Cryotherapy device

Abstract

This cryotherapy device comprises a head part, a cooling mechanism, and a control unit. The head part has a probe that forms a working surface to be brought close to or into contact with the surface of a skin to be treated. The cooling mechanism cools the probe. The control unit controls the cooling mechanism such that the probe is maintained at a target temperature of 0°C or lower. The probe is configured so as to freeze the tissue of the skin through the working surface and thereby selectively induce the apoptosis of diseased cells including at least nevus cells.

Description

Cryotherapy device

[0001] The present disclosure relates to cryotherapy devices.

[0002] U.S. Patent No. 6,279,663 discloses a system having an electrosurgical probe for ablating tissue in the integument or epidermis of a patient, such as tissue abnormalities, birthmarks, superficial lentigines, malignant melanoma, malignant tumor tissue, etc.

[0003] Special Publication No. 11-501555

[0004] The electrosurgical probe disclosed in Patent Document 1 includes an active electrode and a return electrode connected to a high-frequency voltage source. When high-frequency voltage is applied to the active electrode and the return electrode, the active electrode generates an energy source at the distal tip, causing necrosis of tissue in contact with the distal tip or nearby tissue. However, destruction of skin tissue by such an electrosurgical probe is invasive and may leave inflammation, scars, scar contracture, and the like. For this reason, there has been a demand for a treatment device that can remove diseased skin cells, such as mevus cells, while leaving fewer scars.

[0005] An object of the present disclosure is to provide a cryotherapy device capable of removing diseased cells including at least nevus cells while suppressing the occurrence of scars and the like.

[0006] A cryotherapy device according to a first aspect of the present disclosure includes a head unit, a cooling mechanism, and a control unit. The head unit has a probe that forms an active surface for bringing the probe into proximity with or into contact with the surface of the skin to be treated. The cooling mechanism cools the probe. The control unit controls the cooling mechanism to maintain the probe at a target temperature of 0°C or less. The probe is configured to freeze the skin tissue via the active surface, thereby selectively inducing apoptosis of diseased cells, including at least nevus cells.

[0007] The cryotherapy device according to the first aspect selectively induces natural death (apoptosis, in which cells fragment without rupturing their cell membranes) of diseased cells, including at least nevus cells, using a probe cooled to 0°C or below. Removal of diseased cells, including nevus cells, has traditionally been achieved through invasive surgical excision, laser treatment, electrocautery treatment, cryotherapy using cryogenic liquid gas, and other methods. These treatments not only induce necrosis of diseased cells (necrosis, in which the cell membrane ruptures and releases its contents) but also necrosis of nearby, unaffected normal cells, resulting in frequent scarring, scar contracture, and inflammation. After extensive research, the inventors discovered that when both nevus cells and normal cells are cooled to 0°C or below, the proportion of nevus cells undergoing apoptosis is significantly higher than the proportion of normal cells undergoing apoptosis. This is believed to be due to the higher temperature sensitivity of nevus cells compared to normal cells. Based on this finding, a cryotherapy device can preferentially induce apoptosis of diseased cells, which are more temperature-sensitive, while preserving a greater proportion of normal cells.

[0008] Additionally, in the cryotherapy device according to the first aspect, the skin tissue to be treated is frozen via the working surface of the probe, which is cooled to below 0° C. This eliminates the need to prepare low-temperature liquefied gas such as liquid nitrogen or carbon dioxide, and eliminates the burden of complex safety management work for high-pressure gas.

[0009] A cryotherapy apparatus according to a second aspect of the present disclosure is the cryotherapy apparatus according to the first aspect, wherein the probe further forms a pair of surfaces that intersect with the active surface, and the cooling mechanism has a pair of cooling elements capable of cooling the probe, and each of the pair of cooling elements forms a first surface capable of absorbing heat from the pair of surfaces.

[0010] According to the cryotherapy apparatus of the second aspect, the cooling capacity of the cooling element for the probe can be further improved.

[0011] A cryotherapy device according to a third aspect of the present disclosure is the cryotherapy device according to the first or second aspect, wherein each of the pair of cooling elements further forms a second surface capable of releasing heat absorbed from the first surface, and the cooling mechanism further has a cooling jacket through which a refrigerant capable of absorbing heat from the second surface circulates.

[0012] According to the cryotherapy apparatus of the third aspect, the cooling efficiency of the probe can be further improved.

[0013] A cryotherapy device according to a fourth aspect of the present disclosure is a cryotherapy device according to any one of the first to third aspects, wherein the head portion further includes a casing that houses the probe, the pair of cooling elements, and at least a portion of the cooling jacket, and an insulating material arranged between the casing and the cooling jacket.

[0014] According to the cryotherapy apparatus of the fourth aspect, the cooling efficiency of the probe can be further improved.

[0015] A cryotherapy device according to a fifth aspect of the present disclosure is a cryotherapy device according to any one of the first to fourth aspects, wherein the head unit further includes an imaging device for acquiring an image of diseased cells including at least the nevus cells or their vicinity.

[0016] According to the cryotherapy apparatus of the fifth aspect, even when the diseased cells or their vicinity are hidden by the head portion and are difficult to observe visually, the state of the diseased cells or their vicinity can be easily observed.

[0017] A cryotherapy apparatus according to a sixth aspect of the present disclosure is a cryotherapy apparatus according to any one of the first to fifth aspects, wherein the control unit controls the cooling mechanism so that the probe is maintained at a target temperature of −30°C or higher.

[0018] A cryotherapy device according to a seventh aspect of the present disclosure is a cryotherapy device according to any one of the first to sixth aspects, wherein the control unit controls the cooling mechanism so that the probe is maintained at a first target temperature of not less than -30°C and not more than -25°C.

[0019] A cryotherapy device according to an eighth aspect of the present disclosure is a cryotherapy device according to any one of the first to seventh aspects, wherein the control unit controls the cooling mechanism so that the time during which the probe is maintained at the first target temperature is equal to or shorter than a first time.

[0020] According to the eighth aspect, the control unit controls the cooling mechanism so that the time during which the probe is maintained at a first target temperature of −30° C. or higher and −25° C. or lower is equal to or shorter than the first time, thereby preventing the skin to be treated from freezing for longer than necessary.

[0021] A cryotherapy apparatus according to a ninth aspect of the present disclosure is the cryotherapy apparatus according to any one of the first aspect to the eighth aspect, wherein the first time period is one minute.

[0022] A cryotherapy device according to a tenth aspect of the present disclosure is a cryotherapy device according to any one of the first to ninth aspects, wherein the control unit controls the cooling mechanism so that the probe is maintained at a second target temperature of -4°C or higher and 0°C or lower.

[0023] A cryotherapy device according to an eleventh aspect of the present disclosure is a cryotherapy device according to any one of the first to tenth aspects, wherein the control unit controls the cooling mechanism so that the time during which the probe is maintained at the second target temperature is equal to or shorter than a second time.

