Patent Application
20240173574
All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
This invention relates generally to handheld ultrasound devices for use in the genital area for treating vulvovaginal atrophy.
Vulvovaginal atrophy is an inflammation of the vagina, vulva, and outer urinary tract due to thinning and shrinking of these tissues. Vulvovaginal atrophy also may cause a decrease in lubrication in the vulvovaginal area. As a result, women experiencing vulvovaginal atrophy may not only suffer from decreased sexual enjoyment and day-to-day discomfort due to the lack of lubrication in the vulvovaginal area, but also discomfort during urination and urinary incontinence.
Factors that are known to contribute to vulvovaginal atrophy include menopause, treatments for breast cancer including chemotherapy and for some women, breastfeeding. In all of these causes, a change in the estrogen hormone level is a major contributor to vulvovaginal atrophy.
Until recently, there were limited options for women suffering from vulvovaginal atrophy. Vaginal moisturizers and lubricants only offer temporary relief and often do not provide enough symptomatic relief. Hormone replacement products, either applied locally or systematically, may also be an option, but involve risk of adverse side effects associated with their use. For example, hormone replacement therapies have common side effects such as nausea, vomiting, bloating, weight changes, and in addition may increase the user's risk of certain cancers and cardiovascular events. Furthermore, these types of hormone-based treatments are not recommended for women with, or who are survivors of, breast, ovarian, or endometrial cancers, and are contraindicated for women with a history of stroke or myocardial infarction because of these risks.
More recently, the drug Osphena®, a selective estrogen-receptor modulator that acts on specific estrogen receptors but is not itself a hormone, has become available. Osphena is a daily pill approved for dyspareunia in postmenopausal women; however, the drug acts like estrogen in the body and is currently not recommended for survivors of breast, ovarian or endometrial cancer due to the risk of cancer recurrence. Furthermore, women taking Osphena have experienced varying effects on improving vaginal dryness and have even experienced adverse side effects such as puffiness and redness on various parts of their bodies, severe hot flashes, and weight gain to name a few.
Also recently introduced is the MonaLisa Touch® from DEKA Medical Lasers. This therapy uses a transvaginal, CO2 fractional laser to stimulate collagen production in the vaginal tissue over the course of three outpatient procedures. While early data from their first US clinical trial looks promising, the therapy has been slow to gain adoption because of its expense, invasive nature, and lack of multi-year safety data.
There is currently no safe, drug-free and highly effective FDA-approved solution for rejuvenating the thin, dry and inelastic vaginal tissue associated with vulvovaginal atrophy. The devices and methods of the invention described herein have been tested clinically and have shown compelling evidence of safety and efficacy as a treatment for vulvovaginal atrophy in both cancer survivors and pre-, peri-, and post-menopausal women.
In one aspect, a coupling pad for a handheld device for vulvovaginal rejuvenation is provided. The coupling pad comprises a first portion; and a second portion, wherein the second portion has a higher durometer than the first portion, wherein the coupling pad comprises attachment means to attach to an ultrasound energy source of the handheld device.
In some embodiments, the first portion and the second portion comprise a gel.
The first portion can comprise a rounded shape and be configured to engage tissue at or near the vulva and introitus.
In some embodiments, the second portion comprises the attachment means.
The second portion can comprise a magnetic attachment means.
In some embodiments, the second portion comprises one or more metal components configured for magnetic attachment to the handheld device.
In some embodiments, the first and second portions comprise agarose. In some embodiments, the second portion comprises at least 4 times as much agarose as the first portion. The first portion can comprise about 1-2% agarose. The second portion can comprise about 4-6% agarose.
In some embodiments, the second gel portion is shaped to be snap fit onto a face of the handheld device. The snap fit of the coupling pad and the handheld device comprises a first area and a second area, wherein a fit between the coupling pad and the handheld device is tighter in the first area than in the second area.
In some embodiments, the second portion forms a lip around a periphery of a top portion of the coupling pad. A depression formed by the lip can be shaped to receive a transducer face of the handheld device. The bottom surface of the depression can be convex or flat.
In some embodiments, the attachment means is configured to hold a surface of the coupling pad against a transducer face of the handheld device.
The attachment means can comprise foil or wire (e.g., a foil ring or wire ring).
