JP2016508798A - System and method for treating female incontinence and pelvic neuropathy - Google Patents

Abstract

Disclosed are systems and methods for neuromodulation in female patients suffering from pelvic conditions such as incontinence. One, two or more mechanical stimuli, such as pressure, tension, traction, friction or vibration, sufficient to produce a physiological stimulus or inhibition, eg, neuromodulation to treat or prevent a pelvic condition Can be added to the clitoral structure. [Selection figure] None

Description

[Cross-reference of related applications]
This application is a continuation-in-part of US patent application Ser. No. 13 / 769,930, now pending and incorporated by reference in its entirety.

The present invention relates, in some embodiments, to systems and methods for treating pelvic conditions, including but not limited to female urinary incontinence.

Description of Related Fields “Overactive bladder” is defined as “symptom syndrome suggesting lower urinary tract dysfunction” by the International Society for Urinary Continence. Specifically, it is defined as “imminent, with or without urinary urgency, usually with frequent and nocturia”. Women's overactive bladder is an annoying problem for many people. This condition may be caused by involuntary contraction of the bladder muscle. Many prescription drugs are used to treat overactive bladder, but are not very effective and have significant side effects. Other treatments include dietary improvement, Kegel instruction and formal physiotherapy, and various forms of electrical nerve modulation that affect the bladder reflex arch. If these therapies don't help, there are absorbent pad management modalities used to collect leaks.

  Many devices have been proposed to address female urinary incontinence, for example, U.S. Pat. No. 5,074,855, Rosenbluth et al., 6,131,575, Lenker et al., 6,461,340, Lenker et al., 3,789,828, Schulte, 5509427, Simon et al., 4892535, Bjoernberg et al., 6179775, Thompson, 6836684, Rijkhoff, and Statutory Invention Registration (SIR) H1602, Brock, each of which is disclosed Are incorporated herein by reference in their entirety.

  Improvements in systems and methods for the treatment and prevention of pelvic conditions, including but not limited to urinary incontinence, are desirable.

  In some embodiments, and without being limited by theory, one or more stimuli (eg, non-electric, non-magnetic, or non-electromagnetic stimuli) sufficient to elicit a physiological stimulus or inhibitory response Disclosed are methods and devices for treating pelvic conditions by adding to the clitoral structure. In some embodiments, the methods and devices may stimulate (stimulate) one, two or more sensory receptors in selected body regions, such as one, two or more clitoral structures. (Or suppress) to activate. Sensory receptors include, for example, mechanoreceptors, nociceptors, self-acceptors, temperature receptors (eg heat / cold sensation), humidity receptors, magnetic receptors, chemoreceptors, electrical receptors, electromagnetic radiation receptors Etc. and any combination of the above may or may not be included. In some embodiments, stimulation can activate only mechanoreceptors or primarily. In some embodiments, the stimulus may be mechanical including one, two or more of pressure, traction, tension, vibration and / or friction. In some embodiments, the stimulated sensory receptor is one or more of nociceptors, autoreceptors, humidity receptors, magnetic receptors, chemoreceptors, electrical receptors or electromagnetic radiation receptors. None or substantially one or more of them. In some embodiments, the pelvic condition is controlled by neuromodulating (eg, reversibly stimulating or suppressing) neural pathways such as visceral pelvic nerves or somatic nerves in women suffering from pelvic conditions associated with neuropathy Disclosed are methods and devices for treatment. Some embodiments of the present invention include mechanical stimulation devices, such as neuromodulation devices (eg, support structures) and methods of using the same. In some embodiments, the support structure is a patch. Non-electrical, external (external) and / or internal (eg, intracavity, eg, vagina or cervix, etc.) physical stimuli, eg mechanical stimuli, according to some embodiments Can be added to the area. In some embodiments, the applied stimulus is non-vibrating. Without being limited by theory, such stimuli can produce neuromodulation. In some embodiments, the device produces a mild local inflammatory response that leads to stimulation of one or more nerves. Pelvic conditions of neuropathy include, for example, female frequent urination or urgency, overactive bladder, stress, urgency or mixed urinary incontinence, fecal incontinence including stool incontinence, constipation, interstitial cystitis or pelvic pain, such as Can include vulvar pain or endometriosis. In some embodiments, the mechanical force exerted by the device is sufficient to produce neural stimulation to treat a condition such as incontinence or other conditions mentioned above, but at the same time, for example, clitoral congestion Or does not cause or substantially cause female sexual arousal manifested as mental sexual arousal. In other words, neuromodulation may be below the level of clinical sexual arousal, for example below the level of sexual arousal. In some embodiments, a transient and reversible mechanical nerve stimulation device is provided that effectively applies pressure to the clitoral region with sufficient force to treat female urinary incontinence in particular. A curved, shaped and sized adhesive patch that efficiently adds and maintains and / or adds traction. In some embodiments, the device is configured to produce neuromodulation of one, two or more nerves. In some embodiments, the device is a therapeutic agent, such as a drug, chemical, antibody, or the like, as disclosed elsewhere herein, to stimulate or inhibit one or more nerves. Including a combination of

  In some embodiments, applying mechanical pressure, traction, friction, vibration or other stimuli to one or more clitoral structures, for example using the devices and methods disclosed herein. Thus, neural activity involving one, two or more body locations or functional groups disclosed herein can be suppressed or stimulated. In some embodiments, the devices and methods are utilized to inhibit peripheral parasympathetic activity and / or promote sympathetic activity, thereby relaxing the detrusor and / or stimulating the urethral sphincter Can fill the bladder and treat incontinence or maintain urination control. In some embodiments, by applying mechanical stimulation to the clitoral structure, for example, by stimulating a pontine urination depressive center in the reticular network and suppressing the pontine micturition center Stimulation of parasympathetic nervous system central nervous system can be stimulated. The urethra, including the external urethral sphincter and the striated muscle of the pelvic floor (eg, urogenital septum and levator ani) receive somatic input from the anterior horn cells of the S2-S4 segment via the pudendal nerve. The same nerve also contains afferent fibers that act as a “defense reflex”. Urination can usually be interrupted optionally by contraction of the external sphincter. Without being limited by theory, as described herein, applying mechanical pressure, vibration or other stimulus to the clitoral structure blocks the release of acetylcholine and / or reduces the activity of acetylcholinesterase. Can be increased. Thus, in some embodiments, the device applies pressure to and maintains the clitoral structure and affects acetylcholine (eg, inhibits acetylcholine release and / or increases acetylcholine degradation). Including, but not limited to). In some embodiments, the devices and methods disclosed herein can suppress the micturition reflex center at the sacral, eg, S2-S4 level. The nerves of the mesenteric outer cell column can supply parasympathomimetic input to the detrusor muscle via the pelvic nerve and plexus. These fibers synapse in the ganglia near or inside the bladder wall. Centripetal input can also be transmitted primarily through the pelvic nerve through the S2-S3 roots. Self-acceptance (swelling), pain and temperature sensations are carried by these fibers, resulting in a sensation of urination and transmitted through the spinal thalamic tract and posterior column. Any one, two or more of the above body structures or groups of structures can be stimulated or inhibited using the systems and methods disclosed herein.

  In some embodiments, in contrast to incontinence drugs such as oxybutynin, which may have undesirable systemic anticholinergic effects such as mucosal dryness, constipation, dizziness, tachycardia, disturbances of consciousness, etc. The systems and methods disclosed herein can advantageously provide local targeted effects on the bladder control muscle system without the systemic side effects described above. Further, in contrast to botulinum toxin injected directly into the bladder via procedures such as cystoscopy, in some embodiments, each system and method disclosed herein is non-invasive. It would be advantageous to be able to function through an approach. Accordingly, in some embodiments, the present invention includes devices or methods that treat pelvic disorders (eg, incontinence) without utilizing oral or infused drugs or toxins. In some embodiments, the present invention provides non-invasive reversible mechanical neuromodulation, for example not chemical or thermal neuromodulation.

  In some embodiments, topical formulations for the treatment of pelvic conditions such as stress, urgency and / or mixed urinary incontinence are disclosed. The formulation may comprise or consist essentially of a quantity of biocompatible pharmaceutical adhesive sufficient to be applied to the clitoral structure and provided individually or to the device be able to. The amount of formulation applied is sufficient to apply mechanical pressure to the clitoral structure so that one or more clitoral nerves are neuromodulated below the level of sexual arousal. . In some embodiments, the formulation can include from about 90% to about 97% by weight acrylic polymer and from about 3% to 10% by weight acrylic acid. The acrylic polymer can be selected from the group consisting of isooctyl acrylate, 2-ethylhexyl acrylate, isononyl acrylate, acrylic decyl, dodecyl acrylate, butyl acrylate, hexyl acrylate, and mixtures thereof. The formulation can be configured such that when removed from the clitoral structure, less than about 20% or less than 10% of the surface area of the adhesive is covered with skin cells that have detached from the patient. In some embodiments, the device is physically removable by the user. In other embodiments, the device adheres enough to dissolve or peel naturally from the skin, eg, operably attached to the user but after a preselected period or after removal, eg, in a trash can or toilet. Loses sex. In some embodiments, the adhesive is at least partially water resistant, thus allowing complete bathing and normal urination. In still other embodiments, the device is inserted weekly, monthly, quarterly, or more and controlled by the user (eg, electrically and wirelessly). In other words, the user can wirelessly control the amount of pressure, vibrations or other stimuli placed in the clitoral body to control incontinence. In some embodiments, a clitoral cuff is provided that surrounds the glans and / or body, which can be expanded and relaxed (eg, to control neural modulation), eg, to regulate pressure.

In some embodiments, the topical formulation comprises from about 50% to about 97% by weight acrylic polymer (eg, 50% -60%, 60% -70%, 70% -80%, 80% -97%). And about 3% to 50% by weight of acrylic acid (for example, 3% to 20%, 20% to 30%, 30% to 40%, 40% to 50% and their overlapping range) be able to. Topical formulations can also include silicone adhesives such as polydiorganosiloxanes and copolymer silicone resins. The water vapor transmission rate of the formulation when applied is about 400 g / m ² , 500 g / m ² , 600 g / m ² , 1000 g / m ² , 2000 g / m ² , 3000 g / m ² , 4000 g / m ² , ^{4200g / m 2, 4500g / m} 2, 5000g / m 2 or more, or approximately may exceed their transmission rate.

