JP2013176628A - Method and apparatus for reducing sweat production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method and an apparatus for reducing sweat production.SOLUTION: A method and an apparatus are provided for reducing sweat production via the removal, disablement, and disablement of sweat glands in the epidermis 102, dermis 101 and subdermal tissue regions 100 of a patient. There is provided a method of treating a patient which involves: a step of identifying a patient having a condition of excessive sweating; a step of positioning an energy delivery device 111 proximate to a skin tissue of the patient; and a step of delivering energy 112 to sweat glands to halt secretion of sweat. The energy delivery device may include microwave delivery devices, RF delivery devices, and cryogenic therapy devices. Some embodiments may include a step of using: a cooling element for avoiding destruction of non-target tissue; and/or a suction device to localize treatment at specific portions of the skin fold.

Description

(Cross-reference of related applications)
This application is based on US Provisional Patent Application No. 60 / 912,899 (named “Methods and Apparatus for Reducing Sweat Production”, filed April 19, 2007), US Provisional Patent Application No. 61 / 013,274 (named “Methods”). , Delivery and Systems for Non-Invasive Delivery of Microwave Therapeutic, filed December 12, 2007, and US Provisional Patent Application No. 61/045, 937 (named “Systems and Methods United Method”). US Patent Act, Section 119 (e) of “Tissue”, filed April 17, 2008). It claims the benefit of priority. The entire disclosure of all of these priority applications is hereby incorporated by reference in its entirety.

(Field of Invention)
The present application relates to a method and apparatus for reducing sweat production. In particular, this application relates to methods and apparatus for reducing the production of sweat through removal, disabling, and disabling of apocrine and eccrine sweat glands in the dermis and subcutaneous tissue.

(Field of Invention)
It is known that energy therapy can be applied to tissues throughout the body so as to achieve a number of treatment and / or aesthetic results. There remains a continuing need to improve the effectiveness of these energy therapies and provide beneficial pathological changes with minimal adverse side effects or discomfort.

(Outline of treatment)
Sweating is a normal thermoregulatory process for humans as well as a normal physiological response to psychological stress and cyclic stimuli. For most people, sweating is only a minor aesthetic discomfort. However, for other people, sweating is excessive and abnormal, and as a result, there may be a socially unsatisfactory state. Some embodiments of the invention relate to methods for reducing sweat production through removal, disabling, disabling, and destruction of sweat glands in human subcutaneous tissue.
For example, the present invention provides the following.
(Item 1)
An apparatus for treating a patient's sweat glands,
An energy generator;
An energy delivery device configured to be placed proximate to the patient's skin tissue;
The energy delivery device is coupled to the energy generator, the energy delivery device sufficient to at least partially destroy or disable at least one sweat gland in a target tissue in the skin tissue A device configured to deliver energy to the target tissue.
(Item 2)
The apparatus of claim 1, wherein the energy delivery device is configured to be inserted into the target tissue.
(Item 3)
The energy delivery device comprises at least one energy delivery element selected from the group consisting of electrodes, antennas, ultrasonic transducers, lasers, light emitting diodes, light bulbs, cryogenic probes, and combinations thereof. Equipment.
(Item 4)
The apparatus of claim 1, further comprising a cooling element configured to be placed proximate to the non-target tissue of the patient.
(Item 5)
The apparatus of claim 1, further comprising an aspiration device configured to be placed proximate to the skin tissue of the patient.
(Item 6)
An apparatus for treating a target tissue of a patient,
An intervening device comprising at least one needle configured to be inserted proximate to the target tissue of the patient;
A light energy source configured to transmit light energy to the intervening device; and
And the needle is configured to receive the light energy transmitted by the light energy source.
(Item 7)
The apparatus of item 6, wherein the needle comprises a chromophore configured to absorb the light energy received from the light energy source.
(Item 8)
Item 8. The apparatus of item 7, wherein the chromophore generates thermal energy from the light energy absorbed from the light energy source.
(Item 9)
Item 9. The device of item 8, wherein the thermal energy from the chromophore produces a therapeutic effect on the target tissue.
(Item 10)
The apparatus according to item 9, wherein the therapeutic effect on the target tissue includes heating the target tissue.
(Item 11)
The apparatus of claim 9, wherein the therapeutic effect on the target tissue comprises at least partially excising the target tissue.
(Item 12)
Item 10. The item 9, wherein the therapeutic effect on the target tissue comprises at least partially disabling at least one target structure selected from the group consisting of sweat glands, hair follicles, sebaceous glands, collagen, and fat. Equipment.
(Item 13)
10. The apparatus of item 9, wherein the intervening device further comprises a microneedle patch having an optically neutral backing.
(Item 14)
A method for treating a patient, comprising:
Identifying a patient having symptoms of excessive sweating, wherein the patient desires that sweating be reduced in at least a portion of the patient's body;
Placing an energy delivery device proximate to the patient's skin tissue;
Delivering sufficient energy to the sweat gland of the patient to stop sweat secretion by at least partially disabling or destroying the sweat gland;
Including a method.
(Item 15)
Arranging the energy delivery device further comprises placing the energy delivery element on the skin of the patient selected from the group consisting of electrodes, antennas, ultrasonic transducers, lasers, light emitting diodes, light bulbs, cryogenic probes, and combinations thereof. 15. The method of item 14, comprising placing in proximity to the tissue.
(Item 16)
15. The method of item 14, wherein placing an energy delivery device further comprises inserting the energy delivery device into the skin tissue.
(Item 17)
Inserting the energy delivery device into the skin tissue further includes inserting the energy delivery device into the skin tissue to a depth in the range of about 1 mm to about 8 mm below the surface of the skin. The method according to item 16.
(Item 18)
Delivering energy to the patient's sweat gland further comprises electromagnetic, X-ray, radio frequency, microwave, ultrasound, near infrared, infrared, ultrashort pulsed light, visible light, and laser, and combinations thereof 16. The method of item 15, comprising delivering energy selected from a group to the sweat gland.
(Item 19)
19. The method of item 18, wherein delivering energy to the sweat gland further comprises heating the sweat gland.
(Item 20)
20. The method of item 19, wherein heating the sweat gland further comprises at least partially excising the sweat gland.
(Item 21)
15. The method of item 14, further comprising providing protective cooling to the skin tissue.
(Item 22)
28. The method of item 21, wherein providing protective cooling to the skin tissue further comprises positioning a cooling element proximate to the skin tissue.
(Item 23)
15. The method of item 14, further comprising administering to the patient an agent selected from the group consisting of anesthetics, steroids, and antibiotics.
(Item 24)
24. The method of item 23, wherein administering the drug to the patient further comprises administering the drug orally, topically, or via injection.
(Item 25)
15. The method of item 14, further comprising visualizing the sweat gland using medical imaging.
(Item 26)
15. The method of item 14, further comprising monitoring said skin tissue diagnostic parameter.
(Item 27)
27. The method of item 26, wherein the diagnostic parameter is selected from the group consisting of impedance, temperature, reflected light, and reflected power.
(Item 28)
15. The method of item 14, wherein delivering energy to the patient's sweat gland further comprises modulating energy delivery in response to the monitored diagnostic parameter.
(Item 29)
15. The method of item 14, further comprising reducing the sweating achieved in the patient or quantifying the treated part of the patient's body.
(Item 30)
15. The method of item 14, wherein at least a portion of the patient's body includes at least a portion of the patient's axilla.
(Item 31)
15. The method of item 14, further comprising raising the skin tissue away from the underlying tissue prior to delivering energy to the sweat glands.
(Item 32)
Inserting the energy delivery device into the skin tissue further comprises inserting an intervening device selected from the group consisting of a needle, a stylet, a catheter, a probe, and a microneedle into the skin tissue. 16. The method according to 16.
(Item 33)
A method of treating a patient for symptoms of hyperhidrosis, comprising:
Identifying a skin tissue region on a patient comprising a sweat gland layer, the skin tissue region producing excess sweat associated with the hyperhidrosis;
Gripping the skin tissue region to form a skin fold comprising a first side and a second side, wherein the sweat gland layer corresponding to the first side comprises Adjacent to the sweat gland layer corresponding to the second side, so that the layer includes a treatment zone;
Delivering energy to the treatment area to produce a therapeutic effect, the therapeutic effect reducing the amount of sweating from the skin tissue region;
Including a method.
(Item 34)
34. The method of item 33, further comprising applying protective cooling to at least a portion of the skin tissue region.
(Item 35)
35. The method of item 34, wherein applying protective cooling to at least a portion of the skin tissue region further comprises positioning a cooling element proximate to the skin fold.
(Item 36)
Placing a cooling element proximate to the skin fold further comprises a first cooling element proximate to the first side of the skin fold and the second of the skin fold. 36. A method according to item 35, comprising disposing a second cooling element proximate to the side.
(Item 37)
34. The method of item 33, wherein gripping the skin tissue region to form a skin fold further comprises providing suction to the skin tissue region.
(Item 38)
38. The method of item 37, wherein providing suction to the skin tissue region further comprises maintaining suction to the skin tissue region during treatment.
(Item 39)
A method for reducing patient sweating, comprising:
Raising the skin tissue of the patient, the skin tissue comprising a target tissue comprising at least one sweat gland;
Delivering energy to the target tissue, wherein the delivery of energy at least partially disables or destroys the at least one sweat gland to reduce sweating from the skin tissue of the patient; And
Including a method.
(Item 40)
40. The method of item 39, wherein delivering energy to the target tissue further comprises positioning an energy delivery device proximate to the skin tissue of the patient.
(Item 41)
Arranging the energy delivery device further comprises providing an energy delivery element selected from the group consisting of an electrode, an antenna, an ultrasonic transducer, a laser, a light emitting diode, a light bulb, a cryogenic probe, and combinations thereof to the patient. 41. The method of item 40, comprising placing proximate to skin tissue.
(Item 42)
28. The method of item 27, wherein placing an energy delivery device further comprises inserting the energy delivery device into the skin tissue.
(Item 43)
43. The method of item 42, wherein inserting the energy delivery device into the skin tissue further comprises positioning an insertion element energy delivery element proximate to the target tissue.
(Item 44)
40. The method of item 39, wherein the energy delivery element is selected from the group consisting of electrodes, antennas, ultrasonic transducers, lasers, light emitting diodes, light bulbs, and combinations thereof.
(Item 45)
27. A method according to item 26, wherein raising the skin tissue further includes applying suction to the skin tissue.
(Item 46)
40. The method of item 39, further comprising providing protective cooling to the skin tissue.
(Item 47)
47. The method of item 46, wherein providing protective cooling to the skin tissue further comprises positioning a cooling element proximate to the skin tissue.
(Item 48)
Delivering energy to the target tissue further includes delivering energy to the first portion of the target tissue a first time and delivering energy to the second portion of the target tissue a second time. 40. A method according to item 39.
(Item 49)
49. A method according to item 48, wherein the first time and the second time are separated by a predetermined period.
(Item 50)
50. The method of item 49, wherein the predetermined period is selected from the group consisting of 1-7 days, 1-4 weeks, and 1-4 months.

These and other features, aspects and advantages of the various devices, systems and methods presented herein are intended to illustrate, but not limit, such devices, systems and methods, An embodiment will be described with reference to the drawings. It should be understood that the accompanying drawings are for purposes of illustrating the concepts of the embodiments discussed herein and may not be to scale.
FIG. 1 shows a cross-sectional view of the skin, its internal structure, and surrounding tissue. FIG. 2 illustrates a cross-sectional view of a target tissue having a thermal treatment zone, according to one embodiment. FIG. 3 illustrates a device having an energy applicator according to one embodiment. FIG. 4 shows an isometric view of a non-invasive energy delivery device comprising a plurality of microwave antennas electrically connected to a microwave generator, according to one embodiment. FIG. 5 shows a cross-sectional side view of the non-invasive energy delivery device of FIG. 4 that delivers energy into the skin. FIG. 6A illustrates a monopole antenna according to one embodiment. FIG. 6B illustrates a dipole antenna according to one embodiment. FIG. 6C illustrates a helical antenna according to one embodiment. FIG. 6D shows a loop antenna according to one embodiment. FIG. 6E illustrates a monopole antenna with a conductive shield or sleeve, according to one embodiment. FIG. 6F illustrates an antenna having a shaped outer conductor, according to one embodiment. FIG. 6G illustrates an antenna with a shaped outer conductor, according to one embodiment. FIG. 7A illustrates a cross-sectional view of an antenna having an inner conductor disposed within a coaxial cable, according to one embodiment. FIG. 7B illustrates a coiled antenna having coiled conductor elements formed entirely from coaxial cable, according to one embodiment. FIG. 7C illustrates a coiled antenna having a coiled conductor element formed from an inner conductor, according to one embodiment. FIG. 8 shows a needle that injects fluid near the sweat gland and the base of the target tissue, according to one embodiment. FIG. 9 shows a number of possible configurations of bipolar electrodes for the desired therapeutic area. FIG. 10 illustrates an RF delivery device having one or more energy delivery elements comprising an electrode tip needle, microneedle, or stylet for insertion into the skin, according to one embodiment. FIG. 11 illustrates an energy delivery device comprising a needle configured for percutaneous insertion, according to one embodiment. FIG. 12A illustrates a cryogenic system configured to have an intervening element comprising at least two concentric tubes, according to one embodiment. FIG. 12B shows a cryogenic system configured to have intervening elements configured with tubular coils residing inside the element. FIG. 12C shows a cryogenic system configured to have intervening elements configured with tubular coils that are partially inside and partially outside the element. FIG. 12D illustrates a cryogenic system configured to have an inner portion and an outer portion such that nitrous oxide gas exits the distal portion of the inner tube and absorbs thermal energy from the distal portion of the outer tube. Show. FIG. 12E illustrates cryoprotectant injection, according to one embodiment. FIG. 12F illustrates a protected non-target tissue area between the cold source at the skin surface and the cryotherapy area of the target tissue, according to one embodiment. FIG. 13 illustrates a layer of colored bioresorbable microspheres deposited in or around a target tissue, according to one embodiment. FIG. 14 illustrates a carrier solution being introduced by a hollow needle into a planar junction between the dermis layer and the subcutaneous layer, according to one embodiment. FIG. 15 illustrates needles consisting of at least one chromophore on their tips, according to one embodiment. FIG. 16 illustrates a microneedle configuration with an undetectable chromophore tip, according to one embodiment. FIG. 17 shows locally applied aluminum ion particles moving down the sweat gland duct. FIG. 18A illustrates a microneedle patch according to one embodiment. FIG. 18B illustrates an ultrasound transducer that emits waves as part of ultrasound therapy, according to one embodiment. FIG. 18C illustrates a planar ultrasound transducer that emits waves as part of ultrasound therapy, according to one embodiment. FIG. 19 illustrates thermal disabling of sweat glands using controlled chemistry, according to one embodiment. FIG. 20A shows a sweat tube. FIG. 20B shows the sweat tube of FIG. 20A with an insulating layer, according to one embodiment. FIG. 20C shows the sweat tube of FIG. 20B having an insulating layer and being treated with electrical energy, according to one embodiment. FIG. 21A shows a probe equipped with a fixed position retractable blade, inserted percutaneously under a sweat gland, according to one embodiment. FIG. 21B shows the probe of FIG. 21A with a retractable blade in a retracted position, according to one embodiment. FIG. 21C shows the probe of FIG. 21B with a retractable blade in its advanced position from its retracted position so that the sweat glands are sheared, according to one embodiment. FIG. 22A shows a wire device having an actuator to bend the wire into an expanded profile, according to one embodiment. FIG. 22B illustrates an actuator having an outer element and an inner element, according to one embodiment. FIG. 23 illustrates a planar cutting device with a windmill cutter, according to one embodiment. FIG. 24 shows a wire that digs into the target tissue through two points of insertion in the skin, according to one embodiment. FIG. 25 illustrates a wire configured to be inserted into a target tissue and exiting the target tissue through a single insertion point, according to one embodiment. FIG. 26A illustrates a digging instrument having an actuator, according to one embodiment. FIG. 26B shows a drilling instrument having an actuator, according to another embodiment. FIG. 27 illustrates a sweat duct filled with a photodynamic adhesive, according to one embodiment. FIG. 28 illustrates a biocompatible scaffold introduced into a sweat duct, according to one embodiment. FIG. 29 illustrates a piston used to deliver pressurized gas to a sweat gland, according to one embodiment. FIG. 30A shows a sweat gland having a fluid, according to one embodiment. FIG. 30B shows the sweat gland of FIG. 30A ruptured after the liquid has frozen. FIG. 31 shows a device for causing pressure-induced necrosis of sweat glands according to one embodiment. FIG. 32 illustrates a target tissue having microbubbles and microspheres that undergo rupture by an ultrasonic transducer, according to one embodiment. FIG. 33 illustrates a cross-sectional view of a target tissue having a thermal treatment zone, according to one embodiment. FIG. 34A shows an isometric view of a non-invasive energy delivery device comprising multiple microwave antennas electrically connected to a microwave generator, according to one embodiment. FIG. 34B shows a schematic diagram of a cooling source located remotely from an energy source and an energy applicator, according to one embodiment. FIG. 35A shows a needle configured with a proximal region comprising a cooling element and a distal end comprising an electrode tip, according to one embodiment. FIG. 35B shows an energy delivery device element comprising a metal electrode, an inner tube, and an outer peripheral surface, according to one embodiment. FIG. 36 illustrates an energy delivery device comprising a bipolar pair of needle tip electrodes, according to one embodiment. FIG. 37 illustrates a cooling electrode comprising a heat sink disposed between two pairs of bipolar needle electrodes, according to one embodiment. FIG. 37B illustrates cooling electrodes in alternating order with monopolar electrodes, according to one embodiment. FIG. 38 shows a side view of a vacuum pulling and carrying skin, according to one embodiment. FIG. 39 illustrates a needle with an energy delivery element, according to one embodiment. FIG. 40 shows a side view of a vacuum that pulls and carries skin with embedded electrodes, according to one embodiment. FIG. 41 shows an example of a typical skin fold. FIG. 42 illustrates a skin fold being treated by an energy delivery device comprising two energy delivery elements, according to one embodiment. FIG. 43A illustrates a minimally invasive RF delivery device comprising one or more needles for insertion into a skin fold, according to one embodiment. FIG. 43B illustrates a minimally invasive microwave delivery device comprising one or more microwave antennas for insertion into a skin fold, according to one embodiment. FIG. 43C illustrates a minimally invasive cryotherapy device comprising one or more needles, catheters, stylets, cannulas or catheters according to one embodiment. FIG. 44 shows an energy delivery device according to one embodiment, inserted through the edge of the skin fold and positioned along the longitudinal axis of the fold. FIG. 45 shows an energy delivery device according to one embodiment inserted at the top of the skin fold. FIG. 46A illustrates an array of monopolar electrode needles used to deliver treatment along the longitudinal length of a skin fold, according to one embodiment. FIG. 46B shows an array of monopolar electrode needles used to deliver treatment along the length of the skin fold according to another embodiment. FIG. 47A shows an energy delivery device inserted at the top of the skin fold after the needle and blunt dissociation electrode have been inserted, according to one embodiment. FIG. 47B shows an energy delivery device inserted at the top of the skin fold after the needle and blunt dissociation electrode have been inserted, according to an alternative embodiment. FIG. 48 illustrates one or more paddle elements connected to a vibration source removably coupled to each outside of the skin fold, according to one embodiment. FIG. 49 illustrates a skin fold being treated by two ultrasound transducers disposed on two sides of the skin fold, according to one embodiment. FIG. 50A illustrates an ultrasound delivery instrument used to deliver ultrasound therapy on one side of a skin fold, according to one embodiment. FIG. 50B illustrates light energy being emitted from one energy source to a skin fold, according to one embodiment. FIG. 51 shows a perspective view of a suction electrode comprising a housing, a tissue chamber, a vacuum port, and an electrode according to one embodiment. FIG. 52A shows a perspective view of a clamp used to create and carry a skin fold, according to one embodiment. FIG. 52B shows a side view of a clamp used to generate and carry a skin fold according to a second embodiment. FIG. 52C shows a side view of a clamp used to generate and carry a skin fold according to a third embodiment. FIG. 53 illustrates an array of electrodes configured to deliver energy, according to one embodiment. FIG. 54 illustrates one embodiment of a representative grid showing a target treatment site “A” and a target treatment site “B” that may be used over a skin region to identify a particular treatment region. 55A-E show various patterns illustrating particular treatment areas and non-treatment areas that can be used over the skin area. FIG. 56 shows three templates used in staged treatment, each template configured to allow treatment to a different portion of the overall treatment area, according to one embodiment. FIG. 57 shows a single template pattern represented by different chromophores, corresponding to different stages of treatment, according to one embodiment.

