KR20160045626A - Apparatus and method for tissue rejuvenation - Google Patents

Abstract

Methods and apparatus for applying carboxytherapy to a subject are disclosed. The method comprising: contacting a treatment device comprising a source of CO _{2 in} fluid communication with a needle of at least one of a plurality of hollow needles and a plurality of hollow needles attached to a contact surface of a housing to a target body surface of the object; Applying pressure to the housing such that one or more needles of the plurality of hollow needles penetrate the outermost layer of the epidermis or cells of the target body surface; Applying a therapeutic amount of CO ₂ to a subject through a plurality of hollow needles; And removing a plurality of hollow needles from the target body surface. Methods of applying carboxy therapy to improve skin conditions are also disclosed.

Description

[0001] APPARATUS AND METHOD FOR TISSUE REJUNCTION [0002]

The present application relates generally to tissue repair in human subjects. In particular, the present invention relates to an apparatus and method for topical administration of carbon dioxide.

Carbon dioxide (CO ₂ ) therapy or carboxytherapy, also known as CDT, is a safe and effective treatment that can improve the appearance of the treated skin. In countries outside the United States, carboxytherapy finds application as a complementary therapy to other forms of aesthetic and therapeutic treatment such as reduction of skin irregularities, wrinkle reduction and liposuction.

Carboxytherapy has been studied in an academic setting for some diseases, but the exact mechanism of carboxytherapy action is not well understood. Therefore, drug and medical device innovation has been a key pathway to skin treatment. However, as patients and healthcare professionals begin to refrain from the pure medical means of treatment, carboxytherapy provides a more "natural" alternative.

As currently applied, carboxytherapy is a non-surgical procedure, but requires treatment by a medical professional. CO ₂ is injected into the subcutaneous tissue using a needle, for example through a very small needle, such as a 30G needle. From the point of injection, CO ₂ diffuses into adjacent tissue. Carboxytherapy uses a harmless amount of inert CO ₂ gas, but the use of a needle as an application method requires the medical professional to apply the treatment.

Currently, the application method requires a medical professional to insert a single needle into the patient for treatment. This individual insertion is safe and effective for small area treatments such as the patient's eye and lips area. However, for large area treatment, individual treatment is too rigorous and time consuming. The benefits of carboxytherapy to treat a wide range of skin disorders have therefore not been fully provided to patients.

One aspect of the invention relates to a method of applying carboxytherapy to a subject in need of treatment comprising: a plurality of hollow needles attached to a contact surface of the housing; And a CO ₂ source in fluid communication with the at least one needle of the plurality of hollow needles with a target body surface of the subject; Applying pressure to the housing such that at least one needle of the plurality of hollow needles penetrates the outermost layer of the epidermis or cells of the target body surface; Applying 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.

Another aspect of the invention relates to a method for treating hair loss in a target area of a subject comprising injecting an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient period of time, The effective amount of carbon dioxide is injected into the target area through a plurality of hollow needles penetrating the epidermis of the skin and releasing carbon dioxide at a desired rate into the subcutaneous tissue.

Another aspect of the invention relates to a method for treating a skin disorder in a target area of a subject comprising injecting an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient period of time, The effective amount of carbon dioxide is injected into the target area through a plurality of hollow needles penetrating the epidermis of the area and releasing carbon dioxide at a desired rate into the subcutaneous tissue.

Another aspect of the invention relates to a method for promoting wound healing in a target area of a subject comprising injecting 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 injected into the target area through a plurality of hollow needles penetrating the epidermis of the area and releasing carbon dioxide at a desired rate into the subcutaneous tissue.

Another aspect of the invention relates to a disposable skin treatment device comprising a plurality of hollow needles attached to a surface of a base, the hollow needles having a diameter in the range of 0.1-0.5 mm and a length in the range of 0.4-2.5 mm, The base can be attached to a portable device to form a fluid communication with at least one of the plurality of hollow needles, and at least one of the plurality of hollow needles can penetrate the human epidermis under the pressure of the hand Includes sharp edges.

The invention will be better understood with reference to the following drawings. The drawings are merely examples for illustrating specific features that may be used alone or in combination with other features, and the present invention should not be limited to the illustrated embodiments.
Figure 1 shows the external contact surface of an exemplary application.
Figure 2 shows the interior of the contact surface of Figure 1;
Figure 3 shows the valve of the exemplary application of Figure 1;
4 shows a handle and an adjustment device of the exemplary application of Fig.
Figure 5 is a side view of the exemplary application of Figure 1 showing a CO ₂ feed line.
Figure 6 shows another exemplary embodiment of an application device having an attached microneedle.
Figure 7 shows penetration of the skin by the microneedles of the device.
Figure 8 shows an exemplary configuration for a microneedle in a base member.
Figure 9 shows another exemplary configuration for a microneedle in a base member.

The following detailed description is presented to enable one skilled in the art to make and use the invention. For purposes of explanation, specific nomenclature is provided to provide a thorough understanding of the present invention. It will be apparent, however, to one skilled in the art that these specific details are not required to practice the present invention. The description of a particular application is provided only as a representative example. The present invention is not intended to be limited to the embodiments shown, but is to be accorded the widest possible scope consistent with the principles and features disclosed herein.

This description is intended to be read in conjunction with the accompanying drawings, which are to be regarded as a part of the overall written description of the present application. The drawings are not necessarily to scale and certain features of the application may be shown exaggerated in the ratios or may be illustrated in somewhat schematic form for clarity and brevity. In the description and in the claims, the singular forms include the plural unless the context clearly indicates otherwise. The present invention provides an improved method and apparatus for applying carboxytherapy to a region of a patient. The apparatus includes a treatment device that is compatible with the microneedles / base member, wherein multiple microneedles are in fluid communication with the CO ₂ source. To apply CO ₂ , the device is placed on the surface of the skin or scalp of the speaker, as described below.

As used herein, the term " administering to the skin in need of treatment "means contacting (e.g., by use of a hand or applicator) an area of skin that requires treatment. These features include but are not limited to eyes, nose, forehead, cheek, chin, and face under or near the neck as well as arms, chest, back, shoulder, abdomen (e.g., It can exist in different areas of the same body.

The term "treatment" of a skin disorder refers to the treatment (e. G., Reduction or elimination and / or treatment) of a skin disorder and / or prevention or inhibition.

The term "skin disorder" or "skin condition" as used herein means a disease, disorder or defect of the skin.

Fine needle

As used herein, the terms "needle" and "microneedle" refer to penetrating members suitable for passing gas therethrough and also suitable for piercing the skin of a patient or subject according to the carboxytherapy method. These terms are interchangeable unless the context clearly dictates otherwise.

Penetration of the skin surface destroys the stratum corneum. When penetrating only the stratum corneum and / or other layers of the epidermis, the patient generally does not feel pain, trauma (e.g., bleeding and swelling), and / or other discomfort. Carboxytherapy provides a therapeutic effect by allowing CO ₂ gas to migrate through the broken skin. In the present invention, the diameter of the microneedles used to penetrate the patient's skin and apply the carboxytherapy should be a suitable gauge to allow the gas to flow therethrough and at the same time be suitable for penetration of various skin types and thicknesses, It should not be too large to cause discomfort to the patient when penetrating.

The term "multiple microneedles" means a group of microneedles that are configured for use in the apparatus and methods disclosed herein. These multiple microneedles need to be firmly attached to the base material to be properly inserted into the patient ' s skin and also to enable the application of other forms of therapy. Examples of suitable materials for use in the microneedle herein include, but are not limited to, for example, stainless steel, gold, iron, steel, tin, zinc, copper, platinum, aluminum, germanium, zirconium, titanium and molybdenum and titanium And may include one or more metals and metal alloys such as alloys, gold, rhodium, iridium, titanium, platinum, silver, metal or non-metal plated with silver halide, and alloys of these other metals.

When individually considered, the microneedles used in the present invention may have a substantially straight or substantially tapered axis. The diameter of the microneedles may be large at the base end of the microneedles to be tapered at points at the distal end of the microneedles. The microneedles may be circular or semi-circular or any other suitable cross-sectional shape. For example, the cross section of the microneedles may be polygonal (e.g., star, square, triangular, rectangular), rectangular, or other shapes. However, whatever form or length is used in the present invention, the microneedle should be suitable for providing a therapy for carboxytherapy to a patient in need of treatment. The microneedles are thus in fluid communication with a CO ₂ source when the microneedle / base member configuration is firmly attached to the treatment device, as further discussed herein.