Also disclosed herein are devices, such as patches, for treating pelvic conditions in female patients. The device is sized for application only at least between the large labia (e.g., the full length of the large labia) or between the opposing folds of the large labia and can include a configured adhesive layer. The device is configured to directly contact and adhere to the skin of one or more clitoral structures selected from the group consisting of clitoral body part, clitoral foreskin and clitoral glans head when applied can do. When applied, the device can stimulate one or more clitoral nerves, eg, mechanical forces, vibrations or other stimuli that are sufficient to modulate, but do not produce sexual arousal, clitoris. It can be configured to be added to the structure. The adhesive layer comprises an adhesive configured such that when removed from the clitoral structure, less than about 20%, 10%, or less of the surface area of the adhesive is covered with skin cells that have detached from the patient. Can be included. In some embodiments, the weight of the surface area per adhesive layer of the device, about 7 g / m ² ~ about 100 g / m ² (e.g. ^{7g / m 2 ~20g / m 2} , 20g / m 2 ~30g / m in the range of ^{2, 30g / m 2 ~40g /} m 2, 40g / m 2 ~50g / m 2, 50g / m 2 ~75g / m 2, 75g / m 2 ~100g / m 2 and the overlap region thereof) It may be. In some embodiments, the device is up to about 0.5 inches to about 3 inches long (eg, 0.5 inches to 1 inch, 1 inch to 2 inches, 2 inches to 3 inches, and overlaps thereof). Range), with a maximum width of about 0.5 inch to about 2 inch (eg 0.5 inch to 1 inch, 1 inch to 1.5 inch, 1.5 inch to 2 inch and their overlapping ranges) And / or a thickness of about 0.0001 inch to about 0.1 inch (e.g., 0.0001 inch to 0.001 inch, 0.001 inch to 0.01 inch, 0.01 inch to 0). .1 inch and their overlapping range). In some embodiments, the adhesive is configured to separate from the patient's clitoral structure within about 6, 12 or 24 hours and / or to biodegrade within about 6, 12 or 24 hours. Can do. The device can include a backing layer that bonds to the adhesive layer. The backing layer can comprise a flexible film material. The device can also include one or more features selected from the group consisting of a curved portion, a raised portion, a tab, a malleable portion, and any combination thereof. Any of the above portions can be configured to facilitate maintenance of mechanical forces on one or more clitoral structures while the patient is stationary and / or active. The bend may have, for example, about 10% to about 30% bend along the device axis. In this case, the raised portion surrounds the center of the contact surface of the support structure. The contact surface can include a raised portion having a surface area and a non-raised portion having a surface area. The raised portion can have a surface that is, for example, about 10% to about 100% of the surface area of the non-raised portion. The ridges can have a maximum thickness that is at least about 10%, 20%, 30%, 40%, 50% or more thicker than the thickness of the non-ridges of the device. The device may also include one or more protrusions configured to apply a mechanical force to the clitoral structure and / or one or more configured to apply a radial mechanical force to the clitoral structure. A plurality of recesses can be included. The device can also include one or more reinforcing members, which in some cases can include a shape memory material. The reinforcing member can extend around at least a portion of the periphery of the device. The adhesive layer has a surface area of about 1 square inch to about 2 square inches. In some cases, the device includes a tab that extends to one, two or more sides, anterior or ventral sides that facilitate gripping the device, eg, a patch. In some embodiments, the tab does not contain any adhesive that facilitates device application and removal. The adhesive can include an acrylic component, such as from about 50% to about 98% by weight acrylic polymer, from about 2% to about 50% by weight acrylic acid, and the like. The adhesive can include a hydrocolloid component and / or a silicone component. The device can also include an absorbent material that is bonded to the backing layer. In some embodiments, the device applies mechanical stimuli such as pressure, tension, friction, traction and / or vibration to the clitoral structure at least 0.5, 1, 6, 12, 24, 48 and force applied to the tissue to maintain sufficient contact and stimulation for 72 hours (e.g., about ^{0.001g / mm 2 ~0.01g / mm 2} , 0.01g / mm 2 ~0.1g / mm 2, 0.1g ^{/ mm 2 ~0.5g / mm 2,} 0.5g / mm 2 ~1g / mm 2, 0.1g / mm 2 ~1g / mm 2, 1g / mm 2 ~5g / mm 2, 5g / mm 2 ~ 10 g / mm ² and their overlapping range). In many embodiments, these pressure ranges are applied consistently over a desired period of time (eg, over several hours or days).

  Also disclosed herein is a urethral plug device that includes a device described herein and a tubular body configured to fit within a patient's urethra. The device can be coupled to or separated from the urethral plug device. Further disclosed herein is a device for treating a pelvic condition in a female patient that is sized for use in clitoral or clitoral foreskin and includes a structured adhesive layer. When applied, the device can be configured to apply sufficient mechanical stimulation to the clitoris or clitoral foreskin to neuromodulate the clitoral nerve. The adhesive layer can include a pressure sensitive acrylic adhesive and can also include a tab that facilitates securing the device.

  A kit comprising a plurality of patches, dispensers, mirrors and / or housings is also disclosed. In some embodiments, the patches can be linearly arranged on a release sheet having a perforation between each patch and releasably bonded to the release sheet, the release sheet forming a roll Configured to do. The kit can further include a dispenser configured to receive the roll. In some embodiments, the present invention includes several devices (eg, patches) that apply mechanical stimuli, such as pressure and / or traction, and instructions for applying the device to the clitoral area.

  In some embodiments, disclosed herein are methods of treating a patient's pelvic pathology, including but not limited to urinary incontinence. The method includes applying mechanical stimuli, such as pressure, intermittently or continuously to one or more clitoral structures including, for example, the clitoral body, clitoral foreskin and clitoral glans. be able to. The method may also include applying a sufficiently malleable device to the one or more clitoral structures to stably conform to the shape of the one or more clitoral structures. it can. The method can also include deforming at least a portion of the device from a first configuration to a second configuration, where the second configuration is mechanically coupled to one or more clitoral structures. Matches the shape of one or more clitoral structures sufficient to apply a stimulus. The applied mechanical stimulus may not cause sexual arousal, but may be sufficient to neuromodulate one or more clitoral nerves to treat a pelvic condition. Stimulation can be applied for at least about 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, several days or more. Pelvic conditions include female frequent urination, urgency, overactive bladder, stress urinary incontinence, urge incontinence or mixed urinary incontinence, urinary retention, fecal incontinence, constipation, interstitial cystitis, vulva and endometrium There may be one or more of the symptoms. Applying mechanical stimulation to one or more clitoral structures can include applying a device that includes an adhesive layer to the clitoral structures. The adhesive layer comprises an adhesive configured such that when removed from the clitoral structure, less than about 20%, less than 10% or less of the surface area of the adhesive is covered with skin cells that have detached from the patient. be able to. Applying a mechanical stimulus to the one or more clitoral structures can also include, for example, securing a device such as a clamp to the one or more clitoral structures. The device can be carried by a panty, sanitary napkin or another garment. The method can also include inserting a urethral plug into the urethral orifice of the patient. The applied mechanical stimulus may be sufficient to neuromodulate the pudendal and / or cavernous nerve branches.

  In some embodiments, the systems and methods disclosed herein do not necessarily need to include bladder urine, or an absorbent pad to capture urine, need to be inserted into a body cavity, rigid or It does not have a semi-rigid component or protrusion, or does not require an electrical component such as an electrical impulse generator, but in some embodiments it can fully include the above features. In some embodiments, the device can be used without having to be removed during intercourse.

  In some embodiments, mechanical pressure, traction, vibration, friction or other stimulus is applied non-invasively to a clitoral area, such as the clitoral foreskin, with a substance adapted to fix the entire clitoral area . In one embodiment, the material includes an adhesive device and is applied to the clitoral area. The traction provided by the device may be sufficient to stimulate nerves in the clitoral area. The adhesive may be on either or both sides of a backing sheet formed from a flexible material. In some embodiments, the flexible material is about 0.012 mm to about 0.051 mm thick (eg, about 0.012 mm to 0.02 mm, about 0.02 mm to 0.05 mm, and their overlapping ranges). And having an adhesive layer on the backing sheet, the adhesive layer being suitable for direct application to the clitoral area, and the device being shaped to cover the clitoral area. In one embodiment, the thickness is about 0.02 mm. The release sheet can protect the adhesive layer from drying before use. In another embodiment, the device has an adhesive on one side of the backing sheet. A plurality of such patches can be arranged in a straight line and joined together by a tear line. In some cases, a small cloth or paper tab can be secured to the tip of the patch with an adhesive to facilitate handling. A single array of patches can be removed from the dispenser by pulling the tab as an aid to a linear array of patches, and the tab will also act as a stopper when pulling out the patch from the dispenser. Can be mounted on a dispenser.

  In another embodiment, a solid object that is also flexible is secured to the clitoral region. A solid object, for example a solid curvilinear plastic member, can be fixed to the adhesive or placed under the adhesive, for example it can be fixed to the front side of a backing sheet with an adhesive layer on the front side , Thereby applying a solid object directly to the clitoral area and applying a stimulus, eg physical pressure thereto. In other embodiments, other shapes are used.

  In yet another embodiment, the solid object is applied to an auxiliary garment, such as the inside of a panty, and the solid object is applied to the clitoral area when the panty is worn, and a stimulus, such as physical pressure, is applied thereto. It can be mounted at various positions.

  Some embodiments of the present invention provide a simple, low-cost solution to an awkward problem that makes treatment safer, easier and more accessible. Some embodiments can be designed to fit comfortably in almost any human woman suffering from frequent urination or urgency and are necessary elements for comfort, ease of use and reliability including. For example, the device is manufactured using a soft, flexible material that can be continued as a daily habit without the user discomforting or cluttering the device. Although some people may need assistance with some basic activities every day that are put on the device by someone else, some embodiments allow the user to remove the device without any assistance. Designed to allow pasting.

  Devices can be manufactured in various sizes, for example, small, medium and large to accommodate variations in the patient's body. It fits well from women who are less active to women who are very active, such as running, jogging, high or low intensity aerobics or any exercise that requires lower body movements. The product is highly portable and many units are available in individually sealed and sterilized packages, which can be easily adapted to standard purses or pouches. The price, comfort, convenience, portability and ease of use of this device may be able to exceed other products currently available through either prescription and / or consumer over-the-counter transactions.

FIG. 3 is a perspective view of an embodiment of a device configured to reversibly attach to a clitoral structure, with portions separated for better illustration of the configuration. FIG. 2 is a top plan view of the device of FIG. FIG. 2 is a top plan view of a device similar to that of FIG. 1 but rectangular. FIG. 2 is a top plan view of a triangular device similar to that of FIG. It is a side view of one Embodiment of the device which has a projection part. FIG. 6 is a side view of an embodiment of a device having a recess. FIG. 6 is a top view of an embodiment of a device having one or more reinforcing members. FIG. 6 is a top view of an embodiment of a device having a reinforcing member oriented around the periphery of the device. FIG. 6 is a side view of an embodiment of a device having a bias member. It is a sketch figure of the vagina which illustrates each ingredient concerning the present invention, and shows patch application to a clitoral foreskin. It is a sketch figure which shows an internal and external clitoral anatomy figure. FIG. 6 shows an embodiment of a soft clamp that applies a stimulus, eg mechanical pressure, to the clitoral foreskin. FIG. 3 shows an embodiment of a suction cup that applies stimulation, eg mechanical pressure, to the clitoral foreskin. FIG. 6 is a top view of a transparent dispenser showing a plurality of patches arranged in a straight line and joined by a tear line. It is a cross-sectional view of the dispenser of FIG. FIG. 8 shows three back sides of a plurality of patches included in the dispenser of FIG. 7 joined by a tear line. It is a figure which shows the patch by which the solid curvilinear object is being fixed to the front surface of the backing sheet which has an adhesive bond layer in the front surface. FIG. 3 shows a support garment, in this case a panty, having a solid object implemented to apply a stimulus, eg physical pressure, to the clitoral area. FIG. 6 illustrates an embodiment of a sanitary napkin that couples to a device configured to apply a stimulus, eg, mechanical pressure, to the clitoral structure. FIG. 5 shows an embodiment of a urethral plug having a clitoral extension segment. FIG. 10 shows a method of placing a urethral plug having a clitoral extension segment. FIG. 10 shows a method of placing a urethral plug having a clitoral extension segment.

  In some embodiments, disclosed herein are devices that can treat or prevent pelvic conditions such as stress, urgency or mixed urinary incontinence or others disclosed herein. To do. In some cases, the device can take the form of a patch and includes a backing sheet, one, two or more adhesive layers that can have the same or different degrees of adhesion, and a release layer. be able to.

  With reference to FIGS. 1 and 2, a generally oval patch 10 formed from a backing sheet 16 coated with one, two or more adhesives 14 and covered with a release sheet / layer 12 is shown. Show. In some embodiments, the adhesive layer 14 may be pressure sensitive and non-allergenic. In some embodiments having multiple adhesive layers, the first adhesive layer is about 5%, 10%, 15%, 20%, 25%, 30 compared to that of the second adhesive layer. %, 35%, 40%, 50%, 75%, 100% or more. Either the first adhesive layer or the second adhesive layer can be in direct proximity to the skin surface. In some embodiments, the first adhesive layer is proximate to the backing sheet and the second adhesive layer is sprayed directly onto the skin or the second adhesive layer.

