferably used as an animal treatment device.

[0205] Example

[0206] The present invention will be described in more detail below using examples, but the present invention is not limited to these examples.

[0207] (Temperature measurement)

[0208] Except for the specifications described below, a medical treatment device identical to medical treatment device 100 is manufactured. Using this medical treatment device, an AC voltage of 15kVpp and 7.5kHz is applied between the external and internal electrodes to generate atmospheric pressure nitrogen plasma. In a room at 25°C, the measuring part of the thermocouple is positioned 3mm away from the injection port. The injection of the active gas is started, and the temperature read after 60 seconds is taken as the temperature of the active gas on the injected surface.

[0209] The result was 34.9°C at a distance of 3 mm from the nozzle.

[0210] <Specifications>

[0211] • The inner diameter of the injection nozzle 1a is 1mm.

[0212] • Tubular dielectric 3: Made of glass, with an inner diameter of 3mm.

[0213] • Internal electrode 4: Stainless steel, parallel thread, single-start thread; outer diameter 2mm, spacing 0.4mm, thread height 0.214mm.

[0214] External electrode 5: Copper plate.

[0215] • Angle θ: 20°.

[0216] (Determination of hydroxyl radical concentration)

[0217] Nitrogen gas with a purity of 99.99% (volume basis) was introduced into the instrument at a flow rate of 1 L / min to generate plasma, which was then generated using an AC voltage of 15 kVpp and 7.5 kHz. A nozzle with an inner diameter of 1 mm was used.

[0218] DMPO was used as a reagent for detecting hydroxyl radicals. It was dissolved in phosphate-buffered saline solution with a pH adjusted to 7.3–7.5, and the concentration of DMPO was 0.2 mol / L.

[0219] 0.4 mL of DMPO solution was added to a cylindrical trough with an inner diameter of 11.5 mm. The apparatus was set so that the liquid level in the trough was 5 mm from the nozzle. The solution was then sprayed with the reactive gas generated by plasma for 30 seconds. The concentration of hydroxyl radicals in the solution after the reactive gas injection was determined by ESR. The radical concentration (hydroxyl radical concentration) was 3 μmol / L.

[0220] The conditions for setting up the ESR method are as follows.

[0221] The microwave frequency was set to 9.63 GHz, and the microwave power was set to 10 mW. The DMPO solution was placed in a magnetic field of 344 ± 5 ​​mT, and the measurement was performed under the conditions of amplitude modulation of 0.2 mT and scanning time of 20 seconds.

[0222] (Determination of singlet oxygen concentration)

[0223] TPC was used as the reagent for detecting singlet oxygen, and the concentration of TPC was set to 0.1 mol / L. Otherwise, the concentration of singlet oxygen was determined in the same manner as that for the determination of hydroxyl radical concentration.

[0224] The concentration of singlet oxygen is 3 μmol / L.

[0225] (Promoting the healing of trauma, Examples 1-14, Comparative Examples 1-4)

[0226] Skin was incised and harvested from the backs of four pigs, and Staphylococcus aureus was inoculated into these areas to create wound infection models. The infection models were sprayed with active gas as closely as possible to the wound sites, following the active gas generation conditions shown in Table 1. Active gas spraying was performed initially (day 1) and after day 7. The flow rates in Table 1 represent the flow rates of nitrogen gas introduced into the instruments. The voltages in Table 1 represent the AC voltage applied between the internal and external electrodes. The frequencies in Table 1 represent the frequencies of the voltage applied between the internal and external electrodes. In Comparative Examples 1-4, since no voltage was applied between the internal and external electrodes, nitrogen gas without active species was sprayed into the wounds.

[0227] [Table 1]

[0228]

[0229] Clinical symptom scores were determined by visual inspection of each wound for redness, erythema, papules, exudate (containing pus), and pustules. Symptoms across the five items were scored and totaled based on the following indicators. The scores in Table 1 represent the average scores of four pigs with wounds inflicted under the same reactive gas generation conditions. Higher scores indicate more severe trauma.

[0230] 0 points: None.

[0231] 1 point: Mild.

[0232] 2 points: Moderate level.

[0233] 3 points: severe.

