JP2016514004A - Apparatus and method for tissue reactivation - Google Patents

Abstract

A method and apparatus for applying carboxy therapy to a subject is disclosed. The method comprises contacting a treatment device comprising a plurality of hollow needles mounted on a contact surface of a housing and a CO2 source in fluid communication with at least one of the plurality of hollow needles on a target body surface of the subject, Applying pressure to the housing such that one or more of the hollow needles penetrates the epidermis or outermost cells of the target body surface, supplying a therapeutic amount of CO2 to the subject through the plurality of hollow needles, and the target body surface Removing a plurality of hollow needles from. Further disclosed are methods of applying carboxy therapy to ameliorate skin diseases.

Description

  The present application relates generally to subject tissue repair. In particular, the present invention relates to an apparatus and method for local administration of carbon dioxide.

Carboxy therapy, also called carbon dioxide (CO ₂ ) therapy or CDT, is a safe and effective therapy that can improve the appearance of treated skin. Outside the United States, carboxy therapy is known for its use in reducing skin irregularities, in reducing wrinkles, and as a complementary treatment to other forms of cosmetic and therapeutic treatments such as liposuction. Yes.

  Carboxy therapy has been studied in a research environment for several medical conditions, but the exact mechanism of action of carboxy therapy is not fully understood. Therefore, drug and device based innovation has been the main path to skin treatment. However, as patients and physicians are beginning to avoid treatment with purely medical means, carboxy therapy offers a more “natural” alternative.

As currently applied, carboxy therapy is a non-surgical method but requires treatment by a physician. CO ₂ is inserted through a very small needle, eg, a 30G needle, into the subcutaneous tissue using the needle. From the injection location, CO ₂ diffuses into nearby tissue. Carboxy therapy uses a harmless amount of inert CO ₂ gas, but the use of a needle as an application modality requires the physician to perform the procedure.

  Currently, application methods require a physician to insert a single needle into a patient undergoing treatment. Such individual insertions are safe and effective for small treatment areas such as the patient's eye and lip areas. However, for large area treatments, individual treatments are too rigorous and time consuming. Therefore, the benefits of carboxy therapy in the treatment of various skin diseases are not fully obtained for patients.

One aspect of the present invention is a step of contacting a target body surface of a target with a treatment device including a plurality of hollow needles attached to a contact surface of a housing and a CO ₂ source in fluid communication with at least one of the plurality of hollow needles. Applying pressure to the housing such that one or more of the plurality of hollow needles penetrates the epidermis or outermost cells of the target body surface, supplying a therapeutic amount of CO ₂ to the subject through the plurality of hollow needles; and Removing a plurality of hollow needles from a target body surface, to a method of applying carboxy therapy to a subject in need of such treatment.

Another aspect of the present invention comprises introducing the CO ₂ in an effective amount within the subcutaneous tissue of the target area for a sufficient period of time, by puncturing the skin of the target area of CO ₂ at a desired speed in the subcutaneous tissue The present invention relates to a method of treating hair loss in a target area of interest, wherein an effective amount of CO ₂ is introduced into the target area with a plurality of hollow needles that release.

Another aspect of the present invention comprises introducing the CO ₂ in an effective amount within the subcutaneous tissue of the target area for a sufficient period of time, by puncturing the skin of the target area of CO ₂ at a desired speed in the subcutaneous tissue The present invention relates to a method of treating a skin disease in a target area of interest, wherein an effective amount of CO ₂ is introduced into the target area with a plurality of hollow needles that release.

Another aspect of the present invention comprises introducing the CO ₂ in an effective amount within the subcutaneous tissue of the target area for a sufficient period of time, by puncturing the skin of the target area of CO ₂ at a desired speed in the subcutaneous tissue The present invention relates to a method of promoting wound healing of a target area of interest, wherein an effective amount of CO ₂ is introduced into the target area with a plurality of releasing hollow needles.

  Yet another aspect of the invention relates to a disposable skin treatment device comprising a plurality of hollow needles mounted on the surface of a substrate, wherein the hollow needles have a diameter in the range of 0.1-0.5 mm and 0.4. A length in the range of ˜2.5 mm, and the base body is attachable to a hand-held device so as to form fluid communication between at least one of the plurality of hollow needles, and the plurality of hollow needles At least one of them has a sharp edge that can penetrate the human epidermis by hand pressure.

  The invention can be better understood with reference to the following drawings. The drawings are only illustrative of certain features that may be used alone or in combination with other features, and the invention should not be limited to the illustrated embodiments.

FIG. 1 shows the external contact surface of an exemplary application device. FIG. 2 shows the inside of the contact surface of FIG. FIG. 3 shows the valve of the exemplary application device of FIG. FIG. 4 shows the handle and control of the exemplary application device of FIG. FIG. 5 is a side view of the exemplary application device of FIG. 1, showing a CO ₂ supply tube. FIG. 6 shows another exemplary embodiment of an application device having a microneedle mounted thereon. FIG. 7 shows the penetration of the skin by the microneedle of the device. FIG. 8 shows an exemplary configuration of microneedles in the substrate element. FIG. 9 shows another exemplary configuration of microneedles in the substrate element.

  The following detailed description is presented to enable any person skilled in the art to make and use the invention. For purposes of explanation, specific terms are set forth in order to provide a thorough understanding of the present invention. However, it will be apparent to one skilled in the art that these specific details are not required in the practice of the invention. Descriptions of specific applications are provided merely as representative examples. The present invention is not intended to be limited to the embodiments shown, but is to the greatest extent possible consistent with the principles and features disclosed herein.

This description is intended to be read in connection with the accompanying drawings, which are considered a part of the entire description set forth in this application. The drawings are not necessarily to scale, certain features of the present application may be shown in exaggerated dimensions, or may be shown in some outline for clarity and brevity. is there. In the description and claims, the singular forms “a”, “an”, and “the” refer to the plural unless the context clearly dictates otherwise. including. The present invention provides an improved method and apparatus for applying carboxy therapy to a patient area. The apparatus includes a treatment device capable of mounting microneedle / substrate elements, wherein a plurality of microneedles are in fluid communication with a CO ₂ source. As explained below, for supplying CO _2, the device is placed on the skin or scalp surface of the patient.

  As used herein, “applying to skin in need of such treatment” refers to an area of skin in need of such treatment (eg, by using a hand or application device). Means contact. These features include the eyes, nose, forehead, cheeks, chin, and face, such as under or near the neck, as well as the arms, chest, back, shoulders, belly (eg, skin streak), and feet (eg, subcutaneous). May be present in other areas of the body, such as (fat).

  The term “treatment” or “treatment” of a skin abnormality refers to the treatment of a skin abnormality (eg, complete or partial reduction or elimination and / or treatment of symptoms) and / or prevention or Means suppression.

  As used herein, the term “skin abnormality” or “skin disorder” means a skin condition, abnormality or defect.

Microneedle As used herein, the terms “needle” and “microneedle” are piercing elements suitable for passing gas therethrough according to the method of carboxy therapy and also for piercing the skin of a patient or subject. Represents. These terms can be used interchangeably unless the context clearly indicates otherwise.

The execution of skin perforation breaks through the stratum corneum. By perforating only the stratum corneum and / or other layers of the epidermis, patients typically do not feel pain, suffer trauma (eg, bleeding and swelling), and / or other discomfort. I don't feel. Carboxy therapy transfers CO ₂ gas through the breached skin and has a therapeutic effect. The diameter of the microneedles used for both piercing the patient's skin and applying the carboxy therapy of the present invention is a gauge suitable for flowing gas through it, while at the same time, It must be suitable for the type and thickness of the perforation, but it should not be so large that it makes the patient uncomfortable when the needle penetrates the skin.

  The term “plurality of microneedles” refers to a collection of microneedles arranged for use in the devices and methods herein. Such a plurality of microneedles must be secured to the substrate material so that it can be reliably inserted into the patient's skin and so that other forms of treatment can be applied. Exemplary suitable materials used as microneedles herein are, for example, stainless steel, gold, iron, steel, tin, zinc, copper, platinum, aluminum, germanium, zirconium, titanium, and molybdenum and chromium. Including one or more metals and metal alloys such as metals or non-metals plated with titanium alloys, gold, rhodium, iridium, titanium, platinum, silver, silver halide, and alloys of these or other metals obtain.

Considered individually, the microneedles used in the present invention may have a substantially straight or substantially tapered axis. The diameter of the microneedle may be greater at the substrate end of the microneedle and taper towards the end point distal to the substrate. The microneedles may be circular or semi-circular, or any other suitable cross-sectional shape. For example, the cross-section of the microneedle may be polygonal (eg, star, square, triangle, rectangle), oval, or other shape. However, whatever shape or length is used in the present invention, the microneedles must be suitable to provide a carboxytherapy treatment to patients in need of such treatment. Thus, as described further herein, the microneedle is in fluid communication with the CO ₂ source when the microneedle / substrate element configuration is secured to the treatment device.