[0024] According to the eleventh aspect, the control unit controls the cooling mechanism so that the time during which the probe is maintained at the second target temperature of −4° C. or higher and 0° C. or lower is equal to or shorter than the second time, thereby preventing the skin to be treated from freezing for an unnecessarily long period of time.

[0025] A cryotherapy apparatus according to a twelfth aspect of the present disclosure is the cryotherapy apparatus according to any one of the first aspect to the eleventh aspect, wherein the second time period is five minutes.

[0026] A cryotherapy apparatus according to a thirteenth aspect of the present disclosure is the cryotherapy apparatus according to any one of the first to twelfth aspects, wherein the probe is made of metal.

[0027] According to the thirteenth aspect, the probe can be cooled efficiently.

[0028] A cryotherapy device according to a fourteenth aspect of the present disclosure is a cryotherapy device according to any one of the first to thirteenth aspects, wherein the head unit is equipped with a temperature sensor that detects the temperature of the probe, and the control unit feedback-controls the temperature of the probe based on an output signal of the temperature sensor.

[0029] According to the fifteenth aspect, the temperature range of the probe is maintained with higher accuracy.

[0030] A cryotherapy device according to a sixteenth aspect of the present disclosure is a cryotherapy device according to any one of the first to fifteenth aspects, wherein the head portion further has an insulating portion that forms a surface surrounding the active surface.

[0031] According to the fifteenth aspect, it is possible to suppress undesirable effects on cells present around tissues that are close to or in contact with the action surface.

[0032] A cryotherapy device according to a sixteenth aspect of the present disclosure is a cryotherapy device according to any one of the first to fifteenth aspects, wherein the cooling mechanism has a cooling element that cools the probe and a chiller that cools the cooling element, and the probe, the cooling element, and the chiller are connected in this order based on the active surface.

[0033] According to the sixteenth aspect, the cooling element connected to the probe is used as part of the cooling mechanism, thereby making it possible to reduce the size of the entire cryotherapy apparatus.

[0034] A cryotherapy device according to a seventeenth aspect of the present disclosure is a cryotherapy device according to any one of the first to sixteenth aspects, wherein the control unit controls the cooling mechanism according to at least two different operating conditions that are pre-combined with a target temperature of the probe and a time period for which the target temperature should be maintained, and further includes a condition designation unit that allows a user to designate one of the at least two different operating conditions.

[0035] According to the seventeenth aspect, the cryotherapy device can be selectively operated under at least two operating conditions, thereby enabling more effective treatment depending on the diseased cells.

[0036] According to the present disclosure, a cryotherapy device is provided that can remove diseased cells including at least nevus cells while suppressing the occurrence of scars and the like.

[0037] 8A , 8B, 8C, 8D, 8E, 8F, 8G, 8H ... 10A and 10B are micrographs showing the experimental results (Example 6 and Example 7) by the inventors. MODE FOR CARRYING OUT THE INVENTION

[0038] Hereinafter, cryotherapy devices according to some embodiments of the present disclosure will be described with reference to the drawings. For the sake of convenience, some components may be omitted from the drawings. Furthermore, the dimensions of the components shown in the drawings may not necessarily correspond to the actual dimensions of the components.

[0039] 1-1. Configuration of a Cryotherapy Device According to a First Embodiment FIG. 1 is a schematic diagram illustrating an exemplary configuration of a cryotherapy device 1 according to a first embodiment. The cryotherapy device 1 is a device for treating lesional cells, including at least nevus cells (including giant nevus cells), while suppressing the occurrence of scars, scar contracture, and inflammation. Its primary intended users are expected to be medical professionals. Lesioned cells that can be treated with the cryotherapy device 1 are not particularly limited as long as they appear on the skin surface and have higher temperature sensitivity than normal cells. These cells include nevus cells, pigment cells (melanocytes), inflammatory cells, and the like. Targeted diseases include acanthosis nigricans, malignant melanoma, senile lentigo, nevus spilus, acquired melanocytosis (ADM), seborrheic keratosis (senile warts), neurofibroma, dermatofibroma, hypertrophic scars, and keloids.

[0040] 1, the cryotherapy device 1 includes a head unit 2, a cooling mechanism 3 connected to the head unit 2, a control unit 4, and a condition specification unit 5. Each unit operates as described below when power is supplied from a power source (not shown). Each unit will be described below.

[0041] [Head Unit] FIG. 2 is a schematic cross-sectional view showing an example of the configuration of the head unit 2, and FIG. 3 is a plan view of the head unit 2 viewed from the operating surface 200 side. The head unit 2 is a portion that a user grasps during treatment and applies to the surface of the skin to be treated. The head unit 2 includes a probe 20, a temperature sensor 21, a heat insulating unit 22, a light 24, and a casing 23. The casing 23 houses at least a portion of the probe 20, the temperature sensor 21, the light 24, and the heat insulating unit 22, as well as at least a portion of the cooling element 30 and heat dissipation member 31 of the cooling mechanism 3 described below. The material of the casing 23 is not particularly limited, but is preferably a material with a lower thermal conductivity than the material of the probe 20, such as a hard resin. The casing 23 may be configured as a gripping unit that a user grasps and operates the probe 20.

[0042] The probe 20 is an integrally formed metal member that forms an active surface 200 for contacting the surface of the skin to be treated. Hereinafter, the active surface 200 side of the probe 20 is defined as the tip side of the probe, and the opposite side of the active surface 200 is defined as the rear end side of the probe 20. The active surface 200 according to this embodiment is a circular, flat surface when viewed from the tip side, but the shape of the active surface 200 is not particularly limited and can be modified as appropriate. When the active surface 200 is circular or square, its diameter or the length of one side is preferably 1 mm or more and 10 mm or less. The active surface 200 may be exposed from the casing 23.

[0043] The probe 20 according to this embodiment has a substantially flat base portion 201 at its rear end. The base portion 201 is connected to the cooling element 30 so that its rear surface faces the first surface 300 of the cooling element 30. The base portion 201 and the cooling element 30 can be connected by, for example, screws, and thermally conductive grease or the like may be interposed between them. From the viewpoint of efficiently cooling the probe 20, it is preferable that the shape and dimensions of the base portion 201 as viewed from the rear end are the same as the shape and dimensions of the first surface 300 of the cooling element 30, and that the rear surface of the base portion 201 and the first surface 300 completely overlap. In this embodiment, since the first surface 300 is substantially rectangular, the base portion 201 as viewed from the rear end is also formed to be substantially rectangular. For this reason, the probe 20 of this embodiment has an external shape that rises continuously from the base 201 in a substantially circular shape, extends toward the tip while decreasing in diameter, and includes a substantially truncated cone diameter that continues to the periphery of the working surface 200. However, the external shape of the probe 20 is not limited to this, and can be changed as appropriate depending on the shapes of the working surface 200 and the cooling element 30, etc.