[0234] The clinical symptom scores were fractionated for the initial stage of the injury (day 1) and 14 days after each injury, and the score improvement rate (%) was calculated according to the following formula.

[0235] Improvement rate (%) = ((Clinical symptom score (initial) - Clinical symptom score (after 14 days)) / Clinical symptom score (initial)) × 100

[0236] The results are shown in Table 1.

[0237] As shown in Table 1, in Examples 1-4 where the flow rate of the active gas was set to 1 L / min, the score improvement rate was 76.9-84.4%, confirming the effectiveness of the active gas in healing wounds. In Examples 5-8 where the flow rate of the active gas was set to 2 L / min, the score improvement rate was 89.2-93.6%, confirming an even higher effect of the active gas in healing wounds. In Examples 9-14 where the flow rate of the active gas was set to 3 L / min, the score improvement rate was all above 92.2%, confirming an even higher effect of the active gas in healing wounds.

[0238] On the other hand, in Comparative Examples 1-4 (natural healing) where nitrogen gas without active species was sprayed, the score improvement rate was less than 64.8%.

[0239] Photographs of the traumas in Examples 7, 8, 13, and 14 are shown in Figures 4-11 . Figure 4 , 6 Photos 8 and 10 show the traumas in Examples 7, 8, 13, and 14 before the reactive gas was injected. Figure 5 , 7 Photos 9 and 11 are of the injuries taken 14 days after the events in Examples 7, 8, 13, and 14, respectively.

[0240] Photographs of the traumas in comparative examples 2 and 3 are shown in Figures 12-15 . Figure 12 , 14 The images show the traumas in Comparative Examples 2 and 3 before the reactive gas was injected. Figure 13 , 15 The images are photographs of the trauma 14 days later in Comparative Examples 2 and 3, respectively.

[0241] It can be seen that the trauma 14 days after the events of Examples 7, 8, 13, and 14... Figure 5 , 7 The numbers 9 and 11 indicate the trauma 14 days later in comparison to examples 2 and 3. Figure 13 , Figure 15 The healing rate of trauma is better.

[0242] (Cell activation, Examples 10-12, Comparative Examples 1 and 4)

[0243] For the trauma cases of Examples 10-12 and Comparative Examples 1 and 4, pathological tissues were collected 14 days later and fixed in 10% (w / w) neutral buffered formalin. The tissue cells of each case were observed and photographed using an optical microscope after 14 days.

[0244] The results will be displayed in Figures 16-20 . Figures 16-20 The photographs are shown in order for Examples 10-12 and Comparative Examples 1 and 4.

[0245] exist Figures 16-20 In the image, the photograph on the right side of the paper is an enlarged view of the portion of the photograph on the left side of the paper enclosed by the four sides.

[0246] like Figures 16-18 As shown, in Examples 10-12, where an active gas with a spray flow rate of 3 L / min was injected, the wound site completely regenerated from the left and right epidermis, constructed an epidermal structure, and regenerated an epidermis that was close to normal, thus confirming the effect of epidermal regeneration.

[0247] In addition, in the wound site, the infiltration of inflammatory cells, mainly lymphocytes, was observed, but the fibroblast proliferation and the purulent inflammation caused by the infiltration of neutrophils and other cells disappeared. Therefore, this was regarded as the proliferative phase from the middle to the late stage of the wound healing process, confirming the wound healing and anti-inflammatory effects.

[0248] In addition, no infected bacteria were found on the slides, confirming the bactericidal effect.

[0249] On the other hand, such as Figures 19-20 As shown, in Comparative Examples 1 and 4 (natural healing) where nitrogen gas without active species was sprayed, the epidermis at the wound site was separated from side to side, and no epidermal regeneration effect was confirmed.

[0250] In addition, among the inflammatory cells, a relatively large proportion of lymphocytes and neutrophils were found, while the proliferation of fibroblasts was relatively sparse, presenting an image resembling local edema. Therefore, it was considered to be the inflammatory phase from the early to the first half of the middle stage of wound healing, and the wound healing and anti-inflammatory effects as in Examples 10-12 were not confirmed.

[0251] In addition, the bacteria that caused the infection remained directly, and no bactericidal effect was confirmed.

[0252] Industrial applicability

[0253] This invention can be used in the medical field.