  Hyperhidrosis is a clinically diagnosed disease with excessive secretion of sweat from the sweat glands. Excess sweating, thought to result from sympathetic nervous system overactivity, usually occurs in the palms, soles, and axilla. Hyperhidrosis of the palm is a symptom of excessive sweating of the hand. This symptom is often indicated by a cold and wet handshake. Plantar hyperhidrosis is a symptom of excessive sweating of the foot. This condition can cause blisters and fungal infections. Axillary hyperhidrosis is a symptom of excessive sweating under the armpit. Such excessive sweating is not only socially unsatisfactory, but can even cause contamination and decay of clothing.

  The sweat glands in the body consist of apocrine and eccrine sweat glands. Superficially located in the dermis layer of the skin, the eccrine sweat gland is located on one side of the body so that it can secrete sweat and regulate body heat and temperature. Apocrine sweat glands, located within the subcutaneous tissue and the boundary on the junction between the subcutaneous and dermal layers, secrete oily and milky protein-rich products into the hair follicle. Bacterial digestion of apocrine sweat is largely responsible for olfactory or odor sweating or (ie, body odor), which can be most prominent in the foot and heel area.

  There are a variety of treatments used to treat hyperhidrosis. For example, chemical antiperspirants and body odor inhibitors are commonly used as personal hygiene issues. Antiperspirants are aluminum-based salts that mechanically block sweat ducts and thereby prevent sweat from reaching the skin surface. Body odor inhibitors alter the pH of the skin surface, thereby minimizing the presence of bacteria that induce odors. Because the effects of both of these products are temporary and may irritate the skin, depending on the user, these products are suboptimal solutions for cases of excessive sweating.

  In addition to antiperspirants and body odor inhibitors, other topical formulations have been used to treat hyperhidrosis. For example, glutaraldehyde and tannic acid have been used in the treatment of hyperhidrosis of the soles and palms. However, these treatments are generally unsupported because they can cause ugly browning of the skin.

  Anticholinergic agents have also been applied both locally and systemically to treat hyperhidrosis. These drugs block sympathetic stimulation of the eccrine sweat gland by inhibiting the action of acetylcholine at the neural synapse. The use of these drugs is limited due to systemic side effects they can cause, including dry mouth, urinary retention, constipation, and visual impairments such as mydriasis and ciliary muscle paralysis. Also, topical anticholinergic agents can be difficult to absorb into the skin in amounts sufficient to affect cholinergic nerve endings.

  Some patients with hyperhidrosis have used surgical treatments such as sweat gland excision and chest sympathectomy. For example, Takasu, US Pat. No. 5,190,518, which is incorporated herein by reference in its entirety, discloses an ultrasonic surgical device for disabling and excising sweat glands. These treatments may provide a longer period of relief from hyperhidrosis. However, these treatments are rarely indicated due to their invasiveness, adverse effects, and cost. For example, surgery can cause contracture of the skin, muscles, and other surrounding tissues. Sympathectomy may result in complications including infection, pneumothorax, Homer syndrome, and compensatory hyperhidrosis of the torso, back, and thighs.

  Recently, Clostridium botulinum type A neurotoxins (eg, BOTOX®) have proven effective in treating hyperhidrosis in some patients. BOTOX is commonly used by dermatologists to paralyze the nerves at the neuronal junction between the autonomic and sweat glands. When the nerve connection is disabled, acetylcholine cannot reach the eccrine sweat glands, thereby disabling components of the hyperactive sympathetic nervous system of hyperhidrosis patients. However, this treatment is not without its drawbacks. Clostridium botulinum toxin is one of the most deadly substances on earth, and as a result, it is dangerous to inject it into the patient's body. In addition, since Apocrine sweat glands are innervated by adrenergic nerves that are not blocked by Clostridium botulinum toxin, injections of Clostridium botulinum toxin have no clinical impact on body odor caused by secretion from Apocrine sweat glands. Clostridium botulinum toxin treatment also requires multiple painful injections with a needle. Furthermore, the outcome of this treatment lasts only a few months, thereby necessitating repeated expensive and painful treatments.

  In light of the shortcomings of the aforementioned approaches, a minimally invasive, convenient, effective, and lasting treatment with few side effects would be a desirable alternative for treating hyperhidrosis.

(Discussion of biological structure)
FIG. 1 shows an isometric view of a cross-sectional view of the skin, its internal structure, and surrounding tissue. The skin comprises three main layers: epidermis 102, dermis 101, and subcutaneous tissue 100. The epidermis 102 is the thin epithelial surface of the skin. The epidermis 102 consists of several sublayers, including the stratum corneum, the keratinocyte layer, and the basal layer. The epidermis 102 also contains melanogenic melanocytes that are involved in skin pigmentation. The thickness of the epidermis 102 ranges from 0.05 mm to 1.5 mm depending on the location of the skin on the body.

  The dermis 101 is the middle layer of the skin and consists of blood vessels, lymph vessels, hair follicles, sebaceous glands, eccrine sweat glands, and sometimes apocrine sweat glands. The dermis 101 is bound by fibroblasts that may exist as collagen proteins, elastic tissues, and / or reticulofibers. The dermis 101 layer also contains neural receptors corresponding to pain and touch. The thickness of the dermis 101 varies depending on the location of the skin. The thickness of the dermis 101 can range from 0.3 mm at the heel to 3.0 mm at the back.

  The subcutaneous tissue 100 is a layer of fat and connective tissue that houses larger blood vessels and nerves. While apocrine sweat glands may be located in the dermal layer of the skin, it is more common for these sweat glands to be present in the subcutaneous tissue. This layer 100 provides a thermal barrier that helps preserve body heat and an additional cushion that protects the organ from trauma damage. Beneath the subcutaneous layer is the body's muscle support structure.

  Eccrine sweat glands are distributed throughout the body surface with densities ranging from 50 sweat glands per square centimeter to 200 sweat glands per square centimeter. These sweat glands are most closely located on the palms, soles, forehead, and heels. The eccrine sweat gland comprises three different parts: (1) an intraepidermal part, (2) an intradermal tube (coiled and straight), and (3) a secretory part (coiled gland). The coiled gland is located in the deep dermis or at the boundary between the dermis 101 and the subcutaneous layer 100. The intradermal tube extends upwardly from the coiled gland through the dermis 101, initially as a coiled tube and then as a straight tube. The straight tube ends when it enters the epidermis 102, then spirals as it continues through the epidermis 102 and opens directly on the skin surface.

  Human eccrine sweat consists of water, sodium, potassium lactate, urea, ammonia, serine, ornithine, citrulline, aspartic acid, heavy metals, organic compounds, and proteolytic enzymes. In general, the concentration of sodium in eccrine sweat varies from 35 to 65 mmol / l.

  The eccrine sweat glands are controlled by cholinergic sympathetic nerves, which are controlled by the hypothalamus. The hypothalamus directly senses core temperature and obtains input from temperature receptors in the skin. Production of eccrine sweat is initiated by the hypothalamus through post-node fiber production of acetylcholine.

  Apocrine sweat glands are present mainly in the armpit and around the anogenital region. These sweat glands are (1) coiled glands in the deeper part of the dermis or at the junction of the dermis and subcutaneous fat, and (2) directly across the dermis and into the hair follicle isthmus (top). Consists of tubes. The lumen of the coiled portion of the apocrine sweat gland is about 10 times the diameter of its eccrine counterpart. The straight pipe continues from the coiled gland to the hair follicle isthmus and is virtually identical in appearance to the eccrine straight pipe.

  Emotional stressors stimulate adrenergic sympathetic nerves that initiate the release of viscous fatty sweat from apocrine sweat glands. The amount of sweat produced by these sweat glands is significantly less than the amount of sweat produced by the eccrine sweat glands. Initially odorless, apocrine sweat develops odor when in contact with the surface of the skin, and surface bacteria break down organic compounds in the sweat and produce odor.

  Another type of sweat-producing gland, apoecrine sweat glands, may be found in the axilla (under the heel). These complex sweat glands are most commonly found in hyperhidrosis patients and are thought to play a role in axillary hyperhidrosis. Their secretory part has both a small diameter part similar to the eccrine sweat gland and a large diameter part resembling the apocrine sweat gland. These sweat glands are similar to eccrine sweat glands in that they are primarily responsive to cholinergic stimuli and their tubes are long and open directly on the skin surface. However, apoecrine sweat glands secrete almost 10 times more than eccrine sweat glands. Other non-limiting examples of tissue structures and medical conditions that may be treated using the systems, methods, and devices of some embodiments disclosed herein are referred to, for example, in their entirety. On page 1-10 of US Provisional Application No. 61 / 013,274.

(Outline of method and apparatus)
Embodiments of the present application relate to methods and apparatus for reducing sweat production through removal, disabling, disabling, or destruction of apocrine and eccrine sweat glands in the dermis and subcutaneous tissue. It is envisioned that many mechanisms and modalities can be implemented individually or in combination to achieve reduced patient sweat production. It is contemplated that the treatments disclosed herein can be applied to any part of the body that contributes to or contributes to sweat production, secretion, and / or presence.

  In one approach to reducing sweat production, the target area of the target patient is first identified. More preferably, specific sweat glands, or regions containing such sweat glands, may be identified and the sweat glands and / or surrounding tissue can be treated with energy. This energy can take many forms (eg, electromagnetic, microwave, radio frequency, laser, infrared, ultrasound, etc.) and can be in any number of ways (eg, locally, minimally invasive, etc. ) Can be delivered. In addition, devices employed in energy therapy may include one or more electrodes, antennas, transducers, needles, probes, catheters, microneedles, and stylets. Some of the other heat treatments that can be employed include induction heating, resistance heating, high temperature chemical reactions, and / or low temperature therapy.

  In combination with the thermal treatment disclosed herein, protective treatments can be employed to prevent damage or pain to non-target tissues. In one embodiment, heat protection treatment may be used. For example, surface cooling can be applied to protect portions of the epidermis and dermis layers of the skin while deeper regions of skin tissue are heated via energy delivery. Various types of active and passive cooling can be configured to provide thermal protection to this non-target tissue.

  There are also a number of mechanical approaches to reduce sweat production. For example, sweat glands can be surgically excised, sheared using various wires and / or blades, hermetically sealed, ruptured under pressure, and disabled via acoustic cavitation.

  Reduction of sweat production may be facilitated by administering many of the treatments disclosed herein in one or more spatial configurations or skin shapes. For example, treatment can be directed perpendicular to the skin surface, parallel to the skin surface, or at some angle therebetween. In addition, treatment can be delivered to skin in a flat, planar configuration, in an elevated orientation, or in a folded shape.

  Reduction of sweat production may also be facilitated by administering treatment over multiple stages and in a patterned arrangement. This approach can enhance the body's healing response and help with faster recovery with few complications. Various templates have been disclosed to support the administration of staged and patterned treatments.

  Referring to the drawings disclosed herein, details are presented by way of example and for the purposes of demonstrating certain embodiments. In this regard, not all structural details may be shown in detail. Accordingly, it is to be understood that the present invention is not limited to the details of the construction and arrangement of the components set forth in the description or illustrations provided herein. In addition, it should be understood that the terminology used herein is for the purpose of description and should not be considered limiting.

  FIG. 2 shows a cross-sectional view of the skin, its three main layers, and the internal structure. In one embodiment, the treatment is concentrated in the area of the dermis 101 and subcutaneous 100 tissue (lower skin) (eg, “target tissue” 105) where the eccrine and apocrine sweat glands are present, while in the epidermis 102 and dermis 101. It is desirable to perform minimal damage to tissues above the sweat glands of the subject (eg, “superficial non-target tissue” 103) as well as other tissue structures within the subcutaneous layer 100 (eg, “deep non-target tissue” 104). . Depending on the region of the body, the target tissue 105 region may begin anywhere from about 0.5 mm to about 4 mm below the surface of the skin and end anywhere from about 1 mm to about 10 mm below the surface of the skin. Depending on the region of the body, the superficial non-target tissue 103 region may begin at the skin surface and end anywhere from about 0.5 mm to about 4 mm below the surface of the skin. Depending on the region of the body, the deep non-target tissue 104 region may begin anywhere from about 1 mm to about 10 mm below the surface of the skin.

  In the case of the axilla (under the heel), the target tissue region may begin anywhere from about 1 mm to about 3 mm below the surface of the skin and end anywhere from about 3 mm to about 8 mm below the surface of the skin. Thus, a treatment that concentrates energy about 1 mm to about 8 mm below the surface of the axillary skin would be beneficial in treating axillary sweating.

  For purposes herein, the eccrine sweat gland, apoecrin sweat gland, and apocrine sweat gland may be referred to separately or collectively as sweat glands or target structures. Similarly, the terms treatment, therapeutic effect, treatment range / region may refer to treatment of the target tissue and / or any target structure present therein with the purpose of temporarily or permanently reducing or stopping sweating. , The treatment itself is one or more of the following methods: modification, inactivation, disabling, denervation, injury, electroporation, apoptosis, necrosis, coagulation, ablation, and destruction, and the target tissue and / or target structure May affect.

  Although the methods and devices disclosed herein are directed to reducing sweat production of sweat glands, the disclosed methods and devices can be modified and include various types of target tissues and non-skins in the skin. Note that it may be used to treat a target tissue region. For example, the treatments disclosed herein, in certain embodiments, (1) tighten skin, reduce wrinkles by treating collagen, contour skin, induce collagen formation, and / or Contracting collagen, (2) treating acne by targeting sebaceous glands within the dermis layer of the skin, (3) stimulating or delaying hair growth, or treating hair temporarily or by treating hair follicles It is contemplated that it can be used to permanently remove and / or (4) treat cellulite for weight loss and / or body shaping purposes.

(Specific embodiment)
(A. Energy transfer therapy)
One approach to reducing sweat production involves thermally treating the target tissue, either by delivering energy to the target tissue or extracting energy from the target tissue. The system can be configured to include a processor, an energy generator coupled to the processor, and a device operably coupled to the generator. The device can further include an energy delivery applicator or energy delivery element for delivering energy to the target tissue. In the illustrated embodiment, a cable electrically connects the device to the energy generator. In other embodiments, the processor, device, and / or energy generator can be connected wirelessly, eg, via a radio frequency signal.

  For purposes herein, the terms “electrode”, “antenna”, “energy”, “energy element”, “energy delivery element”, “energy delivery applicator”, or “energy source” are used individually or Collectively, adapted and applied in a range, strength, and / or amount sufficient to treat the target skin tissue directly or indirectly (eg, heating the mediator) thermally or by other means. Electromagnetic, X-ray, radio frequency (RF), DC current, AC current, microwave, ultrasound (including high-intensity focused ultrasound (HIFU)), radiation, near infrared, infrared, light / laser, cooling And one or more types of energy transfer modalities including, but not limited to, cryotherapy. Note that although one particular modality may be disclosed in a particular embodiment, the embodiment may be adapted to accommodate other forms of energy transfer. It should be understood that this embodiment can employ such a mechanism even though the energy transfer mechanism is significantly different from that disclosed in the illustrated embodiment. For example, the energy generator in one embodiment can generate an electrical signal having a desired frequency, amplitude, and power level, and the cable can transmit the generated signal to a device that includes electrodes. In this embodiment, the processor is in communication with the energy generator to control the power output of the energy generator to provide the desired amount of energy to heat the target tissue. Alternatively, in embodiments where the device comprises a Peltier electrode, the energy generator can supply voltage to the device to thermoelectrically cool the target tissue.

  In embodiments relating to the delivery of thermal energy, in one embodiment it may be desirable to reach a temperature of at least about 50 ° C. in the target tissue and / or the target structure therein to achieve the desired therapeutic effect. . For example, it is believed that delivering sufficient thermal energy to heat the target tissue to about 60 ° C. will likely result in thermal ablation of the target tissue. In embodiments involving the step of cooling the target tissue, it is believed that cooling the target tissue from about 0 ° C. to −40 ° C. will likely have a therapeutic effect on the target tissue.

(Microwave energy delivery device)
The system illustrated in FIG. 3 includes an energy applicator 111 for non-invasively delivering microwave energy 112 to a target tissue 105 and a microwave generator 113 for supplying the applicator 111 with microwave energy 112. A device 110 is shown having In this embodiment, energy applicator 111 comprises one or more antennas for delivering microwave energy 112 to target tissue 105. The antenna is configured to heat and treat the target tissue 105 and the target structure in the target tissue 105 when the device 110 is placed against or near the patient's skin. Treated tissue can either be left in place to be resorbed by the body's immune system and wound healing response, or can be removed using any number of minimally invasive techniques . As shown, the antenna may also have a horn shape as described below to provide a directional component for the energy field. In one embodiment, the energy generator 113 is located remotely from the energy applicator 111, and the generator 113 can be either stationary or mobile. Alternatively, applicator 111 and generator 113 can be coupled to comprise a portable unit. Still alternatively, the applicator 111 and generator 113 can be combined into a single unit.