[0044] The metal constituting the probe 20 is not particularly limited as long as it is not harmful to the human body, and examples thereof include medical metal materials, aluminum, etc. These metals may be surface-treated to the extent that the thermal conductivity of the working surface 200 is not affected.

[0045] The temperature sensor 21 is disposed in a space 202 formed inside the probe 20. In this embodiment, the space 202 extends from a side circumferential surface 203 of the probe 20 into the interior of the probe 20 and is a space closed on one side. Here, the side circumferential surface 203 of the probe 20 is a surface that extends continuously between the periphery of the operating surface 200 and the base 201. In order to minimize the difference between the temperature detected by the temperature sensor 21 and the temperature of the operating surface 200, the space 202 is preferably formed near the operating surface 200. The temperature sensor 21 detects the temperature of the probe 20 and constantly transmits an output signal representing the detected temperature to the control unit 4 (described later). As described later, the control unit 4 performs feedback control of the cooling mechanism 3 based on the transmitted output signal. The output signal may be transmitted wired via a communication line 7 or wirelessly. The temperature sensor 21 is not particularly limited as long as it can detect the temperature of the probe 20, and known devices such as a resistance temperature detector, a thermocouple, a thermistor sensor, a thermostat, etc. can be used.

[0046] The heat insulating portion 22 is disposed in the casing 23 so as to surround the probe 20, and is a portion that forms a surface 220 that surrounds the active surface 200. In this embodiment, the surface 220 is formed so as to be flush with the active surface 200. The heat insulating portion 22 prevents undesirable effects from being exerted on cells present around the tissue that comes into contact with the active surface 200. An example of an undesirable effect is when the active surface 200 unintentionally cools the air surrounding normal cells that are not the target of treatment, thereby inducing apoptosis in the normal cells.

[0047] The material for the heat insulating portion 22 is not particularly limited as long as it has a lower thermal conductivity than the metal constituting the probe 20 and is not harmful to the human body, and any known heat insulating material can be used. In this embodiment, the heat insulating portion 22 is made of polystyrene foam.

[0048] The probe 20 according to this embodiment further includes an illuminator 24. The illuminator 24 is not particularly limited as long as it can illuminate the skin surface facing the active surface 200, and known light sources such as a laser light source and an LED can be used. The illuminator 24 can be arranged to surround the active surface 200, for example, so that light can be applied to the skin surface from between the active surface 200 and the surface 220. This allows the illuminator 24 to assist in accurately bringing the active surface 200 into close proximity with or into contact with the target skin surface. The illuminator 24 and the temperature sensor 21 are appropriately connected to a power source via conductors or the like (not shown).

[0049] [Cooling Mechanism] The cooling mechanism 3 includes a cooling element 30, a heat dissipation member 31, and a chiller 32. As already described, in this embodiment, the cooling element 30 and the heat dissipation member 31 are housed in the casing 23, and therefore the probe 20, the cooling element 30, and the heat dissipation member 31 are connected in this order with respect to the operating surface 200, and are integrated together by the casing 23. The chiller 32 is connected to the heat dissipation member 31 via a first pipe 320 and a second pipe 321. The heat dissipation member 31, the first pipe 320, the second pipe 321, and the chiller 32 form a refrigerant circulation path for removing heat from the cooling element 30. This will be described below.

[0050] The cooling element 30 is an element capable of cooling the probe 20 from the first surface 300 side, and in this embodiment, a Peltier element is used as the cooling element 30. For this reason, a conductor 6 for passing a direct current is connected to the cooling element 30 in this embodiment. A pair of conductors 6 is connected to one cooling element 30, and the opposite ends of the pair of conductors 6 are each connected to the control unit 4. The control unit 4 applies a direct current to the cooling element 30 so that the first surface 300 is the heat absorption side and the second surface 301 is the heat generation side. As will be described later, the control unit 4 controls the behavior of the cooling element 30 by controlling the direct current passed through the cooling element 30 so that the probe 20 is maintained at a predetermined target temperature of 0° C. or less.

[0051] The heat dissipation member 31 is a member for dissipating heat generated on the second surface 301 side of the cooling element 30. The heat dissipation member 31 of this embodiment has a substantially flat plate-like external shape. The heat dissipation member 31 is connected to the cooling element 30 so that one surface of the heat dissipation member 31 faces the second surface 301 of the cooling element 30. The connection between the heat dissipation member 31 and the cooling element 30 can be performed by, for example, screwing, and thermally conductive grease or the like may be interposed between the two. From the viewpoint of efficiently dissipating heat from the cooling element 30, it is preferable that the above surface of the heat dissipation member 31 and the second surface 301 completely overlap each other.

[0052] A flow path 310 through which the refrigerant flows is formed inside the heat dissipation member 31. The flow path 310 is a continuous flow path with one end connected to a first pipe 320 and the other end connected to a second pipe 321. The shape of the flow path 310 is not particularly limited and can be changed as appropriate taking into account cooling efficiency, etc. The flow path 310 of this embodiment is configured so that the refrigerant cooled by the chiller 32 flows in through the first pipe 320, and the refrigerant that has finished flowing through the flow path 310 flows out through the second pipe 321. The heat dissipation member 31 and the refrigerant are not particularly limited as long as they can remove heat from the cooling element 30, and for example, a known water-cooled heat sink and coolant can be used.

[0053] The chiller 32 is a device that circulates a refrigerant through the first pipe 320, the second pipe 321, and the heat dissipation member 31, and a known cooling water circulation device can be used. The chiller 32 includes a water tank 322 in which the refrigerant is stored while circulating, a cooler 323 for cooling the refrigerant in the water tank 322, and a heat exchanger unit 324. The refrigerant in the water tank 322 is sent from the first pipe 320 to the heat dissipation member 31 by a pump (not shown) or the like (see arrow A0 in FIG. 1 ). Meanwhile, the refrigerant that has absorbed heat in the heat dissipation member 31 is returned from the second pipe 321 to the water tank 322 (see arrow A1 in FIG. 1 ). The heat of the returned refrigerant is removed by the cooler 323. As a result, the refrigerant becomes cooled and is sent again from the water tank 322 to the first pipe 320 and the heat dissipation member 31, repeating the circulation. The cooler 323 is not particularly limited, but for example, a known cooling coil or the like in which a chiller-side refrigerant flows inside can be used.

[0054] The heat exchange unit 324 is a device that circulates the chiller-side refrigerant while removing and discharging heat from the chiller-side refrigerant flowing inside the cooler 323. The heat exchange unit 324 is not particularly limited, and a known heat exchange circuit including a compressor that compresses the chiller-side refrigerant to a high temperature, a condenser, a fan, an expansion valve, etc. can be used. As the chiller-side refrigerant circulates through the heat exchange circuit of the heat exchange unit 324, it repeatedly absorbs heat from the refrigerant in the water tank 322 via the cooler 323 and releases heat from itself. The heat exchange unit 324 in this embodiment is air-cooled and is configured to take in and exhaust air using a fan.