When fixed to the base material, the microneedles may be oriented substantially at right angles thereto or at an angle. In addition, the microneedles can be oriented substantially perpendicular to the base material. In some embodiments, the configuration of the microneedles may include configurations that include various microneedles directions, heights, or other parameters.

In general, the microneedles should have mechanical strength to withstand changes (e.g., bending) when inserted into the skin and removed more than once.

The microneedles may be made of medical steel, such as acupuncture needles, and may have a diameter of about 0.1 to about 0.5 mm. Each microneedle may be approximately 0.4 to approximately 2.1 mm in length. In an embodiment of the invention, each microneedle is approximately 0.1 mm to 1.1 mm. Further, the length of each microneedle is approximately 0.1, 0.3, 0.5, 0.7, 1.0, 1.5, 2.0, or 2.5 mm, and either of these lengths may be used individually as discussed in other parts of the disclosure, Lt; RTI ID = 0.0 > and / or < / RTI > the CO ₂ source.

As noted, the microneedles must be firmly attached to the base material. In one aspect, the microneedles and the base material to which the microneedles are attached comprise one disposable unit otherwise known as "consumables ". The use of a consumable component that is firmly attached to a reusable treatment device can facilitate tailor-made treatments for each patient as well as maintenance of the sterilization treatment regime.

The base material to which the microneedles are securely fastened to provide the microneedle / base member may include a rigid material that is sufficiently rigid to help bring the attached microneedles through the skin of the patient. In this regard, the microneedles and base material may be constructed as one unit, such as that made from stamping stainless steel using a precision method of forming needle-like protrusions from flat or substantially flat base material. The use of metallic materials may facilitate the application of electrical stimulation and / or thermal therapy to a patient with carboxytherapy treatment, as discussed elsewhere herein. In this connection, the microneedles and the base material are made of the same material.

In addition, the base material may comprise an elastic material so that the base material generally conforms to the contours of the skin and can accommodate deformation that may occur when a micro-needle is inserted. In this regard, the microneedles can be firmly attached to the base material, for example, by embedding microneedles in a polymeric material and then applying a suitable adhesive to ensure adhesion. Because the penetration can be limited by the deviation of the attachment surface, the flexible surface can facilitate more consistent penetration in use.

The depth of CO ₂ infusion may vary from treatment to treatment, for example, the treatment may be from about 2 to about 20 mm. The microneedle depth will be substantially the same as the depth of implant.

Skin treatment device

One aspect of the present application is directed to a skin treatment device that is capable of effectively delivering a therapeutic fluid to the skin and / or subcutaneous tissue of a target bodily area. The benefit of the skin treatment device of the present application is that multiple insertion of the therapeutic fluid beneath the skin surface can be accomplished simultaneously by the practitioner at a controlled flow rate. In some embodiments, the therapeutic fluid is a gas or a mixture of gases. In another embodiment, the fluid is a liquid. In yet another embodiment, the fluid is a vaporizing liquid. In certain embodiments, the fluid is CO ₂ gas.

In one embodiment, the skin treatment apparatus of the present application comprises a housing having a contact surface. The contact surface includes a plurality of hypodermic needles for penetrating the skin and delivering the therapeutic fluid into or below the skin layer. A plurality of needles on the contact surface are in fluid communication with the therapeutic fluid source for transferring therapeutic fluid from the therapeutic fluid source into or through the skin. In some embodiments, the plurality of needles protrude from about 0.1 mm to about 10.0 mm from the contact surface. In some other embodiments, the plurality of needles protrude from about 0.15 mm to about 4.0 mm from the contact surface. In another embodiment, the plurality of needles protrude from about 0.3 mm to about 3.0 mm from the contact surface. In yet another embodiment, the plurality of needles protrude from about 0.3 mm to about 2.0 mm from the contact surface. In some embodiments, the needles may have a diameter of about 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, 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. The length of the needle can adjust the depth level and thus the exact position at which the therapeutic fluid is delivered.

In some embodiments, the needles on the contact surface of the device are all the same length. In another embodiment, the needles on the contact surface of the device are lengths that are mixed to project into or through the body tissue at various depths. The needle can be made of stainless steel, and the force of the needle is several hundred times larger than the force of the skin.

In order to reduce patient inconvenience as much as possible while using a skin treatment device, the needle gauge should be small enough to minimize pain and scarring to the patient. In some embodiments, the size of the needle is sufficient to overcome the natural resistance through the stratum corneum. In some embodiments, the needle is approximately 36 gauge at approximately 26 gauge. In some other embodiments, the needle is approximately 34 gauge at approximately 27 gauge. In yet another embodiment, the needle is approximately 33 gauge at approximately 28 gauge. In yet another embodiment, the needle is approximately 32 gauge at approximately 29 gauge. In yet another embodiment, the needle is approximately 32 gauge at approximately 30 gauge. In some embodiments, the needle is selected from 26, 26s, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 gauge. In some other embodiments, the needle is a microneedle. In some embodiments, the needles on the contact surface of the device are all the same gauge. In another embodiment, the needles on the contact surface of the device are gauges that are mixed to deliver various amounts of therapeutic fluid to various regions of the body tissue.

The size and spacing of the needles may vary according to the needs of the therapy. In some embodiments, the needles are spaced approximately 2, 3, 4, 5, 6, 7, 8, 9, 10 mm relative to each other. The distance between any two needles can be constant or varied. In another embodiment, 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. The average needle density of the contact surface used herein 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 10-500 cm ² , about 20-400 cm ^2, or about 40-200 cm ² . In another embodiment, 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 , about 400 cm ² , about 450 cm ^2, or about 500 cm ² . In some embodiments, the contact surface of the skin treatment device can be detached from the housing, and contact surfaces of various sizes and shapes can be attached to the skin treatment device, depending on the treatment area and treatment method. In some embodiments, the contact surface has some degree of flexibility so that the contact surface can be aligned with the contours of the body surface to be treated, such as the curvature of the waist, thighs, and the like.

In some embodiments, the contact surface is in the form of a roller. In certain embodiments, the roller has a diameter of approximately 2, 3, 4, 5, 6, 7, 8, 9 or 10 cm and a width of approximately 4, 6, 8, 10, 12, 14, 16, (I.e., the distance between the side end portions of the rollers). In some embodiments, the rollers have some flexibility to allow the rollers to conform to the contours of the body surface to be treated, such as the curvature of the waist, thighs, and the like.

In some embodiments, the housing further includes one or more valves to control the flow rate of the therapeutic fluid. In another embodiment, the housing further comprises a battery. In another embodiment, the housing further comprises a control module for controlling the flow rate of the fluid through the at least one valve. In some embodiments, the housing further includes a fluid inlet coupled to a fluid source. In another embodiment, the housing includes a fluid tank disposed within the housing. In some embodiments, the contact surface is detachable and disposable. In another embodiment, the skin treatment device is designed for disposable use.

1 to 5 illustrate an embodiment of a skin treatment apparatus 100 designed to inject CO ₂ into the skin tissue of a patient. Figure 1 shows the contact surface 110 of the housing 120 (see Figure 5). In some embodiments, the contact surface 110 is comprised of an elastic material such as, but not limited to, polyethylene, polyurethane, silicone, or rubber. In another embodiment, the contact surface 110 is comprised of a rigid polymeric material such as, but not limited to, polystyrene, polycarbonate, or polyvinyl chloride. In another embodiment, the contact surface 110 is comprised of a rigid polymeric material coated with a layer of resilient material. In another embodiment, the contact surface 110 is comprised of a biodegradable material. The biodegradable material may be selected from a suitable biodegradable material or a mixture of two or more thereof. Suitable materials include, but are not limited to, cellulose and cellulose derivatives, lactic acid polymers (PLA) and derivatives thereof, hydroxyalkanoate polymers (PHA), biodegradable copolymers and polycaprolactone. The biodegradable material may comprise a true biodegradable polymer (e. G., PHA or PLA), or a biodegradable synthetic polymer or a suitable mixture of two or more thereof.