  Microwave energy is absorbed by the tissue in a process called dielectric heating. Molecules in tissues such as water molecules are electric dipoles, which have a positive charge at one end and a negative charge at the other end. As microwave energy induces an alternating electric field, the dipole rotates in an attempt to match the electric field. This molecular rotation generates heat as the molecules collide with each other and cause additional motion. Heating is particularly efficient with liquid water molecules having a relatively high dipole moment.

  Delivery of energy to the target tissue can be facilitated by antenna designs that incorporate dielectric elements. Unlike other forms of electrical energy delivery, such as radio frequency, where energy is typically transmitted through direct electrical contacts between the metal conductor and body tissue, microwave energy is delivered across the dielectric material. be able to. The dielectric element does not prevent microwave energy from radiating to adjacent tissue, but may help to optimize the delivery of energy to the target tissue over the course of treatment. Since the dielectric heating properties and thermal conductivity of skin tissue change over the course of treatment (eg, as the temperature increases) due to loss of moisture, a dielectric that is properly matched to the antenna design will provide energy to the target tissue. Can be maintained.

  The influence of the dielectric on the energy delivery properties of the antenna decreases with distance from the antenna. Thus, in order to optimize energy delivery to the target tissue over the course of treatment, it may be desirable in one embodiment to place a dielectric directly next to the antenna, rather than remote from the antenna. Thus, the antenna design can be optimized by incorporating a coating with a dielectric (eg, ceramic, PTFE, polyimide, etc.) with a dielectric constant that matches the desired amount of heat for treatment. The dielectric may be incorporated into the antenna or may be a separate component of the energy delivery device or system. Further details regarding antenna design are discussed below.

  FIG. 4 is an isometric view depicting a non-invasive energy delivery device 117 comprising a plurality of microwave antennas 120 that are electrically connected to the micro-generator 113. In one embodiment, the antenna 120 is contained in a substantially planar applicator plate 121 that is sized for application to a target area of the patient's skin 119. In one embodiment, device 117 and applicator plate 121 therein can be sized and configured to substantially match the area of tissue being treated. For example, for treatment related to reducing axillary sweating, the device 117 can be configured to cover substantially the entire axillary region of the patient. Alternatively, device 117 can be configured to cover at least a portion of the axilla. In addition, the applicator plate 121 may be flexible to help the device 117 conform to the contours of the patient's skin 119.

  FIG. 5 is a cross-sectional side view of the same device of FIG. 4 showing the delivery of energy 112 into the skin. In such multiple antenna embodiments, it may be useful to orient the antenna 120 along the same plane in the same longitudinal direction to deliver energy 112 in a planar manner. As shown in FIGS. 4 and 5, four or five microwave antennas 120 are arranged parallel to each other. In other embodiments, fewer or more microwave antennas 120 may be provided, eg, 1, 2, 3, 5, 6, 7, 8, 9, 10, or more. This planar configuration allows energy to be delivered to larger tissue areas in a single treatment and in a more consistent manner.

  As described later in this specification, thermal protection measures can be employed in conjunction with thermal treatment. As shown in FIGS. 4 and 5, the applicator plate 121 containing the antenna 120 may be connected to the microwave generator 113 by a conduit 114 so that the cooling fluid is passed from the coolant circulator 118 to the applicator plate 121. Through the conduit 114. The cooling fluid creates a protected area in the patient's epidermis 103 so that the target tissue 105 below the protected area is treated.

  The amount of energy 112 delivered to the target tissue 105 and the resulting extent of the therapeutic effect can be adjusted based on the number of antennas 120, their specific configuration, and the power delivered to each antenna. In one embodiment, a microwave generator 113 with an output frequency of microwave energy 112 in the range of 300 MHz to 20 GHz is suitable for supplying power to the energy delivery device 117. In another embodiment, a microwave signal anywhere from about 915 MHz to about 2450 MHz is preferential for producing a therapeutic effect on the tissue. Alternatively, signals having frequencies in the range of about 2.5 GHz to about 10 GHz may also be preferential. In addition, solid state, traveling wave tube, and / or magnetron components can optionally be used to facilitate delivery of microwave energy 112.

  With respect to antenna design, FIGS. 6A through 6G illustrate several possible antenna variations that can be implemented to achieve the energy delivery functions disclosed herein. In each design, the antenna comprises a distal end of a coaxial cable supply line through which electrical energy is transmitted from the energy generator. The coaxial cable further includes an inner conductor shaft 124 and an outer conductor 125. FIG. 6A illustrates one embodiment of the monopole antenna 122. As shown in FIG. 6E, the antenna may be shielded or occluded by metal 127 to limit the electromagnetic field propagated by the antenna. In such a monopolar configuration, the inner conductor element 123 extends beyond the outer conductor 125 from the inner conductor or shaft 124 such that the electromagnetic field propagated by the antenna originates only from the inner conductor element 123. In the dipole antenna 128 configuration, as illustrated in FIG. 6B, the outer conductor 125 is exposed in such a way that an electromagnetic field is generated between the inner conductor element 123 and the outer conductor 125.

  Depending on the desired performance of the antenna, the antenna may optionally comprise a helical antenna 129 (FIG. 6C), a loop antenna 130 (FIG. 6D), or a horn antenna 131 (FIGS. 6F and 6G). These alternative antenna configurations provide a geometric radiation pattern. For example, as illustrated in FIG. 6F, the outer conductor 125 may be shaped with a horn shape or the like so as to provide a directional component to the electric field generated between the inner conductor element 123 and the outer conductor 125. You may prepare. Optionally, outer conductor element 125 and / or inner conductor element 123 may be bounded by, coupled to or covered by a dielectric element so as to optimize the energy delivery capability of the antenna. .

  In another embodiment for energy delivery to a target tissue, the energy applicator comprises an antenna connected to a coaxial cable that is coupled to a microwave power source. As shown in FIG. 7A, the antenna 132 further includes an inner conductor disposed within the coaxial cable 133, and the inner conductor element 123 extends beyond the distal end of the coaxial cable 133 to form a coil. Forming a conductor element; The coiled conductor element provides a relatively flat structure that can be aligned with the skin surface to deliver an equal amount of energy to the plane of the target tissue. The applicator may optionally further comprise a thin shield made of polymer or ceramic at its distal end. 7B and 7C illustrate additional embodiments of a coiled antenna configuration, where the coiled conductor element may comprise either the coaxial cable 133 or the inner conductor 123 only.

  Note that FIG. 7A illustrates the use of cooling fluid flowing through the coaxial antenna system 132. This antenna embodiment, or any other antenna configuration previously shown, eg, in FIG. 6E, not only cools the skin, but also creates a lower pressure area inside the device chamber than in the surrounding environment. It can also be configured to generate. This lower pressure or suction area in the device (1) causes the device to adhere to the skin, causing the target tissue to be juxtaposed closer to the antenna, and (2) reducing blood flow in the target tissue, thereby reducing tissue Helps to enable more efficient heating of.

  In addition, aspiration may help control pain by inducing stretch and baroreceptors in the skin, thereby blocking pain signals via the pain control portal control theory. The portal control theory believes that excessive neural signals arriving at the dorsal root ganglia of the spinal cord overwhelm the system and obscure or block transmission of pain receptor signals to the brain. This pain management mechanism is exploited by implantable electrical pain control units, TENS systems, Optilase systems, and others.

  Because microwave heating is particularly efficient when water molecules are present in the tissue, it may be desirable to have a relatively high water content or molecular density at or within the target tissue. This high water content results in additional microwave energy absorption and resulting heating at the treatment point. This phenomenon also allows for selective heating of the target tissue, thereby minimizing the impact on non-target tissue.

  There are a number of ways in which the water content in the target tissue can be achieved. For example, by injecting a bolus dose of fluid (eg, water, saline, etc.) into the target tissue or structure, such regions are more susceptible to microwave therapy. FIG. 8 illustrates one embodiment of fluid 116 injection near the base of sweat glands and target tissue 105. In the case of a target sweat gland, the patient can be induced to sweat in the treatment area to achieve a higher water content in the target structure (such as by increasing the ambient temperature or the temperature of the target area). In any of these cases, the water-dense sweat glands can be plugged to prevent any water / sweat from escaping through the sweat tubes. Sealing the gland duct can be accomplished by using an aluminum ion based topical product such as an antiperspirant or any type of biocompatible polymer coating.

  Additional non-limiting examples of microwave system, device, and method embodiments, and components of the embodiments that can be utilized with those described herein, for example, are referred to in their entirety. Previously incorporated by reference to FIGS. 3-9 and 20-26 of US Provisional Application No. 61 / 013,274, and pages 11-20 and 34-48, and also in its entirety. Incorporated, US Provisional Application No. 61 / 045,937, FIGS. 1-25, and pages 9-18 and 56-69. Further, the embodiments and components of the embodiments described herein, as well as, for example, those discussed in the preamble, have been previously incorporated by reference in its entirety. / 045,937, illustrated in FIGS. 26-51 and described on pages 18-39, can be used to generate tissue profiles.

(RF energy delivery device)
Radio frequency (RF) energy is another aspect of electromagnetic energy delivery that can be used to treat target tissue. In one embodiment, a device comprising at least one electrode for delivering electric field therapy is operably connected to an RF generator for delivering RF energy to the target tissue via the electrode. Energy delivery may be continuous or pulsed, thermal or non-thermal. For example, a continuous or pulsed electric field delivered from an electrode can heat the target tissue to the temperature necessary to achieve the desired therapeutic effect. Alternatively, the delivered energy heats and / or resects the nerve, neuromuscular junction, and / or neurogland junction associated with the target structure to temporarily or permanently paralyze the target structure nerve. be able to. A pulsed electric field can also induce electroporation in these neural structures or the target structure itself to achieve a therapeutic effect.

  The electrodes can be individual electrodes that are electrically independent of each other, split electrodes with commonly connected contacts, or continuous electrodes. The split electrodes can be formed, for example, by providing an insulating tube with a slot in which the electrodes are installed or by electrically connecting a series of individual electrodes. Individual electrodes or groups of electrodes can be configured to provide a bipolar signal. Electrodes can be dynamically assigned to facilitate monopolar and / or bipolar energy delivery between any of the electrodes and / or between any of the electrodes and one or more external ground pads Or can be wired. For example, the electrode arrangement can be configured such that both monopolar and bipolar energy fields can be delivered selectively, sequentially, and / or simultaneously. The ground pad can be externally attached to the patient's skin (eg, to the patient's leg), for example.

  There are a wide variety of configurations of active electrodes, either in monopolar or bipolar configurations. They may be flat or curved so as to promote uniform contact across the electrode surface. The contact area of the active electrode may be circular (eg, annular, elliptical) or linear (eg, square, rectangular, polygonal), and virtually any shape is possible. The shape may be selected, for example, to fit the tissue to be treated or to allow optimal coverage for repeated activation. For example, in one embodiment, an electrode with a hexagonal contact area may provide the advantage of providing full coverage when treating an irregular region through multiple activations. It will be appreciated that similar shapes may be used for the applicator plates in the microwave embodiments discussed herein. The number of electrodes may be varied to allow patterned delivery of energy to the tissue, with at least one active electrode for monopolar and at least two active electrodes for bipolar. Desired. The plurality of electrodes can be configured in many different patterns, such as an annular pattern, a radial pattern, a rectangular array, or an approximation of any of the shapes described herein. 9A-F are top and side views of the alternating configuration electrode shown in FIG. 9A, top and isometric views of the alternating planar configuration electrode shown in FIG. 9B, the three-pronged configuration electrode shown in FIG. 9C, and FIG. 9D illustrates a number of possible configurations of the bipolar electrode 201 for the desired treatment area 105, including the sandwich configuration electrode shown, the plate configuration electrode shown in FIG. 9E, and the plated roof configuration electrode shown in FIG. 9F.

  The depth of energy penetration caused by the RF delivery device, the tissue temperature achieved, and the extent resulting from the tissue effects are the power delivered by the RF generator, the spacing of one or more electrodes, the size of the electrodes, It depends on a number of factors, including orientation, the amount of electrode contact with the target tissue, and the nature of the tissue itself.

  The generator operates with a conventional sinusoidal or non-sinusoidal waveform, in one embodiment, conventional power operating at a frequency in the range of about 200 KHz to about 1.25 MHz, more preferably about 400 KHz to about 1.0 MHz. It may be a supply unit. Such power supplies are available from many private suppliers such as Valleyley, Aspen, and Bovie. Depending on the desired therapeutic effect, it may be necessary for the generator to operate at relatively low and relatively high voltage and power levels. For example, the operability of the generator may include power anywhere from about 1 / 2W to about 100W. In some embodiments, it may be desirable to deliver energy continuously over a period as short as ¼ second or as long as 300 seconds to achieve the desired therapeutic effect.

  For embodiments that require delivery of a pulsed electric field (PEF), the PEF parameters can be in any range and combination of voltage, electric field strength, pulse width, pulse duration, pulse shape, number of pulses, and / or pulses. An interval between them (for example, duty cycle) may be included, but is not limited thereto. Suitable pulse widths include, for example, a width of at least 10 seconds up to about 500 milliseconds. Suitable shapes of the pulse waveform include, for example, AC waveform, sine wave, cosine wave, combination of sine wave and cosine wave, DC waveform, AC waveform with DC transition, RF waveform, square wave, trapezoidal wave, exponential decay Including waves, and combinations thereof. A suitable number of pulses includes, for example, at least one pulse. Suitable pulse intervals include, for example, intervals of less than about 10 seconds. These parameters are provided for illustrative purposes and should not be considered limiting in any way.

  In the embodiment illustrated in FIG. 10, the RF delivery device 202 comprises an electrode tip needle, microneedle, or stylet for insertion into or across the epidermis layer 102 of the skin. These forms of energy delivery elements can be formed. Alternatively, the entire energy delivery element can comprise an electrode that is optionally insulated at points along the element where energy delivery is not desired (eg, non-target tissue). This minimally invasive insertion approach allows for more localized treatment of the target tissue 105 such that non-target tissue damage is minimized. After the insertion of the needle 203 to a reasonable depth, which is preferably the depth of the target tissue, but may be more or less, the operator can for subsequent delivery to the target tissue 105 The RF generator 204 can be directed to deliver an electric field to the electrodes. The electric field from the electrode resistively heats the target tissue 105. When the target tissue 105 is outside the electric field and thus outside the resistive heating zone, the target tissue can be conductively heated by the adjacent tissue that is resistively heated by the electric field of the electrode.

  Another potential benefit of having an interstitial needle insulated along its length is to avoid unnecessary heating of non-target tissue via heat conduction from the needle itself. As the electrode resistively heats the surrounding tissue during RF treatment, the electrode also absorbs heat from the tissue. The heat absorbed by the electrode may then be conducted to the rest of the needle, in which case the heat is undesirable and may be passed to the surrounding non-target tissue. A needle 203 configured with an insulating shaft 205, as illustrated in FIG. 10, can prevent heat conduction along the needle shaft 205 to non-target tissue. In this embodiment, the proximal portion of the needle is insulated to the depth of the non-target tissue, while the electrode 206 at the distal portion of the needle 203 is exposed to treat the target tissue 105. Alternatively, the electrode 206 tip can be partially isolated in a manner that provides a directional component for the delivery of RF energy. This directional bias may advantageously provide a means for minimizing energy delivery to the non-target tissue and the resulting thermal damage.

  Protective treatment may be used with certain embodiments (not shown). In the case of thermal treatment, such as with RF energy or microwave energy, a cooling system, cooling element, or cooling component may be provided, as described elsewhere herein. In one embodiment, the cooling element may be used in combination with an insulating element, while in another embodiment, the cooling element may be used as a substitute for the insulating element. When cryotherapy is provided (as described further below), the protective treatment may include heating a portion of the energy delivery device.

  Depending on the target tissue 105 area being treated, the needle electrode 206 of FIG. 10 may have a length as large as, for example, about 1-10 mm, preferably about 8 mm. More preferably, the needle electrode 206 may have a length of about 2-5 mm in some embodiments. It will be appreciated that the length of the needle 203 may be optimized to be inserted to a depth where the target tissue 105 is located.

  In the embodiment illustrated in FIG. 11, the energy delivery device comprises a needle 208 configured for percutaneous insertion. Needle 208 further comprises a distal portion having one or more energy delivery elements 209 for delivering energy 210 to target tissue 105. More specifically, this embodiment may comprise a needle 208 having one or more electrodes for treating target tissue with RF energy 210. As described above, a portion of the needle 208 can be insulated to provide a directional component for energy delivery. This directional component can advantageously allow a more controlled treatment, and less non-target tissue is damaged. In one embodiment, the needle 208 is insulated so that energy is delivered toward the epidermis 102 and away from the subcutaneous 100 tissue. The electrode 206 provided on the needle 208 may have any suitable length to treat a single sweat gland or multiple sweat glands. Alternatively, multiple electrodes 206 can be spaced apart on the needle 208 to treat multiple sweat glands. To treat a larger area of target tissue 105, needle 208 can optionally be configured to translate angularly or “fan out” parallel to target tissue 105. For example, the energy delivery element 209 can be rotationally coupled to the needle 208 so that it may translate in parallel with the target tissue 105. As discussed in previous embodiments, a cooling source may be provided on the skin to protect the skin surface, epidermis 102 and dermis 101 parts.

(Cryogenic therapy device)
Cryotherapy may present an opportunity to provide a therapeutic effect on the target tissue. Because the collagen substrate of the skin is less sensitive to cold air, it is possible to cool the target structure without damaging non-target skin tissue with collagen. The embodiments depicted in FIGS. 10 and 11 can also be utilized to treat target tissue via cryotherapy. In these embodiments, the interstitial element comprising one or more needles, stylets, catheters or probes delivers cryogenic fluid to at least one thermally conductive element adjacent to or near the target tissue. Thus, it can be configured with one or more passages to provide treatment to the target tissue. The system is adjacent to provide cryogenic fluids (eg, liquid nitrogen, liquid helium, liquid argon, liquid carbon dioxide, liquid nitrous oxide, liquid AZ-50, refrigerated antifreeze, refrigerated alcohol, refrigerated saline, etc.) Or can be configured to have a remotely located generator. The generator should deliver enough cryogenic fluid to the device to reduce the temperature of the target tissue to between about 0-40 ° C. In some embodiments, a temperature between about 0-10 ° C. may be sufficient to induce target tissue necrosis, while this may be above the freezing point of the target tissue. Thus, a temperature below about −10 ° C. may be sufficient to freeze the target tissue.