[0254] Symbol Explanation

[0255] 1… Nozzle

[0256] 1a…jet nozzle

[0257] 1b…base section

[0258] 1c…jet pipe

[0259] 2…cover

[0260] 2a…head

[0261] 2b…Main body

[0262] 3…Tube Dielectric

[0263] 4…Internal Electrodes

[0264] 5…External Electrode

[0265] 6~8...Flow path

[0266] 9…Switch

[0267] 10… instruments

[0268] 20…Power Supply Unit

[0269] 30…Gas pipeline

[0270] 40… electrical wiring

[0271] O1~O2…tube shaft

[0272] 100…Medical treatment devices

Claims

1. A medical treatment device that generates plasma and ejects an active gas generated by the plasma through a nozzle, wherein, The concentration of the reactive gas, determined by the following method for measuring hydroxyl radical concentration, is 0.1~300 μmol / L, and the concentration of singlet oxygen, determined by the following method for measuring singlet oxygen concentration, is 0.1~300 μmol / L. The method for determining the concentration of hydroxyl radicals is as follows: The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was injected into a 0.4 mL solution of 5,5-dimethyl-1-pyrroline-N-oxide (0.2 mol / L) for 30 seconds. Then, the concentration of hydroxyl radicals in the solution after the active gas injection was determined by electron spin resonance spectroscopy and used as the radical concentration. The method for determining the concentration of singlet oxygen is as follows: The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL solution of 2,2,5,5-tetramethyl-3-pyrrolline-3-carboxamide 0.1 mol / L for 30 seconds. Then, the singlet oxygen concentration of the solution after the active gas spray was determined by electron spin resonance method and taken as the singlet oxygen concentration.

2. The medical treatment device according to claim 1, wherein, The temperature of the injected active gas is set below 50°C.

3. The medical treatment device according to claim 1, wherein, The temperature of the active gas at the nozzle outlet is below 50°C.

4. The medical treatment device according to claim 1, wherein, The lower limit of the temperature of the active gas at the nozzle outlet is above 0℃.

5. The medical treatment device according to claim 1, wherein, The active gas is injected at a flow rate of 1 L / min to 10 L / min.

6. The medical treatment device according to claim 1, further comprising a power supply unit, The power supply unit includes a pump that supplies plasma-generating gas containing more than 50% by volume nitrogen.

7. The medical treatment appliance according to any one of claims 1 to 6, wherein it is for dental use.

8. A method for generating an active gas for wound healing or anti-inflammatory purposes, wherein, The active gas is generated by plasma produced by a medical treatment device, and the active gas is ejected from the nozzle. The concentration of the reactive gas, determined by the following method for measuring hydroxyl radical concentration, is 0.1~300 μmol / L, and the concentration of singlet oxygen, determined by the following method for measuring singlet oxygen concentration, is 0.1~300 μmol / L. In the aforementioned generation method, plasma generating gas is supplied to a plasma generating unit equipped with electrodes at a rate of 1-10 L / min. A voltage is applied to the electrodes to generate plasma, and hydroxyl radicals and singlet oxygen are generated through the generated plasma. The method for determining the concentration of hydroxyl radicals is as follows: The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was injected into a 0.4 mL solution of 5,5-dimethyl-1-pyrroline-N-oxide (0.2 mol / L) for 30 seconds. Then, the concentration of hydroxyl radicals in the solution after the active gas injection was determined by electron spin resonance spectroscopy and used as the radical concentration. The method for determining the concentration of singlet oxygen is as follows: The distance from the nozzle to the liquid surface was set to 5.0 mm. An active gas was sprayed onto a 0.4 mL solution of 2,2,5,5-tetramethyl-3-pyrrolline-3-carboxamide 0.1 mol / L for 30 seconds. Then, the singlet oxygen concentration of the solution after the active gas spray was determined by electron spin resonance method and taken as the singlet oxygen concentration.

9. The method according to claim 8, wherein, The temperature of the injected active gas is set below 50°C.

10. The method according to claim 8, wherein, The temperature of the active gas at the nozzle outlet is below 50°C.

11. The method according to claim 8, wherein, The lower limit of the temperature of the active gas at the nozzle outlet is above 0℃.

Images