In this non-limiting example, a plurality of needles are embedded in a nodule 112 that resides on a projection 114 in a contact surface 110 disposed on the outer surface of the removable head 122 of the housing 120 . Before charging the device with CO ₂ gas, the penetration tip of the needle is hidden in the nodule. In some embodiments, the removable head 122 of the housing 120 is disposable, since the contact surface 110 is only a part of the skin treatment apparatus 100 in physical contact with the patient's body. In another embodiment, the removable head 122 of the housing 120 is sterilizable. In some embodiments, nodules may be used to irritate or massage the skin of a patient prior to injection of CO ₂ gas. When a device is filled with a CO ₂ gas, the pressure of the CO ₂ gas causes the nodule through the tip of the nodule CO ₂ gas is injected through the skin by extending to the outside and through the skin of the patient. In some embodiments, such stimulation or massage of the skin with nodules serves to alleviate the pain of the needle through the skin.

FIG. 2 shows the inner surface 124 of the removable head 122 of the housing 120. In some embodiments, the inner surface 124 of the removable head 122 includes a chamber through which CO ₂ gas flows into the needle 112 embedded in the contact surface 110. In some embodiments of the skin treatment apparatus 100, the inner surface 124 of the removable head 122 includes a plurality of CO ₂ diverging chambers 126 that promote a more uniform pressure distribution of CO ₂ gas to all the needles . CO ₂ branch chamber 126 is sealed to the base 128 of the housing 120 by holes or nodule seal including 125 and rubber 127.

Figure 3 shows the base 128 of the housing 120. In some embodiments, the base 128 includes a valve 129 that contacts the hole or nodule 125 in the interior surface 124 of the removable head 122. In some other embodiments, valve 129 is a pin valve in contact with hole / nodule 125. The opening of the valve 129 causes CO ₂ gas to flow into the chamber 126 and through the needle 112 embedded in the contact surface 110 into or through the patient's target skin tissue.

Figure 4 shows the control module 130 of the skin treatment device 100. In some embodiments, the control module 130 includes an adjustment device or button 132 for opening or closing the valve 129 to permit or stop the flow of CO ₂ gas to the needle 112. The control module 130 may further include one or more lamps 134. In some embodiments, at least one light bulb represents a ready state of the apparatus for application of CO ₂ . In some embodiments, at least one light bulb is indicative of a power source charge state of the device. In some embodiments, the housing further comprises one or more batteries for powering the device. In some other embodiments, the battery is rechargeable. In an alternative alternative embodiment, the battery is replaceable. In another embodiment, the skin treatment apparatus 100 is powered by a cord attached to a separate control device or by an electrical cord attached to an external power source. The housing 120 further includes means for establishing fluid communication of a CO ₂ source with a needle that transfers CO ₂ into or through the body tissue. In some embodiments, the CO ₂ source is an external tank or reservoir. In an alternative embodiment, the CO ₂ source is a pressurized CO ₂ cartridge that is inserted or attached to the housing 120 of the apparatus. In some embodiments, the CO ₂ cartridge is replaceable for each new patient. In some embodiments, the adjustment device or button 132 or light 134 may be disposed on the side, front, or back side of the device without being disposed on top of the device.

5 is a side view of an exemplary embodiment of the housing 120. Fig. In this non-limiting example, the control module 130 of the housing 120 is in the form of a knob that allows easy grasping and manipulation by the hand of a medical wearer with gloves. In some embodiments, the CO ₂ gas enters the apparatus from the CO ₂ source through the tube 140 connected to the apparatus.

In yet another non-limiting example of a skin treatment device 100, the flat contact surface 110 of the device may be in the form of a roller member. In some embodiments, a plurality of needles are mounted on the roller member, and the rollers are rotatably mounted on an axis or other suitable configuration of the apparatus that allows the roller to rotate, as contemplated herein. Axis or other suitable configuration may include one or more passageways to enable fluid communication between the CO ₂ and the needle. By being in fluid communication with the CO ₂ source, multiple needles appropriately permit CO ₂ infusion into a patient in need of treatment when one or more of the multiple needles are below the skin surface of the patient. The number of needle bars constituting the contact surface of the roller member of the device may vary depending on the desired therapeutic regimen.

In some embodiments, the roller device includes a plurality of needles permanently attached to the roller device. In some embodiments, the roller member can be detached from the device via a releasable engagement. In some embodiments, the roller members are replaceable disposable for each new patient. In another embodiment, the roller unit is sterilizable.

In some embodiments, the plurality of needles in the roller member are detachable and interchangeable. In one embodiment of this detachable needle construction, the needle is incorporated into a disposable roller cover. The roller cover can be firmly attached to the roller, so that the roller member is properly punched to allow CO ₂ to pass through the needle incorporated into the roller cover. When a needle roller cover is mounted on a perforated roller member, CO ₂ will pass through the skin of the patient when the roller device is placed on the patient's skin. This needle roller cover can improve the safety of the roller device of the present application. If the disposable roller cover is removed from the roller after use, the roller member may be sterilized to further enhance safety.

In some embodiments, the skin treatment device 100 is attached to a pressurized therapeutic fluid source, such as a CO ₂ tank or cartridge. In this embodiment, there is little or no need to include a piston or other type of configuration to provide sufficient delivery of therapeutic material beneath the skin. In some embodiments, the skin treatment apparatus and methods of the present application do not include a piston or other type of delivery improvement mechanism. In one embodiment, the application infuses a therapeutic fluid substantially within or beneath the skin surface by pressure from a pressurized therapeutic fluid source.

Another embodiment of a skin treatment device is shown in Figures 6-9.

6 shows a configuration of a treatment apparatus 100 having a handle portion 202. Fig. At the first end of the handle portion 202, a hose member 204 is attached to a CO ₂ gas source (not shown). As an optional feature, regulator 206 may be included on therapy device 100. [ The switch 208 may facilitate operation. In use, the distal end 210 may be attached to the microneedle / base member 212. Microneedles 214 and base material 216 are also shown.

Referring to FIG. 7, a micro-needle / base member 212 is shown that contacts the skin 300 of the patient and penetrates the inner skin portion 302. The microneedle 214 has a hollow end 218 for filling CO ₂ gas (not shown) in the through region 304

Referring to FIG. 8, an exemplary configuration of the microneedle / base member 220 is shown. The region of the base material 216 has a plurality of microneedles 214. Referring to Fig. 9, another exemplary configuration of the microneedle / base member 222 is shown. The region of the base material 216 has a plurality of microneedles 214. The shape of the base member is not limited to the illustrated form. The present application contemplates a base member of any shape suitable for carrying out the method disclosed in this application. The shape can be determined by the contours of the body regions to be treated or by the need to avoid certain physical characteristics.

In another embodiment, the apparatus of the present application comprises a plurality of exchangeable head units having rings of microneedles of various diameters. For example, if the device has a first exchangeable head with rings or rings of microneedles of large diameter, so that when the ring (s) is at the center of the skin disease being treated, the ring (s) As shown in FIG. The apparatus also includes one or more exchangeable heads having a ring (s) of smaller diameter than the ring (s) on the first exchangeable head described above, thereby placing the ring (s) closer to the skin disease being treated can do.

Skin treatment system

Another aspect of the present application is directed to a method of increasing the temperature of a therapeutic fluid, comprising the steps of: providing an independent therapeutic fluid source, a pressure regulator for regulating the pressure of the therapeutic fluid, a filter for filtering contaminants such as bacteria, viruses and other gaseous impurities in the therapeutic fluid, A flow regulator for controlling the flow rate of the therapeutic fluid, and a skin treatment system for delivering the therapeutic fluid into or under the patient's skin. In some embodiments, the therapeutic fluid is CO ₂ gas. In yet another embodiment, the CO ₂ gas is a medical CO ₂ gas and thus reduces or eliminates the need for a filter.

In an exemplary use of the skin treatment apparatus of the present application, the contact surface or roller of the skin treatment apparatus is directed onto the patient ' s skin such that at least a portion of the plurality of needles protruding from the contact surface penetrate the patient ' s skin. While such needles are present below the surface of the skin, a therapeutic fluid such as CO ₂ is applied from a therapeutic fluid source. Because the needle is in fluid communication with the therapeutic fluid source, the therapeutic fluid will move appropriately 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, the therapeutic fluid may be delivered at various distances below the skin surface of the patient. In the case of roller-type contact surfaces, the frequency of movement of the rollers on the skin can determine the number of puncture channels that can be specially controlled and thus determine the extent to which the therapeutic fluid can penetrate the patient's skin.