  It may be desirable to circulate cryogenic fluid through the intervening portion of the device to maintain a constant cooling therapy. For example, as illustrated in FIG. 12A, the device 211 is configured with an intervening element 212 comprising at least two concentric tubes 213, 214. In this embodiment, the cryogenic fluid can be delivered by the inner tube 213 through the interposer element 212 to the thermally conductive element and then circulated out of the interposer element 212 through the outer tube 214. . In this embodiment, the outer tube 214 itself can be a thermally conductive element. Alternatively, as illustrated in FIGS. 12B and 12C, the interstitial element 212 may be configured with a tubular coil 215 that resides either inside or outside the element 212. The cryogenic fluid is routed through the lumen of the coil 215 to provide a thermal treatment effect to the target tissue.

  In other embodiments, the device may comprise a cold balloon catheter and the thermally conductive plate comprises a balloon. In such a balloon configuration, a pressurized liquid, such as nitrous oxide, is routed through the interstitial element passage. As the liquid reaches the balloon, it undergoes an endothermic phase change so that the liquid absorbs heat from the surrounding area and achieves a therapeutic effect on the target tissue.

  Alternatively, an intervening needle or probe can be used in place of the cold balloon catheter to administer cryotherapy to the target tissue. For example, FIG. 12D shows an interstitial element 212 that includes an inner tube 216 and an outer tube 217. Inner tube 216 includes an inner lumen 218 such that liquid nitrous oxide proceeds from the proximal portion 219 of the tube to the distal portion 220. The inner tube 216 further comprises at least one port or nozzle 221 along the distal portion 220 of the tube so that liquid nitrous oxide exits the inner tube 216. Liquid nitrous oxide is preferably fast and undergoes an endothermic phase change as it exits port 221, and outer tube 217 is cooled by nitrous oxide gas. In this embodiment, as the gas absorbs energy from the outer tube 217 with the thermally conductive element and the surrounding target tissue, the gas passes through the annular space between the outer tube 217 and the inner tube 216, and the intervening element. Exit 212.

  The approach disclosed in FIG. 12D allows for a more intensive area of cryotherapy. The nitrous oxide gas exits the distal portion 220 of the inner tube 216 at its lowest temperature and then absorbs thermal energy from the distal portion 1242 of the outer tube 217. After heat exchange with the distal portion 1242 of the outer tube 217, the gas travels toward and out of the proximal end 219 of the interstitial element 212. Thus, the distal portion 1242 of the interstitial element 212, the portion adjacent to the target tissue, is the coldest.

  Various parameters of this cryogenic system can be adjusted to modulate the temperature of the gas and vary the rate and extent of thermal treatment. For example, the shape, size, and number of nozzle / port openings may be related to conduction and convection rates. The size of the annular space between the outer and inner tubes of the interstitial element also affects the heat transfer properties of the device. In addition, the pressure of the nitrous oxide liquid also contributes to the heat exchange capability of the treatment.

  Cryotherapy may also be administered locally to treat the target tissue below the surface of the skin. It may be desirable to use cryoprotectants in conjunction with non-invasive cryotherapy to minimize the risk of damage to the epidermis and other non-target tissues. As illustrated in FIG. 12E, cryoprotectant 222, such as ethylene glycol, glycerol, erythritol, or dimethylformamide, may be applied locally or by injection to minimize the therapeutic effect on non-target tissue 103. Can be applied. Cryoprotectant 222 can also be utilized in conjunction with transdermal therapy utilizing the intervening element discussed above. As shown in FIG. 12F, cryoprotectant 222 may be used to create a protected non-target tissue area 223 between cold source 225 and target tissue cold treatment area 224 at skin surface 119. Can do.

(Phototherapy)
Another approach for treating target tissue comprises the use of phototherapy. In this approach, the unique optical properties of the target structure are used to determine the spectral characteristics of each structure. Light energy can be delivered to the target tissue at a wavelength consistent with the spectroscopic characteristics of the particular structure so as to selectively heat and treat the structure through light absorption.

  Phototherapy can also be performed by coloring the target tissue or the area surrounding the target tissue and then delivering light energy to heat the coloration. For example, a colored substance can be introduced into the target tissue and light energy having a waveform with a specific absorption for this color can be delivered from an internal or external source to treat the target tissue. The main advantage of this approach is that the target tissue can be selectively colored so that treatment can be localized to the target tissue with minimal impact on the non-target tissue. Phototherapy can be performed using various types of light energy including, but not limited to, lasers, ultrashort pulsed light (“IPL”), focused IP, infrared, and near infrared. These various light energies can be implemented with any number of energy delivery elements including, but not limited to, lasers, light emitting diodes (“LEDs”), or light bulbs. Optionally, one or more filters can be used in conjunction with any of these energy delivery elements to remove unwanted wavelengths, including those absorbed by non-target tissue.

  In one embodiment associated with phototherapy, a chromophore (ie, a colored molecule) is introduced into the target tissue. If the target structure is a sweat gland, the chromophore is introduced through the gland duct via local delivery, injected into the target tissue, or ingested by the patient so that coloration appears in the patient's sweat (ie, chromihidrosis) can do. For example, garlic sulfur compounds are known to be metabolized by the body to form allyl methyl sulfide (AMS) that is excreted from the body through sweat. The color can be delivered directly to the sweat glands by combining the chromophore with garlic sulfur so that the chromophore is bound to AMS after metabolism. After the appearance of color in the target tissue, an external source or energy delivery element (eg, a light emitting diode “LED”) is a light energy source, such as a laser or other light delivery system, that specifically matches one or more chromophores. Can be delivered to selectively treat the target tissue. This light energy can travel non-invasively below the sweat ducts or can reach the target tissue across the epidermis and dermis layers. Alternatively, interstitial devices that use optical fibers can deliver light energy directly to the target tissue.

  In another embodiment associated with this approach, a colored bioresorbable element can be introduced into or around the target tissue. For example, as illustrated in FIG. 13, a colored bioresorbable microsphere layer 226 can be deposited in or around the target tissue 105. The microspheres 226 can be injected into or around the target tissue 105 with a syringe 227 as part of a bioinert solution, gel, or other carrier. Once deposited in or around the target tissue 205, the colored microspheres 226 can be heated by the laser light 228 from the laser 229 that matches their particular color, thereby conducting the target tissue 105. To produce therapeutic effects. These microspheres 226 are made of a material such as polytetrafluoroethylene (PTFE), polymethylmethacrylate (PMMA), or calcium hydroxyapatite (CaHA), and are microscopically formed by a laser 229 that has relatively little effect on the tissue in the pathway. It can be colored to match the laser wavelength, which provides the most efficient heating of the sphere 226.

  In phototherapy with chromophore deposition in or around the target tissue, delivery of the chromophore in the presence of the carrier solution may result in a wider and more even distribution of the chromophore prior to treatment. Good. A wider and more even distribution of chromophores may provide a wider and more consistent therapeutic effect. For example, the chromophore may be suspended in a carrier solution of buffered or unbuffered saline prior to treatment of the target tissue. As illustrated in FIG. 14, the carrier solution 230 has a hollow needle 231 at the planar junction between the dermis layer 101 and the subcutaneous layer 100 so as to create a pathway for movement of the chromophore. Introduced using. In addition, the carrier solution 230 may incorporate agents to enhance the distribution and / or effects of chromophores or to promote post-treatment recovery.

  In another embodiment associated with the phototherapy approach, a neurotoxin can be used as a mediator to deliver colorant to the target tissue and / or neuronal gland or neuromuscular junction of the target structure. Botulinum, such as botulinum type A toxin, treats various neuromuscular and neurogland symptoms by binding to cholinergic neurons at these junctions and blocking the release of acetylcholine in neuronal synaptic vesicles. It is generally known that fungal neurotoxins can be administered. This blockage paralyzes the tissue nerve at the junction, but this result is only temporary. By using toxins to color the target tissue and / or target structure nerve junctions, these junctions are thermally excised, and the target tissue / structure nerves are selectively paralyzed and more persistent Light energy can be delivered so as to achieve an effective treatment.

  In this approach, the toxin itself can be colored, or alternatively, a chromophore chemically linked to the toxin may be used. In addition, the light energy delivered to the target tissue is specifically matched to the colorant so as to maximize the energy absorbed at the junction.

  There are seven serologically different types of botulinum toxins designated A to G. A toxin is a double-chain polypeptide with a 100 kDa heavy chain ("heavy chain") joined to a 50 kDa light chain ("light chain") by a disulfide bond. The heavy chain is involved in targeting and binding to the cholinergic neurons at and around the injection site and helping the light chain to cross the nerve cell membrane. The light chain is involved in carrying toxicity to neurons. Although the potential molecular mechanism of botulinum toxin poisoning is discussed here, other toxins, such as butyric acid toxin, tetanus toxin, exotoxin, diphtheria toxin, cholera toxin, ricin, or variants thereof, It may have the same or substantially similar mechanism.

  In this approach, it may be desirable to use only the heavy chain fragment of the toxin as a colorant delivery vehicle. By isolating the heavy chain fragment and excluding the light chain fragment from the toxin molecule, the introduction of toxicity into the body is avoided. In addition, the presence of light chain fragments may make it difficult to determine the success of heat treatment, since intact toxic molecules may provide a temporary therapeutic effect. Thus, coloring a heavy chain toxin fragment or attaching a chromophore to a heavy chain toxin fragment may provide a more attractive treatment. In some embodiments, 100 to 200 units of botulinum toxin is administered to the patient to treat the axillary region. Other doses may also be administered depending on the desired clinical outcome.

  In another embodiment, microneedle technology can be employed to facilitate delivery of the chromophore to the target tissue. For example, the microneedles can be hollow to facilitate delivery of colored substances (eg, liquid or solid chromophores, colored microspheres, etc.) to the target tissue. Alternatively, the needle may be configured to deliver the chromophore across the stratum corneum only from the location where the chromophore can travel to the target tissue via reverse iontophoresis. In additional embodiments, reverse iontophoresis is used to drive the chromophore directly across the epidermis and into the deep dermis.

  In another embodiment as illustrated in FIG. 15, the needle tip 232 consists of at least one chromophore 233 that detaches from the needle 234 when inserted into or along the target tissue. Configured as follows. Needle tip 232 may be coated with chromophore 233 or consist of solid chromophore 233, and needle shaft 235 may be solid or hollow. In embodiments employing a detachable chromophore tip microneedle 234, the microneedle 234 can optionally be configured to engage a tip deployment mechanism 237. A tip deployment mechanism 237, such as a single plunger or an array of plungers, can be utilized to facilitate attachment and removal of the chromophore needle tip 232. For example, a hollow body needle 234 can be used to allow the deployment mechanism 237 to access the removable chromophore tip 232. More specifically, the deployment mechanism 237 can be driven through the needle lumen 238 to disengage the removable tip 232. Alternatively, the deployment mechanism 237 can include a hydraulic element, such as pressurized air, to cause the needle tip 232 to be detached. Additionally or alternatively, needle tip 232 and / or needle shaft 235 can be configured with pre-established vulnerabilities to facilitate deployment. For example, as illustrated in FIG. 15, the needle tip 232 is associated with a notch or groove 236 such that it will fold along the notch or groove 236 after insertion into the target tissue or prior to withdrawal from the target tissue. Can be configured.

  The needles 234 shown in FIG. 15 may be joined with an array of needles such as a linear or planar array. Needle 234 may have a length of about 2-8 mm, more preferably about 4 mm, and the length of removable tip 232 matches the depth of the target tissue. A deployment mechanism 237 such as a plunger or an array of plungers may attach and detach each needle separately, in a prioritized order, or all at once.

  In an alternative embodiment employing chromophore tip microneedles, the microneedle shaft is made of a soluble material so that the microneedle shaft dissolves and leaves the chromophore tip in the target tissue after insertion into the skin. For example, a microneedle array can be cast and cured with a distal tip with a chromophore and a proximal shaft with a sucrose solution. Once the microneedle is inserted into the skin, the sucrose shaft degrades in the interstitial space of the skin tissue so that the chromophore tip is the only part remaining in the skin. In this embodiment, it is desirable to incorporate a flexible backing substrate so that after insertion into the skin, the backing can be peeled away from the microneedles, leaving a portion of the needle shaft and chromophore tip in the skin. May be.

  Optionally, hollow microneedles can be utilized as a route for the delivery of light energy from an extracorporeal energy source to the deposited colored material. Alternatively, the microneedles may comprise a fiber optic material to facilitate delivery of light to color in the target tissue.

  In the above embodiments that provide color delivery to the target tissue, various mechanisms can be employed to minimize the effects of any structure or color fragments left after treatment. For certain colored liquids, gels, and solids, laser delivery can be set with sufficient intensity and duration to excise and evaporate some or all of the deposit. In the case of bioresorbable implants such as microspheres, the implant may eventually be absorbed into the surrounding tissue, so that there are no harmful physiological or aesthetic effects due to the presence of microspheres or color. Additionally or alternatively, the remaining color can be decolorized by light at the treatment wavelength or alternating current wavelength so that it is no longer visible in the skin. Alternatively, the chromophore may not be bioresorbable or depigmented, but rather the light energy breaks up the chromophore into particles that are phagocytosed by the immune system and removed from the body. Also good. This mechanism of action is well known in the field of tattoo removal, where, for example, carbon black tattoo ink is crushed by laser light and removed from the body.

  In another embodiment incorporating a chromophore tip microneedle, the chromophore tip is configured to be removed from the target tissue along the needle. In this configuration, the tip is not detachable from the needle shaft. The configuration of the microneedle 239 that keeps this prototype is shown in FIG. Needle 239 is a proximal portion 240 made of an optically clear material or an optically neutral chromophore (ie, cannot absorb, block, or be activated by the therapeutic wavelength). And a distal portion 241 made of a chromophore. As light energy is delivered across the needle proximal portion 240 and absorbed by the colored distal portion 241, the distal portion 241 begins to heat, thereby conductively heating the surrounding target tissue and treating To do. Alternatively, the proximal portion 240 of the needle 239 can be configured as a light pipe or lens to concentrate light energy on the chromophore tip 232.

  In embodiments utilizing non-removable chromophore tip microneedles, it may be desirable to incorporate an array of needles into an optically neutral backing system. This array, comprising a chromophore tip and an optically neutral shaft, configured with shape and needle density to optimize treatment to the target tissue, so as to form a microneedle patch Can be permanently coupled to an optically neutral backing system. After insertion of this patch into the patient's skin, the light energy is delivered to an optically neutral backing so that this energy is delivered through an optically neutral shaft and absorbed by the chromophore tip of the needle. Can be applied. The absorbed energy heats the chromophore tip, thereby treating the surrounding target tissue. The patch can be any size, shape, and shape needed to conform to the treatment area. Optionally, the patch backing may comprise a flexible material to allow the patch to conform to the patient's skin. The backing system may also include an optically neutral adhesive on the portion closest to the skin to minimize patch movement during treatment. The use of an adhesive may provide a significant benefit in avoiding patient discomfort due to therapeutic target errors or needle movement.

  In any of the above embodiments relating to microneedles or microneedle patches, it may be beneficial to incorporate an agent into the adhesive, backing, or needle shaft proximal portion to facilitate heating of the non-target tissue. Also good. The needle or patch can optionally remain inserted into the patient's skin after treatment of the target tissue to serve as an integral bandage. These healing agents may comprise anti-inflammatory agents such as steroids, non-steroidal analgesics, or antibiotic creams. Alternatively, the needle may be fully or partially coated with a chemical such as a sclerosing agent to enhance treatment of the target tissue.

  In embodiments that incorporate microneedle patches with optically neutral components, energy delivery once a certain threshold is reached to prevent unnecessary damage to target and / or non-target tissues. It may be desirable to configure the system to block. For example, an optically neutral backing, adhesive, and / or needle can cause at least a portion of the component to become optically opaque to the therapeutic wavelength when a defined amount of energy is transmitted through the system, thereby , Can be designed to prevent additional energy from reaching the chromophore tip and heating the target tissue. Alternatively, these components can be sensitive to heat or temperature so that energy delivery is blocked once the target or non-target tissue reaches a defined threshold temperature. Alternatively, the backing material may be configured to be opaque, blocking light delivery to all but the proximal needle shaft that extends through the backing material to the top surface of the alignment system, thereby Blocks light delivery to all tissues except those in direct contact with the chromophore tip.

  In any of the phototherapy applications, it may be desirable to monitor the absorption of the light spectrum in the tissue in order to detect changes in the absorption spectrum. Changes in tissue absorption characteristics indicate changes in the tissue, can be used to detect the effectiveness of treatment, control the extent of treatment, and confirm the completion of treatment.

(Induction heating)
Another method of providing a therapeutic effect to the target tissue includes inductively heating particles in or around the target structure. These particles are preferably metal (eg, iron) and are sized to be introduced into the target tissue region non-invasively or minimally invasively. For example, a solution of small sized ferromagnetic particles can be introduced into the target tissue via injection with a syringe. Alternatively, it may be easier to reach the target tissue using magnetic nanoparticles. Once one or more particles (eg, ferromagnetic particles) are present in or around the target tissue, a source of electromagnetic energy from either the inside or outside of the body generates an electromagnetic field that causes current to flow into the metal particles in the body. Can be generated. These currents cause resistive heating of the particles and resultant conduction heating of the target tissue. The electromagnetic energy source can continue to deliver energy to the particles until the treatment of the target tissue is complete.

  If the target tissue is one or more sweat glands, the particles may be introduced locally via the sweat gland ducts. Similar to the aluminum ion particles in the antiperspirant that are sent down the sweat gland and prevent sweat from reaching the skin surface, locally applied particles can be introduced into the sweat gland. As illustrated in FIG. 17, these particles 242 can naturally travel down the tube 109 and into the coiled gland. Alternatively, pressure can be used to facilitate the progression of particles 242 into the sweat glands. Alternatively or optionally, iontophoresis may facilitate delivery of metal particles 242 into the sweat glands. As described above, the electromagnetic energy 243 so as to heat the particles 242 and the surrounding target tissue 105 until the treatment is complete (eg, sweat production of the sweat glands stops and / or the sweat glands are thermally ablated). May be delivered from an electromagnetic energy source 244.