[0055] [Control Unit] FIG. 4 is a block diagram showing the electrical configuration of the control unit 4. The control unit 4 can be configured with a general-purpose computer unit such as a microcontroller unit (MCU). The control unit 4 of this embodiment includes a central processing unit (CPU) 40, a random access memory (RAM) 41, an I / O interface 42, a read-only memory (ROM) 43, and a non-volatile rewritable storage device 44. These elements are electrically connected to each other via a bus line and can communicate with each other. A program 430 is written to the ROM 43 via network communication, communication with another computer, or a non-volatile computer-readable medium. This completes the manufacture of the control unit 4 according to this embodiment. Note that the program 430 may be written to the storage device 44 instead of the ROM 43.

[0056] By reading and executing the program 430, the CPU 40 virtually operates as a temperature receiving unit 400, a current adjusting unit 401, a display control unit 402, and a condition reading unit 403. The operation of each unit 400 to 403 will be described later. The RAM 41 is used as needed for calculations by the CPU 40.

[0057] The storage device 44 includes a hard disk, an optical disk, a flash memory, and the like. At least two different operating conditions are stored in the storage device 44. The operating conditions are pre-defined combinations of the target temperature of the probe 20 and the time for which the target temperature should be maintained, in order to provide more appropriate and effective treatment depending on the condition of the tissue to be treated. The time for which the target temperature should be maintained can also be referred to as the time for which the working surface 200 of the probe 20 at the target temperature should be maintained in contact with the skin surface. In this embodiment, a first time for maintaining a first target temperature of -30°C or higher and -25°C or lower is set, and a second time for maintaining a second target temperature of -4°C or higher and 0°C or lower is set. Hereinafter, the combination of the first target temperature and the first time will be referred to as the first operating condition, and the combination of the second target temperature and the second time will be referred to as the second operating condition. According to the inventors' investigations, the first time is preferably 1 minute, and more preferably 15 seconds. Alternatively, the first time period is preferably a predetermined time period of less than 1 minute, and more preferably a predetermined time period of less than 15 seconds. The second time period is preferably a predetermined time period of less than 5 minutes, and more preferably a predetermined time period of less than 60 seconds. Alternatively, the second time period is preferably a predetermined time period of less than 5 minutes, and more preferably a predetermined time period of less than 60 seconds.

[0058] The I / O interface 42 functions as an interface for wired or wireless data input / output with the temperature sensor 21, the condition specification unit 5, the display unit 8, and other computers. The condition specification unit 5 and the display unit 8 are electrically connected to the control unit 4, and in this embodiment, are housed together with the control unit 4 in the same housing to form a control unit. The condition specification unit 5 and the display unit 8 will be described below.

[0059] [Condition Designation Unit] The condition designation unit 5 is a unit operated by the user to select one of the at least two different operating conditions and designate it to the control unit 4. The configuration of the condition designation unit 5 is not particularly limited, and may be configured with a push button, a switch lever, a dial, a keyboard, a touch panel, a voice recognition module, or the like. The operating condition can be designated, for example, by inputting a number or symbol assigned to the selected operating condition via the condition designation unit 5, selecting the number or symbol via the condition designation unit 5, or inputting a voice specifying the operating condition into the condition designation unit 5. Note that the condition designation unit 5 may be configured as a unit operated by the user to input other instructions to the control unit 4 in addition to designating the operating condition.

[0060] [Display Unit] The display unit 8 can be configured with a liquid crystal display, an organic EL display, a plasma display, a liquid crystal element, or the like, and when configured with a touch panel display, it may also serve as the condition specification unit 5. The display unit 8 displays various information to the user of the cryotherapy device 1. The displayed information may be, for example, information on operating conditions specified by the user, timer information that notifies the user in real time of the passage of the first or second time period, or the like. The operation of the display unit 8 is controlled by the display control unit 402 of the control unit 4.

[0061] The control unit may be provided with other components as appropriate, such as a speaker that emits sounds or voices to the user based on instructions from the control unit 4 .

[0062] 5 is a schematic diagram showing an example of the configuration of a cryotherapy device 1A according to the second embodiment. Like the cryotherapy device 1, the cryotherapy device 1A includes a head unit 2A, a cooling mechanism 3A connected to the head unit 2A, a control unit 4A, and a condition designation unit 5A, but the configuration of the head unit 2A differs from that of the cryotherapy device 1. Below, the cryotherapy device 1A will be described, focusing on the configuration that differs from the cryotherapy device 1, and descriptions of the configuration that is common to the cryotherapy device 1 will be omitted as appropriate.

[0063] [Head Unit] FIG. 6A is an external perspective view of the head unit 2A, and FIG. 6B is a cross-sectional schematic diagram showing an example configuration of the head unit 2A. The head unit 2A includes a probe 20A, a temperature sensor 21A, a heat insulating material 22A, and a casing 23A. The casing 23A includes a main body 230A and a cover 231A. Like the casing 23, the casing 23A is made of, for example, a hard resin. The hard resin is preferably an engineering plastic with excellent heat resistance, such as POM (polyoxymethylene). The main body 230A has a tip end 2300A that forms an opening and a rear end 2301A that connects to a sleeve material 26A. The sleeve material 26A will be described later. The main body 230A houses at least a portion of the probe 20A, the temperature sensor 21A, and the heat insulating material 22A, as well as at least a portion of a pair of cooling elements 30A and a pair of cooling jackets 31A, which will be described later. In the main body 230A, a pair of cooling elements 30A are arranged to sandwich the probe 20A, and a pair of cooling jackets 31A are arranged to further sandwich the pair of cooling elements 30A from the outside. The heat insulating material 22A is arranged between the pair of cooling jackets 31A and the main body 230A.

[0064] The cover unit 231A is a member that can be externally attached to the outer surface of the main body unit 230A. The cover unit 231A has a holding groove 2310A that holds the imaging device 25A, which will be described later. By fixing the cover unit 231A to the main body unit 230A with the holding groove 2310A facing the main body unit 230A, the imaging device 25A can be fixed to the head unit 2A and used as an integrated unit.

[0065] Like the probe 20, the probe 20A is a member integrally formed from metal. The probe 20A differs from the probe 20 in that it is formed in a substantially plate-like shape. Specifically, the probe 20A has at least an active surface 200A and a pair of surfaces 201A and 202A that intersect with the active surface 200A. Here, "intersecting" two surfaces means that the normals of the respective surfaces intersect. In this embodiment, the pair of surfaces 201A and 202A are parallel to each other and form the front and back surfaces of the substantially plate-like probe 20A. Note that either of the pair of surfaces 201A and 202A may be the front surface (or the back surface). The pair of surfaces 201A and 202A each face first surfaces 300A of a pair of cooling elements 30A (described later). The first surface 300A is a surface that can absorb heat from the pair of surfaces 201A and 202A. The probe 20A preferably includes a shape that narrows toward the tip. This allows the working surface 200A to be formed to a size suitable for contacting typical nevus cells, while the pair of surfaces 201A and 202A can be formed to a size sufficient for cooling by the cooling element 30A.