Kit

In one aspect, the treatment device, microneedle / base member, and one or more accompanying products of the present application are packaged together and sold as a kit. Examples of items in the kit include, but are not limited to, devices comprising a number of disposable or interchangeable microneedle / base member configurations, carboxytherapy and one or more additions of electrical stimulation, galvanic action or thermotherapy (E.g., a tube, bottle, pump, jar, dropper, or unit dose dispenser) for use prior to, during, or after application of the device Topical therapeutic compositions. Additionally, the kit may also include a cleaning product that is used to sterilize / disinfect the skin prior to application of the device. The kit may also include a film-forming composition or bandage used after treatment to protect the treated skin area and improve the therapeutic effect on the treated skin.

Treatment method

Treatment according to the methods of the present application can be localized, such as in acne or wrinkles, razor bumps / ingrown hair, herring wounds, skin infections, blotch, or other target areas of skin disease have. Therapy can also be used in large areas such as scalp (to enhance hair growth) or thighs or other areas (e.g., to treat subcutaneous fat).

In one aspect, a patient is treated by: (a) attaching a treatment device comprising a plurality of microneedles firmly attached to a surface material; (b) applying pressure to penetrate one or more of the plurality of microneedles through the skin of the patient; (c) carboxytherapy treatment and optionally by applying one or more galvanic treatments, electrical stimulation or thermal therapy; And (d) removing micro-needles from the skin of the patient.

In an exemplary aspect, the medical professional places the treatment device so that the microneedle / base member contacts or substantially contacts the patient's skin location. The treatment device is activated by the user by using a plunger, a piston, or the like, thereby allowing at least some of the plurality of microneedles protruding from the base material to penetrate the patient ' s skin. While such needles are present below the surface of the skin, since CO ₂ is applied from the source and the needle is in fluid communication with the CO ₂ source, the gas will properly travel into and under the skin of the patient, Lt; / RTI > By being in fluid communication with the CO ₂ source, a plurality of needles suitably permit the application of carboxytherapy to a patient in need of treatment when one or more of the plurality of microneedles are below the skin surface of the patient.

For example, in the application of carboxy therapy for intradermal treatment such as skin elasticity, regeneration, pregnancy and hair regeneration, the flow rate for CO ₂ gas may be from about 5 to about 300 ml / min. In some embodiments, the CO ₂ flow rate is from about 50 to about 200 ml / min or from about 80 to about 120 ml / min. In addition, the CO ₂ flow rate can be approximately 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 150, 170 or 200 ml / And may form upper or lower endpoints as appropriate. In some embodiments, the flow rate for the CO ₂ gas is 5-10 ml / min, 5-20 ml / min, 5-40 ml / min, 5-80 ml / min, 5-100 ml / min, min, 5-150 ml / min, 5-200 ml / min, 5-250 ml / min, 10-20 ml / min, 10-40 ml / min, 10-80 ml / 10-150 ml / min, 10-200 ml / min, 10-250 ml / min, 10-300 ml / min, 15-20 ml / min, 15-40 ml / 15-100 ml / min, 15-120 ml / min, 15-150 ml / min, 15-200 ml / min, 15-250 ml / min, 15-300 ml / min 20 to 40 ml / min, 20 to 80 ml / min, 20 to 100 ml / min, 10 to 120 ml / min, 20 to 150 ml / min, 20 to 200 ml / min, 40 to 120 ml / min, 40 to 80 ml / min, 40 to 100 ml / min, 40 to 120 ml / min, 40 to 150 ml / 80-100 ml / min, 80-120 ml / min, 80-150 ml / min, 80-200 ml / min, 80-250 ml / min, 80-300 ml / min, 100- 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, 150-300 ml / min, 150-200 ml / min, 150-250 ml / min, 150-300 ml / min, 200-250 ml / min, 200-300 ml / ml / In the range of. In another embodiment, the CO ₂ gas is supplied at a variable flow rate within a single treatment or during multiple sessions of treatment. In some embodiments, a single treatment session may be performed at a high flow rate period (e.g., 100-200 ml / min), a medium flow rate period (e.g., 40-99 ml / min), and a low flow rate period For example, 10-39 ml / min). In some embodiments, the complete therapy regimen includes one or more sessions of high flow rate (e.g., 100-200 ml / min), one or more sessions of intermediate flow rate (e.g., 40-99 ml / min) (E. G., 10-39 ml / min.). ≪ / RTI > Such treatment time may vary from about 30 seconds to about 180 seconds or from about 45 seconds to about 90 seconds. The treatment time may be approximately 30, 45, 60, 75, 90, 105, 120, 135, 150, 165 or 180 seconds, and any value may suitably form upper or lower endpoints.

As another example, for subcutaneous injection for fat reduction in areas such as the chin, arm, knee, thigh, stomach or hips, the flow rate for CO ₂ gas may range from about 40 to about 360 ml / min, or from about 90 to about 240 ml / min. The CO ₂ flow rates for subcutaneous carboxytherapy treatments were approximately 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 may suitably form the upper or lower endpoint. In some embodiments, the flow rate for the CO ₂ gas is 5-10 ml / min, 5-20 ml / min, 5-40 ml / min, 5-80 ml / min, 5-100 ml / min, min, 5-150 ml / min, 5-200 ml / min, 5-250 ml / min, 5-300 ml / min, 5-360 ml / min, 10-20 ml / 10-100 ml / min, 10-100 ml / min, 10-120 ml / min, 10-150 ml / min, 10-200 ml / min, 10-250 ml / 15 to 120 ml / min, 15 to 120 ml / min, 15 to 120 ml / min, 15 to 120 ml / min, 15 to 120 ml / , 15-200 ml / min, 15-350 ml / min, 15-360 ml / min, 20-40 ml / min, 20-80 ml / min, 20-100 ml / min, 20-150 ml / min, 20-150 ml / min, 20-200 ml / min, 20-250 ml / min, 20-300 ml / min, 20-360 ml / min, 40-80 ml / 40-100 ml / min, 40-150 ml / min, 40-200 ml / min, 40-250 ml / min, 40-300 ml / min, 40-360 ml / 80-100 ml / min, 80-150 ml / min, 80-200 ml / min, 80-250 ml / min, 80-300 ml / min, 80-360 ml / min, 100-120 min, 100-150 ml / min, 100-200 ml / min, 100-250 ml / min, 100-300 ml / min, 100-360 ml / min, 120-150 ml / / Min, 120-250 ml / Min, 120-300 ml / min, 120-360 ml / min, 150-200 ml / min, 150-250 ml / min, 150-300 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. In some embodiments, a single treatment session is performed at a high flow rate period (e.g., 200-360 ml / min), a medium flow rate period (e.g., 50-199 ml / min), and a low flow rate period For example, 5-49 ml / min). In some embodiments, complete therapies include one or more sessions of high flow rate (e.g., 200-3600 ml / min), one or more sessions of intermediate flow rate (e.g., 50-199 ml / min) (E. G., 5-49 ml / min.). ≪ / RTI > The subcutaneous fat treatment time can be from about 1 second to about 8 seconds, or from about 2 seconds to about 6 seconds. The treatment time for subcutaneous injection of CO ₂ may be approximately 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7.0, 7.5, 8, 10, 15, , Any value can appropriately form the upper or lower end point.

In one embodiment, the microneedles / base material and treatment leave can be configured such that electrical current can flow into the patient ' s skin during treatment of the patient. The electricity supplied to the destroyed area can also accelerate other benefits that can extend the therapeutic benefits of healing and carboxytherapy alone. Alternatively, the microneedles may include a conductive material to permit application of heat during treatment (and / or to heat CO ₂ ).

In one aspect of the invention, prior to activating electrical stimulation in the device, the microneedles are inserted into the patient ' s skin to destroy the skin at the desired location (s), thereby increasing the passage of current at the selected skin site, Thereby improving the desired effect.

The electrical characteristics of the treatment device of the present invention include a battery, a piezoelectric element, an electro-mechanical element (for example, an electro-mechanical element, Coil magnets) or by a galvanic couple, the disclosure of which is incorporated by reference in its entirety.