  It should be understood that substantially all phototherapy related to color delivery to the target tissue discussed herein can be modified to deliver metal particles for induction heating treatment. For example, ferromagnetic particles can be substituted for chromophores, ferrofluid suspensions can be used instead of colored solutions, and iron tip microneedles are used instead of chromophore tip microneedles be able to.

  It may be desirable to remove ferromagnetic particles from the body after treatment. As such, a microneedle patch comprising a nonmagnetic backing system, a nonmagnetic needle shaft (or proximal portion of the shaft), and a non-removable iron tip microneedle may be employed. Optionally, this embodiment can incorporate electromagnetic elements 245 directly into the backing material 1249, as illustrated in FIG. 18A. The electromagnetic element 245 can be any structure or material, such as a metal wire, that has electromagnetic properties and is electrically connected to an energy source. The electromagnetic element or electromagnetic source delivers an electromagnetic field 246 to resistively heat the tip 247, thereby treating the target tissue 105. After treatment, the microneedle patch 248 is removed from the patient along with the non-removable ferromagnetic tip 247.

As another means of treating the target tissue, ultrasonic energy can be used. For example, ultrasound heat can be induced by delivering ultrasound to the target tissue and causing the tissue to vibrate and heat. Wave frequencies between about 20 kHz and about 18 MHz with powers in the range of about 0-50 W / cm ² can achieve these results. The therapy may be more effective at frequencies between about 0.1 MHz and about 3 MHz and powers from 720 mW / cm ² to 50 W / cm ² .

  In intensive ultrasound therapy, one or more ultrasound transducers emit waves that converge at a specific focal point at a specified distance from the transducer. As shown in FIG. 18B, the focusing of these waves 249 from the ultrasonic transducer 251 causes a strong cumulative effect at the focal point 250. Once each wave 249 passes through the focal point 250, it continues along its radial path and distributes. Multiple transducer embodiments may be oriented in any number of configurations, including linear, radial, and hemispherical arrays.

  In treatment using a planar ultrasonic transducer, the emitted wave is not focused at a particular point. Instead, as illustrated in FIG. 18C, the wave 249 travels in a planar manner from the edge of the transducer 252. In addition, the ultrasound signal can be attenuated so that it terminates at a given distance and does not propagate into deep non-target tissue. Both the plane 252 and the focusing 251 transducer may induce ultrasonic heat. Used in conjunction with techniques for protecting non-target tissue (eg, cooling systems / elements) as described elsewhere herein, both ultrasound methods are used to heat the target tissue Can be isolated.

(Chemical thermal reaction)
Another method for reducing sweat production is illustrated in FIG. In the illustrated embodiment, the sweat glands are thermally disabled by controlled chemical reactions. This chemical reaction can be either exothermic or endothermic and can involve one or more components. The components can be present in one or more chemical vessels 253 that are in communication with the intervening probe 254. The probe 254 comprises at least one lumen 255 in communication with the chemical container 253, a sharp tip 256 for penetrating the skin and entering the target tissue, and a thermally conductive material (eg, a metal such as copper). A thermally conductive element 257. The thermally conductive element portion 257 of the probe 254 is configured to be positioned adjacent to the target tissue. In one embodiment, a portion of skin 177 is raised so that probe 254 with sharp tip 256 approaches the target tissue parallel to the skin and allows tip 256 to pierce through the tissue. The thermally conductive material 257 is placed at a location on the probe 254 so as to be located in the target tissue region. Further details regarding this delivery mechanism are described below. The components can be mixed and delivered simultaneously or sequentially to react within the thermally conductive element 257. For an exothermic reaction, in an amount sufficient to generate enough heat to disable and / or ablate the sweat gland via conduction across element 257, for example, acid (eg, HCl, H ₂ SO ₄ ). And water can be delivered into the thermally conductive element 257. In another embodiment, supersaturated sodium acetate is introduced into the thermally conductive element 257 and heat is generated as the solution crystallizes. In an alternative embodiment, the components can be mixed prior to introduction into the thermally conductive element 257. Optionally, the catalyst can be placed in the thermally conductive element 257 or elsewhere along the probe lumen 255 to promote chemical reactions.

  In another embodiment relating to the target tissue, the solution can be used to carry charge and treat the target tissue. In this embodiment, a conductive liquid, such as a hypertonic solution (eg, saline), is injected into or around the target tissue with a syringe and needle and then charged by an electrode located in proximity to the target tissue. Can do. Alternatively, the needle itself may be equipped with electrodes to directly charge the solution once placed in or adjacent to the target tissue. For example, an array of microneedles (such as that shown in FIG. 14) that also includes an electrode can be used to deliver hypertonic fluid to the target tissue, such that the tissue is conducted through the solution after activation of the electrode. It is treated by a charge.

  It may be advantageous to use the conductivity of the sweat itself to reach the sweat gland, since sweat has already traveled the pathway from the close area of the sweat gland to the surface of the skin. 20A-20C illustrate a method of delivering charge to sweat glands via sweat. In order to prevent damage to the skin surface and surrounding tissue along the sweat gland tube 109, an insulator coating 258 is first applied to cover the skin surface and the wall of the tube 109 while sweat still remains from the sweat gland to the surface. It may be desirable to leave a path to proceed to. After application of insulator 258, by administering an injection of epinephrine or cholinergic agonists or agonists, stimulating nerves with electrical signals, and / or raising the patient's temperature via exercise or other means Can induce the patient to sweat. Once the sweat reaches the surface of the skin, the operator can apply electrical energy 259 from an energy source (eg, RF generator 204) to the surface sweat. Through the electrical conductivity of sweat, electrical energy 259 from energy source 204 can reach the sweat gland and be disabled. In some embodiments, it may be desirable for the operator to induce sweating throughout the treatment to maintain continuity of the conductive pathway.

(B. Chemotherapy)
In another embodiment for treating a target tissue, a chemotherapeutic substance can be introduced into or near the target tissue to cause a chemical reaction and the resulting therapeutic effect. For example, alcohol, acid, or base can be delivered to the target tissue so as to chemically excise the tissue. More specifically, injection of small amounts of acids such as trichloroacetic acid or alpha hydroxy acids can provide a therapeutic effect. Ethanol at a concentration of 5% to 100% has been used to treat hepatocellular carcinoma, thyroid, fibroids, and cysts in the body and should be used to treat the target tissue of the present application Can do. The chemotherapeutic agent can be delivered to the target tissue by any number of mechanisms, including syringes and needles, or microneedle patches as described elsewhere herein.

(C. Mechanical treatment)
(Percutaneous resection)
21A-21C illustrate a method and device for percutaneous resection of sweat glands. A probe 260 equipped with a retractable cutter or blade 261 can be inserted percutaneously under the target tissue 105 comprising one or more sweat glands. Optionally, imaging techniques can be utilized to facilitate installation of the probe / cutter 260. Probe 260 is configured with a hollow chamber 262 such that blade 261 forms the outer wall of chamber 262. Chamber 262 is open when blade 261 is in the retracted position. When the blade 261 is engaged, the chamber 262 is closed. As illustrated in FIG. 21A, probe 260 is placed under one or more sweat glands such that at least one sweat gland is supported by the wall of blade 261 with which it is engaged. When the blade 261 is retracted as shown in FIG. 21B, the sweat glands fall into the open hollow chamber 262. As blade 261 is advanced and engaged, sweat glands are sheared from tube 109 and into probe chamber 262. It may be desirable for blade 261 to rotate, vibrate, and / or oscillate to promote gland shearing. When the blade 261 is engaged, the sheared gland is contained within the chamber 262 so that it can be removed with the probe 260 after treatment or vacuumed in synchrony with the treatment.

(Plane cutting device)
In another embodiment for treating the target tissue, a planar cutting device can be inserted into the target tissue via a small skin incision or puncture. The device shears, scrapes, and / or cuts the target structure in the target tissue to provide a therapeutic effect laterally, longitudinally, and / or at an angle in the plane of the target tissue. And can be configured to move in parallel. More specifically, the device can move across the junction between the dermal and subcutaneous layers of the skin, destroying the eccrine and apocrine sweat glands, or at least making them inoperable .

  In one embodiment of a planar cutting device, the device can have a reduced profile configuration when inserted into the skin and an expanded profile when placed in the target tissue. For example, as illustrated in FIGS. 22A and 22B, a device 263 comprising at least one wire 264 in a thin configuration is inserted into the skin opening. After insertion into the skin, the actuator 265 can be used to bend the wire 264 into an expanded profile and cut and disable the target structure within the target tissue during this expansion. In its expanded configuration, wire 264 has access to a larger target tissue area for treatment. Optionally, wire 264 can be expanded and contracted multiple times with actuator 265 to produce a therapeutic effect. As shown in FIG. 22B, the actuator 265 may include an outer element 266 and an inner element 267. Inner element 267 comprises a shaft having a distal end 268 coupled to wire 264 and a proximal end 269 extending at least partially outside the patient. The outer element 266 may comprise a collar or sheath coupled to the wire 264, and the contraction and expansion of the wire 264 can be actuated by movement of the inner element 267 relative to the outer element 266.

  As illustrated in FIG. 23, in another embodiment, the planar cutting device comprises a windmill cutter 270 that is placed into the target tissue 105 in a reduced profile configuration. The windmill cutter 270 comprises a handle 271 for insertion into at least a portion of the target tissue 105 and at least one blade 272 operably coupled to the distal portion 273 of the handle 271. The blade 272 is configured to rotate around the distal portion 273 of the handle 271 such that the target tissue 105 and target structure in the blade path are damaged and disabled.

  In another embodiment for a planar cutting device, a guide wire can be introduced into the target tissue and routed through the tissue so as to define the plane of the tissue to be treated. As illustrated in FIG. 24, a wire 274 is drilled into the target tissue 105 through two insertion points 275 in the skin. Once the wire 274 is positioned to define the tissue region to be treated and each end of the wire 274 is positioned outside the insertion point 275, the wire 274 is pulled to pull the wire 274 through the tissue-defined plane. Tension can be applied to both ends. As the wire 274 translates through the tissue, it damages and disables the target structure in its path. In an alternative embodiment, as shown in FIG. 25, the wire 274 is inserted into the target tissue 105, guided across the target tissue 105 to define the treatment area, and the single insertion point 275 in the skin. All configured to be sent out of the body. Once the wire 274 is in place and both ends of the wire 274 are positioned outside the insertion point, the wire end can be pulled so that the wire 274 passes through the treatment region.

  In the planar cutting device described above that utilizes a guide wire, it may be desirable to route the wire through the target tissue to define the plane of the target tissue for treatment. A digging instrument with a steerable tip can be used to facilitate positioning and routing of the wire in and through the target tissue. A digging instrument 276 comprising a proximal end 279 and a distal end 278 is shown in FIGS. 26A and 26B. Instrument 276 further includes a hollow passage 277 for routing guide wire 274 from proximal end 279 through distal end 278 for placement in the target tissue. The distal end 278 of the instrument 276 is configured for insertion through the skin into the target tissue. The proximal end 279 of the instrument is located outside the body and is used to facilitate insertion and positioning of the distal end. The instrument 276 further includes a steering actuator 280 at the proximal end 279 to position the distal end 278 of the instrument 276 and facilitate placement of the wire in the target tissue.

  Any of the planar cutting devices described herein can utilize a mechanical force that drives a cutting element (possibly a wire or blade) through the target structure in the target tissue to achieve a therapeutic effect. Be considered. However, it should be understood that the cutting elements of these devices may similarly or alternatively include an energy delivery element to treat the target tissue as the element moves through the tissue. For example, the wire 274 of FIG. 24 can also be a resistive heating element connected to an external power source, where the heated wire ablate and coagulate the target tissue as it translates through the planar area of treatment. Alternatively, the wire can be an energy delivery element (eg, an electrode) for delivering one or more forms of energy (eg, radio frequency, microwave, ultrasound, etc.) to surrounding target tissue. As a further alternative, the wire and its electric field can be used to cut and shear the target structure as it passes through the treatment region.

(Photodynamic adhesive)
In another method for reducing sweating, as illustrated in FIG. 27, the sweat gland tube 109 can be filled with a photodynamic adhesive. In this embodiment, a photosensitive dye 281 is introduced into the sweat tube 109, and the dye 281 is exposed to a fluorescent lamp from an external light source. Dye 281 is preferably introduced into eccrine and / or apocrine sweat glands 106, 107 via topical application. Dye 281 with or without pressure assistance can be applied topically to access sweat gland 109 through the pores. Dye 281 can also be introduced into the gland or duct via injection. When exposed to light of the required wavelength and sufficient duration, dye 281 undergoes a chemical change through cross-linking of proteins in the dye. The cross-linked dye seals sweat gland 109, thereby preventing sweat from reaching the surface of the skin.

  In one embodiment, Janus Green dye is delivered to the sweat duct. Optionally, pressure may be used to facilitate delivery of the dye into the tube. Once the dye enters the tube, an external laser light source can deliver about 650 nanometers of light to the tube, thereby cross-linking the dye and sealing the tube. Rose bengal and indocyanine green are other dyes that can be used for this application. In addition, albumin or other proteins can be added to the dye to promote the sealing action.

  In another embodiment, the chromophore is mixed with a chemical agent, so that the chemical agent and chromophore react when exposed to a fluorescent lamp. Specifically, the chromophore absorbs light and consequently heats the chemical agent, converting the chemical agent into a seal, thereby preventing sweat from reaching the surface of the skin.

  In any of the embodiments disclosed herein relating to sealing the gland duct, such treatment optionally has a specific affinity for water (eg, microwave), or Delivering energy that is specifically configured to be absorbed by water (eg, infrared) can be included. Application of energy to sweat-filled glands may result in selective treatment of these glands with minimal impact on surrounding non-target tissues or structures.

(Fibrin adhesive)
Another method for sealing a sweat gland to reduce sweating includes introducing a biocompatible scaffold into the sweat duct. As illustrated in FIG. 28, by introducing a scaffold structure 282 into the sweat tube 109, the fibroblasts 283 move from the skin onto the scaffold 282 as part of the body's healing response, causing the sweat gland 109 to be permanently removed. Forms scar tissue that seals to the skin. Scaffold 282 can be a biodegradable fibrin hydrogel, such as, for example, a glycosaminoglycan chain attached to a synthetic polyamine. These scaffolds 282 can be introduced into the tube 109 from the skin surface using a variety of delivery techniques, including injection, pressure, and iontophoresis.

(Pressure-induced disabling)
In another embodiment for reducing sweating, the sweat glands are disabled utilizing positive or negative pressure delivered from the skin surface to the sweat glands via the sweat tubes. In one embodiment of this approach, as illustrated in FIG. 29, piston 284 is applied to the sweat gland such that the pressure gradient across the sweat gland wall is sufficient to cause disabling rupture 285 in the coil portion 286 of the gland. Pressurized gas (eg, air) can be delivered. In one embodiment, a pressure of at least about 200, 300, 400, 500, 600, 700 psi, or more may be used. Sufficient pressure can also be achieved by using a volume displacement pump, syringe, or suction device.

  In another embodiment, as illustrated in FIGS. 30A and 30B, the sweat glands are saturated with a liquid (eg, water) having a larger volume density as a liquid than as a solid. The liquid may be introduced into the sweat gland by topical application (eg, a patch), injection, or by inducing the patient to sweat if the liquid is sweat. Any number of cryogenic techniques are then used to cool the liquid in the sweat glands. As the liquid freezes, it expands and exerts pressure on the gland walls. The liquid continues to freeze and gradually increase the pressure in the gland 286 until a rupture 285 is created in the gland and / or tube 109.

(Pressure-induced necrosis)
Sweat glands may be more susceptible to ischemia than surrounding tissues. For example, Pressure-Induced Bullet and Sweat Gland Necrosis Flowing Chemotherapy Induction, The American Journal of Medicine, 15 It is described that blood can cause sweat gland necrosis. Thus, another treatment to reduce sweat production is at a level sufficient to cause necrosis of one or more sweat glands in the region, either alone or in combination with other methods described herein. And applying pressure to a region of the target tissue while at a duration, while minimizing ischemic damage to the non-target tissue. A device 287 for causing pressure-induced necrosis of sweat glands is shown in FIG. The device 287 may include a clamp or pliers 288 for engaging the skin at its distal end and an actuator 289 for the operator to apply and sustain pressure. Alternatively, the actuator 289 may further comprise a spring element 290 so that a constant pressure can be maintained during treatment without the need for operator assistance or interference. Device 287 may include an array of clamps or pliers 288 so that multiple locations can be treated at once. In alternative embodiments, the device 287 may be configured to be worn by the patient over a period of hours or days to achieve the desired therapeutic effect. For example, a variation of the device shown in FIG. 31 can be strapped to the patient's axilla so that it can be worn overnight or a day to achieve axillary anhidrosis .

(Acoustic cavitation)
In another embodiment, microbubbles are introduced into the target tissue and cavified by an ultrasound signal to achieve a therapeutic effect. For example, as illustrated in FIG. 32, encapsulated microspheres or microbubbles 291 (eg, OPTISON® sold by GE Healthcare) are delivered to the target tissue 105, thereby allowing extracorporeal An energy delivery device (eg, ultrasound transducer 292) delivers energy 293 (eg, an ultrasound signal) to the target tissue 105 to rupture the microbubble / microsphere 291. Microbubbles 291 can be introduced into the gland through either local delivery via tube 109 or injection. Since the ultrasonic transducer 292 can be configured to deliver waves with sufficient amplitude and frequency to vigorously disrupt the microbubbles / microspheres 291 present in and around the target structure, Sufficient energy is released to disable and provide a therapeutic effect. Alternatively, cavitation can be induced in the sweat gland by increasing the sonic pressure applied to the tissue above the threshold required to cause natural cavitation without exogenous bubble introduction. Sodium and other ions in sweat may serve as a bubble forming nest. For example, the type of pressure provided by the shock wave lithotriptor may be sufficient to generate this cavitation.

(I. Protection of non-target tissues)
(Thermal therapy protecting non-target tissues)
In tissue thermal treatment, it may be beneficial to protect against unnecessary and potentially harmful thermal destruction of non-target tissues. This is especially the case for subcutaneous treatment, because excess energy delivered to the epidermis and dermis layer of the skin causes pain, discomfort, dryness, charring and peripheral effects. Also, the dry tissue, carbonization, and marginal effects on the surrounding tissue impair the effectiveness of the treatment, as the impedance of the dry tissue may be too high to allow energy to travel into deeper regions of the tissue. obtain.