In some embodiments, the coupling pad comprises foil or wire (e.g., a foil ring or wire ring). The foil or wire can be embedded within the coupling pad.
The coupling pad can comprise a convex device facing surface.
In another aspect, a system for vulvovaginal rejuvenation is provided. The system comprises a handheld ultrasound device comprising a handle and an ultrasound transducer; and a coupling pad configured for removable attachment to the ultrasound transducer and configured to engage tissue of the vulva and introitus, the coupling pad comprising a device surface configured to interface with the ultrasound device, wherein at least one of a surface of the ultrasound transducer, the device surface and any intervening surfaces comprises a convex shape.
In some embodiments, the surface of the ultrasound transducer comprises a convex shape. The device surface can comprise a convex shape. In some embodiments, a lens or cover on the surface of the ultrasound transducer comprises a convex shape.
In yet another aspect, a system of molds for forming a two-part coupling pad for use with a handheld ultrasound device is provided. The system comprises a first mold comprising a first rounded depression, the first rounded depression configured to form a rounded first component of the coupling pad configured to engage tissue; and a second mold comprising a first portion comprising a second rounded depression shaped to receive the molded first component from the first mold, the second rounded depression having a greater depth than the first rounded depression, a second portion comprising a central section configured to rest above the rounded depression and a surrounding section, the central section and the surrounding section defining a slot therebetween, the slot configured to form a lip component of the coupling pad.
In some embodiments, the slot is configured to extend around a periphery of the second rounded depression and positioned over the second rounded depression.
The central section can be configured to rest above the rounded depression such that a periphery of the second rounded depression is exposed around the central section.
In some embodiments, the second portion comprises one or more connecting members connecting the central section to the surrounding section.
The first rounded depression can comprise a protrusion extending from a bottom surface of the depression, the protrusion comprising a flat upper surface and configured to support a component to be embedded within the coupling pad. The protrusion can be configured to support a metal component used for magnetic attachment to the handheld ultrasound device. The protrusion can be configured to support a component to be embedded within the coupling pad.
In some embodiments, the central section comprises a bottom surface of a two part structure, the two part structure comprising a main structure and a removable inner structure. Removal of the inner structure can allow the two part structure to be removed after molding of the coupling pad. In some embodiments, the main structure comprises a feature configured to interact with a feature on the removable inner structure.
The central section can be shaped to correspond to a shape of a transducer face of the handheld ultrasound device.
In some embodiments, the central section comprises a lip around at least a portion of its periphery.
In a further aspect, a mold for forming a coupling pad is provided. The mold comprises a mold comprising a rounded depression; and an insertable mold member configured to be inserted into the rounded depression, the insertable mold member comprising an outer structure and a removable inner structure, the insertable mold member configured to correspond to a transducer face of the handheld ultrasound device and to form an opening in the coupling pad configured to be snap fit onto the transducer face.
In some embodiments, removal of the inner structure allows the insertable mold member to be removed after molding of the coupling pad.
The outer structure can comprise a feature configured to interact with a feature on the removable inner structure.
In some embodiments, the insertable mold member is shaped to correspond to a shape of a transducer face of the handheld ultrasound device. A cross sectional area of the insertable mold member can be shaped to be smaller than a shape of a transducer face of the handheld ultrasound device.
In some embodiments, removal of the inner structure causes a cross sectional area of the outer structure to decrease.
In another aspect, a coupling pad for a handheld device for vulvovaginal rejuvenation is provided. The coupling pad comprises a device surface configured to interface with an ultrasound transducer of the handheld device, the device surface comprising a convex surface; and a tissue engaging surface configured to engage tissue at or near the vulva and introitus, the tissue engaging surface comprising a rounded shape.
In some embodiments, the device surface is configured to interface with the ultrasound device through a cover or lens on the ultrasound device. The device surface can be configured to interface with an ultrasound transducer on the ultrasound device. In some embodiments, the device surface is configured to interface with a cover or lens on an ultrasound transducer on the ultrasound device.
A height of the convex surface can be less than about 3 mm.
In another aspect, a mold for manufacturing a coupling pad for a handheld device for vulvovaginal rejuvenation is provided. The mold comprises a first portion comprising a first depression comprising a flat surface, the first depression comprising a flat inner surface configured to mold a device facing surface of the coupling pad; a second portion comprising a second dome or rounded depression, an interior portion of the second dome or rounded depression configured to mold a dome-shaped or rounded tissue facing surface of the coupling pad; and a port positioned on a convex side of the second dome or rounded depression and configured to allow passage of liquid therethrough, wherein the second portion is configured to be positioned on top of the first portion such that a concave surface of the first depression is facing a concave surface of the second dome or rounded depression.