In addition, the skin treatment apparatus of the present invention includes suitable materials capable of providing galvanic action. In this embodiment, the microneedles and / or the base material may be formed of two different metals that contact each other to form a galvanic couple, thus forming a galvanic current when the microneedles / base material contacts the electrolyte containing medium . For example, the base material may be a zinc sheet prepared by the process described in U.S. Patent Nos. 5,983,136, 6,532,386, 6,050,988, or 6,219,574, the disclosures of which are incorporated herein by reference in their entirety. (For example, silver, silver-silver chloride, copper, gold) may be coated on all or part of one or more microneedle regions of the plurality of microneedles.

During skin treatment, for example, the two metals of the galvanic couple (i. E., Zinc and silver-chloride) on the microneedles / base member may be in contact with the electrolyte medium (e. G., A topical composition or body fluid such as perspiration) The contact serves to serve as a galvanic cell and can generate current, which exits the zinc anode, passes through the electrolyte media and / or skin, and returns to the silver-silver chloride cathode.

Alternatively, the two metals forming the galvanic couple may be formed in contact with a third metal (e.g., titanium, or stainless steel), which may be formed on one or more of the microneedle material or base member material, As shown in FIG. For example, electroplating, electroless plating, or conductive ink, including zinc powder and polymeric binders, can be used to coat the zinc layer in selective areas of the titanium or stainless steel microneedle member. Similarly, silver-silver chloride layers can be coated on other areas of the titanium or stainless steel microneedles. The microneedles of the conductive metal serve as leads connecting galvanic elements zinc and silver-silver chloride. During application of the device, a galvanic current is generated when all of the galvanic elements contact the electrolyte media and / or skin.

In order to further enhance the efficacy of electrical stimulation and / or galvanic action, the patient ' s skin must first be treated with a relatively high concentration of cosmetically acceptable organic solvent (e.g., glycerin, propylene glycol, or polyethylene glycol) (E. G., Low molecular weight saccharides, dextran, or urea).

Another aspect of the present application relates to a method of applying carboxytherapy to a subject in need of treatment. The method includes: a plurality of hollow needles attached to a contact surface of a housing; And a CO ₂ source in fluid communication with a needle of at least one of the plurality of hollow needles, the method comprising: contacting a target body surface of a subject; Applying pressure to the housing such that one or more needles of the plurality of hollow needles penetrate the outermost layer of the epidermis or cells of the target body surface; Applying a therapeutic amount of CO ₂ to a subject through a 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 another embodiment, the mammal is a human. In another embodiment, the mammal is a domestic animal such as a dog, a cat, a monkey, a rat, a mouse, a rabbit, a guinea pig, In another embodiment, the mammal is a farm animal such as cattle, horses, pigs, sheep, goats, and the like. In another embodiment, the mammal is a zoo animal.

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

In some embodiments, the plurality of hollow needles is a microneedle 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.

In some embodiments, the target body surface is selected from the group consisting of acne, psoriasis, skin infection, dullness, hyperpigmentation, hypopigmentation, alopecia, excessive hair growth, unwanted hair growth, rough skin, dry skin, , Wrinkles, blood vessels and hypertrophy, sebum production disorders, excessive pores, excessive sweating, hyperhidrosis, tattoos, rashes, scarring, pain, itching, burns, inflammation, , Snakes, and bites from other animals. In one embodiment, the target body surface is a scalp with alopecia. In another embodiment, the target body surface suffers from alopecia areata. In another embodiment, the target body surface is suffering from a diabetic ulcer. In another embodiment, the target body surface is suffering from striae. In another embodiment, the target body surface is a brittle body surface.

Another aspect of the present application relates to a method for treating hair loss in a target area, such as scalp. The method comprises injecting an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient time. An effective amount of carbon dioxide is injected into the target area through a plurality of hollow needles penetrating the epidermis of the target area and releasing carbon dioxide at a desired rate into the subcutaneous tissue.

In some embodiments, CO ₂ is injected into the target area using the skin treatment device and / or skin treatment system of the present application. A plurality of needles in a skin treatment device are selected to have an appropriate size and spacing relationship for hair loss treatment.

In some embodiments, CO ₂ is injected at a flow rate of 50-200 ml / min for a period of 10-60 min.

In another embodiment, the implantation step is repeated 4-20 times, with an interval of approximately 24-72 hours between any two iterations.

In some embodiments, the method further comprises applying a local anesthetic to the target area prior to the infusion step. Examples of topical anesthetics include, but are not limited to, procaine, amethocaine, cocaine, lidocaine, prilocaine, bupivacaine, levobarbital, But are not limited to, levobupivacaine, ropivacaine, mepivacaine and dibucaine, etidocaine, chloroprocaine, sarapin, benzocaine, benzocaine, tetracaine, pramoxine, oxyprocaine, dyclonine, propoxycaine, chloroxylenol, cinchocaine, dextrin, Include dexivacaine, diamocaine, hexylcaine, pyrrocaine, risocaine, and rodocaine.

In some embodiments, the method further comprises applying a composition comprising a hair growth stimulant to a target area, wherein the composition is formulated for topical application. Examples of hair growth promoters include, but are not limited to, hair growth factors, minoxidil, finasteride and copexil, analogs and derivatives thereof; Cyclosporin 7-thioamide, donepezil hydrochloride, antiandrogenic agent, bimatoprost, Sophora flavescens extract, Serenoa Serrata fruit extract (Serenoa serrulata fruit extract), Serenoa repens extract, and licorice extract.

Another aspect of the present application relates to a method for treating skin conditions in a target area. The method comprises injecting an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient time. An effective amount of carbon dioxide is injected into the target area through a plurality of hollow needles penetrating the epidermis of the target area and releasing carbon dioxide at a desired rate into the subcutaneous tissue. In some embodiments, the subdermal layer comprises adipose tissue.

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

In some embodiments, CO ₂ is injected at a flow rate of 40-360 ml / min for a period of 2-120 minutes.

In another embodiment, the implantation step is repeated 1-40 times at an interval of approximately 6-120 hours between any two iterations.

In some embodiments, the method further comprises applying a local anesthetic to the target area prior to the infusion step. Examples of topical anesthetics include, but are not limited to, procaine, ametocaine, cocaine, lidocaine, frylocaine, bupivacaine, levobupivacaine, lopivacaine, mephvacaine and dibucaine.

Examples of skin diseases include, but are not limited to, eczema, seborrhea, vitiligo, lentigo, scleroderma, sunburn, sun damaged skin, estrogen imbalance, Blemishes, bumps, large pores, ruggedness, surface roughness, swelling, loss of skin elasticity, discoloration, yellowing, black spots, freckles, wrinkles and deep wrinkles, fine wrinkles, skin wrinkles, Hyperplasia, hyperkeratinization, elastosis, fibrosis, enlarged pores, subcutaneous fat formation, bruising, scarring, skin irritation, skin rash, skin softness, dryness, rupture, sagging, thinning, hyperplasia, Acne, cystic acne, acne scars, keloid scars, hypertrophic scars, stretch marks (e.g., pregnancy), dermatitis (e.g., seborrheic dermatitis, nummular dermatitis, contact Dermatitis, contact dermatitis, atopic dermatitis, exfoliative dermatitis, perioral dermatitis, and stasis dermatitis), dermis and epidermis hypoplasia, folliculitis ), Enlarged pores, ichthyosis (e.g., ichthyosis hystrix, epidermolytic hyperkeratosis, and lamellar ichthyosis), follicular disorders (E.g., pseudofolliculitis, senile comedones, nevus comedonicus, and trichostasis spinulosa), benign epithelial tumors (e. G., Flat warts, hair follicular epithelium (E.g., trichoepithelioma, and molluscum contagiosum), perforational dermatoses (e.g., elastosis perforans serpiginosa and Kyrles disease), keratinization disorders (e. Dariers disease, keratodermia, hyperkeratosis plantaris, pityriasis rubra pilaris, lichen planus acanthosis nigricans, and psoriasis), as well as other diseases such as diabetes, Pityriasis (e. G., Pityriasis rosea, pityriasis rosacea and pityriasis rubra), keratosis, impetigo, erysipelas, erythrasma ), Eczema, senile purpura, excessive sebum production, sebaceous hyperplasia (enlarged fat glands), viral infections, fungal infections, bacterial infections, spider veins (telangiectasia) Hirsutism, rosacea, pruritus, hard flesh, tubercle, and corn.