  In order to avoid thermal destruction to non-target tissues and any troublesome problems associated therewith, the energy delivery device provides a cooling effect for superficial non-target tissues (eg, parts of the epidermis and dermis) Cooling elements can be included. By cooling the epidermis conductively and / or by convection, allowing the cooling effect to penetrate the dermis, the cooling element is for superficial non-target tissue as illustrated in FIG. A thermal protection zone 103 is established. This cooling element providing the protective zone 103 allows the target tissue (eg, thermal treatment zone 105 of FIG. 33) to be treated with minimal risk of thermal damage to non-target tissue.

  To further reduce the risk of other unpleasant sensations associated with pain and / or heat treatment, the cooling element can further cool superficial non-target tissue to create an anesthetic effect. Depending on the type of heat treatment employed and the associated need for complementary cooling, the cooling treatment and / or anesthetic effect may be applied before, during, and / or after the heat treatment. Protective cooling may also be applied alternately with heat treatment to maximize energy delivery while minimizing adverse effects on non-target tissues.

  The cooling element can take many forms. The cooling element can be a static refrigerated liquid (eg, water, saline) or a layer of solid coolant (eg, ice, ceramic plate), or some combination thereof (eg, a metal cylinder filled with cold water), etc. Can be a passive heat sink that conductively cools the skin. The cooling element can also provide active cooling in the form of a gas or liquid spray or flow or aerosol particles for convective cooling of the epidermis. A thermoelectric cooler (TEC) or Peltier element can also be an effective active cooling element. Alternatively, the active cooling element can comprise a thermally conductive element with an adjacent circulating fluid to carry away heat.

  The cooling element can also be incorporated into the device as an internal cooling component for conductively cooling non-target tissue. For example, an energy delivery device can couple a cooling component to an energy applicator, in which case the cooling component can actively or passively provide conductive cooling to adjacent tissue. When passive cooling is provided, the cooling component may comprise a cold metal plate or block. When active cooling is provided, the cooling component may comprise a thermally conductive element, and a refrigerated liquid (eg, water, dry ice, alcohol, antifreeze) is circulated through the internal structure of the element. For example, in a microwave energy delivery device that includes a dielectric, the dielectric itself can be a cooling component. In another example, the cooling component can be incorporated into an electrode in embodiments where RF energy is delivered to the skin tissue.

As shown in FIG. 34A, the cooling component 115 can be incorporated into an energy delivery device 117 comprising at least one microwave antenna 120 as described above. In this embodiment, fluid is used to cool adjacent skin tissue 119.
This convective cooling can optionally be enhanced by a coolant circulator 118 that can be integrated into, coupled to, or remotely located within the energy generator 113. As shown in FIG. 34B, the cooling circulator 118 is located remotely from both the energy source 113 and the energy applicator 111. The nature and characteristics (eg, medium, flow rate, temperature) of the circulating fluid (gas or liquid) are selected and modified to achieve the desired cooling effect in light of the amount and rate of energy delivered to the target tissue. be able to.

  The cooling element can also be used to provide a directional component for thermal therapy. For example, the needle 294 illustrated in FIG. 35A can be configured with a proximal region comprising a cooling element 295 and a distal end comprising an electrode tip 296. In this configuration, thermal damage can be isolated to the target tissue while non-target tissue is cooled by the cooling element 295 to protect along the proximal region of the needle. Optionally, electrode 296 itself may allow internally refrigerated fluid to conductively cool adjacent tissue to electrode 296, thereby minimizing unnecessary damage to non-target tissue. Can be equipped with cooling components.

  FIG. 35B shows an energy delivery element comprising a metal electrode 297, an inner tube 298 and an outer peripheral surface 299. In this embodiment, the metal electrode 297 comprises a cooling component. The energy generator provides electrical energy to the metal electrode 297 to deliver an electric field to adjacent tissue. The cooling component of electrode 297 conductively cools adjacent tissue and coolant is delivered to electrode 297 through inner tube 298 and then through the annular space between inner tube 298 and outer surface 299. Circulated.

  In minimally invasive thermal therapy, where the energy delivery device delivers energy from a location near or adjacent to the target tissue, surface cooling is utilized in addition to or instead of subcutaneous cooling to protect the non-target tissue. be able to. For example, in FIG. 11, an energy delivery device comprising a needle 205 that delivers energy 210 subcutaneously is depicted. A cooling element can be incorporated into the delivery device to provide protective cooling adjacent to the thermal treatment and / or, as shown, the cooling element protects superficial non-target tissue. Can be applied locally.

  In another embodiment comprising a minimally invasive treatment, the cooling element can be incorporated into the needle such that the proximal and distal portions of the needle comprise a cooling element. In this configuration, the electrode or other energy delivery element is cooled so that superficial non-target tissue adjacent to the proximal cooling element and deep non-target tissue adjacent to the distal cooling element are protected. Between the distal and distal cooling elements. Thus, thermal treatment is adjusted from above or below the treatment area so that treatment of the target tissue is localized.

  It may also be desirable to utilize a cooling element to improve the overall heat treatment efficiency. As mentioned above, thermal treatment may be attenuated by overheating and drying of the tissue adjacent to the electrode or other energy delivery element. Because dry tissue has a relatively high impedance, energy delivery across dry tissue is compromised, thereby resulting in inefficient, inconsistent and potentially ineffective treatment. By incorporating cooling elements or cooling components proximate to the treatment site, excess heat can be absorbed by the energy delivery device and removed from the body. For example, an electrode or other energy delivery element can include a cooling component to extract excess heat from the electrode and adjacent tissue and promote thermal conductivity for deeper treatment.

  In another embodiment, a heat pipe can be incorporated into the energy delivery element to absorb and expel excess energy from the treatment area. FIG. 36 depicts an energy delivery device 1200 comprising a bipolar pair of needle tip electrodes 1201, 1202, where the electrodes 1201, 1202 are located adjacent to the target tissue 105. Inside these electrodes 1201 and 1202, a cooling component including a heat pipe 1204 is incorporated, and the heat pipe 1204 is connected to a heat sink 1203 located outside the body. The heat pipe 1204 operates on the principle of supercooling so that the fluid (eg, water, alcohol, ammonia, etc.) in the pipe 1204 rapidly condenses to transfer heat along the pipe. And evaporated at the opposite end of the pipe 1204. In this example, the heat sink 1203 draws heat away from the fluid evaporated at the proximal portion of the heat pipe 1204 to condense the fluid into a liquid. Once condensed, the liquid travels toward the electrode at the distal portion of the pipe and absorbs heat from the electrode and surrounding area until it evaporates. The steam then travels up the proximal portion of the heat pipe 1204 to begin another heat exchange cycle.

  In another embodiment, the cooling element can incorporate a heating electrode to achieve the desired thermal protection. For example, as shown in FIG. 37A, a cooling electrode comprising a heat sink 1205 is disposed between two pairs 1206, 1207 of bipolar needle electrodes. The heat sink 1205 can be a thermally conductive metal with a high heat capacity. Optionally, the heat sink 1205 may further comprise a chamber for carrying a static or circulating cooling medium to absorb and carry away excess heat. In the example illustrated in FIG. 37A, the cooling element 1205 removes excess heat from the treatment area, protecting non-target tissue and avoiding the adverse effects of target tissue drying. The length is equal to the delivery element 1206, 1207. In another example, as illustrated in FIG. 37B, the cooling elements 1209 are in alternating order with the monopolar electrode 1208 so that the cooling elements 1209 primarily provide protective cooling to superficial non-target tissues. Shorter than the energy delivery element 1208. In any of these embodiments, the cooling element 1209 may alternatively comprise an electrically active element such as a thermoelectric cooler (TEC) or Peltier element.

  In applications where the target tissue is thermally treated using cryotherapy, it may be beneficial to provide a heating element to protect non-target tissue from the undesirable effects of cooling. As the various aspects of protective cooling are disclosed above with respect to heat treatment, the same conduction and convection techniques can be used in the same way, using heating elements to heat to protect non-target tissue with cryotherapy. Can be adopted. In addition to the previously disclosed modes of conduction and / or convection heat exchange, the heating element also provides resistance, radiation, and / or induction heating to provide the required amount of heat to protect non-target tissue. It can also be used. Such protective heat treatment can be applied before, during, after, and / or alternating with the application of cryotherapy to treat the target tissue.

(Ii. Shape)
In many of the embodiments disclosed herein, treatment is administered locally and / or minimally invasively to achieve the desired therapeutic effect on the target tissue. In some of these embodiments, the skin is represented as a flat multilayer of tissue, and the treatment can be administered to the target tissue in a manner that is substantially perpendicular to that plane. Treatments may be disclosed with respect to specific skin shapes (eg, vertical topical delivery, vertical percutaneous insertion, etc.), but such treatments may be any number or variety, including those discussed below. It should be understood that it may be administered in the form of

(Rising skin treatment)
In energy therapy involving delivery of RF, infrared, microwave, or ultrasound, for example, the delivered energy penetrates too deeply into the body, leading to deep non-target tissue, related critical structures (eg, blood vessels, lymph nodes, muscle tissue, etc. ), And there is a risk of causing harm to body organs. Thus, it may be beneficial to raise the target tissue comprising a portion of the skin from the underlying tissue. Such elevation can be achieved through manual manipulation by the clinician or can be facilitated using any number of devices. For example, as shown in FIG. 38, a vacuum 147 can be used to pull and carry the skin 119, thereby raising the skin for treatment. Optionally, a vacuum and suction device can be incorporated into the energy delivery device so that suction and energy delivery can be applied simultaneously.

  In another embodiment, a tool that utilizes a sterile adhesive can effectively support the skin for treatment. More simply, however, the clinician can use any number of clamps, tongs, or other devices for treatment and to achieve and maintain skin elevation during treatment.

(Non-vertical percutaneous insertion)
In treatments that involve a minimally invasive insertion of the treatment device, it may be desirable to administer the treatment by inserting the device into the skin tissue in a non-vertical manner. This approach may provide multiple benefits. First, by inserting the device at an angle, the risk of reaching and damaging critical structures in the subcutaneous tissue may be minimized. For example, angular insertion may avoid blood vessels, lymph nodes, and muscle tissue located under the subcutaneous tissue. Second, a non-vertical approach may have a higher chance of achieving planar treatment. It is believed that the angular approach can produce a broader treatment for insertion because the target tissue is in a plane parallel to the surface of the skin.

  For example, the device can be inserted obliquely into the skin and then drilled between the dermal and subcutaneous layers parallel to the target tissue region. As shown in FIG. 39, a needle 1210 with an energy delivery element can be delivered to deliver energy therapy to the target tissue in a planar manner. In this embodiment, the needle 1210 comprises an electrode, and as the needle is withdrawn longitudinally along its insertion path, a small portion of the needle 1211 is used to administer multiple treatments to a parallel plane of the target tissue. used. Alternatively, the electrode is slidably engaged inside the needle 1210 and treatment is performed by translating the electrode longitudinally along the needle 1210 while the needle 1210 itself remains in place. Be administered. In another alternative embodiment, the length of the needle 1210 is electrically insulated from the electrode so that the sleeve can be translated along the length of the electrode so that only a portion of the electrode is exposed at a time. You may provide the division | segmentation insulator sleeve provided with a body (for example, polyimide). As a further alternative, the needle 1210 has a plurality of electrodes (eg, monopolar, bipolar) that are dynamically activated simultaneously, or sequentially, so as to produce a therapeutic effect across the plane of the target tissue. Prepare along.

  In addition, it may be beneficial for the operator to manipulate the patient's skin to facilitate non-vertical insertion. By pulling, carrying and / or squeezing the skin before, during and / or after insertion of the device, the operator can dig the device along the plane of the target tissue to achieve planar treatment. can do. This skin manipulation can be performed manually by the operator or can be facilitated by any number of devices, including those discussed above with respect to skin elevation. As shown in FIG. 40, a vacuum suction 147 having a plurality of vacuum channels 1212 can be used to raise the skin 119 and facilitate non-vertical insertion of one or more energy delivery elements 120. FIG. 40 shows six vacuum channels 1212 but as few as 1, 2, 3, 4, 5 and as many as 8, 8, 9, 10, or more to provide suction. It should be understood that channels can be used.

  In another skin configuration, it may be beneficial to first pinch and fold the patient's skin before delivering energy to the target tissue. After optimal administration (local or subcutaneous) of a local anesthetic such as lidocaine, the patient's skin can be grasped and partially pulled away so that the epidermis, dermis, and subcutaneous layer are separated from the underlying skeletal muscle. Once separated, the skin can be folded so that the proximal portions of the skin are adjacent to each other and the subcutaneous layer on one side of the fold faces the subcutaneous layer on the other side of the fold. Isolating these adjacent subcutaneous layers results in a therapeutic zone where the target tissue and target structures are dense. FIG. 41 shows an example of a typical skin fold 148. The skin fold 148 includes a top 149, two sides 150 (only one shown), two edges 151 (only one shown), and the length of the fold in the longitudinal direction. With a “tipped” target tissue area 152 (ie, a treatment area).

  By concentrating the treatment in an area rich in target tissue within the skin fold 148, two adjacent layers of the target tissue can be treated with a single treatment, thus allowing a more efficient procedure. In addition, treatment can be administered from one or more orientations (eg, on both sides of the fold 148), which can result in a more effective and reliable treatment. Also, because the skin is pulled away from the body, damage to critical subcutaneous structures is minimized. In addition, since the target tissue is further away from the blood supply and the action of pinching or evacuating the skin fold 148 in place temporarily interrupts the blood supply to the folded tissue, the thermal conductivity of the blood flow The risk of collapse due to is small. In addition, neural activity caused to the skin by the folded configuration may reduce the patient's pain sensation during treatment based on the pain management portal control theory described above.

  In one embodiment, the skin fold 148 is treated from the opposite side by an energy delivery device 153 comprising two energy delivery elements 154, as illustrated in FIG. The energy delivery element 154 is configured to deliver energy to the central treatment area 152 of the fold 148. In the case of an energy delivery device 153 comprising one or more microwave antennas connected to one or more microwave generators, the microwave energy traverses the outer epidermal layer from each side of the skin fold 148; It can penetrate deep into the treatment area 152. Optionally, a dielectric can be used in this treatment to optimize the delivery of microwave energy to the target tissue. As shown in FIG. 42, a cooling element 115 can also be used on the skin surface to create a protected area 155 of non-target tissue. In addition, the device 153 can be configured with cooling elements 115 and / or dielectric elements on both sides of the skin fold 148 to stabilize the fold during treatment.

  Alternatively, the embodiment illustrated in FIG. 42 can achieve a therapeutic effect by delivering RF energy instead of microwave energy. The energy delivery device comprises one or more electrodes on either or both sides of the skin fold. These electrodes are either in contact with the skin surface or in close proximity to the skin to deliver an electric field to the skin tissue. Each part of the skin tissue is resistively heated by the electric field and the surrounding part is conductively heated. One or more cooling elements can be used on either or both sides of the skin fold to cool the superficial non-target tissue conductively and / or by convection. . Alternatively, the electrode itself can have a cooling component so as to provide a cooling effect at the point of contact between the skin surface and the electrode.

  43A-43C show treatment devices using different energy sources (RF, microwave, and cryogenic) configured for insertion into or across skin fold 148. Figure 3 depicts three embodiments. Minimally invasive insertion allows for more localized treatment of the target tissue so that tissue into non-target tissue is minimized. The device depicted in these figures may include one or more needles, microneedles, stylets, or catheters for insertion into the epidermal layer of the skin fold so that the device reaches at least a portion of the treatment area 152 May be included. Optionally, the device can be inserted on one side of the skin fold 148 such that the distal end of the device retracts from the opposite side of the fold 148. The device may further comprise one or more stabilizing plates on either side of the skin fold 148 to support each end of the inserted device. The stabilizing plate can optionally include a cooling element to treat the epidermal tissue and create a protected non-target tissue area. The device can also be physically or electrically connected to an energy generator for supplying energy to be delivered to the target tissue.

  FIG. 43A illustrates a minimally invasive RF delivery device 1245 that includes an RF generator 204 with one or more needles 207 for insertion into a skin fold. Needle 207 includes one or more electrodes 206 that are strategically placed along the length of needle 207 to optimize energy delivery and treatment to target tissue 152. Alternatively, the needle 207 itself can be an electrode. In order to minimize treatment of non-target tissue, the portion 206 comprising the electrode of each needle 207 can be insulated in the portion 205 that is not proximate to the target tissue 152. To reduce peripheral effects, carbonization, and / or risk of drying and resulting loss of conductivity at or near the contact between electrode 206 and tissue, needle 207 may include one or more cooling elements. Or the electrodes themselves can incorporate cooling components.

  The embodiment depicted in FIG. 43B includes a minimally invasive microwave delivery device 1213 that includes one or more microwave antennas 120 for insertion into a skin fold 148. The antenna 120 can be inserted adjacent to the target tissue 152 to maximize the delivery of microwave energy to the sweat glands within the treatment area 152. In order to optimize the delivery of microwave energy to the target tissue over the course of treatment, one or more antennas 120 of device 1213 may optionally be insulated with a dielectric material.

  The embodiment depicted in FIG. 43C includes a minimally invasive cryotherapy that includes a cryotherapy source container 1244 and one or more needles, stylets, cannulas or catheters for insertion into a skin fold 148. A device 1243 is provided. The stylet 211 is a 1 for delivering cryogenic fluid to the target tissue 152 at a rate and volume sufficient to freeze, ablate, and / or disable one or more sweat glands in the target tissue 152. There should be more than one passage and opening. Optionally, a heating element may be used to protect non-target tissue from disruptive or destructive damage. The heating element may be located as part of or along the stabilizer so as to treat the skin tissue from the skin surface. Alternatively or additionally, the heating element may be located along the intervening portion of the device so as to provide protective heating for non-target tissue.

  In the minimally invasive treatment illustrated in FIGS. 43A-43C, the energy delivery device is inserted across the skin fold 148 (eg, perpendicular to the longitudinal axis of the fold). However, it should be understood that these devices can also be configured to be inserted through either edge and along the longitudinal axis of the wall. For example, as illustrated in FIG. 44, the energy delivery device 1214 is shown inserted through the edge 151 of the skin fold 148 and positioned along the longitudinal axis of the fold 148. As shown in FIG. 44, the needle can optionally pierce the edge of the fold 148 opposite the insertion point. The energy delivery device 1214 comprises a needle having a thermally conductive outer wall 1215 and an inner resistance heating element 1216. A power source (eg, battery, outlet, generator, etc.) delivers power to resistively heat the heating element and outer wall, thereby thermally treating the surrounding target tissue.