  In one embodiment, the patch 10 has a length of, for example, about 1 inch to about 3 inches, a length of about 1 inch to about 2 inches (eg, about 1 inch, about 1.25 inches, about 1. 5 inches, about 1.75 inches or about 2 inches long), about 1 inch to about 1.5 inches long, about 1.5 inches to about 2 inches long, about 1.25 inches to about It may be 1.75 inches long, about 1.4 inches to about 1.6 inches long, or approximately 1 and 1/2 inches long. In one embodiment, the patch 10 is, for example, 0.5 inches to 2 inches wide at its maximum width, about 0.75 inches to about 1.5 inches wide, about 0.75 inches to about 1.25 inches wide. Width or about 3/4, 13/16, 7/8, 15/16, 1, 1 and 1/16, 1 and 1/18, 1 and 3/16 or 1 and 1/4 inch Good. In some embodiments, the patch (eg, all layers of the patch together) is about 0.0001 inches to about 0.1 inches, about 0.0004 inches to about 0.004 inches, about 0.007 inches. Can have an average thickness of about 0.013 inch or about 0.008 inch, 0.009 inch, 0.010 inch, 0.011 inch or 0.012 inch or the thickness of its thickest portion. The patch can have a constant, substantially constant, or variable thickness throughout. In some embodiments, the patch is about or at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 300% or It can be configured with higher strength / extension. The patch may be die cut or may be formed by other manufacturing techniques, some of which are disclosed herein.

  In some embodiments, a device, such as a patch, can also include one, two, or more therapeutic agents that are coated or otherwise operatively attached. In some embodiments, the therapeutic agent may be an anesthetic so as to be comfortable while the device is being applied and when removed. The anesthetic may be, for example, lidocaine, bupivacaine, or a combination thereof. In some embodiments, the therapeutic agent may also be a hormone, such as estrogen or progesterone. In some embodiments, the therapeutic agent may be a sympathetic agonist or antagonist or a parasympathetic agonist or antagonist. In some embodiments, the therapeutic agent may be oxybutynin or botulinum toxin.

  The backing sheet 16 can be a membrane material and can be manufactured from a thin flexible plastic film, although other flexible liquid materials can also be used. As used herein, the term “flexible” refers to a material that is compliant and easily conforms to the general shape and curvature of the clitoral region. The material of the backing sheet 16 may be that described in Brock's Legal Invention Registration (SIR) No. H1602 backing sheet material, which is incorporated herein by reference. In some embodiments, the backing sheet is a woven or non-woven fabric, a polymer film, such as a polyethylene or polypropylene thermoplastic film, and / or from about 0.005 mm to about 0.01 mm, or from about 0.012 mm to about 0.00. A composite material such as a film-coated nonwoven fabric exemplified by a polyethylene film having a thickness of 051 mm is included. In some embodiments, the backing sheet 16 or other component of the patch is one, two or more to absorb moisture, for example to absorb a portion of sweat, vaginal fluid or urine leakage. Of absorbent material. Absorbent materials include, for example, natural or synthetic silk fibers, ceramic fibers, raw or recycled bamboo fibers, cotton fibers, rayon fibers, linen fibers, ramie fibers, jute fibers, sisal fibers, flux fibers, soybean fibers, com fibers (com fibers), cannabis fiber, lyocell fiber, wool, lactide and / or glycolide polymer, lactide / glycolide copolymer, silicate fiber, polyamide fiber, feldspar fiber, zeolite fiber, zeolite-containing fiber, acetate fiber, and combinations thereof Can do. In some embodiments, the absorbent material can have an absorptance of about or at least about 10 g / g, 15 g / g, 20 g / g, 25 g / g or more.

  The release layer / sheet 12 can retain the adhesive from drying and can be formed from an adhesive release material. Other non-limiting examples of adhesive release materials / sheets include paper, resin film, non-woven fabric and non-woven fabric laminated with resin film, each treated with silicone. The release layer is removed before applying the patch 10.

  FIG. 3, in one embodiment, shows a generally rectangular patch 10A that is similar to the patch of FIG. 1 but is about 1 and 1/2 inches long and about 1 and 1/16 wide. Other dimensions described are possible.

  FIG. 4 shows, in one embodiment, a generally triangular patch 10B that is similar to the patch of FIG. 1 but is about 1 and 1/2 inches high and about 1 and 3/4 on the bottom. Other dimensions described are possible.

  Although generally oval, rectangular and triangular patches (with or without circular edges) are described and illustrated above, devices such as patches include clitoral glans heads and / or clitoral foreskins. Optional (either from a top view or a cross-sectional view) as long as it is configured to cover at least part of the clitoral area and / or to provide mechanical stimulation, eg pressure, to at least part of the clitoral area Can have any suitable shape or size. In some embodiments, the patch has a generally arcuate shape, such as circular, semi-circular, square, diamond, lobe (eg butterfly), hourglass, hexagon, star or irregular shape, etc., or tab Alternatively, it may be any of the above-described ones in which the wings are extended radially, axially or otherwise. In some embodiments, the one, two or more tab portions are about 0.25 inches to about 1 inch, about 0.25 inches to about 0.75 inches, about 0.25 inches to about 0. .5 inch, about 0.5 inch to about 0.75 inch, about 0.75 inch to about 1 inch, about 0.25 inch, 0.5 inch, 0.75 inch, about 1 inch long and those It may be an overlapping range. In some embodiments, the one, two or more tab portions are about 0.25 inches to about 1 inch, about 0.25 inches to about 0.75 inches, about 0.25 inches to about 0. .5 inch, about 0.5 inch to about 0.75 inch, about 0.75 inch to about 1 inch, about 0.25 inch, 0.5 inch, 0.75 inch, about 1 inch wide and those It may be an overlapping range. In some embodiments, the patch has any desired shape and surface area sufficient to partially or fully cover the clitoral glans head and / or clitoral foreskin, eg, in some embodiments, about 0. 5 square inches to about 4 square inches, about 1 square inch to about 2 square inches, about 1 square inch to about 1.25 square inches, about 1.25 square inches to about 1.75 square inches, or about 1.25 It may be square inches, about 1.5 square inches, or about 1.75 square inches. In other embodiments, the patch may be dimensioned to avoid covering the patient's urethra, but the patch is capable of covering at least a portion or the entire patient's urethra. In one embodiment, the patch comprises having a curvature of about 10% to 30% (eg, about 10%, 15%, 20%, 25% or 30%) along the axis of the patch, Can be curved into the area. In some embodiments, the patch is curved in one, two or more dimensions, such as length, width and / or thickness dimensions. In some embodiments, the entire device or portions thereof are highly malleable (ie, deform under stress and do not return to their original shape when the stress is removed), one or more clitoris Force can be fixed or maintained in the structure. In some embodiments, the entire device or portions thereof are highly ductile (can be deformed under tensile strength without tearing). In some embodiments, the device is about or at least about 5%, 10%, 15%, 20%, in one, two or more directions (eg, length, width and / or thickness), 25%, 30%, 35%, 40%, 50%, 60%, 75%, 100%, 200%, 300% or more can be stretched without partial or complete crushing. In some embodiments, the device can be applied to one or more clitoral structures, and at least a portion of the device stably conforms to the shape of the one or more clitoral structures. And / or sufficiently malleable to apply sufficient force to neuromodulate one or more clitoral structures below the level of sexual arousal. The device or at least a portion of the device can be deformed from a first configuration to a second configuration, the second configuration comprising one or more clitoral structures for mechanical stimulation, eg pressure or traction Match the shape of one or more clitoral structures sufficient to add to

  In some embodiments, as illustrated in the schematic side view of FIG. 4A, the patch 10C includes one, two or more raised or recessed areas, such as protrusions 15 or edges, such as a device. About or at least about 10% around the periphery of the device, in the central region of, at or near the center, close to one, two or more corners of the patch 10C or around the entire periphery %, 30%, 40%, 50%, 60%, 70%, 80% or more. Protrusions 15 are, for example, large stimuli when the backing sheet and / or the adhesive layer are thick with respect to their other areas and when the patient rests and / or moves or changes position, For example, it can be formed in an area where it is advantageous to apply pressure and / or maintain good stimulation in the area on the body of interest. In some embodiments, the device is used only when the patient is stationary (static stimulation, eg pressure), while only in motion, eg during walking (motor stimulation, eg pressure) or both stationary and in motion. In, a stimulus, such as pressure and / or traction, is applied. In some embodiments, as illustrated in the schematic side view of FIG. 4B, the patch 10D can include one, two or more recesses 17, such as in the central region of the patch. When the patch 10D is molded along the female body, the recess 17 can further apply pressure to the patch, for example to the clitoral glans head and / or foreskin, for example radially and / or circumferentially, such as in the direction of the arrow. . In some embodiments, a device such as a patch can have a basic surface area and a surface area of the ridges and / or recesses that is different from the thickness of the basic surface area, in which case the ridges and / or recesses relative to the basic surface area. The surface area ratio is about or at least about 0.1: 1, 0.2: 1, 0.3: 1, 0.4: 1, 0.5: 1, 0.6: 1, 0.7: 1. 0.8: 1, 0.9: 1, 1: 1, 1.1: 1, 1.2: 1, 1.3: 1, 1.4: 1, 1.5: 1, 1.6 1: 1.7: 1, 1.8: 1, 1.9: 1, 2: 1, 2.5: 1, 3: 1 or more. In some embodiments, the device, such as a patch, is at least about or about 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140 compared to the thickness of the non-raised area of the device. %, 145%, 150%, 175%, 200% or more thick areas. In some embodiments, the raised area can include a second adhesive having different properties than the first adhesive, including various adhesive properties. In some embodiments, the device, such as a patch, is at least about or about 0.0005 inches, 0.001 inches, 0.002 inches, 0.003 inches,. 004 inch, 0.005 inch, 0.006 inch, 0.007 inch, 0.008 inch, 0.009 inch, 0.010 inch, 0.015 inch, 0.02 inch, 0.03 inch,. It can have raised or recessed areas having a thickness of 04 inches, 0.05 inches, 0.1 inches or more. In some embodiments, the raised or recessed areas can have a generally conical, triangular pyramid, cube or other desired shape and / or selective additional stimuli such as pressure or traction (device Applying additional stimuli substantially selective to the clitoral structure, such as the clitoral glans head, body or foreskin, eg pressure or traction, to the adjacent non-clitoral structure It was set as the dimension added so that it might not exist. In some embodiments, the device has one, two or more openings sized and configured such that at least a portion of the one or more clitoral structures remain within the openings. The device can have that portion of one or more clitoral structures forward, ventral, or laterally, eg, one or more nerves, eg, clitoral nerves or disclosed herein. Add traction in a direction appropriate enough to neurally modulate the others.

  In some embodiments, as illustrated in the schematic top view of FIG. 4C, the patch 10E is one, two, or otherwise oriented in the exemplary longitudinal or axial direction, diagonally or otherwise. Further reinforcing members 13 can be included. FIG. 4D illustrates in a schematic top view an embodiment of a patch 10F that includes a reinforcing member 13 that surrounds the patch 10F. The reinforcing member 13 is, for example, in close proximity to the adhesive layer and therefore in direct contact with the patient's body, between the adhesive layer and the backing layer or on a surface backing layer further away from the patient's body. Can be arranged. The reinforcing member 13 can be made of any suitable material, such as plastic, metal or shape memory material, such as shape memory metal or polymer, and the body part of interest, such as the clitoral glans head and / or foreskin. It can be configured to be malleable and / or moldable to add further irritation.

  FIG. 4E illustrates a side schematic view of an embodiment of a patch 10G having a recess 17, as shown in FIG. 4B, where a biasing member 130, such as a shape memory metal or polymer, is placed on a body part of interest, such as a clitoral glans. It is configured to apply further pressure radially and / or circumferentially on the part and / or foreskin. In some embodiments, the bias member 130 can take a partial or complete ring form.