  When secured to the substrate material, the microneedles may be substantially orthogonal thereto or oriented at some angle relative thereto. Further, the microneedles may be oriented so as to be substantially orthogonal to the substrate material. In some embodiments, the microneedle configuration may comprise configurations with various microneedle orientations, heights, or other parameters.

  In general, the microneedles must have mechanical strength to withstand distortion (such as bending) during one or more insertions into the skin and removal.

The microneedles can be medical grade steel such as acupuncture type needles and can be about 0.1 to about 0.5 mm in diameter. Each microneedle can be about 0.4 to about 2.1 mm in length. In one aspect of the invention, each microneedle is from about 0.5 mm and 1.1 mm. Further, the length of each microneedle can be from about 0.1, 0.3, 0.5, 0.7, 1.0, 1.5, 2.0 or 2.5 mm in length, these Any of these lengths can be used individually or in combination in anchoring to a substrate material and are in fluid communication with a CO ₂ source as described elsewhere herein.

  As explained, the microneedles must be secured to the substrate material. In one aspect, the microneedles and the substrate material to which they are attached comprise a single, disposable, single use unit, also referred to as a “consumable”. The use of a consumable configuration that is secured to a reusable treatment device can facilitate sterilization procedures and customized procedures for each patient.

  To provide a microneedle / substrate element, the substrate material to which the microneedles are to be fixedly attached is rigid enough to assist in directing the attached microneedles through the patient's skin Materials may be included. In this regard, the microneedle and substrate material can be configured as a single unit, for example, by stamping stainless steel using a precision method of forming needle-like protrusions from a flat or substantially flat substrate material. . The use of metallic materials can facilitate the application of electrical stimulation and / or thermal therapy to a patient in conjunction with carboxy therapy treatment, as described elsewhere herein. In this regard, the microneedle and the base material include the same material.

  Further, the substrate material may include a flexible material that allows the substrate material to generally conform to the contour of the skin and adapt to deformations that may occur when the microneedles are inserted. In this regard, the microneedles can be secured to the substrate material, such as by embedding them in a polymeric material, and then applying an appropriate adhesive to ensure attachment. A flexible surface can facilitate more stable penetration during use, as penetration can be limited by distortion of the mounting surface.

The CO ₂ injection depth may vary depending on the procedure, for example, the procedure may be from about 2 to about 20 mm. The length of the microneedles will be substantially equal to the implantation depth.

Skin Treatment Device One aspect of the present application relates to a skin treatment device that can effectively deliver treatment fluid into the skin and / or subcutaneous tissue of a subject body region. An advantage of the skin treatment device of the present application is that multiple injections of treatment fluid below the skin surface can be accomplished simultaneously by the physician at a controlled flow rate. In some embodiments, the treatment fluid is a gas or a mixture of gases. In other embodiments, the fluid is a liquid. In other embodiments, the fluid is a vaporized liquid. In certain embodiments, the fluid is CO ₂ gas.

  In one embodiment, the skin treatment device of the present application includes a housing having a contact surface. The contact surface comprises a plurality of hypodermic needles that penetrate the skin and deliver the treatment fluid into or under the skin layer. A plurality of needles on the contact surface are in fluid communication with the treatment fluid source to allow delivery of treatment fluid into or through the skin from the treatment fluid source. In some embodiments, the plurality of needles protrude from the contact surface from about 0.1 mm to about 10.0 mm. In some further embodiments, the plurality of needles protrude from the contact surface from about 0.15 mm to about 4.0 mm. In a further embodiment, the plurality of needles protrude from the contact surface from about 0.3 mm to about 3.0 mm. In another further embodiment, the plurality of needles protrude from the contact surface from about 0.3 mm to about 2.0 mm. In some embodiments, the needle has a length of 0.1 mm, 0.15 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.0 mm, 1.5 mm, 2.0 mm, 2.5 mm, 3.0 mm, 3.5 mm, 4.0 mm, 4.5 mm, 5.0 mm, 6.0 mm, 7.0 mm, 8. 0 mm, 9.0 mm or 10.0 mm or close to these. The length of the needle can control the depth level at which the treatment fluid will be delivered, and consequently the exact position.

  In some embodiments, the needles on the contact surface of the device are all the same length. In other embodiments, the needles on the contact surface of the device are mixed in different lengths so that they protrude to different depths into or through the body tissue. The needle can be made from stainless steel and the breaking strength of the needle is hundreds of times greater than the insertion force of the skin.

  In order to minimize patient discomfort while using the skin treatment device, the needle gauge should be small enough to minimize patient pain and scarring. In some embodiments, the size of the needle is sufficient to overcome the natural resistance when piercing the stratum corneum. In some embodiments, the needle is between about 26 gauge and about 36 gauge. In some further embodiments, the needle is between about 27 gauge and about 34 gauge. In other further embodiments, the needle is between about 28 gauge to about 33 gauge. In yet another further embodiment, the needle is between about 29 gauge to about 32 gauge. In yet another further embodiment, the needle is between about 30 gauge to about 32 gauge. In some embodiments, the needle is in some other embodiments selected from 26, 26s, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 gauges. It is a micro needle. In some embodiments, the needles on the contact surface of the device are all the same gauge. In other embodiments, the needles on the contact surface of the device are mixed with different gauges to deliver different volumes of treatment fluid to different regions of body tissue.

Needle size and spacing may vary depending on the needs of the treatment plan. In some embodiments, the needles are spaced from each other by about 2, 3, 4, 5, 6, 7, 8, 9, 10 mm. The distance between any two needles may be constant or indefinite. In other embodiments, the needles are arranged at an average density of 1, ^2, 3, 4, 5, 6, 7, 8, 9 or 10 needles per cm ^{2 of} contact surface. As used herein, the average needle density of the contact surface is defined as the total number of needles divided by the total surface area of the contact surface.

In some embodiments, the contact surface has a total area of about 10～500Cm ^2, about 20～400Cm ² or about 40~200cm ^2. In other embodiments, the contact surface is about 20 cm ² , about 40 cm ² , about 60 cm ² , about 80 cm ² , about 100 cm ² , about 150 cm ² , about 200 cm ² , about 250 cm ² , about 300 cm ² , about 350 cm ² , It has a total area of about 400 cm ² , about 450 cm ² or about 500 cm ² . In some embodiments, the contact surface of the skin treatment device is removable from the housing, and various sizes and shapes of contact surfaces can be attached to the skin treatment device, depending on the treatment area and treatment method. . In some embodiments, the contact surface is somewhat flexible so that the contact surface will conform to the contours of the body surface to be treated, such as the curvature of the head, thigh, etc.

  In some embodiments, the contact surface is roller-shaped. In certain embodiments, the roller is about 2, 3, 4, 5, 6, 7, 8, 9 or 10 cm in diameter and has a width (ie, a distance from the side edge of the roller to the side edge) of about 4 , 6, 8, 10, 12, 14, 16, 18, 20 cm. In some embodiments, the roller may have some degree of flexibility that allows the roller to conform to the contour of the body surface to be treated, such as the curvature of the head, thigh, etc.

  In some embodiments, the housing further comprises one or more valves that control the flow rate of the treatment fluid. In other embodiments, the housing further comprises a battery. In other embodiments, the housing further comprises a control module that controls the flow rate of the fluid through the one or more valves. In some embodiments, the housing further comprises a fluid inlet connected to the fluid source. In other embodiments, the housing comprises a fluid tank disposed within the housing. In some embodiments, the contact surface is removable and disposable. In other embodiments, the skin treatment device is designed to be used only once.

1-5 illustrate one embodiment of a skin treatment device 100 designed to introduce CO ₂ into a patient's skin tissue. FIG. 1 shows the contact surface 110 of the housing 120 (see FIG. 5). In some embodiments, the contact surface 110 is composed of a flexible material such as, but not limited to, polyethylene, polyurethane, silicone or rubber. In other embodiments, the contact surface 110 is comprised of a rigid polymeric material such as, but not limited to, polystyrene, polycarbonate, or polyvinyl chloride. In other embodiments, the contact surface 110 is comprised of a rigid polymeric material that is coated with a layer of flexible material. In yet another embodiment, the contact surface 110 is comprised of a biodegradable material. The biodegradable material can be selected from any suitable biodegradable material or from a mixture of two or more thereof. Suitable materials include, but are not limited to, cellulose and cellulose derivatives, polylactic acid (PLA) and its derivatives, polyhydroxyalkanoates (PHA), biodegradable copolyesters and polycaprolactone. The biodegradable material may comprise a true biopolymer (eg, PHA or PLA), or a synthetic polymer that is suitably biodegradable or a suitable mixture of two or more thereof.