  FIG. 45 illustrates another approach for minimally invasive treatment that utilizes a skin fold configuration. In this embodiment, the energy delivery element 209 is inserted through the top of the skin fold 148 so that it is positioned approximately in the center of the treatment area 152. This approach offers certain advantages over other approaches in that treatment is delivered directly to the surrounding target tissue 152 with minimal treatment to non-target tissue. As shown in FIGS. 46A and 46B, an array or row of monopolar electrode needles 207 can be used to deliver treatment along the length of the skin fold. These elements can include an insulator 205 at their proximal ends to prevent unnecessary treatment of non-target tissue at the top of the skin fold. Alternatively, a row of bipolar electrode pairs 1206, 1207 can be used to deliver treatment that results in a consistent planar lesion within the target tissue.

  47A-47B illustrate a variation of the embodiment illustrated in FIG. 45 depicting device insertion at the top of the skin fold 148. In this embodiment, a needle 207 having a hollow passage 1218 is first inserted through the superficial non-target tissue 103 into the top of the fold 148. Once the needle 207 is in place, the blunt dissociation electrode 1217 is inserted into the needle passageway 1218 and driven through the target tissue 152. Blunt electrode 1217, when placed in treatment area 152, can be activated to deliver an electric field to the treatment area to administer thermal treatment. Optionally, the inserted hollow needle 207 can be insulated by an insulator 1219 (as shown in FIG. 47B) to protect the non-target tissue 103 from an electric field.

  The use of blunt electrodes may provide certain advantages over those available using needle electrodes. First, blunt dissociation tends to follow the naturally occurring tissue plane that exists at the junction of the dermis and subcutaneous layer, but one or more needle embodiments dissociate whatever tissue is in the path There is a case. Thus, blunt dissociation can facilitate accurate electrode placement. Second, the current density of the blunt electrode is more evenly distributed than the needle electrode. The current density of the needle electrode is concentrated at the sharp tip so that the tissue in contact with the tip is heated and dried before a significant amount of energy can reach the surrounding tissue. Conversely, the current density of the blunt electrode is evenly distributed to allow a more consistent and predictable treatment.

  Another embodiment utilizing the folded skin 148 configuration is depicted in FIG. In this embodiment, one or more paddle elements 1221 are removably coupled to each outside of the skin fold 148 (eg, via an adhesive). The paddle element 1221 is operably coupled to a vibration source 1222 that drives the movement of the paddle 1221 in alternating order. The alternating movement of the paddle element 1221 creates friction between adjacent subcutaneous layers sandwiched within the skin fold 148, particularly between paddles on each side of the skin fold 148. Because the sweat glands in these subcutaneous layers possess a hard granular configuration, the frictional contact between adjacent subcutaneous layers is high. The friction generated by the movement of the subcutaneous layer in the opposite direction mechanically deforms and damages these sweat glands and also provides a sufficient amount of friction to disable or excise at least one sweat gland in the target tissue. Heat can also be generated. The amount of frictional heat generated depends on a number of factors, including the speed and power of paddle movement, the frequency of paddle oscillation, the contact force between adjacent subcutaneous layers, and the adhesion of paddle elements 1221 within the skin surface. To do.

In another embodiment employing the shape of a skin fold, focused ultrasound can be used to focus and localize the treatment on the target tissue. As illustrated in FIG. 49, an ultrasound transducer 1223 can be used to deliver continuous ultrasound therapy from both sides of the skin fold 150 using one or more channels. The energy waves from each transducer 1223 are stepped so that the waves from the first transducer 1223 harmonize with the waves from the other transducers 1223 and can produce a cumulative therapeutic effect in the target tissue region 152. obtain. The waves can also be synchronized to cancel each other in areas where treatment is not desired (ie, non-target tissue 155). Optimal treatment thus comprises an oscillator that is configured and coordinated to deliver energy waves that are additive in areas where the target tissue is dense but subtractive in other areas. In this embodiment, the energy wave can be delivered with a wave frequency of about 20 kHz to 18 MHz and a power in the range of about 0 W / cm ² to about 50 W / cm ² . More specifically, treatment may be most effective at a frequency of about 0.5 MHz to about 3 MHz and a power of about 720 mW / cm ² to about 50 W / cm ² .

  Another embodiment that utilizes ultrasonic energy and the shape of the skin fold is shown in FIG. 50A. In this embodiment, the vibrator 1223 is located on one side 150 of the skin fold, and instead of the vibrator 1223, a reflector 1224 is used on the other side 150 of the skin fold. As described above, the parameters of the remaining transducers 1223 can be set so that the propagation wave reaches the peak amplitude when it reaches the treatment area 152 in the folding unit 148. In this embodiment, the frequency of the oscillator wave and the position and angle of the reflector 1224 on the opposite side of the skin fold 148 can be matched to produce a resonant frequency, and the reflector 1224 The wave reflected through the skin fold is virtually identical to the initial wave. Accordingly, treatment area 152 receives cumulative treatment despite the use of only one transducer 1223. In addition, the use of reflector 1224 may provide the added benefit of preventing ultrasound from leaving the treatment site and damaging non-target structures elsewhere in the body.

  Many skin treatments that use light energy cannot deliver maximum energy because the moisture in the skin tissue absorbs much of the energy. The embodiment illustrated in FIG. 50B provides a means for minimizing moisture absorption of delivered energy. In this embodiment, light energy 1225 is configured to be delivered non-invasively to treatment area 152 and absorbed by target tissue 152 to produce a therapeutic effect. In some embodiments, the near-infrared light is selected at a wavelength off the peak of the highest water absorption frequency so that a minimum amount of light is absorbed by the blood and a significant amount of energy penetrates the treatment area. In one embodiment, the energy can be delivered at a wavelength of about 1300-1600 nanometers. In another embodiment, the energy wavelength can be about 1400-1450 nanometers.

  In one embodiment of the approach illustrated in FIG. 50B, light energy 1225 can be emitted from a single energy source to the skin fold 148. The energy penetration associated with this treatment, and the resulting therapeutic effect, can be enhanced by increasing its spot size and optical fluence. In another embodiment, the light energy 1225 can be emitted from multiple sources concentrated in the treatment area 152 so that energy from the multiple sources is focused on the treatment area 152. In addition to near infrared, some of the various energy types that can be employed in this configuration include, but are not limited to, infrared and IPL. Although the embodiment shown in FIG. 50B discloses administering light energy 152 treatment to the shape of the skin fold 148, the treatment can also be administered using a planar shape. One benefit of using a folded or pinched skin shape is that some of the blood in the microvasculature of the skin fold 148 is forced out of the fold tissue and the tissue is More light energy 1225 is allowed to pass. This benefit is better in the presence of vacuum pressure, as shown in FIG. 50B, because the vacuum 147 facilitates the drainage of blood from the skin fold.

  In the embodiments disclosed herein relating to administering thermal treatment that employs the shape of the skin fold, it may be desirable to thermally protect the non-target tissue. Thermal protection can be particularly useful in this configuration because protection can be applied to non-target tissue from both sides of the skin fold as well as from the top of the skin fold. For example, for treatments where the energy delivery device is configured to deliver thermal energy to the target tissue in the treatment area, both sides of the folds and to protect the non-target tissue and localize the thermal treatment to the target tissue A cooling element can be used at the top of the fold. The cooling element can also be incorporated into stabilizers on both sides of the fold that are used to maintain the fold during treatment.

  As described with respect to many of the embodiments discussed above, it may be desirable to generate a skin fold using suction. For example, a suction / vacuum cavity can be incorporated into any of the aforementioned devices. FIG. 51 includes a housing 156, a suction chamber 157, a vacuum port (not shown) for connection to a vacuum source (not shown), and an electrode 1227 connected to a power source by leads 1228. A suction electrode 1226 is shown. The vacuum source can be configured to provide sufficient vacuum force to grasp and hold the skin in the folded orientation within the tissue chamber 157. The device may utilize suction 1226 to simply grasp the skin at the beginning of the procedure, or to hold the skin in place throughout part or all of the treatment. This lower pressure or suction area in device 1226 helps to cause device 1226 to adhere to the skin so that the target tissue is juxtaposed to electrode antenna 1227 and reduces blood flow in the target tissue, thereby Allows more efficient heating of the tissue.

  In addition, aspiration may help control pain by inducing stretch and baroreceptors in the skin, thereby blocking pain signals via the pain control portal control theory. The portal control theory believes that excessive neural signals arriving at the dorsal root ganglia of the spinal cord overwhelm the system and obscure or block transmission of pain receptor signals to the brain. This pain management mechanism is exploited by implantable electrical pain control units, TENS systems, Optilase systems, and others.

  52A, 52B, and 52C illustrate an alternative embodiment in which a clamp 1229 is used to create a skin fold 148. FIG. As shown in FIG. 52A, a device 1230 comprising an insulating clamp 1229 and a conductive metal plate 1231 is used to deliver treatment to the skin fold 148. The metal plate 1231 is electrically connected to a power source for delivering energy to the target tissue within the skin fold 148. Optionally, a conductive gel can be used to ensure contact and that the energy is properly delivered to the target tissue. Alternatively, the embodiment depicted in FIGS. 52B and 52C shows a minimally invasive treatment, where skin folds 148 are maintained by stabilizers 1232 on both sides of folds 148 while referenced to stabilizers 1232. The needle 207 is inserted through the top of the fold 148 to deliver therapy. The stabilizer 1233 of the embodiment of FIG. 52C is spring loaded with one or more springs 1234 to maintain the fold during treatment. Other non-limiting examples of tissue acquisition systems, devices, and methods described herein are, for example, US Provisional Application No. 61 / 045,937, previously incorporated by reference in its entirety. No. 69-71.

(Iii. Strengthening)
(1. Drug)
In many of the treatments disclosed herein, the target tissue is damaged to produce a therapeutic effect. However, non-target tissues can also be affected in some of these treatments. Such treatment may have complications such as pain, inflammation, infection, and scarring that may occur both during and after treatment. Thus, it may be beneficial to provide medication to the patient before, during, and / or after treatment to minimize the incidence and impact of these complications. Drugs that can be anesthetics for pain, steroids for inflammation, and antibiotics for infections can be administered orally, topically, or via local injection.

(2. Imaging)
For any of the embodiments disclosed herein, it may be desirable to administer treatment using medical imaging techniques. For example, ultrasound, magnetic resonance imaging (MRI), and light to localize, identify, and visualize target tissue before, during, and after treatment to optimize treatment effectiveness High resolution imaging such as coherence tomography (OCT) can be used. Alternatively, imaging can be used in combination with other diagnostic techniques to identify the target tissue for treatment or to determine the effectiveness of the treatment. For example, iodine staining can be used to determine where the patient is sweating after treatment.
3. Controlled energy delivery by a physiological feedback loop
In some of the treatments disclosed herein for delivering energy to a target tissue, controlled delivery of energy results in unnecessary damage to target and non-target tissues as a result of overheating. (Eg, drying, carbonization, etc.) may be avoided. Controlled delivery of energy may also result in a more consistent, predictable and efficient overall treatment. Thus, it may be beneficial to incorporate a controller with programmed instructions for delivering energy to the tissue into the energy delivery system. In addition, these programmed instructions may comprise algorithms for automating controlled delivery of energy.

  In embodiments employing controlled delivery of energy, the aforementioned controller can be incorporated into or coupled to the generator, the controller in accordance with a preset algorithm with temperature and / or power profile. Command. These profiles may define parameters that can be used to achieve the desired therapeutic effect in the target tissue. These parameters may include, but are not limited to, power and time increments, maximum allowable temperature, and ramp rate (ie, rate of temperature / power increase). Feedback signals comprising real time or delayed physiological and diagnostic measurements can be used to modulate the overall delivery of these parameters and energy. Among the measurements that can be obtained, temperature, impedance, and / or reflected power at the treatment site and / or target tissue can be particularly useful. These measurements may help to monitor the effect of energy delivery on the treatment site and target tissue over the course of treatment. The energy controller may have a fixed factor, or the controller factor may be varied depending on the tissue response to energy delivery. In addition, algorithms with safety profiles may be employed to limit energy delivery or to limit sensed tissue temperature. These algorithms may stop energy delivery or modulate energy delivery. In addition, in treatments where thermal protection such as active cooling elements is employed, the protective cooling can be modulated based on the monitored data.

  By taking into account temperature measurements in the delivery of energy, the treatment can be administered to achieve the required therapeutic effect while avoiding unnecessary complications of the treatment. For example, energy delivery to the target tissue can be steadily increased (i.e., increased at a constant rate) until the desired threshold temperature is reached for the target tissue, the threshold temperature being used to produce a therapeutic effect Necessary temperature. By suspending the increase in power or delivery of energy, once the threshold temperature is reached, harm to non-target tissue due to additional and excessive heating can be avoided.

  The temperature can be measured using any number of sensors, including thermocouples and thermistors, and such sensors can be incorporated into energy delivery elements, energy delivery devices, and / or energy delivery systems. . For example, in an RF energy delivery system, the thermocouple is embedded in an electrode that delivers RF energy, placed adjacent to the electrode as part of an energy delivery device, or the thermocouple is wired directly to the generator. Can be located away from the device. The measured temperature can be the temperature of the tissue immediately adjacent to the device, the target tissue, or any other tissue that may provide useful temperature measurements. When the energy delivery element is in thermal communication with the surrounding tissue (eg, via conduction), a sensor incorporated into the energy delivery element may measure the temperature of the element itself.

  Impedance can be measured by observing the tissue response to electrical stimulation. This measurement is useful because it can help assess the extent of energy delivery to and through the tissue. For example, energy directed to tissue having a high impedance may be difficult to penetrate deeper regions of the tissue. This is particularly important in the case of skin tissue because the impedance of the skin can change over the course of treatment. As tissue is heated, it loses moisture, its conductivity decreases and impedance increases. When the tissue is heated to dryness, the tissue resistance may impair energy delivery to the surrounding tissue via electrical conduction. Employing impedance measurement feedback in the energy delivery system can optimize the delivery of energy to the target tissue while avoiding adverse effects on target and non-target tissues.

  FIG. 53 illustrates another embodiment for controlled delivery of energy to a target tissue. In this embodiment, the array of electrodes 1235 can be configured to be continuously activated as adjacent bipolar pairs (eg, 1236, 1237). For example, in the first activation, the first electrode 1236 is an anode and the second electrode 1237 is a cathode. In the second activation, the second electrode 1237 functions as an anode, and the third electrode 1238 is a cathode. Accordingly, the first electrode 1236 and the second electrode 1237, the second electrode 1237 and the third electrode 1238, the third electrode 238 and the fourth electrode 1239, and the fourth electrode 1239 and the fifth electrode 1240 are displayed. In between, a therapeutic effect can be achieved. In addition, since only one electrode pair is activated at a time, each treatment in the sequence can be customized based on the properties of the tissue being treated. For example, if the impedance between the first electrode 1236 and the second electrode 1237 is higher than the impedance between the second electrode 1237 and the third electrode 1238, the first treatment It may be applied over a longer duration than treatment. This results in a higher resolution per activation and a more accurate overall treatment.

(4. Staged treatment)
For many of the treatments disclosed herein, it may be desirable to perform treatment in stages. In addition, the treatment can be patterned so that the target tissue portion is treated at an early stage while other portions are treated at a later stage. For example, as illustrated in FIG. 54, a patient has an area marked “A” that is treated in the first stage and an area marked “B” that is treated in the second stage. Can have. In addition, it can be differentiated into further stages and additional regions. Optionally, treatment can be administered to the same region in multiple stages, such that each region receives multiple treatments. In one embodiment, at a later stage, treatment to a particular area may vary with increased or decreased amounts of energy, different treatment types, and the like.

  This approach has a number of potential benefits. First, phased treatment provides the body with an opportunity to heal between treatments. This means that treating or heat damaging discontinuous areas of tissue over several sessions is less and less severe compared to treating or heat damaging relatively larger tissue areas in one session. This is especially important because it can have non-complications. Secondly, patterned treatment with a small treatment area elicits a more favorable healing response. Since the healing time is related to the distance that the fibroblasts must travel from the surrounding tissue, the smaller treatment area heals much faster than the larger treatment area. 55A-E illustrate examples of various patterned treatments.

  For medical practitioners, staged and patterned treatment may provide an opportunity to track the effectiveness of the treatment and provide follow-up treatment tailored to the patient's specific needs. For example, in the treatment of axillary hyperhidrosis, the clinician may map sweating to (1) identify the remaining treatment area and (2) determine the overall reduction in sweating in the area under the armpit. (E.g. iodine staining) can have a tracking session. For patients who do not necessarily desire 100% anhidrosis, staged treatment may allow treatment to be interrupted at a particular time. For example, a patient suffering from a severe case of axillary hyperhidrosis may be satisfied with a 70% reduction in sweating and only wants to participate in the number of treatments necessary for such reduction There is.

  In addition, graded and patterned treatment can minimize the body contracture response during the healing process. In a process called fibrosis (or scarring), fibroblasts lay down the collagen network to promote tissue healing. As the scar density increases, the treated area contracts, thereby tightening the skin within the area. In the treatment of axillary hyperhidrosis, contracture can potentially compromise the full range of motion of the patient's arm. The treatment can be patterned and staged to minimize contracture and / or its impact on the patient. For example, the narrow treatment area depicted in FIG. 55C results in minimal axillary contracture and resultant dysfunction for arm range of motion.

  Templates can be used to facilitate the application of staged and / or patterned treatments. FIG. 56 illustrates a series of phased treatments comprising three templates 158, 159, 160, each template configured to allow treatment to a different portion of the overall treatment area. The template may be configured to engage an energy delivery device or one or more energy delivery elements to facilitate application of staged and / or patterned therapy. The template can consist of a single frame made of wood, plastic, or metal with removable or adjustable parts to reflect the desired pattern and / or stage. Alternatively, the template can also be in one or more patterns drawn on the patient's skin using temporary markers, tattoos, or dyes (eg, henna) that remain over the course of multiple step treatments. Can also be.

  In another embodiment, as illustrated in FIG. 57, the template pattern can be represented by different chromophores 1246, 1247, 1248 corresponding to different stages of treatment. For example, different chromophores 1246, 1247, 1248 are injected into the patient's skin such that each chromophore 1246, 1247, 1248 and the area 1241 colored by such chromophore corresponds to one treatment stage. be able to. Once all areas are properly colored, laser treatment can begin. At each stage of treatment, the treatment area is illuminated with a different laser, and the wavelength of each laser is specifically matched to the absorption characteristics of the different chromophore areas.

  In another application employing the above color coordination template, an energy delivery device, energy applicator, or energy delivery element may comprise this template. For example, in the microneedle configuration that retains the original shape illustrated in FIG. 16, the microneedle patch 239 at the chromophore tip can be configured with selective colors according to the color coordination template described above. The same patch can be used at each treatment stage, and different treatments are administered by irradiating the patch with lasers of different wavelengths.