  Many adhesives currently used in conjunction with skin and wound healing bandages stick to skin and other tissues. The level of bond strength can be increased even just hours after wearing. The sensory perception felt when peeling such an adhesive that has been in the skin for only a few hours can be very painful and can cause damage to, for example, the epidermis layer of the skin or other epithelium. Injury to the skin can cause pain by inducing edema and / or erythema.

  Further, the adhesive is repeatedly and chronically applied to the same part of the body, and the adhesive is removed and reapplied repeatedly. When applied and removed repeatedly, such adhesives tend to remove portions of the skin or other skin layers along with the adhesive. Tissue damage may be manifested as percutaneous water loss increases. These adhesives may also stay strong on the hair, thereby increasing the discomfort and irritation that occurs when removing the adhesive. Furthermore, since the tissue layer exfoliated by the adhesive at the time of removal loses the adhesion and adhesive properties, the re-sticking ability of the adhesive disappears.

  Therefore, there is little or no pain, little or no trauma to the skin, but it can be easily reapplied or repositioned when used in conjunction with tape, patches or other goods It is desirable to use an adhesive that does not round the edges. The adhesive can be configured to give the adhesive the ability to re-adhere without the loss of adhesive strength associated therewith, after which the patch floats over time. This also allows the patient to reuse the adhesive patch if the adhesive patch is incorrectly applied or overlapped.

  In some embodiments, less pain occurs upon removal, even if up to 1 day, 2 days or more from the time of wearing, adhesion does not increase significantly over time, does not cause skin maceration, and It is desirable to utilize an adhesive that does not substantially contain skin or other epithelial cells when peeling the adhesive.

  The biocompatibility of the adhesive is characterized by cytotoxicity, skin irritation and skin sensitivity. In some embodiments, the cytotoxicity of the adhesive does not exceed 2 when using the International Organization for Standardization (ISO, eg, ISO 10993) agarose overlay method, and the cytotoxicity is less than 1, eg, zero. It may be. In some embodiments, skin irritation does not exceed 2 when using ISO skin irritation rating, less than 1, 0.8, 0.5, or 0.4 (no irritation) It may be. The adhesive in the exemplary embodiment does not act as a skin sensitizer in the Globally Harmonized System (GHS) standard for chemical classification and labeling.

  Some embodiments allow patches, bandages, adhesive tapes or other medical devices that adhere to the skin to be applied to the skin, either individually or together, and then have little pain. Or an adhesive composition that can be removed without or at all. While it is difficult to accurately measure the pain that occurs during adhesive removal, the Wong-Baker pain scale is recognized in the medical field to quantify pain intensity measurements, due to the influence of a wide range of factors. ing. This is a scale of 0 to 5 with 5 being the highest pain level and is often used to assess an individual's pain sensation. Some embodiments of the adhesive are less than about 2.5 at the time of adhesive removal even after up to 2 hours, 3 hours, 4 hours, 6 hours, 12 hours, 18 hours, 1 day, 2 days or more from the time of wearing. An average Wong-Baker pain rating of In some embodiments, the average Wong-Baker pain rating upon removal of the adhesive is less than about 2.0, 1.5, 1.0, or even lower.

  If the peeling of the adhesive from the skin does not occur at the adhesive / skin interface, some adhesive bond breakage will occur, which will instead occur at the interface between the upper skin cells and the dermis . This represents a large amount of skin cells adhering to the peeled adhesive. Therefore, the force required to remove the adhesive from the skin is essentially the same as the force by which the adhesive pulls a large amount of skin cells away from the dermis layer (ie, the wearer has to Converted into a feeling of pain). In some embodiments, the adhesive bond breakage occurs at the adhesive-skin interface, indicating no or very little skin cells attached to the adhesive. Using this fundamental difference in the mechanism of bond breaking when peeling from the skin, the adhesive can retain a high peel force and a low pain sensation upon removal.

  The adhesive in some embodiments has an exfoliation action of less than 50%, ie it can be removed from the skin with less than 50% adherence of peeled skin cells to the adhesive surface area, typically The exfoliation action is about 40%, 30%, 20%, 10%, less than 5% or less. In some embodiments, the exfoliation action is about 10% so that up to 90% or more of the previous binding force is available such that the adhesive can be repositioned and reattached to the skin. Is less than. Furthermore, less skin cell removal can correlate with less pain in the wearer.

  Some embodiments also result in an adhesive with suitable wear performance. If the peel is significantly reduced, the adhesive will have poor wear properties, i.e. it will tend to round off and peel off prematurely. In some embodiments, the adhesive is applied to the skin for about or about 72 hours, 48 hours, 24 hours, 18 hours, 15 hours, 12 hours, 11 hours, 10 hours, 9 hours, 8 hours, 7 hours, 6 Adhesive enough to bond releasably in less than 5 hours, 4 hours, 3 hours or 2 hours. In some cases, the peel force is close to, but not exceeding, the force required to remove large amounts of skin cells from the skin area in contact with the adhesive, but for example based on the type of skin, climatic conditions and diet There may be slight differences between them.

  In order for an adhesive bandage or adhesive tape for skin application to function efficiently, the adhesive strength of the adhesive to the skin exceeds the load experienced during normal use. The peel force may be a force on the order of 0.2 N per centimeter width when peeling or peeling from the skin at an angle of 90 degrees. In some embodiments, the force is 0.3 N / cm, 0.6 N / cm, 0.8 N / cm, greater than 1.0 N / cm or more, so that the sample binds to the skin for several days. Is possible. In some embodiments, the peel force is 0.6 N / cm using 1 hour residence on the skin and greater than 0.8 N / cm after 24 hours residence. In some embodiments, peel or exfoliate at an angle of 90 or 180 degrees when bonded to light-colored annealed No. 302 or 304 ANSI hard iron according to ASTM standard adhesion test methods Sometimes the adhesive can have, for example, the following properties: about 12-16 ounces / inch width, such as about 12, 13, 14, 15 or 16 ounces / inch width (eg, about 340-460 gms / 25 mm, For example, about 340, 350, 360, 370, 380, 390, 395, 397, 400, 403, 405, 410, 420, 430, 440, 450 or 460 gms / 25 mm) (about 3.5 to 4.5 N / 25 mm, For example, about 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, or 4.5 N / 25 mm) or those Overlapping range.

  One method for quantifying the wearing performance is an edge lift method. The edge lift method is a means for measuring the ratio of the total area where the patch to which the adhesive is applied is no longer bonded to the skin during the wearing time. Some embodiments achieved less than 10%, 8%, 5%, 3% or less edge lift over 2, 4, 6, 8, 12, 18 or 24 hours.

The adhesive in some embodiments can exhibit a relatively high water vapor transmission rate (MVTR). In some embodiments, the MVTR is, for example, about 400 g / m ² or more per day, 500 g / m ² or more, 600 g / m ² or more, 700 g / m ² or more, 800 g / m ² or more, 900 g / m ² or more, 1000 g / m ² or more, 1100 g / m ² or more, 1200 g / m ² or more, 1300 g / m ² or more, 1400 g / m ² or more, 1500 g / m ² or more, 2000 g / m ² , 2500 g / m ² , 3000 g / m ² above, 3500 g / m ² or more, 4000 g / m ² or more, 4500 g / m ² or more, it may be 5000 g / m ² or more, or more. In some embodiments, MVTR is 1 day to about ^{3500g / m 2 ~5000g / m 2} , may be about 4000g / m ² ~4500g / m ² or about 4200 g / m ² or overlapping range thereof. In some embodiments, this can be an advantage of being able to breathe skin. In some cases, non-venting adhesives accumulate moisture at the skin-adhesive interface, which causes skin maceration. The macerated skin becomes weak and can tear easily, causing pain when removing the adhesive. The accumulation of moisture can also promote bacterial growth on the skin.

  Patches and other devices that use adhesives in some embodiments may also exhibit little or no sliding or creep from the application site. Patches and other devices are cleanly removed with little or no residue left on the skin or clothing even when contacted by liquids (eg, water, isopropanol, wound overflow, etc.).

  The adhesive layer may comprise or consist essentially of a tacky hydrophilic adhesive composition, a viscous gel or a substantially solid composition. The adhesive layer may be one, two or more pressure sensitive adhesives (PSA), such as tackifying rubber adhesives such as natural rubber, olefin, silicone, polyisoprene, polybutadiene, polyurethane, styrene-isoprene. Styrene and styrene-butadiene-styrene block copolymers, and other elastomers, vinyl esters and vinyl amides, and tackified or non-tackified acrylic or methacrylic adhesives such as copolymers of isooctyl acrylate and acrylic acid, and / or Ester homopolymers or copolymers can also be included. The adhesive can be polymerized by radiation, solution, suspension or emulsion methods. The adhesive can be cross-linked and given a high shear force, for example by radiation and / or chemical cross-linking agents. Such an adhesive has a high shear force, can have a low peel force, and can be easily removed when stretched.

  In some embodiments, the pressure sensitive adhesive is an acrylic polymer such as isooctyl acrylate, 2-ethylhexyl acrylate, isononyl acrylate, decyl acrylate, dodecyl acrylate, butyl acrylate, hexyl acrylate, and mixtures thereof. Pure rubbery copolymer (from about 50% to about 98%, from about 70% to about 98%, from about 80% to about 97%, from about 90% to about 96%, about 92% by weight To about 96 wt%, or about 94 wt%) and acrylic acid (about 2 wt% to about 50 wt%, about 2 wt% to about 30 wt%, about 3 wt% to about 20 wt%, about 4 wt% To about 10 wt%, about 4 wt% to about 8 wt%, or about 4 wt%, and their overlapping ranges). In some embodiments, the adhesive is a 2-ethylhexyl acrylate-vinyl acetate copolymer or a blend of this copolymer and 2-ethylhexyl acrylate-n-tert-butylacrylamide copolymer, a suitable catalyst, such as a Zirco desiccant, It comprises or consists essentially of a mixture crosslinked or cured with a zirconium organic complex catalyst.

The adhesive layer also includes (i) a polydiorganosiloxane (eg, having an average molecular weight of about 5000 to about 10000000, such as about 50,000 to about 1000000) and (ii) a copolymer comprising triorganosiloxy units and SiO _4/2 units. Containing or consisting essentially of a blend of a silicone-based resin (typically also referred to as an “MQ resin” having an average molecular weight of about 100 to about 1000000, eg, about 500 to about 50000). In some embodiments, the weight ratio of polydiorganosiloxane to copolymeric silicone resin is about 1: 1, 1.05: 1, 1.1: 1, 1.2: 1, 1.3: 1, 1.4: 1, 1.5: 1, 1.6: 1, 1.7: 1, 1.8: 1, 1.9: 1, 2: 1, 3: 1, 4: 1, 5: Approximately equal to or exceeding a ratio of 1, 7: 1, 8: 1, 10: 1 or more. In some embodiments, the weight ratio of polydiorganosiloxane to copolymeric silicone resin is about 1: 1, 0.95: 1, 0.9: 1, 0.8: 1, 0.7: 1, Approximately equal to or less than 0.6: 1, 0.5: 1, 0.4: 1, 0.3: 1, 0.2: 1, 0.1: 1 or less . In other embodiments, the adhesive layer does not include a silicone adhesive.

In some cases, with respect to improving PSA properties, it is beneficial to have a chemical mechanism for reacting the copolymeric silicone resin with the polydiorganosiloxane. In order to obtain such a reaction, two different reactive chemicals have been commonly used: condensation chemicals and addition cure chemicals. Condensed chemical silicone PSA can be prepared by mixing a silanol functional copolymer resin containing triorganosiloxy units and SiO _4/2 units with a silanol-endblocked polydiorganosiloxane. Such admixtures are usually solvent solutions of copolymeric silicone resins and polydiorganosiloxanes, which are generally applied to the backing, heated to remove the solvent, cross-linked if necessary, and improve the physical properties of the PSA. Can be improved. The copolymer silicone resin and the polydiorganosiloxane are subjected to intermediate condensation, and internal condensation and intermediate condensation are performed in the adhesive. With reference to these, the condensation between the copolymeric silicone resin and the polydiorganosiloxane can be performed either in the presence of an ambient temperature or a high temperature catalyst, or in the absence of a catalyst at a high temperature, as well as on the backing. This can be done before applying the PSA or after applying the PSA to the backing. Effective catalysts for promoting the silanol condensation reaction include organometallic compounds and metal salts of carboxylic acids. A further method of intermediate condensation of silicone resins and polydiorganosiloxanes is through the addition of orthosilicates and polysilicates.