In this non-limiting example, the needle group is embedded in a bump 112 that resides on a ridge 114 in the present contact surface 110, which is located on the outer side of the removable head 122 of the housing 120. . Prior to filling the device with CO ₂ gas, the piercing tip of the needle is hidden in the hump. Since the contact surface 110 is the only part of the skin treatment device 100 that makes physical contact with the patient's body, in some embodiments, the removable head 122 of the housing 120 is disposable. In other embodiments, the removable head 122 of the housing 120 can be sterilized. In some embodiments, a hump can be used to irritate or massage the patient's skin prior to the injection of CO ₂ gas. When the device is filled with CO ₂ gas, the pressure of CO ₂ gas, the piercing tip of the needle, out of the hump, and is extended so as to pass through the skin of the patient, injecting CO ₂ gas through the skin. In some embodiments, this irritation or massage of the skin using a hump serves to relieve the pain of a needle that pierces the skin.

FIG. 2 shows the inner portion 124 of the removable head 122 of the housing 120. In some embodiments, the inner portion 124 of the removable head 122 comprises a chamber through which CO ₂ gas flows to a needle 112 embedded in the contact surface 110. In some embodiments of the skin treatment device 100, the inner portion 124 of the removable head 122 has a plurality of CO ₂ distribution chambers 126 that facilitate a more uniform pressure distribution of CO ₂ gas to all needles. The CO ₂ distribution chamber 126 includes a gap or hump 125 and is sealed with respect to the base 128 of the housing 120 by a rubber sealing body 127.

FIG. 3 shows the base body 128 of the housing 120. In some embodiments, the base 128 includes a valve 129 that contacts a gap or hump 125 in the inner portion 124 of the removable head 122. In some further embodiments, the valve 129 is a pin valve that contacts the gap / hump 125. By opening the valve 129, the CO ₂ gas is passed into the chamber 126 and through the needle 112 embedded in the contact surface 110 into or through the patient's target skin tissue. I can flow.

FIG. 4 shows the control module 130 of the skin treatment device 100. In some embodiments, the control module 130 includes a control or button 132 for opening and closing the valve 129 to allow and stop the flow of CO ₂ gas through the needle 112. The control module 130 may further comprise one or more lights 134. In some embodiments, at least one of the illumination indicates the readiness of devices for the supply of CO _2. In some embodiments, at least one illumination indicates the state of charge of the device. In some embodiments, the housing further comprises one or more batteries that power the device. In some further embodiments, the battery is rechargeable. In an alternative further embodiment, the battery is replaceable. In other embodiments, skin treatment device 100 is powered by a cord that connects to a separate control device or by an electrical cord to an external power source. The housing 120 further comprises means for establishing fluid communication of the CO ₂ source to or into the needle that delivers CO ₂ through the body tissue. In some embodiments, the CO ₂ source is an external tank or vessel. In an alternative embodiment, the CO ₂ source is a pressurized CO ₂ cartridge that is inserted into or attached to the device housing 120. In some embodiments, the CO ₂ cartridge is disposable and replaceable with each new patient. In some embodiments, the controls or buttons 132 or lights 134 are not located on the top of the device, but can be located on the side, front or back of the device.

FIG. 5 is a side view of an exemplary embodiment of housing 120. In this non-limiting example, the control module 130 of the housing 120 is knob shaped that can be easily grasped and manipulated by a gloved doctor's hand. In some embodiments, the CO ₂ gas flows from the CO ₂ source into the device via a tube 140 connected to the device.

In another non-limiting example of skin treatment device 100, the flat contact surface 110 of the device can be in the form of a roller element. In some embodiments, the plurality of needles are mounted on a roller element, the roller rotating axis of the device or other suitable configuration that will allow the roller to rotate as contemplated herein. It is mounted in a rotatable manner. The axis of rotation or other suitable configuration may include one or more passages so that CO ₂ can be in fluid communication with the needle. Because one or more of the plurality of needles is below the surface of the patient's skin because it is in fluid communication with the CO ₂ source, the plurality of needles injects CO ₂ into the patient in need of such treatment. Make it possible. The number of rows of needles forming the contact surface of the roller element of the device can vary depending on the desired treatment plan.

  In some embodiments, the roller device comprises a plurality of needles permanently attached to the roller device. In some embodiments, the roller element can be removed from the device via a removable connection. In some embodiments, the roller element is disposable and replaceable with each new patient. In other embodiments, the roller unit is sterilizable.

In some embodiments, the plurality of needles of the roller element are removable and replaceable. In one embodiment of this removable needle configuration, the needle is integrated into a disposable roller cover. The roller cover can be secured to the roller so that the roller element is appropriately pierced to pass CO ₂ through a needle integrated within the roller cover. When the needle with the roller cover to the roller element with a hole drilled is mounted, when the roller unit is disposed in the patient's skin, CO ₂ becomes the be sent to the patient's skin. This needled roller cover can increase the safety of the roller device of the present application. After use, once the disposable roller cover is removed from the roller, the roller element may be sterilizable to further increase safety.

In some embodiments, the skin treatment device 100 is attached to a pressurized treatment fluid source, such as a CO ₂ tank or cartridge. In such embodiments, there is little or no need to include a piston or other type of configuration to provide proper delivery of the therapeutic substance under the skin. In some embodiments, the skin treatment devices and methods of the present application do not include a piston or other form of transport improvement mechanism. In one embodiment, the application introduces treatment fluid into or below the skin surface substantially by pressure from a pressurized treatment fluid source.

  Another embodiment of a skin treatment device is shown in FIGS.

FIG. 6 shows one configuration of the treatment device 100 having a handle portion 202. At the first end of handle portion 202, hose element 204 is attached to a CO ₂ gas source (not shown). As an optional feature, a regulator 206 may be included in the treatment device 100. The switch 208 can facilitate operation. In use, the end piece 210 can be attached to the microneedle / substrate element 212. Microneedle 214 and substrate material 216 are further shown.

Referring to FIG. 7, a microneedle / substrate element 212 is shown in contact with the patient's skin 300 and penetrating through the skin interior 302. The microneedle 214 has a hollow end 218 that will fill the penetrating region 304 with CO ₂ gas (not shown).

  Referring to FIG. 8, an exemplary configuration of microneedle / substrate element 220 is shown. A plurality of microneedles 214 are provided in the region of the substrate material 216. Referring to FIG. 9, another exemplary configuration of microneedle / substrate element 222 is shown. A plurality of microneedles 214 are provided in the region of the substrate material 216. The shape of the base element is not limited to the illustrated shape. This application contemplates substrate elements of any shape that are suitable for carrying out the methods disclosed in this application. The shape may be determined by the contours of the region of the body undergoing treatment or by the need to avoid certain physical characteristics.

  In other embodiments, the apparatus of the present application comprises a plurality of interchangeable head units having microneedle rings of various diameters. For example, the device may be large so that when the ring (s) is placed around the skin abnormality undergoing treatment, the ring (s) is located at the maximum distance from / the skin abnormality. A first interchangeable head having one or more rings of diameter microneedles is provided. The apparatus further comprises one or more replaceable heads having a smaller diameter ring (s) than the first replaceable head ring (s), thereby treating the ring (s) Closer to the skin abnormality receiving.

Skin Treatment System Other aspects of the present application include a built-in treatment fluid source, a pressure regulator that regulates the pressure of the treatment fluid, a filter that filters out contaminants such as bacteria, viruses, and other gaseous impurities in the treatment fluid. The invention relates to a skin treatment system comprising a heating system that raises the temperature of a treatment fluid, a flow regulator that controls the flow rate of the treatment fluid, and a skin treatment device that delivers the treatment fluid into or under the skin of a patient. In some embodiments, the treatment fluid is CO ₂ gas. In a further embodiment, the CO ₂ gas is medical grade CO ₂ gas, thereby reducing or eliminating the need for a filter.

In an exemplary use of the skin treatment device of the present application, the contact surface or roller of the skin treatment device is placed on the patient's skin such that at least some of the plurality of needles protruding from the contact surface penetrate the patient's skin. Oriented at. During the period when such a needle is below the surface of the skin, a treatment fluid such as CO ₂ is supplied from the treatment fluid source. Because the needle is in fluid communication with the treatment fluid source 2, the treatment fluid will be properly moved into and under the patient's skin in the desired amount over the desired period of time to provide the desired treatment. Depending on the length of the needle, treatments can be performed at various distances below the patient's skin surface. For roller contact surfaces, the frequency of roller movement on the skin defines the number of puncture channels that can be specifically controlled, thereby further defining the extent to which treatment fluid can penetrate the patient's skin. obtain.