In some embodiments, the method further comprises applying a composition comprising a therapeutic agent to a target area, wherein the composition is formulated for topical application. Examples of therapeutic agents include, but are not limited to, antimicrobial agents, analgesics and / or non-steroidal anti-inflammatory agents (NSAIDs), steroidal / corticosteroid agents, wound healing agents, And beneficial agents. Exemplary antibacterial agents include, but are not limited to, antimicrobial agents (e.g., clindamycin and erythromycin, azithromycin, minocycline, tetracycline, kanamycin, Metronidazole, neomycin, bacitracin, polymixin, mafenide acetate, silver sulfadiazine, gentamicin sulfate, and the like; The use of antifungal agents (terbinafine, itraconazole, miconazole nitrate, thiabendazole, tolnaftate, clotrimazole and griseofulvin caprylate Griseofulvin caprylyl glycol, triclosan, phenoxyethanol, nystatin or clotrimazole); antiviral agents (e. G. Acyclovir, brivudine, cidofovir, desciclovir, didanosine, famciclovir, 5-fluorouracil, 5-fluorouracil, ), 2-deoxy- and 5-deoxy-5-fluorouridine, ganciclovir, idoxuridine, lamivudine but are not limited to, lamivudine, lobucavir, penciclovir, retrovir, sorivudine, trifluridine, valacyclovir, valganciclovir, The compounds of the present invention may be used in combination with other therapeutic agents such as vidarabine, zalcitabine, zidovudine, imiquimod, docosanol, brivudine, interferon, famvir, cidofovir, podophyllin, podophyllotoxin); Salicylates including analgesics (e.g., aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), salicylic acid, methyl salicylate, olsalazine, sulfasalazine and salsalate; The compounds of the present invention may be used in combination with other compounds such as diflunisal, para-aminophenol derivatives, acetanilide, acetaminophen, phenacetin, fenamates, mefenamic acid, Meclofenamate, sodium meclofenamate, heteroaryl acetic acid, tolmetin, ketorolac, diclofenac, propionic acid derivatives, ibuprofen, naproxen sodium, , Naproxen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin, enolic acid, oxicam derivatives, , Oil But are not limited to, pyroxicam, meloxicam, tenoxicam, ampiroxicam, droxicam, piroxicam, pyrazolone derivatives, phenylbutazone, but are not limited to, phenylbutazone, oxyphenbutazone, antipyrine, aminopyrine, dipyrone, coxib, celecoxib, rofecoxib, a combination of nabumetone, apazone, indomethacin, sulindac, etodolac, isobutylphenyl propionic acid, lumiracoxib, etoricoxib, parenterally administered drugs such as etoricoxib, parecoxib, valdecoxib, tiracoxib, etodolac, darbufelone, dexketoprofen, aceclofenac, , Licofelone, bromfenac, loxoprofen, pranoprofen, piroxi (piroxi) cam, nimesulide, cizolirine, 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran- 7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one, meloxicam, lornoxicam, d-indobufen, mofezolac, But are not limited to, amtolmetin, pranoprofen, tolfenamic acid, flurbiprofen, suprofen, oxaprozin, zaltoprofen, Alminoprofen and tiaprofenic acid); The use of opioid analgesics such as propoxyphene, meperidine, hydromorphone, dihydromorphine, pethidine, hydrocodone, oxycodone, , Morphine, codeine, and tramodol); NMDA antagonist analgesics (for example, derivatives of 2-piperidino-1 alkanol, ketamine, dextromethorphan), eliprodil, and Ifenprodil); Skeletal muscle relaxants (e. G., Flexeril, carisoprodol, robaxisal, norgesic, and dantrium); Cell differentiation and antiproliferative agents (e. G., Retinoids such as retinol, retinal, and retinyl acetate, retinyl acetate, retinyl butyrate, retinyl propionate retinyl propionate, retinyl octanoate, retinyl laurate, retinyl palmitate, retinyl oleate, and retinyl linoleate. , Vitamin D, E is a vitamin D analogue (calcipotriene)); Chemotenervation agents including botulinum type A and B toxins as well as serotype C-G toxin; Mitochondrial inhibitors (e.g., anthraline (dithranol, chrysarobin, or coal tar)); A topical steroid (for example, clobetasol propionate, betamethasone, betamethasone dipropionate, halobetasol propionate, fluocinonide, , Diflorasone diacetate, mometasone furoate, halcinonide, desoximetasone, fluticasone propionate, fluoranthraquinone, The present invention relates to a pharmaceutical composition comprising flurandrenolide, triamcinolone acetonide, fluocinolone acetonide, hydrocortisone, hydrocortisone valerate, prednicarbate, desonide, or alclometasone dipropionate); Immunosuppressive compounds (e. G., Tacrolimus (FK-506)); JAK2 inhibitors (e. G., INCB18424); JAK3 inhibitors (e. G., CP-690,550); A parathyroid hormone-related protein (PTHrP) antagonist (e.g., PTH (1-34)) and a cell adhesion blocking agent (e.g., a pan-selectin antagonist bacteriophage T4 pyrimidine dimer-specific endonuclease, micrococcus luteus N-glycosylase / AP lyase (Micrococcus luteus N apos; -glycosylase / AP lyase), Saccharomyces cerevisiae N-glycosylase / apurinic-apyrimidinic lyase, Schizosaccharomyces lyase, (PBCV-1 pyrimidine dimer-specific glycosylase), PBCV-1 pyrimidine dimer-specific glycosylase (PBCV-1 pyrimidine dimer-specific glycosylase), UV damage endonuclease Anacystis nidulans photolyase), caffeine (1,3,7-trimethylxanthine), theophylline (1,3-dimethylxanthine), aminophylline, theobromine ; Methylxanthine for use in the present invention including 3,7-dimethylxanthine), paraxanthine, isobutylmethyl xanthine, butyl methylxanthine; salicylic acid The present invention relates to a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of benzoyl peroxide, caffeine, caffeic acid compounds, avobenzone, oxybenzone, octylmethoxycinnamate, titanium dioxide, ), Palmitoyl pentapeptide, argireline, interleukins such as IL6 and IL10, growth factors such as EGF and TGF.

Another aspect of the present application relates to a method for promoting wound healing in a target area, such as scalp. The method comprises injecting an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient time. An effective amount of carbon dioxide is injected into the target area through a plurality of hollow needles penetrating the epidermis of the target area and releasing carbon dioxide at a desired rate into the subcutaneous tissue.

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

In some embodiments, CO ₂ is injected at a flow rate of 5-300 ml / min for a period of 10-60 min.

In another embodiment, the implantation step is repeated 5-20 times, with an interval of approximately 24-120 hours between any two iterations or sessions.

In some embodiments, a session of a method of treating a skin disorder comprises multiple application steps. The first application step includes inserting a needle into the ring at a distance of, for example, 2 to 4 inches from the skin disease being treated. During the first application step, the flow rate of the device is relatively high, for example, 120 to 200 ml / min. After the first application step, at least one intermediate step is continued, wherein the insertion of the ring is closer to the skin disease being treated than the first application step or the previous intermediate step. During each intermediate step, the flow rate is reduced at the immediately preceding application step, for example at a flow rate of 40 to 120 ml / min. The session includes a final application step to the skin around the periphery of the skin disease being treated (such as for open wounds) or inside (such as for scarring or stretch marks). Said final application step is carried out at a relatively low flow rate, for example at a flow rate of from 5 to 20 ml / min.

In some embodiments, the method further comprises applying a local anesthetic to the target area prior to the infusion step. Examples of topical anesthetics include, but are not limited to, procaine, ametocaine, cocaine, lidocaine, frylocaine, bupivacaine, levobupivacaine, lopivacaine, mephvacaine and dibucaine.