[0066] The action surface 200A is a circular, flat surface when viewed from the tip side of the probe 20A, and is perpendicular to the pair of surfaces 201A and 202A. The periphery of the action surface 200A may be separated from the peripheries of the pair of surfaces 201A and 202A. In other words, the action surface 200A may be configured to be continuous with the pair of surfaces 201A and 202A via another surface. The same description as for the action surface 200 applies to the shape and size of the action surface 200A. In this embodiment, the tip of the probe 20A, including the action surface 200A, protrudes outward from the tip 2300A of the main body 230A. A space 203A is formed inside the tip of the probe 20A. A temperature sensor 21A is built into the space 203A. The configuration of the temperature sensor 21A is the same as that of the temperature sensor 21.

[0067] The heat insulating material 22A is a member that prevents heat from being transferred from the pair of cooling jackets 31A to the main body 230A. The heat insulating material 22A may be configured in any manner as long as it inhibits heat exchange between the pair of cooling jackets 31A and the main body 230A. Preferably, the heat insulating material 22A is disposed so as to surround the pair of cooling jackets 31A from the outside. The material constituting the heat insulating material 22A is not particularly limited as long as it has a lower thermal conductivity than the material constituting the cooling jackets 31A and sufficient heat resistance, and may be any of mineral-based, resin-based, and naturally derived materials. Among these, resin-based foams such as rigid urethane foam, phenolic foam, polystyrene foam, and polyester foam are preferred in terms of processability.

[0068] The conductor 6A and the communication line 7A share the same configuration as the conductor 6 and the communication line 7, respectively. The conductor 6A and the communication line 7A according to this embodiment pass through the main body 230A and extend into the sleeve 26A via a through-hole (not shown) formed in the rear end 2301A. The sleeve 26A according to this embodiment accommodates the conductor 6 and the communication line 7, as well as refrigerant tubes 311A ​​and 312A connected to a pair of cooling jackets 31A. The refrigerant tubes 311A ​​and 312A will be described later. The sleeve 26A is not particularly limited, and may be, for example, a hose-shaped member such as a known spiral tube or corrugated tube. Note that, similar to the cryotherapy device 1, if the temperature sensor 21A can transmit an output signal wirelessly, the communication line 7A can be omitted.

[0069] The imaging device 25A is installed for the purpose of acquiring images of lesion cells containing at least nevus cells or their vicinity. The imaging device 25A is not particularly limited as long as it can image the target, but it can be configured, for example, as a general-purpose camera. The imaging device 25A may be connected to a general-purpose display 9A. This allows the user to view the images acquired by the imaging device 25A on the display 9A in real time.

[0070] [Cooling Mechanism] The cooling mechanism 3A has a pair of cooling elements 30A, a pair of cooling jackets 31A, and a chiller 32A, and cools the probe 20A with the pair of cooling elements 30A while dissipating heat from the pair of cooling elements 30A. Like the cooling element 30, each cooling element 30A is a Peltier element having a first surface 300A and a second surface 301A. The control unit 4A applies a direct current to each cooling element 30A so that the first surface 300A of each cooling element 30A is the heat absorption side and the second surface 301A is the heat generation side.

[0071] Each of the pair of cooling jackets 31A has a generally plate-like external shape. Each cooling jacket 31A faces the second surface 301A, sandwiching the cooling element 30A between the surface 201A and the surface 202A of the probe 20A. A flow path 310A is formed inside each cooling jacket 31A, through which a refrigerant capable of absorbing heat from the second surface 301A circulates. In this embodiment, an inlet (not shown) through which the refrigerant flows into the flow path 310A and an outlet (not shown) through which the refrigerant flows out of the flow path 310A are formed on the rear end surface of each cooling jacket 31A. The flow path 310A can be shaped, for example, to extend from the inlet to the tip of the cooling jacket 31A, make a U-turn at the tip, and extend to the outlet. The inlet of each cooling jacket 31A is connected to the first piping 320A via a refrigerant tube 311A ​​that branches into two upstream of the inlet. The outlet of each cooling jacket 31A is connected to a second pipe 321A via a refrigerant tube 312A that branches into two downstream of the inlet. The pair of cooling jackets 31A according to this embodiment are made of aluminum, although this is not limited to this material. The other configurations of each cooling jacket 31A and the refrigerant are the same as those of the heat dissipation member 31 and the refrigerant in the first embodiment.

[0072] The pair of cooling jackets 31A, the refrigerant tubes 311A, the refrigerant tubes 312A, the first pipe 320A, the second pipe 321A, and the chiller 32A form a refrigerant circulation path for removing heat from the pair of cooling elements 30A. The first pipe 320A, the second pipe 321A, and the chiller 32A have the same configuration as the first pipe 320, the second pipe 321, and the chiller 32, respectively.

[0073] [Control Unit, etc.] The control unit 4A and the condition specification unit 5A have the same configuration as the control unit 4 and the condition specification unit 5, respectively. The display unit 8A is electrically connected to the control unit 4A and constitutes a control unit together with the control unit 4 and the condition specification unit 5. The configuration of the control unit can be the same as the control unit according to the first embodiment. The display unit 8A may have the same configuration as the display unit 8, or may be configured to also serve as the display 9A.

[0074] 2. Operation of the Cryotherapy Apparatus> Figure 7 is a flowchart showing an example of the operation flow of the cryotherapy apparatuses 1 and 1A. The operation shown in Figure 7 is performed, for example, when the cryotherapy apparatuses 1 and 1A are powered on and the refrigerant in the refrigerant circulation path is sufficiently cooled. The operation of the cryotherapy apparatus 1 will be described below as an example, but the same description applies to the operation of the cryotherapy apparatus 1A.

[0075] First, the temperature receiving unit 400 sequentially receives the time-series output signals transmitted from the temperature sensor 21 (step S1). The temperature receiving unit 400 converts the received output signals into temperature data as needed, and temporarily stores the data in the RAM 41 or in the storage device 44.

[0076] Next, the control unit 4 receives a specification of the operating conditions from the user (step S2). After selecting either the first operating condition or the second operating condition, the user can operate the condition specification unit 5 to specify the selected operating condition to the control unit 4.

[0077] Next, the condition reading unit 403 reads information about the operating conditions (target temperature and time) from the storage device 44 based on the accepted operating condition designation (step S3). In addition, in step S3, the display control unit 402 may display the designated operating conditions and a message asking the user whether or not the designated operating conditions are acceptable on the display unit 8. In this case, the cryotherapy apparatus 1 may be configured to confirm the operating conditions displayed on the display unit 8 or accept re-designation of the operating conditions by having the user operate the condition designation unit 5.