Kit In one aspect, the treatment device, microneedle / substrate element, and one or more accessories of the present application are packaged together and sold as a kit. Exemplary members in the kit apply a device comprising a predetermined number of disposable or replaceable microneedle / substrate element configurations, carboxy therapy and one or more additional treatments of electrical stimulation, galvanic action or thermal therapy. In a reusable treatment device, in a suitable container / dispenser (such as a tube, cylinder, pump, bottle, drop bottle, or unit dose dispenser) used before, during or after application of the device It may include, but is not limited to, a local treatment configuration. Furthermore, the kit may further comprise a cleaning tool used to disinfect / sterilize the skin prior to application of the device. The kit may further comprise a film-forming member or bandage that is used to protect the location of the treated skin after the treatment to enhance the effectiveness of the treatment on the treated skin.

Treatment methods Treatments according to the method of the present application may include pimples or other skin spots, wrinkles, ridges / inner hair growth, herpes wounds, skin infections, old age spots, or any other skin It may be local so that the abnormality becomes the target position. In addition, treatment can be used on larger areas such as the scalp (to promote hair growth) or the thigh or other areas (eg, to treat subcutaneous fat).

  In one aspect, the patient (a) wears a treatment device comprising a plurality of microneedles secured to a surface material; (b) the device so that one or more of the plurality of microneedles penetrates the patient's skin. Applying pressure, (c) applying carboxy therapy treatment and optionally one or more of galvanic treatment, electrical stimulation, or thermal therapy, and (d) removing microneedles from the patient's skin. , Receive treatment.

In an exemplary embodiment, the physician positions the treatment device such that the microneedle / substrate element contacts or substantially contacts the location of the patient's skin. The treatment device is triggered by the user, such as by using a plunger, piston or the like, so that at least some of the plurality of microneedles protruding from the substrate material penetrate the patient's skin. While such needles are below the surface of the skin, CO ₂ is supplied from the source and the needles are in fluid communication with the CO ₂ source so that the gas moves properly in and under the patient's skin. And thereby provide a treatment for carboxy therapy. Because of the fluid communication with the CO ₂ source, when one or more of the plurality of microneedles is below the surface of the patient's skin, the plurality of needles are suitable for application of carboxy therapy to a patient in need of such treatment. To make it possible.

Skin bumping, reactivation, in the example, such as the application of carboxy therapy in intradermal treatment such as stretch marks, and regrowth of hair, the flow rate of the CO ₂ gas can be from about 5 to about 300 ml / min. In some embodiments, the CO ₂ flow rate is 50 to about 200 ml / min, or about 80 to about 120 ml / min. Further, the flow rate of CO ₂ is about 5,10,15,20,30,40,50,60,70,80,90,100,110,120,150,170 or 200ml / min at and obtained, needs Depending on the value, either value can be an upper limit or an upper limit. In some embodiments, the flow rate of CO ₂ gas, 5-10 ml / min, 5-20 ml / min, 5～40Ml / min, 5～80Ml / min, 5 to 100 ml / min, 5～120Ml / min, 5-150 ml / min, 5-200 ml / min, 5-250 ml / min, 10-20 ml / min, 10-40 ml / min, 10-80 ml / min, 10-100 ml / min, 10-120 ml / min, 10 150 ml / min, 10-200 ml / min, 10-250 ml / min, 10-300 ml / min, 15-20 ml / min, 15-40 ml / min, 15-80 ml / min, 15-100 ml / min, 15-120 ml / min Min, 15-150 ml / min, 15-200 ml / min, 15-250 ml / min, 15-300 ml / min, 20-40 ml / min, 20-80 ml / min, 20-100 ml / min, 10-120 ml / min, 20-150 ml / min, 20-200 ml / min, 20-250 ml / min, 20-300 ml / min, 40-80 ml / min, 40-100 ml / min, 40-120 ml / min, 40- 150 ml / min, 40-200 ml / min, 40-250 ml / min, 40-300 ml / min, 80-100 ml / min, 80-120 ml / min, 80-150 ml / min, 80-200 ml / min, 80-250 ml / min Min, 80-300 ml / min, 100-120 ml / min, 100-150 ml / min, 100-200 ml / min, 100-250 ml / min, 100-300 ml / min, 120-150 ml / min, 120-200 ml / min, 120-250 ml / min, 120-300 ml / min, 150-200 ml / min, 150-250 ml / min, 150- 100 ml / min, 200～250Ml / min, falling in the range of 200-300 ml / min or 250～300Ml / min. In another embodiment, CO ₂ gas, in a single treatment, or treatment of multiple sessions, is supplied at various flow rates. In some embodiments, a single treatment session consists of a high flow rate (eg, 100-200 ml / min) period, a medium flow rate (eg, 40-99 ml / min) period, and a low flow rate (eg, 10-200 ml / min). 39 ml / min). In some embodiments, the overall treatment plan consists of one or more sessions with a high flow rate (eg, 100-200 ml / min), one or more sessions with a medium flow rate (eg, 40-99 ml / min), and a low flow rate. Includes one or more sessions (eg, 10-39 ml / min). The duration of such treatment can vary from about 30 seconds to about 180 seconds or from about 45 seconds to about 90 seconds. The duration of treatment can be from about 30, 45, 60, 75, 90, 105, 120, 135, 150, 165 or 180 seconds, and any value can be an upper or upper limit, as needed.

As a further example, the flow rate of CO ₂ gas for subcutaneous injection for fat reduction in areas such as the chin, arms, knees, thighs, stomach or buttocks is about 40 to about 360 ml / min or about 90 to about It can be 240 ml / min. Further, the flow rate of CO ₂ for the treatment of subcutaneous carboxy therapy is about 5, 10, 15, 20, 30, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340 or 360 ml / min, and any value can be an upper limit or an upper limit as required. In some embodiments, the flow rate of CO ₂ gas, 5-10 ml / min, 5-20 ml / min, 5～40Ml / min, 5～80Ml / min, 5 to 100 ml / min, 5～120Ml / min, 5-150 ml / min, 5-200 ml / min, 5-250 ml / min, 5-300 ml / min, 5-360 ml / min, 10-20 ml / min, 10-40 ml / min, 10-80 ml / min, 10 100 ml / min, 10-120 ml / min, 10-150 ml / min, 10-200 ml / min, 10-250 ml / min, 10-300 ml / min, 10-360 ml / min, 15-20 ml / min, 15-40 ml / min Min, 15-80 ml / min, 15-100 ml / min, 15-120 ml / min, 15-150 ml / min, 15-200 ml / min, 15-250 ml / min, 15-300 ml / min, 15 to 360 ml / min, 20 to 40 ml / min, 20 to 80 ml / min, 20 to 100 ml / min, 20 to 120 ml / min, 20 to 150 ml / min, 20 to 200 ml / min, 20 to 250 ml / min, 20 to 20 ml 300 ml / min, 20-360 ml / min, 40-80 ml / min, 40-100 ml / min, 40-120 ml / min, 40-150 ml / min, 40-200 ml / min, 40-250 ml / min, 40-300 ml / min Min, 40-360 ml / min, 80-100 ml / min, 80-120 ml / min, 80-150 ml / min, 80-200 ml / min, 80-250 ml / min, 80-300 ml / min, 80-360 ml / min, 100-120 ml / min, 100-150 ml / min, 100-200 ml / min, 100-250 ml / min, 100-300 ml / min, 0-360 ml / min, 120-150 ml / min, 120-200 ml / min, 120-250 ml / min, 120-300 ml / min, 120-360 ml / min, 150-200 ml / min, 150-250 ml / min, 150- Within the range of 300 ml / min, 150-360 ml / min, 200-250 ml / min, 200-300 ml / min, 200-360 ml / min, 250-300 ml / min, 250-360 ml / min, or 300-360 ml / min is there. In some embodiments, a single treatment session consists of a period of high flow rate (eg, 200-360 ml / min), a period of medium flow rate (eg, 50-199 ml / min), and a low flow rate (eg, 5-5 49 ml / min). In some embodiments, the overall treatment plan consists of one or more sessions with a high flow rate (eg, 200-360 ml / min), one or more sessions with a medium flow rate (eg, 50-199 ml / min), and a low flow rate. Includes one or more sessions (eg, 5-49 ml / min). The treatment time for the subcutaneous face treatment can be about 1 to about 8 minutes, or about 2 to about 6 minutes. Furthermore, the treatment time for subcutaneous injection of CO ₂ is approximately 1, 1.5, ₂ , 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7.0, 7 .5, 8, 10, 15, 20 or 30 minutes, and any value may include an upper limit or an upper limit, if desired.

In one aspect, the microneedle / substrate element and the treatment device can be configured to flow current into the patient's skin during the treatment of the patient. The current delivered to the breached area may further promote healing and other benefits that may increase the effectiveness of carboxy therapy alone treatment. Alternatively, the microneedles may comprise a conductive material that allows for the supply of heat (and / or heats CO ₂ ) during the procedure.