  As noted above, silicone PSA comprising an intermediate condensation product of silanol functional polydiorganosiloxane and silanol functional copolymeric silicone resin optionally includes a free radical polymerization catalyst, such as a diaryl peroxide crosslinker, an adhesive composition. Can be included to cross-link objects, thereby improving the high temperature shear properties of the PSA with only a slight loss of adhesion due to debonding.

The polydiorganosiloxanes used in preparing the silicone PSA component can include, for example, polydimethylsiloxane polymers and poly (dimethylsiloxane / diphenylsiloxane) copolymers. The copolymeric silicone resin can include a copolymeric silicone resin having one or more of the following functional groups: silicon-bonded hydrogen, silicon-bonded alkenyl, and silanol. Other useful silicone resins include R ₃ SiO _1/2 , SiO _4/2 and R ₂ SiO _2/2 structural units (MQD resins) where R is an alkyl radical containing 1 to 3 carbon atoms. And the ratio of R ₃ SiO _1/2 units to SiO ₂ is about 0.5 to about 1.0, such as about 0.6 to about 0.9 or about 0.7 to A three-component terpolymer containing about 0.8).

Silicone PSA prepared with addition curing chemicals is generally comprised of polydiorganosiloxanes having alkenyl groups, SiO _4/2 and R ₃ SiO _1/2 structural units (where R is the functional group below, silicone bonded type) A copolymeric silicone resin containing hydrogen, a silicone-bonded alkenyl group, eg, one or more selected from the group consisting of vinyl, allyl and propenyl), or silanol, optionally a crosslinker or chain A silicone PSA is cured containing an extender and platinum or other noble metal hydrosilylation catalyst.

  In some embodiments, the adhesive layer can include that of a bioadhesive (BA). In some cases, BA exhibits good tack when adhered to a hydrated biomatrix / tissue. Non-limiting examples include blends of polyethylene glycol with slightly crosslinked polyacrylic acid and polymethacrylic acid and hydrophilic cellulose derivatives (40% -95%). In other embodiments, the adhesive layer can include various combinations of PSA and various hydrophilic BA polymer materials, so that the tissue region in contact with the adhesive layer can be secreted into the water or liquid that is secreted. Solubility varies. Hydrogels and hydrocolloids can also be blended to provide a gentler adhesive. Gel adhesives are an alternative to pressure sensitive adhesives and are gentle to the skin. Gel adhesives are weakly peeled off the skin, can be removed with little damage, and are typically wetted to remove the surface. Common gel adhesives include but are not limited to silicone gels and polyurethane gels. In some embodiments, a gel adhesive can be utilized to temporarily occlude the urethra and assist in urinary retention.

  In some embodiments, inactivation of the adhesive can be utilized to provide painless removal. For example, acrylic, polyurethane or rubber adhesives can be used in conjunction with the deactivation method. A deactivated adhesive can form a strong bond until removal. Using a trigger mechanism, the adhesive is made to lose its bond strength when removal is required. Various trigger mechanisms such as light sources, use of liquid solutions such as water or saline, or solvents such as dipropylene glycol methyl ether, isoparaffin C10-C11 or isopropyl alcohol. The use of microcapsules filled with oil can be utilized. Such materials can be included in the rupturable reservoir or other location of the device when removal is desired. Some examples are plant extracts, petroleum extracts and animal extracts. Plant extracts can include olive oil, safflower oil, cottonseed oil, peanut oil, soybean oil, castor oil, sesame oil, aloe vera and eucalyptus oil. Animal extracts can include fatty acids such as those present in emu oil. The petroleum extract can include white oil (petrol) and mineral oil. An example of white oil is a white oil USP skin protectant, which is a semi-solid mixture of hydrocarbons that can break down some adhesives, such as cyanoacrylic acid. Any of the above components or combinations thereof can act as a lubricant in addition to or instead of adhesive deactivation. In some embodiments, the device or device adhesive layer does not include a lubricant.

  In some embodiments, the adhesive (or the entire device or part thereof) may be biodegradable and / or bioabsorbable and initially has a very high bond strength and is relatively fast over time. Decomposes and dissolves spontaneously within the desired time, eg within about 24 hours, 18 hours, 12 hours, 10 hours, 8 hours, 6 hours, 5 hours, 4 hours, 3 hours, 2 hours or less And / or fall off the skin. One advantageous example is an adhesion that can be sprayed or otherwise applied to an area on the body of interest, such as a clitoral structure, without necessarily requiring the additional patch layer described above. It is an agent. Such an embodiment could also be beneficial in simplicity and cleanliness in that the patient does not need to touch the body directly. In some embodiments, an adhesive (such as a gel) can be contained in an applicator, such as a tube having a movable wall similar to a spray can or toothpaste tube. The applicator is an actuator configured to repeatedly dispense a consistent amount of adhesive sufficient to apply the desired mechanical stimulus to the clitoral structure each time the applicator is actuated (eg, lever, button or Triggers, etc.).

  In some embodiments, the device comprising the adhesive layer is water resistant or otherwise liquid resistant. In some cases, this may be beneficial in water sports, such as swimming active patients, and / or to prevent or reduce the likelihood of early detachment, such as during urination. In some embodiments, the adhesive and / or device is a biodegradable feature, for example, without the risk of clogging, such as the adhesive and / or device described above being inconspicuous and easily discarded, for example, in the toilet. It was possible to make it flow into water, and it seemed that the sewer pipe and the sewage treatment system had characteristics such as safety. In some embodiments, the device is not biodegradable or bioabsorbable. In some embodiments, about or less than about 20%, 15%, 10%, 5% of the total mass of the device comprises a non-biodegradable material.

  Biodegradable adhesives include, for example, natural biodegradable polymers such as collagen, atelocollagen, alkali solubilized collagen, gelatin, keratin, albumin, globulin, fibrinogen, glycosaminoglycan, chitin and chitosan, and derivatives thereof, and One or more biodegradable polymers may be included that may include / or synthetic biodegradable polymers including polyamino acids and polyalcohols, and derivatives thereof. The solvent that dissolves the biodegradable polymer may be, for example, distilled water, a buffer solution and / or an organic solvent. Examples of the organic solvent include dimethyl sulfoxide (DMSO), N, N-dimethylformamide (DMF), lactic acid, lactic acid oligomer, polyethylene glycol and / or polypropylene glycol.

In some embodiments, the adhesive is one, two or more polymer-type, elastomer-type microspheres (where the microspheres are at least one C ₄ -C ₁₄ alkyl (meth) acrylic acid monomer and For the polymerizable monomer starting material present in an amount of 0.1 to about 2 parts by weight per 100 parts by weight of the polymerizable monomer starting material. Initiator; polymer stabilizer in an amount of about 0.1 to about 3 parts by weight per 100 parts by weight of the microspheres; about 10 parts by weight, 5 parts by weight, 3 parts by weight, 2 parts by weight per 100 parts by weight of the microspheres; Parts by weight or less of surfactant; and to produce 20% to 99% or 30% to 98% of the heptane soluble portion of the microsphere It may include one or more partial amounts of chain transfer agent.

  In some embodiments, the adhesive may be either directly coated on the backing layer or formed as a separate layer and then laminated to the backing. The adhesive can be applied to the backing layer by various techniques including, for example, transfer methods, spray methods, screen printing, slot die coating, use of “kiss” rolls or reverse roll coating. In some cases, the adhesive assembly can be strongly bonded to the backing layer, and a primer is optionally used.

  In some migration techniques, an adhesive assembly can be formed from a solvent into a release layer having a heat resistant, insoluble, non-tacky surface, such as a silicone release coated carrier. It is passed through an oven to remove the solvent and, if necessary, the assembly is sprayed and cured. The backing layer can then be laminated to the assembly by pressing at the end of the oven line, and finally the release layer is peeled off. When the adhesive aggregate is applied by spraying, the volatile substances therein are flushed, and the aggregate is arranged on the backing layer in a streak pattern. The streak mass is fixed during the subsequent oven treatment, resulting in a very breathable coating.

  In some cases, in order to improve the adhesion of the adhesive layer to the backing, the following methods can be used before the coating or lamination step: corona discharge, plasma discharge, flame treatment, electron beam irradiation, It can be pretreated in one or more of ultraviolet radiation, acid etching or chemical priming. Such pretreatment can be performed with or without reactive chemical adhesion promoters such as hydroxyethyl acrylate or hydroxyethyl methacrylate or other low molecular weight reactive species.

  In some embodiments, the adhesive layer can also include additives such as tackifiers, plasticizers, antioxidants, process oils, stabilizers to increase shelf life, and the like. Agents added to stabilize the adhesive against the harmful effects of gamma sterilization include Irganox 1010, Irganox 1076, Irganox 245, Irganox 3052F, Irganox E201, Irganox B225, Ubiquinone, Tinuvin 662 and Tinuvin 662 and Tinuvin 662 It is not limited to them.

  In some embodiments, the adhesive layer further comprises a tackifier and / or a plasticizer. The plasticizer is selected for its biocompatibility and its ability to modify the compliance of the adhesive formulation and obtain other properties described herein. The plasticizer may be non-volatile and insoluble in water and in some cases shall not further absorb water or other bodily fluids. In some cases, the adhesive layer may be from about 5% to about 70% by weight plasticizer, and in some cases from about 15% to about 60% by weight plasticizer. In some embodiments, the plasticizer may be present in a range from about 25% to about 50% or from about 30% to about 40% by weight.

  Some examples of plasticizers that can be used include: triisodecyl trimellitate; tributyl trimellitate; tri-n-hexyl trimellitate; tris of branched and linear 1,2,4-benzenetricarboxylic acid n- (C7-11) alkyl ester; butyl benzoate; di-ethylhexyl phthalate; di-octyl phthalate; di-butyl phthalate; diethyl hexyl adipate; dibutyl adipate; triethyl citrate; tributyl citrate; acetyl triethyl citrate; -Butyl citrate; n-butyryl tri-n-hexyl citrate; triacetin; glycerin; caprylic / capric triglyceride; tricaprin; tricaprylin; propylene glycol dicaprate; Relate / dicaprate; poly (ethylene glycol) (PEG); hydrogenated vegetable oils; hardened seed oil; PEG dilaurate; PEG diethyl hexyloxy sulfonate (Diethylhexylonate); and combinations thereof.

  Some adhesive layers can further comprise up to about 5 wt%, 10 wt%, 20 wt%, 30 wt%, 40 wt%, 50 wt% or more of a tackifier. The tackifier can be selected from the group consisting of rosin esters, polymerized rosins, hydrogenated rosins, polyterpenes, styrenated terpenes, polymerized hydrocarbon resins, alphamethylstyrene, alphamethylstyrene phenolic resins, and combinations thereof. Some specific tackifiers include those marketed as Escorez 1310, Sylvares SA120, Sylvares TP105, Foral85 and Sylvares 540. Like plasticizers, tackifiers are biocompatible (ie, capable of safely contacting skin and / or body fluids) and compatible with adhesive (ie, ability to form a single phase with the adhesive). ) Is selected.

In some embodiments, the weight of the dry adhesive layer per surface area of the backing layer to which the adhesive is applied is from about 7 g / m ² to about 100 g / m ² , from about 14 g / m ² to about 55 g / m. ² , about 20 g / m ² to about 80 g / m ² , about 20 g / m ² to about 40 g / m ² , about 40 g / m ² to about 60 g / m ² , about 60 g / m ² to about 80 g / m ² , It can be in the range of about 80 g / m ² to about 100 g / m ² or their overlapping range.