In some embodiments, the method further comprises applying a composition comprising a wound healing promoter to a target area, wherein the composition is formulated for topical application. Examples of wound healing accelerators include, but are not limited to, TGF-related related growth factors (TGF-? 1, TGF-? 2, TGF-133), PDGF-associated growth factors (PDGF-M, PDGF-BB, VEGF) (IGF-1, IGF-II, insulin), EGF-related growth factors (EGF, HB-EGF, TGFα, IL-8, interferon, IL-4, IL-10, IL-6, IL-10, MMP-1, -2, -3, -7, -8, -9, 10, -11, -12, -13, -14, -15, - < / RTI > -2, -2, -2, -28, -27, -27, -27, -27, -27, -27, -29, A tissue inhibitor of metallopeptidases (TIMPs), plasmin, a serratiopeptidase (serralysin, serratiapeptase, serratia peptidase, serratia peptidase, peptidase), ceratopeptide Serratia E-15 protease, also known as serratio peptidase or serrapeptidase), carboxylates, cipemastat, doxycycline, hydrosa Hydroxamates, marimastat, phosphinyls, tetracyclines, thiols, and combinations thereof. The term " hydroxamates "

Compositions formulated for topical administration may be in the form of creams, lotions, gels, serums, tonics, emulsions, pastes, or sprays for topical administration. The term "cream ", as used herein, refers to a well-spreading composition that is generally formulated for skin charts. Creams generally include oil and / or fatty acid-based matrices.

An effective amount of CO ₂ is determined by the treatment method. In some embodiments, an effective amount of CO ₂ is defined as the ratio of CO ₂ given to the target area, and the treatment period is a single session. An effective amount of carbon dioxide may vary from patient to patient, however, in some embodiments, the CO ₂ is administered in a single session for about 05-60 minutes, about 0.5-5 minutes, about 0.5-10 minutes, about 0.5-20 minutes, About 2-50 minutes, about 2-50 minutes, about 2-5 minutes, about 2-10 minutes, about 2-20 minutes, about 2-30 minutes, about 2-40 minutes, about 2-50 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- About 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 minutes, about 30-50 minutes, about 30-60 minutes, about 40-50 minutes, about 40-60 minutes, or about 0.1-20 ml / cm ² / min for a period of approximately 50-60 minutes, about 0.1-1 ml / cm ² / min, about 0.1-2 ml / cm ² / min, about 0.1-5 ml / cm ² / min, about 0.1-10 ml / cm ² / min, ² / min approximately 0.1-15 ml / cm, approximately 0.5-2 ml / cm ² / min, about 0.5-5 ml / cm ² / min, about 0 .5-10 ml / cm ² / min, about 0.5-15 ml / cm ² / min, about 0.5-20 ml / cm ² / min, ² / min approximately 1-2 ml / cm, approximately 1-5 ml / cm ² / min, about 1-10 ml / cm ² / min, about 1-15 ml / cm ² / min, about 1-20 ml / cm ² / min, about 2-5 ml / cm ² / 2-10 ml / cm ² / min, about 2-15 ml / cm ² / min, about 2-20 ml / cm ² / min, about 5-10 ml / cm ² / min, about 5-15 ml / cm with ² / min, about 5-20 ml / cm ² / min, about 10-15 ml / cm ² / min, about 10-20 ml / cm ² / min or a flow rate of ² / min, about 15-20 ml / cm Is injected into the target area.

In some embodiments, the treatment is administered at 2-40, 2-30, 2-20, 2-10, 2-5, and 4-24 intervals at approximately 12-72, 12-48, 12-24 hour intervals between each two sessions -40, 4-30, 4-20, 4-10, 6-40, 6-30, 6-20, 6-10, 8-40, 8-30, 8-20, 10-40, 10-30 , 10-20, 15-40, 15-30, 15-20, 20-40, or 20-30 sessions.

The multi-needle approach also reduces the time required to provide a beneficial amount of CO ₂ to a patient in need of such treatment without diminishing the efficacy of the treatment. In addition, beneficial CO ₂ treatment can be applied to large surfaces within a short time.

In some embodiments, the method of treatment using the apparatus of the present application does not involve the application of other active ingredients besides CO ₂ . In another embodiment, the method of using the device consists essentially of applying CO ₂ below the skin of a patient in need of treatment.

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

Example

Example  1: Treatment of alopecia areata

One female patient had alopecia areata and suffered from this disease for more than 7 years. The patient visited 14 diverse specialists in search of appropriate treatment, but fell to the point of wearing a wig. Treatments, including topical application of minoxidil and hair growth factors, did not provide satisfactory relief for the disease. The patient received a weekly carboxytherapy treatment in a clinical setting. Warmly heated CO ₂ was administered at a flow rate of 80 ml / min. In addition, the patient was instructed to continue topical administration of minoxidil and hair growth factor once a day.

After 10 clinical sessions of two and a half months, the patient showed significant hair ingrowth into the bald patches. The clinical treatment protocol was reduced to twice a month for carboxytherapy treatments. After approximately 20 sessions of clinical carboxytherapy treatment for approximately 6 months, the patient showed hair over the entire bald patches.

Example  2: Treatment of male baldness

One adult male patient had hair loss around the kiln. This patient was clinically treated with carboxytherapy and significant hair regrowth around the kiln within 3 months. After 5 months of carboxytherapy, the patient experienced complete growth of normal textured hair around the kiln.

Example  3: Treatment of overall hair thinning

One male patient had an overall thinning of hair over the entire crown of the scalp. This patient received a monthly clinical carboxytherapy treatment. After 3 months, the patient showed significant internal filling of the tapered area. The treatment protocol was changed to two doses of carboxytherapy per month, and at 5 months the patient was covered with normal textured hair with a crown area.

Example  4: Treatment of diabetic ulcers

Ten insulin-dependent diabetics with chronic scarring were treated with CO ₂ transdermal therapy. The control group consisted of five patients, three of whom had claustrophobia and two who refused CO ₂ inhalation therapy for symbolic reasons. Five patients received 30 CO ₂ inhalation treatments at the wound healing protocol (30 minutes per day, 5 days per week). All patients were evaluated with transcutaneous oxygen measurement and early surgical necrosis of the wound was removed.

An exemplary protocol for CO ₂ inhalation therapy of ulcerated wounds involves several steps of applying CO ₂ . The first application step includes inserting a needle into a ring of large radius around the wound, e.g., about 2 inches at the wound edge. The CO ₂ gas is sucked at a high flow rate of, for example, 120 to 200 ml / min, more particularly about 150 ml / min. Followed by a second application in a small ring approximately 1 inch from the wound edge. The CO ₂ gas is sucked at a low flow rate of, for example, 50 to 100 ml / min, more specifically about 80 ml / min. Followed by a third application in a smaller ring approximately 1/2 inch from the wound edge. The CO ₂ gas is sucked at a lower flow rate, for example, from 30 to 50 ml / min, more specifically about 40 ml / min. The final application step occurs in the skin just around the wound using one microneedle insertion tool at a very low flow rate of about 5 to 25 ml / min, more particularly about 15 to 20 ml / min.

One weekly tracing of the wound surface was performed by a nurse or resident who did not know the group assignment. At the end of 7 weeks, the average wound area as a percentage of the pretreatment reference area was compared between groups (variance analysis, Duncan's post hoc). There were no significant differences between the groups in terms of age, sex, reference wound area, wound site O ₂ partial pressure, or presence of osteomyelitis. At the completion of each 7-week treatment period, there was a significant reduction in wound surface (P < 0.05) in CO ₂ for the control.

A 65 - year - old male diabetic patient with hypertension and lower limb hemorrhagic disorder (ankle brachial index 0.4) showed a 3 - month post - traumatic wound in the tribo - oval area of the left foot. Prior to carboxytherapy, the patient was treated with antibiotics and necrotizing cholestasis without vascular reconstruction procedures. After 6 applications of the carboxytherapy treatment, the wound began to clog and a new skin formed on the wound after 12 doses of carboxytherapy. After 16 doses of carboxytherapy treatment, there was a significant reduction in the size of the wound and the rest was covered with a scab. After 20 applications of carboxytherapy, the wound was completely covered by new skin growth.

A 51 - year - old male diabetic patient with chronic venous insufficiency in the left lower leg showed secondary deep vein thrombosis. This patient had an open ulcer (clinical, aetiological, anatomical and pathological (CEAP) factor classification C6) that did not respond to traditional healing and compressive therapy for the previous 12 months. The patient began the carboxytherapy treatment process with maintenance of the existing therapies already in use. After four applications of carboxytherapy treatment, the wound began to close and was covered with a scab after eight carboxytherapy applications. There was a decrease in the size of the wound after 12 carboxytherapy treatments, and the wound was substantially closed after 16 carboxytherapy treatments.