  In one aspect of the invention, prior to the initiation of electrical stimulation in the device, a microneedle is inserted into the patient's skin to pierce the skin at the desired location (s), thereby causing current at the selected skin location. To increase the desired effect of electrical stimulation.

  The electrical aspects of the treatment device of the present invention may be powered by a power source such as a battery, piezoelectric, electro-mechanical (eg, coil magnet), or galvanic pair, the disclosure of which is incorporated by reference in its entirety. As a result, the stratum corneum breakthrough and electrical stimulation processing steps are performed on the same device without the need to change the device during the procedure.

  Furthermore, the skin treatment device of the present invention may comprise a suitable material that provides galvanic action. In this embodiment, the microneedle and / or substrate material is formed from two dissimilar metals that are in contact with each other so that they form a galvanic pair and, as a result, the microneedle / substrate material is an electrolyte. A galvanic current can be generated when in contact with the containing medium. For example, the substrate material may be U.S. Pat. Nos. 5,983,136, 6,532,386, 6,050,988, or 6,219,574 (the disclosures of which are hereby incorporated by reference) May comprise a thin zinc plate produced by the production method disclosed in US Pat. No. 5,077,096, incorporated herein in its entirety, while other metals (eg, silver, silver-silver chloride, copper, gold). Can be formed into a film on one or more, all or a part of the plurality of microneedles.

  During skin treatment, for example, both metals (ie, zinc and silver-silver chloride) of the galvanic pair of microneedles / substrate element members are electrolyte media (eg, localized compositions, or bodily fluids such as sweat), And / or by contacting the skin, it may function as a galvanic battery (eg, about 1 volt) to generate an electrical current that exits the zinc anode and drains the electrolyte medium and / or skin. And then back to the silver-silver chloride cathode.

  Alternatively, the two metals forming the galvanic pair can be contacted with a third metal (eg, titanium or stainless steel) that can be configured on or in one or more of the microneedle material or substrate element material. . For example, the zinc layer can be filmed on selective areas of titanium or stainless steel microneedle members by electroplating, by electroless plating, or using a conductive ink containing zinc powder and a polymer binder. May be. Similarly, the silver-silver chloride layer may be coated on other regions of titanium or stainless steel microneedles. The conductive metal microneedles function as conductors connecting the galvanic elements zinc and silver-silver chloride. During application of the device, a galvanic current is generated when both galvanic elements are in contact with the electrolyte medium and / or the skin.

  In addition, to further enhance electrical stimulation and / or galvanic effects, the patient's skin is first prepared with a relatively high concentration of an organic solvent, such as glycerin, propylene glycol, or polyethylene glycol. Or a non-conductive solute (eg, a low molecular weight saccharide, dextran, or urea).

Another aspect of the present application relates to a method of applying carboxy therapy to a subject in need of such treatment. The method comprises: contacting a treatment device comprising a plurality of hollow needles mounted on a contact surface of a housing and a CO ₂ source in fluid communication with at least one of the plurality of hollow needles to a target body surface of the subject; Applying pressure to the housing such that one or more of the hollow needles penetrates the epidermis or outermost layer of cells on the target body surface, supplying a therapeutic amount of CO ₂ to the subject through the patient's skin, the plurality of hollow needles; And removing a plurality of hollow needles from the target body surface.

  In some embodiments, the subject is a mammal. In other embodiments, the mammal is a human. In other embodiments, the mammal is a domestic animal, such as a dog, cat, monkey, mouse, mouse, rabbit, guinea pig, and the like. In other embodiments, the mammal is a domestic animal such as a cow, horse, pig, sheep, goat and the like. In yet another embodiment, the mammal is an animal in a zoo.

  In some embodiments, the method further includes applying one or more additional treatments selected from the group consisting of galvanic treatment, electrical stimulation, thermal therapy, and phototherapy to the target body surface. In some other embodiments, one or more additional treatments are provided concurrently with carboxy therapy using the same treatment device. In some other embodiments, one or more additional treatments are provided before or after carboxy therapy. In some other embodiments, the method further comprises applying an effective amount of the treatment composition formulated for topical administration to the target body surface.

  In some embodiments, the plurality of hollow needles are microneedles that are about 0.1 mm to about 0.5 mm in diameter and about 0.4 mm to about 2.1 mm in length.

  In some embodiments, the target body surface is acne, psoriasis, skin infections, skin spots, hyperpigmentation, decreased pigmentation, alopecia, hirsutism, wasted hair growth, rough skin, psoriasis, skin Sagging, wrinkles, hypervascularized skin, abnormal sebum production, excessive pore conspicuousness, sweating, hyperhidrosis, tattoos, rash, scar, pain, itching, burns, inflammation, warts, fish eyes, skin stiffness, Suffers from skin diseases selected from the group consisting of edema, ivy / oak poisoning, and biting by insects, spiders, snakes, and other animals. In one embodiment, the target body surface is a scalp suffering from hair loss. In other embodiments, the target body surface suffers from regional alopecia. In other embodiments, the target body surface suffers from a diabetic ulcer. In another embodiment, the target body surface suffers from a streak. In yet another embodiment, the target body surface is a scard body surface.

Another aspect of the present application relates to a method of treating hair loss in a target area such as the scalp. The method includes introducing an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient period of time. An effective amount of carbon dioxide is introduced into the target area using a plurality of hollow needles that puncture the epidermis of the target area and release carbon dioxide at a desired rate within the subcutaneous tissue. The

In some embodiments, CO ₂ is introduced into the target area using the skin treatment device and / or skin treatment system of the present application. The plurality of needles of the skin treatment device are selected to have a size and spatial relationship suitable for hair loss treatment.

In some embodiments, CO ₂ at a flow rate 50～200Ml / min, is introduced over a period of 10 to 60 minutes.

  In other embodiments, the introducing step is repeated 4-20 times with an interval of about 24-72 hours between any two repeats.

  In some embodiments, the method further includes applying local anesthesia to the target area prior to the introducing step. Exemplary local anesthetics include procaine, amethokine, cocaine, lidocaine, prilocaine, bupivacaine, levobupivacaine, ropivacaine, mepivacaine and dibucaine, etidocaine, chloroprocaine, SARAPIN, benzocaine, tetracaine, plamoxine, oxyprocaine, dioxyne, Including, but not limited to, chloroxylenol, cyncocaine, dexibacaine, diamocaine, hexylcaine, pilocaine, lysokine and rhodocaine.

  In some embodiments, the method further comprises applying a composition comprising a hair growth-promoting agent to the target area, the composition being formulated for topical application. Exemplary hair growth promoters are hair growth factors, minoxidil, finasteride and copexil (including analogs and derivatives thereof); cyclosporine 7-thioamide, donepezil hydrochloride, antiandrogen, bimatoprost, kudin extract, saw palmetto fruit extract Products, saw palmetto extract, licorice extract, but not limited to these.

Another aspect of the present application relates to a method of treating a skin disease in a target area. The method includes introducing an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient period of time. An effective amount of carbon dioxide is introduced into the target area using a plurality of hollow needles that puncture the epidermis of the target area and release carbon dioxide at a desired rate within the subcutaneous tissue. The In some further embodiments, the subcutaneous layer comprises adipose tissue.

In some embodiments, CO ₂ is introduced into the target area using the skin treatment device and / or skin treatment system of the present application. The plurality of needles of the skin treatment device are selected to have a size and spatial relationship suitable for the treatment.

In some embodiments, CO2 is introduced over a period of ₂ to 120 minutes at a flow rate of 40 to 360 ml / min.

  In other embodiments, the introducing step is repeated 1 to 40 times with an interval of about 6 to 120 hours between any two iterations.

  In some embodiments, the method further includes applying local anesthesia to the target area prior to the introducing step. Exemplary local anesthesia includes, but is not limited to, procaine, amethocaine, cocaine, lidocaine, prilocaine, bupivacaine, levobupivacaine, ropivacaine, mepivacaine and dibucaine.