In some embodiments, the mold comprises a third portion configured to be positioned above the second portion and comprising features configured to interact with features of the first and second portions to hold the first, second, and third portions together in a proper position.
The first depression can be shaped to receive a support ring of the coupling pad around a periphery of the first depression.
In some embodiments, the first portion comprises a third depression for receiving a metal component configured to be positioned within the coupling pad.
In another aspect, a method of manufacturing a coupling pad for a handheld device for vulvovaginal rejuvenation is provided. The method comprises providing a first portion of a mold for forming a deformable portion of the coupling pad, the mold comprising a first depression comprising a flat surface, the first depression comprising a flat surface configured to mold a device facing surface of the coupling pad; and providing a second portion of a mold for forming a deformable portion of the coupling pad, the second portion comprising a second dome or rounded depression, an interior portion of the second dome or rounded depression configured to mold a dome-shaped or rounded tissue facing surface of the coupling pad, the second dome or rounded depression comprising a port configured to allow passage of liquid therethrough.
In some embodiments, the method comprises positioning the second portion on top of the first portion, such that the concave portion of the second dome or rounded depression is facing the concave portion of the first depression.
The method can comprise pouring liquid through the port after a first component of the coupling pad has at least partially hardened.
In some embodiments, the method comprises positioning the second portion over the first portion.
In yet another aspect, a coupling pad for use with a handheld device for vulvovaginal rejuvenation is provided. The coupling pad comprises a deformable pad comprising a convex upper surface for engaging tissue at or near the vulva or introitus; and a support ring comprising a ring of material and a central aperture, the support ring connected to and supporting the deformable pad which is positioned within the central aperture, the ring of material comprising one or more openings through which material of the deformable pad extends.
In some embodiments, the support ring comprises plastic.
The deformable pad can comprise a hydrogel.
In some embodiments, the support ring is configured to snap fit onto the handheld device. The snap fit can be configured to hold a lower surface of the coupling pad against a transducer face of the handheld device.
In some embodiments, the coupling pad has a thickness of 3-5 mm. The coupling pad can have a thickness of 4 mm.
In some embodiments, the coupling pad has an ovular cross sectional shape.
The coupling pad can have a length of about 35-45 mm.
The coupling pad can comprise a width of about 25-35 mm.
In some embodiments, the openings comprise any one or a combination of holes grooves, slits, and undercuts. One or more of the openings can extend partly through the ring of material. One or more of the openings can extend entirely through the ring of material.
The novel features of the invention are set forth with particularity in the claims that follow. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
The invention described herein provides devices and methods that may be used to promote rejuvenation of a women's vulvovaginal area. The term “vulvovaginal rejuvenation” used herein refers to improving the overall function of the vulvovaginal area that may have suffered from decrease in lubrication, loss of elasticity and resilience, and/or decreased blood flow. Thus, vulvovaginal rejuvenation can refer to any one or a combination of alleviating vaginal dryness, increasing vaginal lubrication, increasing elasticity and/or resilience, and increasing blood flow.