[0078] Once the operating conditions are determined in step S3, the current adjusting unit 401 and the temperature receiving unit 400 start feedback control of the DC current flowing through the cooling element 30 (step S4). Specifically, based on the latest output data of the temperature sensor 21 received by the temperature receiving unit 400, the current adjusting unit 401 adjusts the magnitude of the DC current flowing through the cooling element 30 so that the probe 20 is maintained at the target temperature determined by the currently specified operating conditions.

[0079] When the temperature control accuracy by the feedback control in step S4 is stabilized within a certain range, the next step S5 is executed. In step S5, the display control unit 402 causes the display unit 8 to display a message prompting the user to issue a start instruction.

[0080] After checking the message, the user operates the condition specification unit 5 to instruct the control unit 4 to start treatment. At the same time, the user grips the head unit 2, for example, to bring the action surface 200 into contact with or close to the surface of the skin to be treated. This causes the control unit 4 to accept the instruction to start treatment and start counting the time determined by the currently specified operating conditions (step S6).

[0081] Step S7 is executed when the time defined by the currently specified operating conditions has elapsed. In step S7, the current adjusting unit 401 ends the feedback control started in step S4 and stops the flow of DC current to the cooling element 30. The display control unit 402 also causes the display unit 8 to display a message notifying that the time defined by the operating conditions has elapsed. Additionally or alternatively, the control unit 4 may be configured to emit a sound or voice via a speaker (not shown) to notify that the time has elapsed.

[0082] 3. Features Based on the inventors' findings, the cryotherapy devices 1 and 1A according to the above embodiments are configured to freeze skin cells using probes 20 and 20A maintained at a target temperature of -30°C or higher and 0°C or lower, thereby selectively inducing apoptosis in nevus cells. Thus, the cryotherapy devices 1 and 1A are based on a mechanism that is different from that of surgical excision, laser cauterization, excision using an electric scalpel, and cryotherapy using low-temperature liquefied gas, which induce necrosis in both nevus cells and normal cells. The cryotherapy device 1 suppresses damage to normal cells, making scarring, scar contracture, and inflammation less likely to occur even after removal of nevus cells, allowing for treatment that is more cosmetically friendly.

[0083] In the cryotherapy devices 1 and 1A according to the above embodiments, the metal probes 20 and 20A are cooled by Peltier elements. This allows the heads 2 and 2A to be made smaller, improving user operability. Additionally, the temperature of the probes 20 and 20A can be controlled with relatively high precision. Furthermore, there is no need to prepare high-voltage voltage or high-pressure gas, reducing the burden on facility management.

[0084] In the cryotherapy devices 1 and 1A according to the above embodiments, at least two operating conditions are defined in advance, each of which is a combination of the target temperature of the probes 20 and 20A and the time for which the target temperature is to be maintained, thereby enabling appropriate treatment to be provided depending on the condition of the lesion cells.

[0085] Furthermore, in the cryotherapy devices 1 and 1A according to the above embodiments, the control units 4 and 4A execute the above control based on the operating conditions specified by the user, thereby preventing the user from mistaking the appropriate maintenance time for the target temperature of the probes 20 and 20A, which could result in inappropriate treatment being performed.

[0086] In the cryotherapy device 1 according to the above embodiment, the surface 220 of the heat insulating part 22 surrounds the working surface 200. This more reliably protects normal cells present around the tissue that comes into contact with the working surface 200. Furthermore, since the surface 220 is configured to be flush with the working surface 200, providing the heat insulating part 22 does not interfere with the operation of bringing the working surface 200 into contact with the skin.

[0087] In the cryotherapy apparatus 1A according to the above embodiment, the probe 20A is configured such that a pair of surfaces 201A and 202A intersecting the active surface 200A are cooled by a pair of cooling elements 30A, rather than a surface parallel to the active surface 200A being cooled by a cooling element. This reduces constraints on the formation of the active surface 200A, making it easier to reduce its area, while allowing a relatively large surface of the probe 20A to face the heat-absorbing surface of the cooling element 30A. This allows the probe 20A to be cooled via two relatively large surfaces, thereby further improving cooling efficiency.

[0088] In the cryotherapy apparatus 1A according to the above embodiment, the pair of cooling elements 30A are sandwiched between a pair of generally plate-shaped cooling jackets 31A, with the probe 20A at the center. This further improves the cooling efficiency of the pair of cooling elements 30A. In addition, in the head unit 2A, the probe 20A, the pair of cooling elements 30A, and the pair of cooling jackets 31A, each of which has a generally plate-shaped external shape, are stacked. This allows the overall size of the head unit 2A to be relatively compact.

[0089] In the cryotherapy apparatus 1A according to the above embodiment, the imaging device 25A can be used to check the condition of the skin to be treated on the display 9A, as needed, thereby improving the operability of the head unit 2A.

[0090] 4. Modifications Although one embodiment of the present disclosure has been described above, the present disclosure is not limited to the above embodiment, and various modifications are possible without departing from the spirit of the present disclosure. For example, the following modifications are possible. Furthermore, the gist of the following modifications can be combined as appropriate.

[0091] (1) In the above embodiment, the target temperatures of the operating conditions stored in the storage device 44 include a first target temperature of −30°C or higher and −25°C or lower, and a second target temperature of −4°C or higher and 0°C or lower. However, the target temperature range is not limited to this and can be changed as appropriate. Even if the target temperatures of the probes 20 and 20A are predetermined temperatures of −25°C or higher and −4°C or lower, the effect of selectively inducing apoptosis of lesion cells, including nevus cells, can be achieved, similar to the first and second target temperatures. In other words, the target temperature of the probe 20 can be any target temperature of −30°C or higher and 0°C or lower. The time for which the target temperature is to be maintained can be appropriately determined depending on the target temperature. In other words, the number of operating conditions pre-stored in the storage device 44 may be three or more, and operating conditions may exist for the same target temperature but with different maintenance times. The cryotherapy devices 1 and 1A may be configured so that the user does not specify the above-mentioned operating conditions, but instead specifies at least one of an appropriate target temperature and a maintenance time for that temperature to the controllers 4 and 4A.

[0092] (2) At least one of the temperature sensor 21 and the heat insulating unit 22 may be omitted. Similarly, the lighting 24 is not essential and may be omitted, or its location and number may be changed. Furthermore, the surface 220 of the heat insulating unit 22 may not be flush with the action surface 200. For example, the surface 220 of the heat insulating unit 22 may protrude toward the skin surface beyond the action surface 200, so that when the surface 220 is brought into contact with the skin surface, the action surface 200 is close to the skin surface at a certain distance from the skin surface. Furthermore, at least one of the condition specifying unit 5, the display unit 8, and the storage device 44 may be omitted or configured separately from the housing accommodating the control unit 4. This also applies to the condition specifying unit 5A, the display unit 8A, and the control unit 4A. Furthermore, the casing 23, like the casing 23A, may have a member capable of fixing the imaging device 25A.