  Exemplary skin diseases are eczema, seborrhea, vitiligo, mole, scleroderma, sunburn, sun-damaged skin, estrogen imbalance, hyperpigmentation, decreased pigmentation, wrinkles and coarse deep wrinkles, fine wrinkles , Skin lines, bear under eyes, crevices, humps, large pores, unevenness, surface roughness, excessive blotting, yellowing, lack of skin elasticity, discoloration, yellowing, aging spots, freckles, skin atrophy, skin Rash, skin fragility, dryness, cracks, sagging, thin hair, hyperplasia, hyperkeratosis, elastic fibrosis, fibrosis, pore opening, subcutaneous fat formation, bruise, acne vulgaris, cystic acne, Acne scars, keloid scars, hypertrophic scars, striatum (eg, skin striatum), dermatitis (eg, seborrheic dermatitis, coin-like dermatitis, contact dermatitis, atopic dermatitis, exfoliative dermatitis , Surrounding dermatitis, and stasis dermatitis), hypodermic skin and epidermis Folliculitis, open pores, ichthyosis (eg, ichthyosis ichthyosis, exfoliative keratophytosis, and foliar ichthyosis), follicular abnormalities (eg, pseudofolliculites, senile comedones, comedones) Nevus comidonicas and trichostatis spinulosa, benign epithelial tumors (eg, flat warts, follicular epithelioma, and infectious molluscum), perforated dermatoses ( For example, serpentine perforans seripiginosa and culle disease, keratinization abnormalities (eg Darier's disease, keratosis, plantar keratosis, erythematous brux, lichen planus black epidermis) Disease, and psoriasis), urticaria (eg, pitiri) sis rosea), rosacea rosacea and erythema eruption), keratosis, impetigo, erysipelas, erythema, eczema, senile purpura, excessive sebum (fat) production, Including sebaceous gland hyperplasia (sebaceous gland enlargement), viral infection, fungal infection, bacterial infection, telangectasia, hirsutism, rosacea, pruritis, scleroderma, warts, and fish eyes However, it is not limited to these.

  In some embodiments, the method further comprises applying a composition comprising a therapeutic agent to the target area, the composition being formulated for topical application. Exemplary therapeutic agents include, but are not limited to, antibacterial agents, analgesics and / or non-steroidal anti-inflammatory (NSAID) agents, steroid / corticosteroid agents, wound repair agents, anticancer agents, and skin ameliorating agents. . Exemplary antibacterial agents include antibacterial agents (eg, clindamycin and erythromycin, dysomycin, minocycline, tetracycline, kanamycin, metronidazole, neomycin, bacitracin, polymyxin, maphenide acetate, silver sulfadiazine, gentamicin sulfate; antifungal agents (terbinafine, itraconazole , Miconazole nitrate, thiapendazole, tolnaftate, clotrimazole and griseofulvin caprylyl glycol, triclosan, phenoxyethanol, nystatin or chlortrimazole); antiviral drugs (eg, acyclovir, brivdine, cidofovir, dicyclovir, didanosine, famciclovir, 5-fluorouracil, 2-deoxy- and 5-deoxy-5-fluorouridine Ganciclovir, idoxuridine, ramubideine, lobukavir, penciclovir, retrovir, sorivudine, trifluridine, valacyclovir, valganciclovir, vidarabine, zalcitabine, zidovudine, imiquiodo, docosanol, brivdine, interferon, famvir, cidofovir, podophyllotine); Analgesics (eg, aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), salicylates (including salicylic acid), methyl salicylate, olsalazine, sulfasalazine and salsalate; diflunisal, para-aminophenol derivatives, acetanilide, acetaminophen, phenacetin, Phenamates, mefenamic acid, meclofenamate, sodium meclofenamic acid, heteroallylacetic acid Conductor, tolmethine, ketorolac, diclofenac, propionic acid derivatives, ibuprofen, naproxen sodium, naproxen, phenoprofen, ketoprofen, flurbiprofen, oxaprozin; enolic acid, oxicam derivatives, piroxicam, meloxicam, tenoxicam, droxicam, piroxicam , Pyrazolone derivatives, phenylbutazone, oxyphenbutazone, antipyrine, aminopyrine, dipyrone, coxib, celecoxib, rofecoxib, nabumetone, apazone, indomethacin, sulindac, etodolac, isobutylphenylpropionic acid, luminacoxib, etoroxixib, parecoxib, barcoxib, barcoxib Etodolac, dulbferon, dexketoprofen, Aceclofenac, lycoferon, bromfenac, loxoprofen, pranoprofen, piroxicam, nimesulide, schizolin, 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-1, meloxicam, lornoxicam, d-indobufen , Mofezolac, amtormetine, pranoprofen, tolfenamic acid, flurbiprofen, suprofen, oxaprozin, zaltoprofen, aluminoprofen and thiaprofenic acid); opioid analgesics (eg propoxyphene, meperidine, hydromorphone, dihydromorphine, pethidine, hydrocodone) , Oxycodone, morphine, codeine, and tramodol); NMDA antagonist analgesics (eg, 2-piperidino-1 Lucanol derivatives, ketamine, dextromethorphan, eliprozil, and ifenprodil); skeletal muscle relaxant analgesics (eg, flexaril, carisoprodol, robaxisar, norgesic, and danthorium); cell differentiation and antiproliferative agents (eg, retinoids, eg, retinol, retinal And retinyl esters such as retinyl acetate, retinyl butyrate, retinyl propionate, retinyl octanoate, retinyl laurate, retinyl palmitate, retinyl oleate, and retinyl linoleate), vitamin D, or vitamins D analogs (calciportrienes)); chemical denervating agents, including botulinum type A and / or type B toxins, and serum CG toxins; mitochondrial inhibitors (eg, anthralin (disranol, chrysa) Topical steroids (for example, clobetasol propionate, betamethasone, betamethasone dipropionate, halobetasol propionate, fluoconide, diflorazone diacetate, mometasone furoate, halcinonide, desoxymethasone, fluticasone propionate, flulandreno) Lido, triamcinolone acetonide, fluocinolone acetonide, hydrocortisone, hydrocortisone valerate, prednicarbate, desonide, or alcrometasone dipropionate; immunosuppressive compounds (eg, tacrolimus (FK-506)); JAK2 inhibitors (eg, , INCB18424); JAK3 inhibitors (eg CP-690,550); parathyroid hormone related protein (PTHrP) agonists (eg PT H (1-34)); as well as cell adhesion blockers (eg, pan-selectin antagonist Vimosiamos), DNA repair enzymes (eg, bacteriophage T4 pyrimidine dimer specific endonuclease, Micrococcus luteus N-glycosylase / AP lyase, Saccharomyces cerevisiae N-glycosylase / apronate-apyrimidine lyase, Schizosaccharomyces pombe UV damage endonuclease (UVDE), Chlorella virus isolated PBCV-1 pyrimidine dimer-specific glycosylase, and cyanobacterial photolyase); The methylxanthines used in the invention are caffeine (1,3,7-trimethylxanthine), theophylline (1,3-dimethylxanthine), aminophylline, theobromine (3,7-dimethylxanthine), paraxa Contains tin, isobutylmethylxanthine, butymethylxanthine; salicylic acid, benzoyl peroxide, caffeine, caffeic acid compound, avobenzone, oxybenzone, octyl methoxycinnamate, titanium dioxide, zinc oxide, dihydroxyacetone, palmitoylpentapeptide, argylline, IL6 And growth factors such as, but not limited to, interleukins such as IL10, EGF and TGF.

Another aspect of the present application relates to a method of promoting wound healing in a target area such as the scalp. The method includes introducing an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient period of time. An effective amount of carbon dioxide is introduced into the target area using a plurality of hollow needles that puncture the epidermis of the target area and release carbon dioxide at a desired rate within the subcutaneous tissue. The

In some embodiments, CO ₂ is introduced into the target area using the skin treatment device and / or skin treatment system of the present application. The plurality of needles of the skin treatment device are selected to have a size and spatial relationship suitable for the treatment.

In some embodiments, CO ₂ is introduced over a period of 10 to 60 minutes Oyobi at a flow rate of 5～300Ml / min.

  In other embodiments, the introducing step is repeated 5-20 times at intervals of about 24-120 hours between any two iterations or sessions.

  In some embodiments, a method session for treating skin abnormalities includes several application steps. The first application step involves the insertion of a looped needle at a distance, eg 2-4 inches, away from the abnormality of the skin undergoing treatment. In the first application step, the flow rate of the device is relatively large, for example 120-200 ml / min. The first application step is followed by at least one intermediate step in which the insertion ring is more abnormal for the skin undergoing treatment than the first application step or the preceding intermediate step. To be close to. In each intermediate step, the flow rate is reduced from the immediately preceding application step, for example to a flow rate of 40-120 ml / min. Sessions are the immediate surroundings of the periphery of the abnormal condition of the skin being treated (eg in the case of an open wound) or the skin in the skin being treated (eg in the case of a scar or streak) Including a final application step. The final application step is performed at a relatively low flow rate, for example at a flow rate of 5-20 ml / min.

  In some embodiments, the method further includes applying local anesthesia to the target area prior to the introducing step. Exemplary local anesthesia includes, but is not limited to, procaine, amethocaine, cocaine, lidocaine, prilocaine, bupivacaine, levobupivacaine, ropivacaine, mepivacaine and dibucaine.