In general, the devices described herein are handheld ultrasound devices that provide ultrasound energy. Ultrasound energy is a form of energy that is created by vibrating or moving particles within a medium, where the medium in needed to conduct and propagate its energy. Ultrasound energy is defined by vibrations with a frequency greater than 20 kHz. As shown in
The energy delivery element 112 may include an acoustic coupler 114 or coupling pad and an attachment mechanism 116. Because the acoustic coupler 114 is intended to contact a user's tissue, it is deformable enough to be able to conform readily to the user's anatomy while still having enough structure such that it is able to maintain its overall shape. The acoustic coupler 114 may have a general size and shape that conforms to the female vulvovaginal region (i.e., vulva, labia majora, labia minora, and introitus). The acoustic coupler 114 may be formed of one or more compartments or one or more regions of material or combination of materials. A more detailed discussion on the types of materials useful in forming the acoustic coupler 114 may be found in the sections below. The acoustic coupler 114 may be permanently or releasably attached to the attachment mechanism 116. The acoustic coupler 114 and the attachment mechanism 116 may be mated through any suitable means not limited to hooks and loops, snaps, clasps, magnets, glue, stitching and so forth. The attachment mechanism 116 may be formed of one or more than one layer of semi-rigid material (e.g., foam, rubber) configured to maintain contact with the acoustic coupler 114. The attachment mechanism 116 is also configured to provide acoustic contact with the ultrasound energy source 102 in the device body 110. An example of this is found in
Variations on the handheld ultrasound device are shown in
The ultrasound energy source 102 may be a piezoelectric (PZT) ceramic or electromagnetic transducer and wave generator disposed within device 100 and in acoustic communication with the acoustic coupler 114 of energy delivery element 112. The PZT may be constructed from piezoelectric materials such as lead zirconate titanate, potassium niobate, sodium tungstate, etc. The transducer assembly may consist of either one or an array of piezo-ceramic ultrasound transducers. The transducer assembly may also be Capacitive Micro-machined Ultrasound Transducers (CMUT) to appropriately apply diffuse ultrasound or provide constructive ultrasound wave interference and focus the ultrasound energy to the target tissue and appropriate vascular bed. The target of the ultrasound energy (unfocused or focused) may be further tuned to cover the mucosal layers of the vaginal canal. In some instances, the ultrasound transducer may have an effective radiating area between 0.1 cm2 and 10 cm2. In some instances, the effective radiating area may follow the general outline of the outer female genitalia. In some embodiments, the ultrasound may be preferentially focused on the introitus and/or vestibule only, the bottom third of the vagina, the bottom half of the vagina, or cover the entire vaginal canal.
The energy delivery element 112 of the handheld ultrasound delivery device 100 is configured to engage tissue around the subject's vagina as well as the outer genitalia. As mentioned earlier, the energy delivery element 112 may include an acoustic coupler 114 or coupling pad that aids with delivering ultrasound energy to the tissue. The acoustic coupler 114 may be in the form of a preformed gel (e.g., polyethylene glycol-based polymer hydrogel, agar, pectin, carrageenan, etc.), malleable solid or porous pad (e.g., silicone rubber, low durometer polymer, fabrics or flexible foams) or acoustic conducting gel (e.g., ultrasound gel) or fluid-filled bag or compartments, wherein the fluid is water (e.g., deionized, distilled), oil (e.g., mineral), gel, gelatin or other sonolucent and biocompatible fluid. The bag or compartments may be constructed of silicone rubber, low durometer polymer such as poly tetra fluoroethylene (PTFE), Nylon, Latex, low or high density polyethylene (LDPE, HDPE), nitrile, polyisoprene, polyurethane, or urethane; a fabric or a natural (organic) material such as animal skin, agar, pectin of carrageenan. In some instances, acoustic coupler 114 may be biocompatible, non-allergenic, bacteriostatic, and/or antimicrobial. In general, the bag or compartment walls of the acoustic coupler 114 are approximately 0.001 mm to approximately 10 mm in thickness.
The acoustic medium within the acoustic coupler 114 or coupling pad is able to transmit, with minimal loss of acoustic power, ultrasonic energy from the surface of the ultrasonic energy transducer to the target tissue of one or more of the vaginal vestibule, vaginal canal, introitus, vulva, labia minora, labia majora, clitoris, or surrounding area to the genitalia (e.g., perineum, rectum, etc.). The acoustic coupler 114 may also function to collimate and/or focus ultrasonic energy from the ultrasonic energy transducer surface to specific targeted regions within the vaginal canal, introitus, vulva, and/or external genitalia regions. The malleability of the acoustic coupler 114 allows it to fill the spaces of air between the transducer and user's variably shaped genital tissues, but it does not extend beyond the introitus and hence does not penetrate the vaginal canal. In some embodiments, it may penetrate the vaginal canal. The acoustic coupler 114 may act as a safety feature by preventing the occurrence of hot spots from converging waves of incident and reflected ultrasound energy (i.e., standing waves), which may otherwise occur at the interface between the surface of the ultrasound transducer and the genital tissue. It may also prevent surface heating and pain due to inadequate coupling (acoustic impedance mismatch) between the device and the user's tissue. The acoustic coupler 114 may also control the feedback to an open- or closed-loop treatment and/or safety algorithm.