[0093] (3) The cooling mechanism 3 may have two or more Peltier elements as the cooling elements 30. In addition to Peltier elements, the cooling elements 30 and 30A may be, for example, heat exchange elements that generate thermionic emission cooling when a current is passed through them.

[0094] (4) The configuration of the cooling mechanisms 3 and 3A is not limited to the configuration in the above embodiment, and may be modified as appropriate, as long as it is capable of controlling the temperatures of the probes 20 and 20A. For example, at least one of the cooling elements 30 and 30A, the heat dissipation member 31, the cooling jacket 31A, and the chillers 32 and 32A may be omitted or replaced with another configuration. For example, the probes 20 and 20A may be cooled by low-temperature liquefied gas or the like. The chillers 32 and 32A may be water-cooled. The cooling jacket 31A may be configured as a single cooling jacket 31A that cools the pair of cooling elements 30A together, rather than as a pair of cooling jackets 31A.

[0095] (5) The probe 20 and the working surface 200, as well as the probe 20A and the working surface 200A, may be made of a material other than metal. The probe 20 itself may also be made of a cooling element. Furthermore, the working surface 200 and the working surface 200A are not limited to being in direct contact with the surface of the skin to be treated, but may be configured to be in close proximity to the surface of the skin or indirectly contact the surface via another substance.

[0096] (6) At least one of the temperature sensor 21A, the heat insulating material 22A, the cover 231A, and the imaging device 25A may be omitted. Furthermore, the imaging device 25A is not limited to a camera and may be, for example, an imaging device such as an ultrasonic echo device.

[0097] (7) The configuration of the probe 20A is not limited to that of the above embodiment. For example, the shape of the working surface 200A and its surroundings of the probe 20A can be modified as shown in FIGS. 8A to 8D. FIG. 8A shows an example in which a substantially cylindrical columnar portion 204A is formed at the tip of the probe 20A shown in FIG. 6A. In this example, the circular flat surface at the tip of the columnar portion 204A constitutes the working surface 200A that is perpendicular to the pair of surfaces 201A and 202A. FIG. 8B shows an example in which a substantially truncated columnar portion 205A is formed at the tip of the probe 20A shown in FIG. 6A. In this example, the surface at the tip of the columnar portion 205A constitutes the working surface 200A. The working surface 200A is inclined with respect to the central axis of the columnar portion 205A. The configuration examples of FIGS. 8A and 8B make it easier to bring the working surface 200A into proximity with or into contact with skin tissue. FIG. 8C shows an example in which the tip surface of the cylindrical portion 204A in FIG. 8A is a part of a sphere. In this example, the surface excluding a portion of the periphery of the sphere (the boundary between the part of the sphere and the cylindrical portion) constitutes the action surface 200A. The configuration example of FIG. 8C not only makes it easier to bring the action surface 200A closer to or into contact with skin tissue, but also further reduces the risk of the action surface 200A physically damaging the skin tissue. FIG. 8D shows an example in which an extension portion 206A is formed from the tip surface of the cylindrical portion 204A in FIG. 8A, extending at an angle relative to the central axis of the cylindrical portion 204A and forming a flat surface at its tip. The flat surface of the extension portion 206A constitutes the action surface 200A. The extension portion 206A may be configured in any manner as long as its projected shape, as viewed from the central axis direction of the cylindrical portion 204A, is different from the projected shape of the cylindrical portion 204A and the active surface 200A intersects with the pair of surfaces 201A and 202A. The configuration example shown in Figure 8D provides greater design freedom for the active surface 200A and reduces the likelihood of the probe 20A obstructing the field of view when the probe 20A approaches or contacts the skin surface. In the configuration examples shown in Figures 8A to 8D, the cylindrical portion 204A or 205A may be modified to have a substantially rectangular columnar shape, a substantially oblique columnar shape, a substantially oblique columnar shape, a substantially truncated conical shape, a substantially truncated pyramidal shape, or the like. Furthermore, the probe 20A may be configured as an integrated unit or may be composed of two or more members.

[0098] The following describes experiments conducted by the inventors and the results thereof, but the present disclosure is not limited thereto.

[0099] <Experiment> Multiple skin tissue samples were collected and placed on a hot plate heated to approximately 35°C. The state of cells in the skin tissue was observed in two cases: when no treatment was performed on the skin tissue (Comparative Example) and when the working surface of a metal probe was directly contacted with the surface of the skin tissue and the cooling treatment of the above-described embodiment was performed (Example). Specifically, after the cooling treatment of the skin tissue according to the Example, both the skin tissue according to the Example and the Comparative Example were cultured for 12 hours and then fixed using formalin. The fixed skin tissue was stained with DAPI, a fluorescent dye that binds to DNA, and the cells contained in the skin tissue were identified by observing the fluorescent dye under a fluorescence microscope (1). Furthermore, the skin tissue was stained with MART-1, which is used to immunostain melanoma and nevus cells, and the nevus cells contained in the skin tissue were identified under a fluorescence microscope (2). However, in Example 3, the skin tissue was stained with α-SMA, which selectively stains vascular smooth muscle, and cells constituting blood vessels, rather than nevus cells, were identified (2'). Furthermore, skin tissue was stained using a marker that binds to DNA fragmented by apoptosis according to the TUNEL method, and the occurrence of apoptosis in cells in the skin tissue was confirmed using a fluorescence microscope (3). In the following figures, (1) to (3) are micrographs of each marker taken with a fluorescence microscope, and (4) is a superposition of (1) to (3). Note that (1) to (4) are photographs of cross sections of skin tissue, with the epidermis at the top.

[0100] The cooling treatment was performed under the following seven conditions. Figure 9A is a side view of the probe used in Examples 1 to 6. As shown in Figure 9A, the probe had a circular working surface with a diameter of 5 mm and a side peripheral surface that expanded from the periphery of the working surface. The side peripheral surface was formed to have a rounded surface with a radius of 20 mm in side view. Experiments by the inventors confirmed that there was no significant difference in the temperature change of the dermis over time between a probe with a generally truncated cone shape whose side peripheral surface was linear in side view, as shown in Figure 9B, and the probe shown in Figure 9A. In Example 7, a probe (head portion) such as that shown in Figures 6A and 6B was used. The probe had a circular working surface with a diameter of 5 mm. The probe temperature was detected by a temperature sensor installed within the probe and was consistent with the temperature of the working surface. The temperature sensor used was either a Pt100 platinum resistance thermometer, a K thermocouple, or a T thermocouple. In the probe shown in Figure 9A, the temperature sensor was positioned at a distance of 7 mm from the active surface. Example 1: Probe temperature -25°C, contact time with skin tissue 15 seconds Example 2: Hair follicles present in skin tissue Probe temperature -25°C, contact time with skin tissue 15 seconds Example 3: Blood vessels present in skin tissue Probe temperature -25°C, contact time with skin tissue 15 seconds Example 4: Probe temperature -4°C to -2°C, contact time with skin tissue 60 seconds Example 5: Hair follicles present in skin tissue Probe temperature -4°C to -2°C, contact time with skin tissue 60 seconds Example 6: Skin appendages (sebaceous glands) present in skin tissue Probe temperature -4°C to -2°C, contact time with skin tissue 60 seconds Example 7: Probe temperature -25°C, contact time with skin tissue 10 seconds