  In some embodiments, the method further comprises applying a composition comprising a wound healing promoter to the target area, the composition being formulated for topical application. Exemplary wound healing promoters include TGF-related growth factors (TGF-β1, TGF-β2, TGF-133), PDGF-related growth factors (PDGF-M, PDGF-BB, VEGF), FGF-related growth factors (a− FGF, b-FGF, KGF), IGF-related growth factor (IGF-1, IGF-II, insulin), EGF-related growth factor (EGF, HB-EGF, TGFα, amphiregulin, betacellulin), HGF / SF, VEGF CTGF, TNFα, IL-1, IL-2, IL-6, IL-8, γ-interferon, IL-4, IL-10, matrix metalloproteinase (MMP; MMP-1, -2, -3,- 7, -8, -9, 10, -11, -12, -13, -14, -15, -16, -17, -19, -20, -21, -23A, 23B -24, -25, -26, -27, -28), metallopeptidase tissue inhibitor (TIMP), (including TIMP-1, -2, -3 and -4), plasmin, seratiopeptidase (seralysin) Serratia Peptase, Serratia Peptidase, Serratopeptidase, or Serratia E-15 Proteolytic Enzyme, also called Serrapeptidase), carboxylate, cype mustat, doxycycline, hydroxamate, marimastat, phosphinyl, tetracycline, thiols and their Including, but not limited to, combinations.

  A composition formulated for topical administration may be in the form of a cream, lotion, gel, serum, tonic, emulsion, paste, or spray for topical administration. As used herein, the term “cream” refers to a composition that can be spread and stretched, typically formulated for application to the skin. Creams typically contain oil and / or fatty acid based matrix.

The effective amount of CO ₂ depends on the method of treatment. In some embodiments, the effective amount of CO ₂ is determined by the rate of CO ₂ delivered to the target area, and the duration of treatment is a single session. While the effective amount of carbon dioxide may vary from patient to patient, in some embodiments, the CO ₂ has a flow rate of about 0.1 to 20 ml / cm ² / min, about 0.1. 1~1ml / cm ² / min, about 0.1 to 2 mL / cm ² / min, about 0.1 to 5 ml / cm ² / min, about 0.1~10ml / cm ² / min, about 0.1 15 ml / cm ² / min, about 0.5 to 2 / cm ² / min, about 0.5 to 5 ml / cm ² / min, about 0.5 to 10 / cm ² / min, about 0.5～15Ml / cm ² / min, about 0.5-20 ml / cm ² / min, about 1-2 ml / cm ² / min, about 1-5 ml / cm ² / min, about 1-10 ml / cm ² / min, about 1 15ml / cm ² / minute, about 1~20ml / cm ² / minute, about 2~5ml / cm ² / minute, about 2~10ml / m ² / min, about 2~15ml / cm ² / min, about 2~20ml / cm ² / min, about 5-10 ml / cm ² / min, about 5-15 mL / cm ² / min, about 5-20 ml / cm ² / min, about 10-15 ml / cm ² / min, about 10-20 ml / cm ² / min or about 15-20 ml / cm ² / min, about 0.5 to 60 minutes, about 0.5 to 5 Minutes, about 0.5 to 10 minutes, about 0.5 to 20 minutes, about 0.5 to 30 minutes, about 0.5 to 40 minutes, about 0.5 to 50 minutes, about 2 to 5 minutes, about 2 -10 minutes, about 2-20 minutes, about 2-30 minutes, about 2-40 minutes, about 2-50 minutes, about 2-60 minutes, about 5-10 minutes, about 5-20 minutes, about 5-30 Minutes, about 5-40 minutes, about 5-50 minutes, about 5-60 minutes, about 10-20 minutes, about 10-30 minutes, about 10-40 minutes, about 10-50 minutes, about 10-60 minutes, About 20-30 minutes, about 20- 40 minutes, about 20-50 minutes, about 20-60 minutes, about 30-40 minutes, about 30-50 minutes, about 30-60 minutes, about 40-50 minutes, about 40-60 minutes or about 50-60 minutes Is introduced into the target area over a period of.

  In some embodiments, the treatment is performed between 2-40, 2-30, 2-20, 2 with approximately 12-72, 12-48, 12-24 hours between each two sessions. 10, 2-5, 4-40, 4-30, 4-20, 4-10, 6-40, 6-30, 6-20, 6-10, 8-40, 8-30, 8-20, Includes 10-40, 10-30, 10-20, 15-40, 15-30, 15-20, 20-40 or 20-30 sessions.

The multi-needle approach reduces the time required to provide a beneficial amount of CO ₂ to a patient in need of such treatment without simultaneously reducing the effectiveness of such treatment. Furthermore, beneficial CO ₂ treatment, in a short period of time, may be applied over a large surface.

In some embodiments, methods of treatment using the apparatus of the present application, in addition to the CO ₂ does not involve the application of any of the active ingredient. In a further aspect, the method of using the device consists essentially of supplying CO ₂ beneath the skin of the patient in need of treatment.

  The invention is further illustrated by the following examples which should not be construed as limiting. All references, patents and published patent applications, and drawings and tables cited in this application are hereby incorporated by reference.

Example 1: Treatment of regional alopecia A female patient suffered from regional alopecia and had been suffering from this disease for 7 years. The patient has asked 14 different specialists for appropriate treatment, but has been given a wig. None of the treatments, including topical application of minoxidil and hair growth factor, resulted in satisfactory disease improvement. The patient received a weekly carboxy therapy procedure performed in the clinical setting. Warmed CO ₂ was administered at a flow rate of 80 ml / min. In addition, the patient was instructed to continue topical application of minoxidil and hair growth factor once a day.

  After 10 clinical sessions over two and a half months, the patient showed significant hair ingrowth into the hair loss area. The clinical treatment protocol has been reduced to treatment of carboxy therapy twice per month. After 20 sessions of clinical carboxytherapy treatment for about 6 months, the patient showed hair growth throughout the hair loss area.

Example 2: Treatment of androgenetic alopecia An adult male patient suffered from hair loss near the toothpick. The patient was treated clinically with carboxy therapy and during the 3 months there was significant hair regrowth near the toothpicks. After 5 months of carboxy therapy, the patient experienced full ingrowth of hair with normal texture near the toothpick.

Example 3: Overall thin hair treatment A male patient suffered from overall thin hair across the top of his scalp. The patient received monthly carboxytherapy treatment. At 3 months, the patient showed sufficient filling of the thinned area. The treatment protocol was changed to bimonthly carboxy therapy, and at 5 months the patient was fully covered with crested hair with normal hair.

Example 4: Treatment of diabetic ulcers Ten insulin dependent diabetic patients with chronic lower limb wounds were targeted for CO ₂ transcutaneous treatment. The control group consisted of 5 patients, 3 with claustrophobia and 2 who refused CO ₂ aeration treatment for logistic reasons. Five patients received 30 CO ₂ ventilation procedures with the problem wound protocol (30 minutes / day, 5 days / week). All patients were evaluated using transcutaneous oximetry and received an initial surgical debridement of the wound.

An exemplary protocol for CO ₂ aeration treatment of ulcerated wounds includes several steps of CO ₂ application. The first application step involves inserting a large radius annular needle around the wound, eg, about 2 inches from the wound edge. CO ₂ gas, high flow rates, e.g., 120～200Ml / min, and more details are vented at about 150ml / min. This is followed by a second application with a smaller ring about 1 inch from the edge of the wound. CO ₂ gas is smaller flow rates, e.g., 50-100 ml / min, more particularly aerated at about 80 ml / min. This is followed by a third application with a smaller ring about 1 / 0.5 inch from the edge of the wound. CO ₂ gas is smaller flow rate, for example, 30-50 ml / min, and more details are vented at about 40ml / min. The final application step uses a single microneedle application device at a very small flow rate of about 5-25 ml / min, more specifically about 15-20 ml / min, around the perimeter of the wound. Done on the skin.

Wound surface area was recorded once a week by a nurse or resident who did not know the grouping. At the end of 7 weeks, average wound areas expressed as a percentage of baseline area before treatment were compared between groups (ANOVA, Duncan's post-comparison). Significant differences related to the presence of the age, sex, reference wound area, O ₂ pressure of the wound position, or osteomyelitis was seen between groups. At the completion of each of the 7 week treatment periods, there was a significant reduction in CO ₂ in wound surface area compared to the control group (P <0.05).

  A 65-year-old male diabetic patient suffering from hypertension and obstructive arterial disease of the lower extremity (ankle brachial blood pressure ratio 0.4) suffered a post-treatment wound in the metatarsal region of the left foot for 3 months. Prior to carboxy therapy, the patient was treated with antibiotics and extensive debridement without revascularization, and after six applications of carboxy therapy, the wound began to close, and carboxy therapy After 12 applications, new skin is being formed to cover the wound. After 16 applications of carboxy therapy treatment, the wound size was significantly reduced and the rest covered with scabs. After 20 applications of carboxy therapy, the wound was completely covered with freshly grown skin.