The acoustic coupler 114 or coupling pad may be covered with acoustic coupling gel where it interfaces with the person's tissue, which will most often be the vulva and/or introitus. The gel layer may be pre-applied to the acoustic coupler 114 at the time of manufacture and require the removal of a covering strip or protective, containing layer upon use. The gel layer may also be applied by the user at time of use.
The acoustic coupler 114 or coupling pad may be convex in its profile and elliptical, ovoid or otherwise shaped for roughly conforming to the shape of the vulva and introitus of the vagina (
The acoustic coupler 114 may be reusable and capable of being disinfected after use. Alternatively, the acoustic coupler 114 or coupling pad may be disposable and discarded after each individual use or several uses of the device.
In the case where only the acoustic coupler 114 portion of the energy delivery element 112 may be disposable, the energy delivery element 112 may be attached to the device body 110 in a multitude of ways. The coupling mechanism may include, but is not limited, to an open slot feature whereby the acoustic coupler 114 may slide into place (e.g., as shown in
The relative orientation of the ultrasound energy source 102 and the energy delivery element 112 may be achieved using couplers 118 that mate between the ultrasound energy source 102 and the attachment mechanism 116 (see
As mentioned above, the device has features that provide feedback to the user to inform whether or not contact between the transducer face and the coupling pad or the contact between the coupling pad and the user's tissue is non-optimal (for safety to the user, for the integrity of the device, and for efficacy of treatment). These feedback mechanisms include simple feature locks that may provide “snap” sounds to inform the user the part is seated; pressure, impedance or other sensors between the transducer and the coupling pad that provide direct feedback to the user; or alarms (e.g., vibrating alarm) on the ultrasound generator that are based on sensor feedback. Such feedback can reflect inadequate and/or unsafe coupling between the transducer and the acoustic coupler 114, or inadequate and/or unsafe coupling between the acoustic coupler 114 and the user's tissue. The device may have a closed-loop algorithm to automatically shut off ultrasound delivery if unsafe coupling has been detected for a period of time.
The feedback may be based on reflected ultrasound energy or on some other parameter, such as tissue temperature measured by a temperature sensor. The contact feedback information can be displayed to assist in adjustment of the acoustic coupler 114 to the user's tissue or the attachment mechanism 116 to the device body 110. This display may include blinking lights of different colors similar to a tuning instrument, audible cues, mechanical/vibratory cues, and so forth. The surface-to-surface contact between the transducer face and the acoustic coupler 114, and/or the interface between the acoustic coupler 114 and the user's anatomy may be adjusted just before and/or during ultrasound treatment administration to maintain good acoustic coupling between the surfaces. This adjustment can be achieved by spring-loaded features, magnetic or mechanical snap fits, elastic materials (e.g., silicone or elastic bands) that wrap around the back of the transducer, adhesives, or visual, audio, or other types of cues to alert the user to move the device slightly and/or apply more force herself.
In some instances, the handheld ultrasound device may have several sensors embedded within the acoustic coupler 114 that allows for measurement of various physiologic parameters. Physiological parameters may include mucosal/dermal blood flow, possibly measured with Doppler ultrasound, Doppler laser imaging, temperature measurement (thermometer), infrared imaging, thermography, or photoplethysmography. Parameters may include vaginal lubrication measured for example utilizing humidity sensors, absorbent materials, or other methods for detecting lubrication and/or secretion. Parameters may include tissue temperature, measured for example utilizing thermometers or thermocouples, or other methods for detecting temperature changes. Additional physiologic parameters relating to vulvovaginal health and sexual function may also be measured utilizing the appropriate sensor setup. Parameters may include tissue impedance and other various markers of vulvovaginal tissue health such as: tissue elasticity, type and amount of vulvovaginal fluid present, vulvovaginal pH, friability of vulvovaginal mucosa, amount of vaginal moisture present, degree of inflammation present, and percentage of parabasal, intermediate, and/or superficial squamous cell types present in the vulvovaginal epithelium. Parameters may also include cellular calcium uptake, cellular activity and metabolism, protein synthesis by fibroblasts, collagen synthesis and deposition, cell proliferation, cell degranulation, synthesis of non-collagenous protein (NCP), production and signaling of Vascular Endothelial Growth Factor (VEGF), formation of endothelial cells, release of endothelial growth factors, angiogenesis, release of angiogenesis-related chemokines or cytokines (e.g., Interleukin 8, IL-8, or basic Fibroblast Growth Factor, bFGF, or TNF-alpha). The parameters measured may also include biomarkers of negative side effects of ultrasound treatment, such as markers of inflammation and histamine production.