  Regardless of the adhesive composition used, in some embodiments the final adhesive layer may be pressure sensitive, hydrophilic and non-allergenic (eg, latex free in some embodiments).

  In some embodiments, the adhesive layer has a thickness of about 25 micrometers to about 1000 micrometers, about 25 micrometers to about 50 micrometers, about 50 micrometers to about 400 micrometers, about 50 micrometers to It may be about 200 micrometers, about 100 micrometers to about 200 micrometers (eg, about 150 micrometers), or about 100 micrometers to about 300 micrometers. In some embodiments, the adhesive layer thickness is about 0.002 inches to about 0.010 inches, about 0.004 inches to about 0.008 inches, about 0.005 inches to about 0.007 inches. Or about 0.006 inches.

  In some embodiments, a device, such as a patch, can include a fragrance-releasing element, such as a perfume composition or polyethylene beads, configured to provide a pleasant olfactory scent. In some embodiments, the device may be completely or partially transparent, or may have various skin tones in harmony with surrounding body parts. In other embodiments, the device has a color or other visual or tactile indication (eg, a fluorescent material that illuminates in the absence of light) to contrast with surrounding body parts to aid in placement and / or removal. be able to.

  Patch 10 or other device can be applied directly to the clitoral region or other body structure shown with an adhesive layer. FIG. 5 is a sketch of the vagina showing several components of the vagina including the vaginal opening 18, the urethral opening 20, the small labia 22, the large labia 24, the clitoral foreskin 26 and the clitoris 28. In this embodiment, the patch 10 is applied only to the clitoral region by applying the patch 10 to the clitoral foreskin 26. Without being limited by theory, the adhesive layer 14 physically stimulates the clitoral nerve, exerts an inhibitory action on the bladder, and relieves urgency and frequent urination. In some embodiments, the device, such as a patch, preferably provides pressure, traction, friction, vibration or other stimulation to one or more clitoral structures. In some embodiments, the device, such as a patch, is machined into one or more clitoral structures rather than to any adjacent body structure, such as the large labia, labia, urethra, vagina, or pubis. It only gives a realistic stimulus. In some embodiments, the device, such as a patch, is about or at least about 10%, 25%, relative to adjacent non-clitoral body structures, such as any non-clitoral body structure disclosed herein, A force that is 50%, 100%, 150%, 200%, 250%, 300%, 400%, 500% or more is applied to the clitoral structure.

  FIG. 5A schematically illustrates in detail some parts of the female body, both internal and external. The clitoris 28 is a complex structure and includes both external and internal components. The clitoris 28 includes a non-erectating glans 280, a clitoral body or body 281 (both internal and external) and a clitoral or foreskin 26. Internally, the clitoris includes two erectile trunks known as clitoral caverns 282, two clitoral leg 283 and anterior chamber or clitoral bulb 284. A vaginal opening 18 and a urethral opening 20 are also shown. In one study, clitoral tissue has also been reported to extend inward toward the anterior wall of the vagina and localize from about 1 inch to about 3 inches of the anterior wall of the vagina between the vaginal opening 18 and the urethra 20. It is shown to include a graphenberg (“G”) spot (not shown). The clitoral glans head 280 typically has a width of about 0.098 inches to about 0.177 inches, and the total clitoral length including the tortoise head 280 and trunk 281 is typically about 0.63 inches ± About 0.17 inch. An adhesive layer configured to provide mechanical stimulation, eg, pressure, to a component of the device, eg, clitoral structure, has a length or width that matches that of the body structure described above, or about 50 %, 40%, 30%, 20%, 15%, 10%, within 5% or less.

  Without being limited by theory, clitoral innervation and perineal nerve vascular bundles are a pair of distal ends of the pudendal neurovascular bundle. The clitoral neurovascular bundle travels along the periosteum of the sciatic pubic branch from the other side close to the midline, intersecting the neurovascular bundle. When the legs are integrated into the clitoral trunk, the clitoral neurovascular bundle passes through the upper surface of the clitoral trunk. After some branching, the dorsal clitoral nerve transitions to the clitoral glans as an intact large nerve trunk. The perineal nerve vascular bundle is supplied to the urethra and spheroids. The cavernosal or autonomic anatomy is often microscopic and is supplied to the female urethral sphincter complex and the clitoris. The cavernous nerve branch joins the dorsal clitoral nerve at the portal part of the clitoral trunk. The cavernous nerve starts from the vagina plexus component of the pelvic plexus, moves to the 2 o'clock and 10 o'clock positions generally along the anterior vaginal wall, and then moves to the 5 o'clock and 7 o'clock positions along the urethra. . Any of the above components of the clitoris to neuromodulate any of the nerves listed herein to treat or prevent physical stimuli such as pressure, including but not limited to urinary incontinence. One, two or more can be added. To innervate inner clitoral structures to innervating nerves, mechanical stimuli, such as pressure, are applied to the anterior vaginal wall, thus the clitoral cavernous body, clitoral leg and anterior near the anterior vagina For example, a device can be inserted inside the vagina to stimulate the tuft or clitoral sphere. The device can take the form of a tampon or stent-like structure configured to provide mechanical stimulation, eg, pressure, to the anterior vaginal wall or e.g., vaginal extension of an intraurethral device.

  Without being limited by theory, the clitoris including the foreskin has a nerve pathway to the parasympathetic medial efferent and afferent fibers originating from the sacral central (S2-S4), and the thoracolumbar central (T10-T12 and / or Or T11-L2) to other pelvic structures such as bladder, urethra and rectum that may have neural pathways from sympathetic preganglionic afferents and medial efferent fibers that have similar innervation Can help to explain the beneficial effects of. The parasympathetic nervous system (PNS) excites detrusor muscles, suppresses urethral smooth muscles, and promotes urination through actions on cholinergic receptors in the bladder and urethra. T10-T12 prenodal sympathetic nerves are conduits of postnodal neurons that travel in the lower abdominal and synapses of adrenergic ganglia in the pelvic plexus. Through its action on beta-adrenergic receptors, the sympathetic nervous system (SNS) suppresses detrusor muscles, stimulates urethral smooth muscles through alpha-adrenergic receptors, and thus promotes urinary suppression.

  FIG. 5B illustrates that an embodiment of a clamp 300, such as a region of the clitoris, such as the clitoral foreskin 26 shown, is subjected to a mechanical stimulus, such as pressure, but not so much as to cause substantial discomfort to the patient. 1 schematically illustrates a small clothespin-like device having a fulcrum and a plurality of lever arms configured to provide. In some embodiments, a ring or band can be used in place of or in addition to clamp 300. In some embodiments, the clamping force may be about or about 300 mmHg, 250 mmHg, 200 mmHg, 150 mmHg, 125 mmHg, 100 mmHg, 80 mmHg, 60 mmHg, 40 mmHg, 30 mmHg, 20 mmHg, less than 10 mmHg or even less.

  FIG. 5C shows a suction cup 302 configured to apply a mechanical stimulus, such as pressure, to a region of the clitoris, such as the illustrated clitoral foreskin 26, but not so much as to cause great discomfort to the patient. An embodiment of is schematically illustrated. In some embodiments, the vacuum pressure is sufficient to maintain a seal on the desired clitoral structure and is about or approximately negative 300 mmHg, 250 mmHg, 200 mmHg, 150 mmHg, 125 mmHg, 100 mmHg, 80 mmHg, It may be less than 60 mmHg, 40 mmHg, 30 mmHg, 20 mmHg, 10 mmHg or even less.

  While a single patch 10 is shown in FIG. 1, a plurality of such patches can be packaged as a kit in actual manufacture and / or sale. In some embodiments, patches can be formed or placed on a single release sheet and packaged as a kit, whereby individual patches can be removed and applied as needed. FIGS. 6, 7 and 8 show an embodiment in which a dispenser 30 is provided containing a roll 32 of an array 34 of linearly arranged patches 36. Each roll 32 may include any number of patches, for example, about or at least about 5, 10, 20, 30, 40, 50, 100 or more patches 36. With particular reference to FIG. 8, the back side of three patches 36 of a linear patch array 34 is shown. The patch 36 is joined by a tear line 38 and has a paper tab or fabric tab 40 at each end. Each patch has a backing sheet 42 (FIG. 7) and an adhesive layer 44 (FIG. 9). The tab 40 is secured to the back side of the patch with an adhesive layer 44. The dispenser 30 can be placed in a housing such as a small case. The case can also include an antibacterial gel for mirror and hand wipe or hygiene purposes to assist the patient when placing the device. In some embodiments, the kit comprises a plurality of patches, housings, mirrors, instructions for placing the patches on the clitoral structure, and any combination of dispensers configured to dispense the patches individually. Can be included. Patches can be placed in a release layer in a roll configuration and separated by perforations as described above.

  In operation, the tab end of the patch extending from the slot 46 of the dispenser with the slot is grasped and pulled until the tab 40 of the next patch is momentarily stopped by the closure of the dispenser port 46. The removed patch is then moved away from the array along tear line 38.

  Referring to FIG. 9, a solid but flexible curve 48 is secured to the back of a backing sheet 50 having an adhesive layer 52 on the back of the patch carrying the solid 48 and a paper tab or fabric tab 54. A patch 47 is shown. The device of FIG. 9 can be carried as a linear array separated by a tear line, such as the patch 35 of FIGS. The separated patch is applied directly to the clitoral area of the entire foreskin, and physical pressure is applied to the clitoral area. Other shapes of the solid material can be provided, for example, in a spherical shape.

  Referring to FIG. 10, a panty 56 or other undergarment is applied to the clitoral area, for example, the entire foreskin, and applied with physical pressure thereon, such as by adhesive or sewing. 9 with a solid 58 that may be the solid 48 of FIG. In some embodiments, as illustrated in FIG. 11, the solid or patch 62 described and illustrated herein is operable on a sanitary napkin 60, such as a sanitary pad, tampon or diaper, etc. It can also be attached and can be configured to apply physical pressure to the clitoral region. In some embodiments, the solid may be a soft molded component, does not necessarily require an adhesive layer, can be easily slid between the labia and is in contact with the clitoris. be able to. Such an object can be held in place by the labia and for example in the patient's underwear.

  In some embodiments, the devices disclosed herein can be configured to apply mechanical pressure to the clitoris, such as a patch or the like for urethral insertion for the treatment or prevention of pathological conditions such as incontinence. It can be used in a synergistic combination with an object (for example, a plug). Non-limiting examples of female urethral inserts are described in US Pat. No. 5,090,424, Simon et al., Which is hereby incorporated by reference in its entirety. Another example is FemSoft ™ Insert, Rochester Medical Corp. (Stewartville, MN).

  In some embodiments, the modified urethral insert is operably coupled to a device configured to physically press against the clitoral region. FIG. 12A illustrates one embodiment of a modified urethral plug 310 that includes a clitoral component. The bellows 311 defines a void 321 and is used to transport the liquid 332 contained in the void 321 via a check valve 322 located in the metal plate 313. The extension from the plate 313 is a clitoral extension segment 350 configured to physically press against the clitoral region. In some embodiments, the clitoral extension segment 350 can be biased toward the body if it indicates more optimal pressing against the clitoral structure. In some embodiments, the clitoral extension segment 350 has an adhesive layer 352 (which can be shown as above in the patch embodiment) and reversibly adheres well and remains constant in the clitoral region. Includes a patch that applies The clitoral extension segment 350 can also include a suction cup, clamp, or other element as described herein for applying physical pressure to the clitoral region. In some embodiments, the clitoral extension segment 350 can extend from the body of the bellows 311 or plug 310 rather than from the plate 313.