  A 51-year-old male diabetic with chronic venous insufficiency in his left leg with secondary deep vein thrombosis. Patients had open ulcers (clinical, pathological, anatomical and pathological elements (CEAP) classification C6) that had not been cured by conventional curative and compressive therapy over the previous 12 months Suffered from. The patient began treatment with carboxy therapy while continuing the conventional therapy already received. The wound began to close after 4 carboxy therapy treatments were applied and covered with a scab after 8 carboxy therapy applications. After 12 cart treatments, the wound size decreased and after 16 carboxy therapy treatments, the wounds were substantially closed.

Example 5: Treatment of striatum The striatum is commonly referred to as the skin striatum and can appear when there is rapid elongation of the skin. They are often associated with abdominal enlargement due to pregnancy. They can also be found in rapidly obese children, or can occur during the rapid growth of adolescent men and women. The filaments are most commonly located in the chest, buttocks, thighs, buttocks, abdomen, and flank.

  A female patient suffered from strie on the buttocks and received a series of carboxy therapy treatments once a month at a dosing rate of 80 ml / min. After 6 carboxy therapy treatments, the appearance of strie was significantly reduced.

Example 6: Treatment of surgical scars Scars are a natural result in several types of injury to the skin. They can be caused by surgical scars, accidental injuries, acne or infection. As the skin heals, the area can become thick, bulge, and can discolor, resulting in a permanent scar. Some scars fade over time, but many remain visible. Even those that fade will take years to do so. In some cases, scar tissue can cause physical discomfort. In other cases, visible scars, such as scars that remain after some type of reconstruction surgery, can cause confusion or emotional discomfort to the patient.

  The patient suffered a scar that remained near the ear after facial wrinkle removal surgery. The appearance of scars and scars after 4 treatments was greatly reduced.

  The female patient suffered from a raised, dark keloid scar on the chest and abdomen after the reconstruction operation. The patient received a series of carboxy therapy treatments once a month at a flow rate of 80 ml / hour. After 6 treatments, the scar disappeared and became brighter and closer to the patient's natural skin tone.

  The above description is intended to teach those skilled in the art the manner of carrying out the invention, and all such obvious modifications and variations that will become apparent to those skilled in the art upon reading this description are described in detail. There is no intention. However, all such obvious modifications and variations are intended to be included within the scope of the present invention, which is defined by the following claims. The claims are intended to cover the elements and steps in any order effective to accomplish their intended purpose, unless explicitly stated otherwise in the context. .

Claims (36)

Applying carboxy therapy to a subject in need of such treatment comprising:
Bringing a treatment device comprising a plurality of hollow needles mounted on a contact surface of a housing and a CO ₂ source in fluid communication with at least one of the plurality of hollow needles into contact with the target body surface of the target;
Applying pressure to the housing such that one or more of the plurality of hollow needles penetrates the epidermis or outermost layer of the target body surface;
Providing a therapeutic amount of CO ₂ to the subject through the plurality of hollow needles; and
Removing the plurality of hollow needles from the target body surface;
Including methods.   The method of claim 1, further comprising the step of applying to the target body surface one or more additional treatments selected from the group consisting of galvanic treatment, electrical stimulation, thermal therapy and phototherapy.   3. The method of claim 2, wherein the one or more additional treatments are provided concurrently with the carboxy therapy using the treatment device.   3. The method of claim 2, wherein the one or more additional treatments are provided before or after the carboxy therapy.   2. The method of claim 1, further comprising applying an effective amount of a treatment composition formulated for topical administration to the target body surface.   The method of claim 1, wherein the plurality of hollow needles have microneedles having a diameter of about 0.1 mm to about 0.5 mm and a length of about 0.4 mm to about 2.1 mm.   The target body surface is acne, psoriasis, skin infection, skin spots, hyperpigmentation, decreased pigmentation, alopecia, hirsutism, growth of wasted hair, rough skin, dry skin, sagging skin, wrinkles, blood vessels Excessive skin, abnormal sebum production, excessive pore conspicuousness, sweaty, excessive sweating, tattoos, rash, scar, itching, itching, burns, inflammation, warts, fish eyes, skin hardening, edema, ivy / oak poisoning, and 2. The method of claim 1, suffering from a skin disease selected from the group consisting of insects, spiders, snakes, and bites by other animals.   The method according to claim 1, wherein the target body surface is a scalp suffering from hair loss.   The method of claim 1, wherein the target body surface suffers from regional alopecia.   The method of claim 1, wherein the target body surface suffers from a diabetic ulcer.   The method of claim 1, wherein the target body surface suffers from a striatum.   The method of claim 1, wherein the target body surface is a scard body surface. A method of treating hair loss in a target area target area comprising:
Introducing an effective amount of CO ₂ into the subcutaneous tissue of the target area over a sufficient period of time, a plurality of hollow needles that puncture the epidermis of the target area at a desired rate within the subcutaneous tissue _The effective amount of CO ₂ is introduced into the target region using the plurality of hollow needles that release ₂ ;
Method. The CO ₂ is introduced at a flow rate of 5～300Ml / min The method of claim 13.   14. The method of claim 13, wherein the sufficient period is 10-60 minutes.   14. The method of claim 13, wherein the introducing step is repeated 4-20 times with an interval of about 24-72 hours between any two iterations.   14. The method of claim 13, further comprising applying local anesthesia to the target area prior to the introducing step.   14. The method of claim 13, further comprising administering to the target area a composition comprising a hair growth promoter, wherein the composition is formulated for topical administration.   Further comprising applying to the target area one or more additional treatments selected from the group consisting of galvanic treatment, electrical stimulation, thermal therapy and phototherapy, wherein the one or more additional treatments are performed concurrently with the introducing step. The method of claim 13. A method of treating a skin disease in a target area of a subject comprising introducing an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient period of time, wherein the effective amount of CO ₂ is in the target area. A method wherein a plurality of hollow needles that puncture the epidermis are introduced into the target region using the plurality of hollow needles that release CO ₂ at a desired rate within the subcutaneous tissue. The CO ₂ is introduced at a flow rate of 5～360Ml / min The method of claim 20.   21. The method of claim 20, wherein the sufficient period is 2 to 120 minutes.   21. The method of claim 20, wherein the introducing step is repeated 1 to 40 times with an interval of about 6 to 120 hours between any two iterations.   21. The method of claim 20, further comprising applying local anesthesia to the target area prior to the introducing step.   21. The method of claim 20, further comprising administering a composition comprising a therapeutic agent to the target area, wherein the composition is formulated for topical administration.   Further comprising applying to the target area one or more additional treatments selected from the group consisting of galvanic treatment, electrical stimulation, thermal therapy and phototherapy, wherein the one or more additional treatments are performed simultaneously with the introducing step. 21. The method of claim 20, wherein: A method of promoting wound healing in a target area of a subject comprising introducing an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient period of time, wherein the effective amount of CO ₂ is the target area A plurality of hollow needles that puncture the epidermis of the skin and are introduced into the target region using the plurality of hollow needles that release CO ₂ within the subcutaneous tissue at a desired rate. The CO ₂ is introduced at a flow rate of 5～300Ml / min The method of claim 27.   28. The method of claim 27, wherein the sufficient period is 10-60 minutes.   28. The method of claim 27, wherein the introducing step is repeated 5 to 20 times with an interval of about 24-120 hours between any two iterations.   28. The method of claim 27, further comprising applying local anesthesia to the target area prior to the introducing step.   28. The method of claim 27, further comprising administering a composition comprising a wound healing promoter to the target area, wherein the composition is formulated for topical administration.   Further comprising applying to the target area one or more additional treatments selected from the group consisting of galvanic treatment, electrical stimulation, thermal therapy and phototherapy, wherein the one or more additional treatments are performed simultaneously with the introducing step. 28. The method of claim 27, wherein:   Comprising a plurality of hollow needles mounted on the surface of the substrate, the hollow needles having a diameter in the range of 0.1 to 0.5 mm and a length in the range of 0.4 to 2.5 mm; And the base body is attachable to a hand-held device so as to form fluid communication with at least one of the plurality of hollow needles, and at least one of the plurality of hollow needles is human A disposable skin treatment device comprising a sharp end capable of penetrating the epidermis. Wherein the plurality of hollow needles, comprising at least 10 needles, and the surface of said substrate, with at least 10 cm ² sizes, disposable skin treatment device according to claim 34. Further comprising a housing, said substrate, said mounted to the housing, wherein the housing is mountable on CO ₂ source, disposable skin treatment device according to claim 34.