(5. Diagnosis)
Embodiments of the present invention also include methods and apparatus for identifying and diagnosing hyperhidrosis patients. Such a diagnosis can be based on subjective patient data (eg, patient response to questions regarding observed sweating) or objective examination. In one embodiment of the objective test, an iodine solution can be applied to the patient to identify where on the skin surface the patient is sweating and not sweating. For example, Tapper et al., US Pat. No. 4,190,056, incorporated herein by reference in its entirety, describes a method and means for recording sweat gland activity. Also, a specific patient can be diagnosed based on excessive sweating of different parts of the body to specifically identify which area is being treated. Thus, treatment may be selectively applied to different parts of the body in need of treatment, including, for example, hands, armpits, feet, and / or faces.

(6. Quantification of treatment success)
After completion of any of the above treatments, or any stage of treatment, success can be qualitatively assessed by the patient or may be quantitatively assessed by any number of methods. For example, a measurement of the number of disabled or destroyed sweat glands per treated surface area can be made. Such an evaluation can be performed by imaging the treated area or by determining the amount of treatment administered to the treated area (eg, the amount of energy delivered, the measured temperature of the target tissue, etc.). Can be broken. The iodine solution test described above may also be employed to determine the degree of therapeutic effect. In addition, treatment can be initiated or modified such that the amount of sweating experienced by the patient may be reduced by a desired percentage under defined test criteria compared to before treatment. For example, especially for patients diagnosed with severe hyperhidrosis, the amount of sweating is about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, Or it may be reduced further. For patients diagnosed with less severe or more normal sweat profiles, a gradual reduction of sweat may be achieved, but due to low resolution. For example, such a patient may only be able to achieve partial anhidrosis by 25%.

Overview of certain methods, systems, and other embodiments
In one embodiment, the present specification identifies a patient having symptoms of excessive sweating, wherein the patient desires that sweating be reduced in at least a portion of the patient's body; and Placing an energy delivery device proximate to the skin tissue and delivering sufficient energy to the patient's sweat gland to stop sweat secretion by at least partially disabling or destroying the sweat gland; A method relating to treating a patient is provided.

  In some embodiments, the step of disposing the energy delivery device further comprises an energy delivery element selected from the group consisting of electrodes, antennas, ultrasonic transducers, lasers, light emitting diodes, light bulbs, cryogenic probes, and combinations thereof. May be placed proximate to the patient's skin tissue. In one embodiment, delivering energy to the patient's sweat gland further comprises electromagnetic, X-ray, radio frequency, microwave, ultrasound, near infrared, infrared, ultrashort pulsed light, visible light, and laser, and their Delivering energy to the sweat glands, selected from the group consisting of combinations. Delivering energy to the sweat gland may further include heating the sweat gland, and heating the sweat gland may further include at least partially excising the sweat gland.

  In one embodiment, positioning the energy delivery device may further include inserting the energy delivery device into the skin tissue. In one embodiment, inserting the energy delivery device into the skin tissue may further comprise inserting the energy delivery device into the skin tissue to a depth in the range of about 1 mm to about 8 mm below the surface of the skin. . Inserting the energy delivery device into the skin tissue may further include inserting an intervening device selected from the group consisting of a needle, a stylet, a catheter, a probe, and a microneedle into the skin tissue.

  In one embodiment, the method may further include providing protective cooling to the skin tissue. Providing protective cooling to the skin tissue may further include placing a cooling element proximate to the skin tissue.

  In one embodiment, the method may further comprise administering to the patient an agent selected from the group consisting of anesthetics, steroids, and antibiotics. Administering the drug to the patient may further comprise administering the drug orally, topically, or via injection.

  In one embodiment, the method may further comprise visualizing the sweat glands using medical imaging.

  In one embodiment, the method may further comprise the step of monitoring diagnostic parameters of the skin tissue. The diagnostic parameter may be selected from the group consisting of impedance, temperature, reflected light, and reflected power.

  In one embodiment, delivering energy to the patient's sweat gland may further include modulating energy delivery in response to the monitored diagnostic parameter.

  In one embodiment, the method may further comprise the step of reducing the sweating achieved in the patient or quantifying the treated part of the patient's body.

  According to the method, the patient may desire that sweat be reduced in at least a portion of the patient's body, including at least a portion of the patient's axilla.

  In one embodiment, the method may further comprise raising the skin tissue away from the underlying tissue prior to delivering energy to the sweat glands.

  In one embodiment, identifying a skin tissue region on a patient comprising a sweat gland layer, the skin tissue region producing excess sweat associated with hyperhidrosis, a first aspect, and a second A skin tissue region so as to form a skin fold, wherein the sweat gland layer corresponding to the first side includes a second treatment area such that the layer comprises a treatment area. Adjoining the sweat gland layer corresponding to the side of the skin and delivering energy to the treatment area to produce a therapeutic effect, the therapeutic effect reducing the amount of sweating from the skin tissue region And a method relating to treating a patient for symptoms of hyperhidrosis is provided.

  In one embodiment, the method may further include applying protective cooling to at least a portion of the skin tissue.

  In one embodiment, applying protective cooling to at least a portion of the skin tissue region may further include positioning a cooling element proximate to the skin fold. The step of positioning the cooling element proximate to the skin fold further comprises a first cooling element proximate to the first side of the skin fold and a second proximate to the second side of the skin fold. The step of disposing the cooling elements.

  In one embodiment, grasping the skin tissue region to form a skin fold may further include providing suction to the skin tissue region. Providing suction to the skin tissue region may further include maintaining suction to the skin tissue region during treatment.

  In one embodiment, elevating a patient's skin tissue, the skin tissue comprising a target tissue comprising at least one sweat gland, and delivering energy to the target tissue, the energy of Delivery is provided that relates to the step of reducing patient sweating, comprising at least partially disabling or destroying at least one sweat gland to reduce sweating from the patient's skin tissue. The

  In one embodiment, delivering energy to the target tissue may further include positioning the energy delivery device proximate to the patient's skin tissue. In one embodiment, the step of deploying the energy delivery device further comprises an energy delivery element selected from the group consisting of electrodes, antennas, ultrasonic transducers, lasers, light emitting diodes, light bulbs, cryogenic probes, and combinations thereof. , May include placing in close proximity to the patient's skin tissue. In another embodiment, positioning the energy delivery device may further include inserting the energy delivery device into the skin tissue. Inserting the energy delivery device into the skin tissue may further include positioning the insertion element energy delivery element proximate to the target tissue.

  In one embodiment, the energy delivery element may be selected from the group consisting of electrodes, antennas, ultrasonic transducers, lasers, light emitting diodes, light bulbs, and combinations thereof.

  In one embodiment, raising the skin tissue may further include applying suction to the skin tissue.

  In one embodiment, the method may further comprise providing protective cooling to the skin tissue. Providing protective cooling to the skin tissue may further include placing a cooling element proximate to the skin tissue.

  In one embodiment, delivering energy to the target tissue further comprises delivering energy to the first portion of the target tissue a first time and delivering energy to the second portion of the target tissue a second time. But you can. The first time and the second time may be separated by a predetermined period. The predetermined period may be selected from the group consisting of 1-7 days, 1-4 weeks, and 1-4 months.

  In one embodiment, there is provided an apparatus related to treating a patient's sweat gland comprising an energy generator and an energy delivery device configured for placement in proximity to the patient's skin tissue. Coupled to the energy generator, the energy delivery device is adapted to deliver sufficient energy to the target tissue in the skin tissue to at least partially destroy or disable at least one sweat gland in the target tissue. Composed.

  In some embodiments, the energy delivery device may be configured for insertion into the target tissue.

  In some embodiments, the energy delivery device comprises at least one energy delivery element selected from the group consisting of electrodes, antennas, ultrasonic transducers, lasers, light emitting diodes, light bulbs, cryogenic probes, and combinations thereof. You may prepare.

  In one embodiment, the first device may further comprise a cooling element configured for placement proximate to the patient's non-target tissue.

  In one embodiment, the first apparatus may further comprise a suction device configured for placement in proximity to the patient's skin tissue.

  In one embodiment, the present application provides an intervening device comprising at least one needle configured for insertion proximate to a patient's target tissue and light energy configured to transmit light energy to the intervening device And a second device related to treating the target tissue of the patient, wherein the needle is configured to receive light energy transmitted by the light energy source.

  In one embodiment, the chromophore may generate thermal energy from light energy absorbed from the light energy source. The chromophore may generate thermal energy from light energy absorbed from the light energy source. Thermal energy from the chromophore may cause a therapeutic effect on the target tissue. In one embodiment, the therapeutic effect on the target tissue may include heating the target tissue. In another embodiment, the therapeutic effect on the target tissue may include at least partially excising the target tissue. In yet another embodiment, the therapeutic effect on the target tissue comprises at least partially disabling at least one target structure selected from the group consisting of sweat glands, hair follicles, sebaceous glands, collagen, and fat. But you can.

  In one embodiment, the intervening device may further comprise a microneedle patch having an optically neutral backing.

  Unless otherwise explicitly required by context, throughout the description and claims, the terms “comprising”, “comprising”, and the like are intended to be inclusive, as opposed to exclusive or inclusive meanings. In a specific sense, that is, meaning "including but not limited to". Words using the singular or plural number also include the plural or singular number respectively. When a claim refers to a list of two or more items and uses the word “or”, the word is any of the items in the list, all items in the list, and any of the items in the list It covers all interpretations of words, such as combinations.

  The above detailed description of embodiments of the invention is not intended to be exhaustive or to limit the invention to the precise form disclosed above. While specific embodiments and examples of the invention have been described above for purposes of illustration, various equivalent modifications are possible within the scope of the invention, as one skilled in the art will recognize. For example, although the steps are presented in a given order, alternative embodiments may perform the steps in a different order.

The various embodiments described herein may also be combined to provide further embodiments. Additional details regarding related methods, devices, and systems that utilize microwaves and other therapies, including other forms of electromagnetic radiation, and treatments that may be performed by such therapies are hereby incorporated by reference. US Provisional Patent Application No. 60 / 912,889 entitled “Methods and Apparatus for Reducing Sweat Production” filed on April 19, 2007, “Methods, Delivery and Systems, filed December 12, 2007” US Provisional Patent Application No. 61 / 013,274 entitled “For Non-Invasive Delivery of Microwave Therapeutic”, “Systems and Methods for Creaties” filed Apr. 17, 2008. g an
No. 61 / 045,937 referenced above, such as US Provisional Patent Application No. 61 / 045,937 entitled “Effective Using Microwave Energy in Specified Tissue”, each of which is incorporated herein by reference in its entirety. Incorporated. The applications described above may be incorporated by reference with respect to particular subject matter as described herein before, but Applicants will be aware of any of the disclosures of applications incorporated by reference herein. The entire disclosure of the above-identified application is intended to be incorporated herein by reference in that either or all may be combined and incorporated with the embodiments described herein.

  In general, the terms used in the following claims should be construed to limit the invention to the specific embodiments disclosed herein, unless the above detailed description explicitly defines such terms. Should not. While certain aspects of the invention are presented below in certain claim forms, the inventors contemplate the various aspects of the invention in any number of claim forms. Accordingly, the inventors reserve the right to add such additional claims after filing this application in order to pursue additional claims for other aspects of the invention.

(Additional reference material for incorporation)
The following references describe methods, devices, and other embodiments that may be incorporated into or used in combination with the embodiments described herein. Each of these references is hereby incorporated by reference in its entirety.

■ Pressure-Induced Bulle and Sweat Gland Necrosis Flowing Chemotherapeutic Induction, The American Journal of Medicine (September 15, 15), Vol.
■ U. S. Patent No. 5, 190,518 to Takasu title Surgical Device for the Treatment of Hyper Hydrosis.
■ U. S. Patent No. 4, 190, 056 to Tapper et al. titled Method and Means for Recording Sweat Gland Activity.
■ U. S. Patent No. 6,050,990 to Tankovich et al. title Methods and Devices for Inhbiting Hair Growth and Related Skin Treatments.
■ A comparative study of the surgical treatment of axially osmosis by instrument, manual and combined sub- scrucial procedures. , Anals of
Plastic Surgary, Volume 41, November 1998, pg. 488-497.
Electrosurgical Usage Insulated Needles: Treatment of Axially Bromhidiosis and
Hyperhydrosis by Kobayashi, Journal of Dermatological Surgical and Oncology, July 1988, pg. 749-752.
■ Selective sweatland removable with minimal reciprocal clinical and histologic. , British Journal
of Dermatology, 2006, pg. 115-118.
■ U. S. Patent Application Publication No. US 2006/0111744 to Makin et al. title Method and System for Treatment of Sweats Grands.
■ U. S. Patent Application Publication No. US 2003/0158566 to Brett title Percutaneous Cellulite Removable System.

Claims (27)

A device for treating a patient's sweat gland,
A microwave generator;
A gripping mechanism configured to grip a skin tissue region to form a skin fold having a first surface and a second surface;
A cooling element configured to apply protective cooling to at least a portion of the skin tissue region;
A first microwave antenna and a second microwave antenna coupled to the microwave generator and associated with the gripping mechanism when the skin fold is formed; The first microwave antenna is disposed on the first surface of the skin fold, and the second microwave antenna is disposed on the second surface of the skin fold. And wherein the first microwave antenna and the second microwave antenna deliver at least one in the skin tissue region by delivering microwave energy to the skin tissue region via the cooling element. A first microwave antenna and a second microwave antenna configured to at least partially destroy or disable a sweat gland;
Including the device. The apparatus of claim 1, wherein the cooling element is adapted to be placed proximate to the skin fold when skin tissue is placed on the grasping mechanism. The cooling element is adapted to be disposed proximate to the first surface of the skin fold when skin tissue is disposed on the grasping mechanism; and the skin And a second cooling element adapted to be disposed proximate to the second surface of the fold. The apparatus of claim 1, wherein the gripping mechanism includes a suction mechanism configured to provide suction to the skin tissue when the skin tissue is disposed on the gripping mechanism. The apparatus according to claim 4, wherein the suction mechanism is configured to provide suction to the skin tissue to place the skin tissue on the gripping mechanism. An apparatus (153) for treating a skin tissue region (152) to reduce sweat production, said skin tissue region (152) comprising a sweat gland layer that produces excessive sweat;
The device (153)
At least two microwave antennas (154) connectable to one or more microwave generators, said microwave antennas transmitting microwave energy across each outer skin layer from each side of the skin fold. At least two microwave antennas configured to deliver energy to a treatment area in the center of the skin fold by delivery
Including the device. The apparatus of claim 6, further comprising a cooling element for applying protective cooling to at least a portion of the skin tissue region. A first microwave antenna (154) is disposed on the first surface of the skin fold (148), and a second microwave antenna (154) is disposed on the skin fold (148). The device according to claim 6, wherein the device is disposed on a second surface of the device. The apparatus (153) of claim 6, 7 or 8, wherein the cooling element (115) is disposed proximate to the skin fold. The cooling element (115) includes a first cooling element (115) disposed proximate to the first surface (150) of the skin fold (148) and the first of the skin fold. The apparatus (153) according to claim 6, 7, 8 or 9, comprising a second cooling element (115) arranged proximate to the second face (150). 11. The device according to claim 6, 7, 8, 9 or 10, wherein the device further comprises a vacuum cavity for forming the skin fold. The device (153) of claim 6, 7, 8, 9, 10 or 11, wherein the skin tissue region (152) is an axillary region. A system for treating a patient,
Means for identifying a skin tissue region comprising a sweat gland layer, wherein the skin tissue region generates sweat; and
Means for grasping the skin tissue region to form a skin fold including a first surface and a second surface, the sweat gland corresponding to the first surface when folded Means adjacent to and adjacent to the sweat gland layer corresponding to the second surface, so that the layer includes a treatment area;
A cooling element for applying protective cooling to at least a portion of the skin tissue region;
A therapeutic effect configured to be disposed on the first and second surfaces of the skin fold and delivering microwave energy to the treatment area via the cooling element; A microwave antenna configured to provide a therapeutic effect, wherein the therapeutic effect reduces sweating from the skin tissue region;
Including the system. The system of claim 13, wherein the skin tissue region includes at least a portion of an axilla. The system of claim 14, wherein the cooling element for applying protective cooling to at least a portion of the skin tissue region is configured to be positioned proximate to the skin fold. The cooling element has a first cooling element disposed proximate to the first surface of the skin fold and a second cooling element proximate to the second surface of the skin fold. The system of claim 15, wherein the system is configured to be positioned proximate to the skin fold. 14. The system of claim 13, wherein the means for grasping the skin tissue region to form the skin fold further comprises means for providing suction to the skin tissue region. The system of claim 17, wherein the means for providing suction to the skin tissue region further comprises means for maintaining suction to the skin tissue region during treatment. The system of claim 18, wherein the skin tissue region is an axillary region. A system for positioning a device for treating a skin tissue region for sweat reduction comprising:
Means for identifying a skin tissue region comprising a sweat gland layer, wherein the skin tissue region generates sweat; and
Means for forming a skin fold, wherein the skin fold includes a first surface and a second surface, and when folded, the sweat gland layer corresponding to the first surface is Means adjacent to and adjacent to a sweat gland layer corresponding to the second surface, so that the layer includes a treatment zone;
A microwave antenna configured to be disposed on the first surface and the second surface of the skin fold, and crossing an outer epidermis layer from each surface of the skin fold A microwave antenna for delivering microwave energy via the microwave antenna to a treatment area at the center of the skin fold by delivering microwave energy and providing an aesthetic therapeutic effect; and
Including
The system wherein the therapeutic effect improves appearance by reducing the amount of sweat from the skin tissue region. 21. The system of claim 20, further comprising means for applying protective cooling to at least a portion of the skin tissue region. The system of claim 21, wherein the means for applying protective cooling to at least a portion of the skin tissue region includes a cooling element configured to be disposed proximate to the skin fold. The cooling element has a first cooling element disposed proximate to the first surface of the skin fold and a second cooling element proximate to the second surface of the skin fold. 23. The system of claim 22, wherein the system is configured to be disposed in proximity to the skin fold. The means for forming the skin fold is configured to form the skin fold by suction to the skin tissue region and maintain suction of the skin tissue region during treatment. The system according to any one of claims 20 to 23. The system according to any one of claims 20 to 24, wherein the skin tissue region is an axillary region. 13. The device according to any one of claims 1 to 12, wherein the device is configured to improve the appearance of sweating by reducing the amount of sweating from the skin tissue region. 26. A system according to any one of claims 13 to 25, wherein the microwave antenna is arranged and configured to deliver microwave energy so as to allow selective heating of sweat glands. .