  The bellows 311 can be made from a material that is conformable to the body and comfortable for the patient when the urethral plug is in place. The liquid 332 is transported to the gap 323 localized in the plug 310 and becomes the liquid 333. The wall of the plug 310 can have a relatively constant outer diameter to allow easy insertion of the device. However, the wall thickness varies from the metal plate 313 starting at location 314 to the proximal end 315 where the wall is thinnest and most expandable. The liquid 332 may be any liquid that can be moved back and forth from the gap 321 to the gap 323 through the check valve 322.

  As shown in FIG. 12B, the deflated urethral plug 310 is inserted into the patient's urethra 20. Insertion, as shown in FIG. 12C, the distal end expands preferentially into the space 342 behind the sphincter 343 and / or into the bladder neck or bladder so that the device 310 seals the urethra 20 As such, the patient moves the bellows 311 back and forth while the clitoral extension segment 350 applies physical pressure to the clitoral region, eg, the clitoral foreskin 26. For removal, the enlarged proximal end 315 contracts, thereby allowing the urethral plug 310 to be easily removed from the urethra 20 and the clitoral extension segment 350 as described herein. The patient slowly pulls out the bellows 311 so that it is separated from the body.

  The devices, such as patches, described herein allow for neuromodulation, such as stimulation, of those pathways in women suffering from visceral pelvic or somatic nerves or pelvic conditions of neuropathy. The systems and methods described herein can apply non-electrical, external physicomechanical stimuli, for example, to the clitoral region. Without being limited by theory, as described elsewhere herein, the physical stimuli described above can produce neuromodulation. The conditions that can be treated or prevented include: female frequent urination or urgency, overactive bladder, stress, urgency or mixed urinary incontinence, fecal incontinence including stool incontinence, constipation, interstitial cystitis or pelvic pain, Examples include, but are not limited to vulvar pain or endometriosis. In some embodiments, the systems and methods disclosed herein include pudendal nerves, cavernosal nerves, sacral nerves and their nerve branches (eg, inferior rectal nerve, perineum nerve, clitoral dorsal nerve and / or (Including the posterior labia nerve), and can affect the external urethral sphincter, the internal urethral sphincter, the detrusor, the external anal sphincter, the internal anal sphincter, and the like. In some embodiments, the devices disclosed herein provide sufficient mechanical force to produce neuromodulation to treat the above-listed conditions, such as incontinence, while at the same time e.g. It can be configured to cause no or substantially no female sexual arousal manifested as clitoral enlargement, vaginal lubrication and / or nipple erection.

  The devices disclosed herein can be applied at desired time intervals depending on the desired clinical outcome. For example, a patient can apply a device, such as a disposable patch, to a desired body area, such as daily, twice daily, three times daily, and after showering or bathing. In some embodiments, the device is placed on the desired body region for about or about 72 hours, 48 hours, 24 hours, 18 hours, 12 hours, 10 hours, 8 hours, 6 hours, 4 hours, 3 hours or Apply for 2 hours or less. In some embodiments, the device is applied during intense physical activity, normal daily activities and / or sleep.

  The following examples further illustrate non-limiting embodiments of the invention.

Example 1
Give the patient suffering female urinary incontinence the dispenser of Figure 6 and instruct along the thin line (for example perforation) to break the part containing the patch and apply it to the entire clitoral foreskin to treat or prevent urinary incontinence. Can be clothed. As long as urinary incontinence continues, new patches should be applied daily and after each shower or bath. The patch acts to stimulate the visceral pelvis or somatic nerve or the pelvic pathway to treat neurological disorders. There appear to be no adverse side effects.

Example 2
Following the procedure of Example 1, to stimulate visceral pelvic nerves or somatic nerves or pelvic pathways to treat neuropathy, the following conditions: frequent urination or urgency, overactive bladder, urinary retention, fecal incontinence, Any of constipation, interstitial cystitis or vulvodynia can be relieved. There appear to be no adverse side effects.

Example 3
Give a patch as shown in Fig. 6 to 8 to a patient suffering from female frequent urination or urgency, overactive bladder, urinary incontinence or urinary retention, fecal incontinence, constipation, interstitial cystitis or vulvovaginal pain. It can be supported to stick to the nuclear turtle head, body and / or foreskin. As long as urinary incontinence continues, new devices can be applied daily and after each shower or bath. In some embodiments, the device is water resistant and remains adhered after bathing. In some embodiments, the device acts to stimulate the visceral pelvic nerve or somatic nerve or pelvic pathway to treat a neurological disorder. There appear to be no adverse side effects.

Example 4
In one embodiment, a device (eg, a specialist's) is applied to a subject identified as having a pelvic disorder (eg, stress urinary incontinence) in a pelvic region (eg, one or more clitoral structures). Without interference), where the device includes one or more (or all) of the following features:

  (I) Adhesive.

  (Ii) The adhesive forms one, two or more layers and is configured to be suitable for application at least between the opposing folds of the large labia and spreads over the labia or only between the labia Is the size to be.

  (Iii) When the adhesive is removed from the clitoral structure, less than about 50%, 40%, 30%, 20%, 10% or less of the surface area of the adhesive covers the skin cells that have detached from the patient. Can be configured.

  (Iv) The device or adhesive can be configured to be detached from the patient's clitoral structure within about 24 hours, 18 hours, 12 hours, 10 hours, 8 hours, 6 hours or less.

  (V) The device or adhesive can be configured to partially or fully biodegrade within about 24 hours, 18 hours, 12 hours, 10 hours, 8 hours, 6 hours, or less.

(Vi) Range by weight of the adhesive layer is about 7 g / m ² ~ about 100 g / m ² per surface area of the patch (e.g., ^{7g / m 2 ~20g / m 2} , 20g / m 2 ~30g / m 2, 30g ^{/ m 2 ~40g / m 2,} 40g / m 2 ~50g / m 2, 50g / m 2 ~75g / m 2, 75g / m 2 ~100g / m 2, and their overlap region).

  (Vii) The adhesive layer has a surface area of about 1 square inch to about 2 square inches.

  (Viii) The adhesive contains an acrylic component and no silicone component.

  (Ix) the acrylic component comprises from about 50% to about 97% by weight acrylic polymer (eg 50% -60%, 60% -70%, 70% -80%, 80% -97%, and their overlapping ranges) ) And acrylic acid from about 3% to about 50% (e.g., 3% to 20%, 20% to 30%, 30% to 40%, 40% to 50%, and their overlapping ranges).

  (X) The acrylate is selected from the group consisting of isooctyl acrylate, 2-ethylhexyl acrylate, isononyl acrylate, decyl acrylate, dodecyl acrylate, butyl acrylate, hexyl acrylate, and mixtures thereof.

  (Xi) The adhesive contains a hydrocolloid component.

(Xii) Adhesive is about 400 g / m ² or more, 500 g / m ² or more, 600 g / m ² or more, 700 g / m ² or more, 800 g / m ² or more, 900 g / m ² or more, 1000 g / m ² or more per day. 1100 g / m ² or more, 1200 g / m ² or more, 1300 g / m ² or more, 1400 g / m ² or more, 1500 g / m ² or more, 2000 g / m ² or more, 2500 g / m ² or more, 3000 g / m ² or more, 3500 g / m ² or more, 4000 g / m ² or more, 4500 g / m ² or more, 5000 g / m ² or more, or more, or 1 day to about 3500 g / m ² ～5000G / m ^2, about 4000g / m ² ~4500g / m ² or MVTR, which can be about 4200 g / m ² .

  (Xiii) The device has a maximum length of about 0.5 inches to about 3 inches (e.g., 0.5 inches to 1 inch, 1 inch to 2 inches, 2 inches to 3 inches and overlapping ranges thereof), maximum width Is about 0.5 inches to about 2 inches wide (e.g., 0.5 inches to 1 inch, 1 inch to 1.5 inches, 1.5 inches to 2 inches, and their overlapping ranges), and / or Thickness of about 0.0001 inch to about 0.1 inch thickness (e.g. 0.0001 inch to 0.001 inch, 0.001 inch to 0.01 inch, 0.01 inch to 0.1 inch and the like) (Overlapping range).

  (Xiv) one or more clitoral structures wherein the support structure when applied is selected from the group consisting of one or more of the following: clitoral body part, clitoral foreskin and clitoral glans A contact surface configured to directly contact and adhere to the skin of the body.

  (Xv) when applied, the support structure is sufficient to neuromodulate one or more clitoral nerves, but provides one or more mechanical forces that do not produce sexual arousal. Configured to add to the clitoral structure.

  (Xvi) The support structure also further includes one or more features selected from the group consisting of a curved portion, a raised portion, a tab, and a malleable portion.

  (Xvii) The bends, ridges and / or malleable portions are configured to facilitate maintenance of mechanical forces on the one or more clitoral structures while the patient is stationary and / or active.

  (Xviii) the bend has about 10% to about 30% bend along the axis of the device.

  (Xix) The support structure includes a curved portion.

  (Xx) The raised portion surrounds the central portion of the contact surface of the support structure.

  (Xxi) the contact surface includes a ridge having a surface area and a non-bump having a surface area, the ridge having a surface area that is about 10% to about 100% of the surface area of the non-bump.

  (Xxii) the raised portion has a maximum thickness that is at least about 10% greater than the thickness of the non-raised portion of the device.

  (Xxiii) The tab contains no adhesive.

  (Xxiv) The malleable part is sufficiently malleable to stably deform from the first configuration to the second configuration, and the second configuration matches the shape of one or more clitoral structures To do.

  (Xxv) The device comprises a backing layer bonded to an adhesive layer, the backing layer comprising a flexible membrane material.

  (Xxvi) The device includes one or more recesses configured to apply a radial mechanical force to the clitoral structure.

  (Xxvii) The device includes one or more reinforcing members.

  (Xxviii) The reinforcing member includes a shape memory material.

  (Xxix) A reinforcing member extends around at least a portion of the periphery of the device.

Example 5
In one embodiment, only a formulation for application to a pelvic area (eg, one or more clitoral structures) is applied to a subject identified as having pelvic disorder (eg, stress or urge incontinence), Given in any of the formulations on the device (eg, without professional intervention), where the formulation includes one or more (or all) of the following features:

  (I) A biocompatible adhesive containing no silicone, sufficient for topical application to a clitoral structure.

  (Ii) the formulation is sufficient on a device sufficient to apply mechanical pressure or traction to the clitoral structure to neuromodulate one or more clitoral nerves below the level of sexual arousal; Quantity provided.

  (Iii) When the formulation is removed from the clitoral structure, about 50%, 40%, 30%, 20%, less than 10% or less of the surface area of the adhesive is covered with skin cells that have detached from the patient. Can be configured.

  (Iv) The formulation can be configured to be detached from the patient's clitoral structure within about 24 hours, 18 hours, 12 hours, 10 hours, 8 hours, 6 hours or less.

  (V) The formulation can be configured to partially or fully biodegrade within about 24 hours, 18 hours, 12 hours, 10 hours, 8 hours, 6 hours, or less.

  (Vi) The formulation contains an acrylic component and no silicone component.

  (Vii) the acrylic component comprises from about 50% to about 97% by weight acrylic polymer (eg, 50% -60%, 60% -70%, 70% -80%, 80% -97% and their overlapping ranges) And about 3% to 50% by weight of acrylic acid (eg 3% to 20%, 20% to 30%, 30% to 40%, 40% to 50% and their overlapping ranges).

  (Viii) The acrylate is selected from the group consisting of isooctyl acrylate, 2-ethylhexyl acrylate, isononyl acrylate, decyl acrylate, dodecyl acrylate, butyl acrylate, hexyl acrylate, and mixtures thereof.

  (Ix) The formulation includes a hydrocolloid component.

(X) The formulation is about 400 g / m ² or more, 500 g / m ² or more, 600 g / m ² or more, 700 g / m ² or more, 800 g / m ² or more, 900 g / m ² or more, 1000 g / m ² or more per day. 1100 g / m ² or more, 1200 g / m ² or more, 1300 g / m ² or more, 1400 g / m ² or more, 1500 g / m ² or more, 2000 g / m ² or more, 2500 g / m ² or more, 3000 g / m ² or more, 3500 g / m ² or more, 4000 g / m ² or more, 4500 g / m ² or more, 5000 g / m ² or more, or more, or 1 day to about 3500 g / m ² ～5000G / m ^2, about 4000g / m ² ~4500g / m ² or MVTR, which can be about 4200 g / m ² .