Example  5: Stretchy  cure

Stretch marks, commonly referred to as stretch marks, can appear when the skin is rapidly swollen. These are often associated with abdominal enlargement of the pregnancy. They can also be found in fast-paced, obese children, or during the rapid growth of male and female puberty. Stretch is most commonly found in the chest, buttocks, thighs, buttocks, abdomen, and flank.

One female patient was treated with a once-monthly carboxytherapy treatment course at a rate of 80 ml / min. After six carboxytherapy treatments, the appearance of the stretch marks has significantly decreased.

Example  6: Treatment of surgical trauma

Scars are a natural consequence of any damage to the skin. This can happen as a result of surgery, accidental injury, acne or infection. As the skin heals, the area becomes thicker, bulging and discolored, and becomes a permanent scar. Some scars fade with time, but most are still noticeable. It can take several years to get even faded. In some cases, scar tissue can cause discomfort in the body. In addition, visible scars can cause awkwardness and emotional discomfort to the patient, such as left over after some types of reconstructive surgery, for example.

One patient had a scar remaining near the ear after wrinkle removal surgery. After 4 treatments, the visibility of the scar was greatly reduced.

A female patient had a keloid scar that had been spotted on the chest and abdomen after a revision operation. The patient was treated with a monthly carboxytherapy treatment at a flow rate of 80 ml / min. After six treatments, the scar did not rise any further and became almost as bright as the patient's natural skin color.

The foregoing description is intended to teach those skilled in the art how to make and use the invention and is not intended to be exhaustive of all obvious variations and modifications of the invention that will become apparent to those skilled in the art upon reading the description. However, such obvious changes and modifications are intended to be included within the scope of the present invention as defined by the appended claims. The claims are intended to include the elements and steps in any order effective for achieving the intended purpose, unless the context clearly dictates otherwise.

Claims (36)

A method of applying carboxytherapy to a subject in need of treatment,
A plurality of hollow needles attached to a contact surface of the housing; And
Contacting a treatment device comprising a CO ₂ source in fluid communication with at least one needle of the plurality of hollow needles to a target body surface of the subject;
Applying pressure to the housing such that at least one needle of the plurality of hollow needles penetrates the outermost layer of the epidermis or cells of the target body surface;
Applying a therapeutic amount of CO ₂ to the subject through the plurality of hollow needles; And
And removing the plurality of hollow needles from the target body surface.
The method according to claim 1,
Further comprising the step of performing at least one additional treatment on said target body surface selected from the group consisting of galvanic therapy, electrical stimulation, thermal therapy and phototherapy.
3. The method of claim 2,
Wherein said at least one additional treatment is provided concurrently with said carboxy therapy using said treatment device.
3. The method of claim 2,
Wherein said one or more additional treatments are provided before or after said carboxy therapy.
The method according to claim 1,
Further comprising the step of applying to said target body surface an effective amount of a therapeutic composition formulated for topical administration.
The method according to claim 1,
Wherein the plurality of hollow needles are microneedles having a diameter of approximately 0.1 mm to approximately 0.5 mm and a length of approximately 0.4 mm to approximately 2.1 mm.
The method according to claim 1,
The surface of the target body may be damaged by acne, psoriasis, skin infection, dullness, hyperpigmentation, hypopigmentation, alopecia, excessive hair growth, unwanted hair growth, rough skin, dry skin, loose skin, wrinkles, , Bruises from bites from insects, spiders, snakes, and other animals, including excessive pores, excessive sweating, hyperhidrosis, tattoos, rashes, scarring, pain, itching, burns, inflammation, varicose veins, corns, Lt; RTI ID = 0.0 > 1, < / RTI >
The method according to claim 1,
Wherein the target body surface is a scalp with alopecia.
The method according to claim 1,
Wherein the target body surface is suffering from alopecia areata.
The method according to claim 1,
Wherein the target body surface is suffering from a diabetic ulcer.
The method according to claim 1,
Wherein the target body surface is suffering from stretch marks.
The method according to claim 1,
Wherein the target body surface is a brittle body surface.
A method for treating hair loss in a target area of a subject, the method comprising injecting an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient period of time to penetrate the epidermis of the target area, Wherein the effective amount of carbon dioxide is injected into the target area through a plurality of hollow needles that emit carbon dioxide at a desired rate.
14. The method of claim 13,
Wherein said CO ₂ is injected at a flow rate of 5-300 ml / min.
14. The method of claim 13,
Wherein the sufficient time is 10-60 minutes.
14. The method of claim 13,
Characterized in that the implantation step is repeated 4-20 times with an interval of approximately 24-72 hours between any two iterations.
14. The method of claim 13,
Further comprising applying a local anesthetic to the target area prior to the injecting step.
14. The method of claim 13,
Wherein the method further comprises administering a composition comprising a hair growth promoter to the target area, wherein the composition is formulated for topical administration.
14. The method of claim 13,
The method of claim 1, further comprising the step of performing at least one additional treatment on the target area selected from the group consisting of galvanic therapy, electrical stimulation, thermal therapy and phototherapy, wherein the at least one additional treatment is performed simultaneously with the implantation step How to.
A method for treating a skin disorder in a target area of a subject, the method comprising injecting an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient period of time to penetrate the epidermis of the target area Wherein the effective amount of carbon dioxide is injected into the target region through a plurality of hollow needles that emit carbon dioxide at a desired rate within the tissue.
21. The method of claim 20,
Wherein said CO ₂ is injected at a flow rate of 5-360 ml / min.
21. The method of claim 20,
Wherein the sufficient time is 2-120 minutes.
21. The method of claim 20,
Wherein said injecting step is repeated 1-40 times at an interval of about 6-120 hours between any two iterations.
21. The method of claim 20,
Further comprising applying a local anesthetic to the target area prior to the injecting step.
21. The method of claim 20,
Further comprising administering to the target area a composition comprising a therapeutic agent, wherein the composition is formulated for topical administration.
21. The method of claim 20,
The method of claim 1, further comprising the step of performing at least one additional treatment on the target area selected from the group consisting of galvanic therapy, electrical stimulation, thermal therapy and phototherapy, wherein the at least one additional treatment is performed simultaneously with the implantation step How to.
A method for promoting wound healing in a target area of an object, the method comprising injecting an effective amount of CO ₂ into the subcutaneous tissue of the target area for a sufficient period of time to penetrate the epidermis of the target area Wherein an effective amount of carbon dioxide is injected into the target region through a plurality of hollow needles that emit carbon dioxide at a desired rate within the tissue.
28. The method of claim 27,
Wherein said CO ₂ is injected at a flow rate of 5-300 ml / min.
28. The method of claim 27,
Wherein the sufficient time is 10-60 minutes.
28. The method of claim 27,
Characterized in that the implantation step is repeated 5-20 times at intervals of approximately 24-120 hours between any two iterations.
28. The method of claim 27,
Further comprising applying a local anesthetic to the target area prior to the injecting step.
28. The method of claim 27,
Further comprising administering a composition comprising a wound healing promoter to the target region, wherein the composition is formulated for topical administration.
28. The method of claim 27,
The method of claim 1, further comprising the step of performing at least one additional treatment on the target area selected from the group consisting of galvanic therapy, electrical stimulation, thermal therapy and phototherapy, wherein the at least one additional treatment is performed simultaneously with the implantation step How to.
1. A disposable skin treatment device comprising a plurality of hollow needles attached to a surface of a base, the hollow needles having a diameter in the range of 0.1-0.5 mm and a length in the range of 0.4-2.5 mm, Wherein the at least one needle of the plurality of hollow needles comprises a sharpened end capable of penetrating the skin of a human under the pressure of the hand, Gt; a < / RTI > disposable skin treatment device.
35. The method of claim 34,
A plurality of said hollow needle includes at least 10 needles, disposable skin treatment device, characterized in that a size of the surface is at least 10 cm ² of the base.
35. The method of claim 34,
Further comprising a housing, the base being attached to the housing and the housing being attachable to a CO ₂ source.

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