[0101] <Results> Micrographs of the skin tissues of Examples 1 to 7 and the Comparative Example are shown in Figures 10 to 16. Comparing (3) between the Comparative Example and Example 1 in Figure 10, the fluorescence of the marker was barely detectable in the Comparative Example, whereas the fluorescence of the marker was detected over a wide area in Example 1. The area in which fluorescence was detected roughly overlaps with the area where nevus cells are present, as shown in (2). These results confirmed that the cooling treatment according to the above embodiment induces apoptosis in nevus cells.

[0102] The dashed-lined areas in (1) to (4) of Figure 11 indicate hair follicles present in skin tissue. As can be seen from Figure 11, most of the cells in the hair follicles were preserved without undergoing apoptosis. These results confirmed that the cooling treatment according to the above embodiment induces apoptosis in nevus cells while significantly suppressing damage to normal hair follicle keratinocytes. This confirms that the cooling treatment according to the above embodiment can selectively induce apoptosis in nevus cells without affecting hair follicles.

[0103] In Figure 12 (1) to (4), the lower photographs are enlarged versions of the rectangular framed areas in the upper photographs. The white dotted lines in the lower photographs (1) to (4) indicate the cells constituting the blood vessels. As can be seen from Figure 12, most of the cells constituting the blood vessels were preserved without undergoing apoptosis. This result confirmed that the cooling treatment according to the above embodiment has almost no effect on blood vessels. This confirms that the cooling treatment according to the above embodiment can selectively induce apoptosis in nevus cells without affecting blood vessels.

[0104] Figure 13 confirms that apoptosis was induced in the area where nevus cells were present. These results confirm that apoptosis of nevus cells can be induced by adjusting the contact time, even when the probe temperature is relatively high, at -4°C to -2°C.

[0105] Figure 14 (1) to (4) are photographs of skin tissue near hair follicles. As can be seen from Figure 14, most of the cells in the hair follicles were preserved without undergoing apoptosis. These results confirmed that even when the probe temperature was relatively high, between -4°C and -2°C, apoptosis was selectively induced in nevus cells, while damage to normal hair follicle keratinocytes was significantly suppressed.

[0106] The white dotted-line areas in (1) to (4) of Figure 15 indicate sebaceous glands present in skin tissue. As can be seen from Figure 15, most of the constituent cells of the sebaceous glands were preserved without undergoing apoptosis. These results confirmed that the cooling treatment according to the above embodiment selectively induced apoptosis in nevus cells while significantly suppressing damage to normal skin appendage cells.

[0107] In Figure 16, it was confirmed that apoptosis was induced in the area where the presence of nevus cells was confirmed. In particular, a large amount of fluorescence was confirmed in the lower area of ​​image (3), which confirmed that apoptosis was induced even in deep nevus cells.

[0108] Furthermore, the results of Examples 1 to 7 showed that apoptosis can be induced in keratinocytes (epidermal keratinocytes) to a certain extent, but it was confirmed that such damage to normal cells is limited to the epidermal level, and the possibility of scarring or the like is sufficiently low.

[0109] 1, 1A Cryotherapy device 2, 2A Head unit 3, 3A Cooling mechanism 4, 4A Control unit 5, 5A Condition designation unit 20, 20A Probe 21, 21A Temperature sensor 22 Heat insulation unit 22A Heat insulation member 30, 30A Cooling element 31 Heat dissipation member 31A Cooling jacket 220 Surface

Claims

1. A cryotherapy device comprising: a head unit having a probe that forms an active surface for bringing the probe into close proximity with or into contact with the surface of the skin to be treated; a cooling mechanism that cools the probe; and a control unit that controls the cooling mechanism so that the probe is maintained at a target temperature of 0°C or below, wherein the probe is configured to freeze skin tissue via the active surface, thereby selectively inducing apoptosis of diseased cells, including at least nevus cells.

2. The cryotherapy device according to claim 1, wherein the probe further forms a pair of surfaces intersecting the active surface, the cooling mechanism has a pair of cooling elements capable of cooling the probe, and each of the pair of cooling elements forms a first surface capable of absorbing heat from the pair of surfaces.

3. The cryotherapy device according to claim 2, wherein the pair of cooling elements each further forms a second surface capable of releasing heat absorbed from the first surface, and the cooling mechanism further has a cooling jacket through which a refrigerant capable of absorbing heat from the second surface circulates.

4. The cryotherapy device of claim 3, wherein the head portion further comprises: a casing that houses at least a portion of each of the probe, the pair of cooling elements, and the cooling jacket; and an insulating material disposed between the casing and the cooling jacket.

5. The cryotherapy device according to claim 1, wherein the head portion further comprises an imaging device for acquiring an image of lesion cells including at least the nevus cells or their vicinity.

6. The cryotherapy device according to any one of claims 1 to 5, wherein the control unit controls the cooling mechanism so that the probe is maintained at a target temperature of -30°C or higher.

7. The cryotherapy device according to claim 1 or 2, wherein the control unit controls the cooling mechanism so that the probe is maintained at a first target temperature of -30°C or higher and -25°C or lower.

8. The cryotherapy device according to claim 7, wherein the control unit controls the cooling mechanism so that the time during which the probe is maintained at the first target temperature is equal to or shorter than a first time.

9. The cryotherapy device according to claim 1 or 2, wherein the control unit controls the cooling mechanism so that the probe is maintained at a second target temperature of -4°C or higher and 0°C or lower.

10. The cryotherapy device according to claim 9, wherein the control unit controls the cooling mechanism so that the time during which the probe is maintained at the second target temperature is equal to or shorter than a second time.

11. A cryotherapy device as described in any one of claims 1 to 5, wherein the head unit is provided with a temperature sensor that detects the temperature of the probe, and the control unit feedback-controls the temperature of the probe based on an output signal of the temperature sensor.

12. The cryotherapy device of claim 1, wherein the cooling mechanism has a cooling element that cools the probe and a chiller that cools the cooling element, and the probe, the cooling element and the chiller are connected in this order with respect to the working surface.

13. A cryotherapy device as described in any one of claims 1 to 5, wherein the control unit controls the cooling mechanism according to at least two different operating conditions that are pre-combined with a target temperature of the probe and a time for which the target temperature should be maintained, and further comprises a condition designation unit for allowing a user to designate one of the at least two different operating conditions.

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