  (Xi) a prescription for female stress, urgency and / or mixed urinary incontinence, frequent urination, urgency, overactive bladder, interstitial cystitis, pelvic pain, vulvodynia or endometriosis Can be used to treat various pelvic conditions, including one or more, in which case the formulation is placed on a patch and the formulation is configured to facilitate adhesion and pressure to the clitoral area. The

  Certain features and aspects of the embodiments disclosed above can be variously combined or partially combined, and these combinations are considered to be within one or more of the scope of the present invention. Further, any particular feature, aspect, method, property, feature, quality, attribute, element, etc. disclosed herein in connection with certain embodiments may be It can be used in all embodiments. Therefore, it is to be understood that various features and aspects of the disclosed embodiments can be combined or replaced with one another to form various modes of the disclosed invention. Accordingly, it is intended that the scope of the invention disclosed herein is not limited to the specifically disclosed embodiments described above. Furthermore, while the invention is susceptible to various modifications and alternative forms, specific embodiments thereof are shown in the drawings and will be described in detail herein. However, the invention is not limited to the specific forms or methods of disclosure, but on the contrary, the invention is intended to cover all modifications and equivalents that fall within the spirit and scope of the various embodiments described and the appended claims. It should be understood to encompass products and alternatives. Any methods disclosed herein need not be performed in the order recited. Although the methods disclosed herein include some actions of the performer, they can also include any indication from a third party of these actions, either explicitly or implicitly. . For example, actions such as “place device on patient's clitoris” include “instruct to place device on patient's clitoris”. The scope disclosed herein encompasses any overlap, subranges and combinations thereof. Terms such as “maximum”, “at least”, “greater”, “less than”, “between” include the recited numbers. As used herein, numerical values preceded by terms such as “approximately”, “about”, and “substantially” include the recited numerical values (eg, about 10% = 10%) and are further desired It also represents an amount close to the amount of description that performs the function or obtains the desired result. For example, the terms “approximately”, “about” and “substantially” refer to less than 10%, less than 5%, less than 1%, less than 0.1% and 0.01% of the stated amount. It can refer to an amount that is within less than.

Claims (58)

A topical formulation for treating urinary incontinence,
Contains sufficient biocompatible adhesive for topical application to the clitoral structure,
The formulation is provided in a sufficient amount on a device sufficient to apply mechanical pressure or traction to the clitoral structure to stimulate one or more clitoral nerves below a level of sexual arousal;
Configured such that when the formulation is removed from the clitoral structure, less than about 20% of the surface area of the adhesive is covered with skin cells detached from the patient;
The formulation comprises an acrylate polymer adhesive comprising from about 80 wt% to about 97 wt% acrylate and from about 3 wt% to about 20 wt% acrylic acid;
A topical formulation wherein the formulation does not comprise a silicone adhesive.   The topical formulation of claim 1, wherein when the formulation is removed from the clitoral structure, less than about 10% of the surface area of the adhesive is covered with skin cells that have detached from the patient. object.   The topical formulation of claim 1 comprising from about 90% to about 97% by weight acrylic polymer and from about 3% to 10% by weight acrylic acid.   The acrylate is selected from the group consisting of isooctyl acrylate, 2-ethylhexyl acrylate, isononyl acrylate, decyl acrylate, dodecyl acrylate, butyl acrylate, hexyl acrylate, and mixtures thereof. 4. The topical formulation according to any one of 3.   4. A topical formulation according to any one of claims 1 to 3 for treating stress urinary incontinence.   4. A topical formulation according to any one of claims 1 to 3 for treating urge urinary incontinence. 4. The topical formulation according to any one of claims 1 to 3, wherein the formulation has a water vapor transmission rate of greater than about 4000 g / m < ² > per 24 hours when applied. A device for treating a pelvic condition in a female patient,
Including a support structure that is sized for application between opposing folds of the large labia and includes an adhesive layer configured to be suitable for this;
When applied, the support structure is directly on the skin of one or more clitoral structures selected from the group consisting of one or more of a clitoral body part, a clitoral foreskin, and a clitoral glans head. Having a contact surface configured to contact and adhere;
When applied, the support structure is sufficient to stimulate one or more clitoral nerves, but provides a mechanical force that does not produce sexual arousal, the one or more clitoral structures. Configured to add to the body,
An adhesive configured such that when the adhesive layer is removed from the clitoral structure, less than about 20% of the surface area of the adhesive is covered with skin cells that have detached from the patient;
The weight of the adhesive layer per surface area of the patch ranges from about 7 g / m ² to about 100 g / m ² ;
The support structure may have a maximum length of about 0.5 inches to about 3 inches, a maximum width of about 0.5 inches to about 2 inches, and a thickness of about 0.0001 inches to about 0.00. Has a thickness of 1 inch,
The support structure is
(A) a curved portion;
(B) a raised portion;
(C) a tab;
(D) the malleable part;
Further comprising one or more features selected from the group consisting of:
The bend, ridge and / or malleable portion are configured to facilitate maintenance of the mechanical force on the one or more clitoral structures while the patient is stationary and / or active. ,device.   The device of claim 8, wherein the support structure includes the curved portion.   The device of claim 9, wherein the curved portion has a curvature of about 10% to about 30% along the axis of the device.   The device of claim 8, wherein the support structure includes the ridge.   The device of claim 11, wherein the ridge surrounds a central portion of the contact surface of the support structure.   13. The contact surface of claim 11 or 12, wherein the contact surface includes the raised portion having a surface area and the non-raised portion having a surface area, the raised portion having a surface area that is about 10% to about 100% of the surface area of the non-raised portion. The device described.   13. A device according to claim 11 or 12, wherein the ridge has a maximum thickness that is at least about 10% greater than the thickness of a non-ridge of the device.   The device of claim 8, further comprising the tab.   The device of claim 15, wherein the tab does not include an adhesive.   The device of claim 8 further comprising the malleable portion.   The malleable part is malleable enough to stably deform from the first configuration to the second configuration, and the second configuration matches the shape of the one or more clitoral structures The device of claim 17.   16. When the adhesive is removed from a clitoral structure, less than about 10% of the surface area of the adhesive is configured to be covered with skin cells that have detached from a patient. The device according to any one of 17.   18. The device of any one of claims 8-12 or 15-17, wherein the adhesive is configured to separate from the patient's clitoral structure within about 24 hours.   18. The device of any one of claims 8-12 or 15-17, wherein the adhesive is configured to biodegrade within about 24 hours.   18. A device according to any one of claims 8-12 or 15-17, comprising a backing layer bonded to the adhesive layer, the backing layer comprising a flexible membrane material.   18. A device according to any one of claims 8-12 or 15-17, comprising one or more recesses configured to apply a radial mechanical force to the clitoral structure.   18. A device according to any one of claims 8-12 or 15-17, comprising one or more reinforcing members.   25. The device of claim 24, wherein the reinforcing member comprises a shape memory material.   25. The device of claim 24, wherein the reinforcing member extends around at least a portion of the periphery of the device.   18. The device of any one of claims 8-12 or 15-17, wherein the adhesive layer has a surface area of about 1 square inch to about 2 square inches.   The device according to any one of claims 8 to 12 or 15 to 17, wherein the adhesive contains an acrylic component and does not contain a silicone component.   30. The device of claim 28, wherein the acrylic component comprises from about 50% to about 98% by weight acrylic polymer and from about 2% to about 50% by weight acrylic acid.   The device of any one of claims 8-12 or 15-17, wherein the adhesive comprises a hydrocolloid component.   The device of any one of claims 8-12 or 15-17, wherein the adhesive comprises a silicone component.   24. The device of claim 22, further comprising an absorbent material that is bonded to the backing layer.   9. A system comprising a urethral plug comprising the device of claim 8 and a tubular body configured to fit within the urethra of the patient.   34. The system of claim 33, wherein the device is coupled to the urethral plug. A device for treating a pelvic condition in a female patient,
A size for applying to the clitoris or the clitoral foreskin, including an adhesive layer configured to be suitable for this,
The device is configured to apply sufficient physical pressure to the clitoris or the clitoral foreskin when applied to stimulate the clitoral nerve;
The adhesive layer comprises a pressure sensitive acrylic adhesive;
The device further comprising a tab that facilitates securing the device.   36. The device of claim 35, comprising a patch comprising a backing sheet that is operably bonded to the adhesive layer.   40. The device of claim 36, wherein the patch is approximately 1.5 inches long.   38. The device of claim 36, wherein the patch is approximately 1 and 1/16 inch wide.   39. A kit comprising a plurality of patches according to any one of claims 36 to 38 and a dispenser configured to dispense the patches individually.   39. A kit comprising a plurality of devices according to any one of claims 9 to 38, further comprising a dispenser and a housing.   41. The kit of claim 40 further comprising a mirror.   41. The kit of claim 40 further comprising an applicator.   The device is arranged linearly on a release sheet having a perforation between the devices, and is releasably bonded to the release sheet, and the release sheet is configured to form a roll, and the kit includes: 43. A kit according to any one of claims 40 to 42, further comprising a dispenser configured to receive the roll. A method of treating a patient's pelvic condition, comprising:
Applying to the one or more clitoral structures a device that is malleable enough to stably conform to the shape of the one or more clitoral structures;
At least a portion of the device from the first configuration to the shape of the one or more clitoral structures sufficient to apply mechanical pressure or traction to the one or more clitoral structures. Transforming to a matching second configuration;
Including
The applied mechanical pressure is sufficient to stimulate one or more clitoral nerves to treat a pelvic condition but not cause sexual arousal;
Applying the pressure for at least about 2 hours.   45. The method of claim 44, wherein the clitoral structure is selected from the group consisting of a clitoral body part, a clitoral foreskin and the clitoral glans.   46. A method according to claim 44 or 45, wherein the pressure is applied continuously.   47. The method of any one of claims 44 to 46, wherein the pressure is applied for at least about 4 hours.   45. The pelvic condition is selected from the group consisting of female frequent urination, urgency, overactive bladder, urinary incontinence, urinary retention, fecal incontinence, constipation, interstitial cystitis, vulvodynia and endometriosis. 48. A method according to any one of -47.   49. The method of any one of claims 44 to 48, wherein the pelvic condition comprises stress urinary incontinence.   Applying mechanical pressure to the one or more clitoral structures comprises applying a patch including an adhesive layer to the clitoral structure, the adhesive layer comprising the clitoral structure. 50. An adhesive according to any one of claims 44 to 49, comprising an adhesive configured such that when removed from the body, less than about 20% of the surface area of the adhesive is covered with skin cells that have detached from the patient. Method.   51. Any one of claims 44-50, wherein applying mechanical pressure to the one or more clitoral structures comprises securing a device relative to the one or more clitoral structures. The method according to item.   52. Any one of claims 44-51, wherein applying mechanical pressure to the one or more clitoral structures includes securing a clamp against the one or more clitoral structures. The method according to item.   53. A method according to any one of claims 44 to 52, wherein the device is carried by panties or other garments.   54. The method of any one of claims 44 to 53, further comprising inserting a urethral plug into the urethral orifice of the patient.   55. The method of any one of claims 44 to 54, wherein the mechanical pressure is sufficient to stimulate a nerve branch of the vulva nerve.   56. The method of claim 55, wherein the nerve branch of the pudendal nerve is a clitoral nerve.   57. A method according to any one of claims 44 to 56, wherein the mechanical pressure is sufficient to stimulate a cavernous nerve branch.   Use of a formulation according to any of claims 1 to 7 for treating female urinary incontinence, wherein the formulation is placed on a patch that facilitates adhesion and pressing to the clitoral area. Configured to use.