The sensors embedded within the device may allow for closed-loop feedback control of ultrasound application, as shown by the flow chart shown in
In one example, vulvar tissue temperature may be measured by a sensor in the coupling pad. If the temperature rises to a level that could potentially cause damage to the user, the feedback loop automatically adjusts the energy delivery parameters or turns off the energy delivery altogether. In another example, the device increases energy delivery if the temperature of the user's vaginal or external genitalia tissue is not high enough. In another example, the device measures physiologic outcome parameters (e.g., vaginal blood flow and/or lubrication) and automatically increases or decreases ultrasound delivery to achieve the desired outcome (e.g., more or less vaginal blood flow and/or lubrication). In another example, the device may monitor for adverse treatment effects and automatically titrates the ultrasound energy delivery to minimize side effects while still achieving the desired treatment outcome.
In general, the handle 120 allows the user to comfortably position and maintain the ultrasound device against her vaginal or external genitalia tissue. In some variations, the handle 120 of the handheld ultrasound device may also include a variety of components. In some instances, the handle 120 may include an ultrasonic wave generator, an ultrasound transducer, accompanying electronics, or any combination of these elements inside. Alternatively, the handle 120 may merely support the structure that generates and delivers ultrasound treatment, but lacks any other parts required for ultrasound generation and ultrasound treatment administration. In the latter case, the handle would physically connect to the ultrasound transducer, and also be connected via a cord or wirelessly to another device that houses the electronics needed to supply the power and generate the ultrasound energy through the ultrasound transducer. In yet other examples, the handle may include a display for showing various parameters such as session time, adequate/inadequate contact, and so forth.
The handheld ultrasound device may also include a power source that is rechargeable and can be recharged with an external recharging station, or that is disposable and consists of replaceable lithium-ion or other sources of direct current (i.e., batteries). The device may also be powered by alternating current from an external source (e.g., an electrical outlet). Where the device is rechargeable, the recharging station may physically couple to the ultrasound handle. A portable recharging component may be coupled to the handle through corresponding geometric features on the handle and the recharging component. (
The device body 110 of the handheld ultrasound device may be any suitable size and shape. In some instances, the device body 110 may be elliptical in shape (
In general, the handheld ultrasound device may be used at home or in a clinical setting. If used at home, the user may be able to apply the ultrasound treatment herself. The device may be designed in such a way to be conducive to one-hand self-application (
The methods for using the handheld ultrasound devices described herein may be used to improve vulvovaginal and vulvar tissue health. A device of the invention may be used on an as-needed basis, for example, prior to sexual intercourse to increase blood-flow and induce lubrication. The overall health of the vaginal and vulvar tissue may be improved by use of the device multiple (more than one), times a day, daily, weekly, multiple (two, three, four, five, or more than five) times a week, or monthly as a periodic treatment. The actual length of time for each session may be on the order of seconds to tens of minutes. In practice, the ultrasound sessions may be a few minutes to ten minutes. During such sessions, increases in blood flow to vulvovaginal tissue and vulvovaginal lubrication may be measurable. In some aspects of the invention, the device may be used a single time prior to a sexual encounter. In other aspects of the invention, the device may be used repeatedly unrelated to sexual activity. In both regimens, periodic use may revitalize vulvovaginal lubrication and/or tissue and improve vulvovaginal health.
In other instances, methods for using the handheld ultrasound devices may be used as a preventative measure. The output from the handheld ultrasound device may improve mucosal vascularity, restore tissue elasticity, promote angiogenesis, encourage collagen growth/regrowth, improve muscle tone, promote the repair of soft tissue, and/or to increase constitutive lubrication.
The devices and methods described herein for rejuvenating the user's vulvovaginal area and external genitalia may be used in the privacy of her own home although application of the ultrasound therapy may also be performed in a medical office setting.
In general, the handheld ultrasound devices described herein may be placed external to the vagina and locally apply ultrasound energy to all or a portion of the vaginal vestibule, vaginal canal, introitus, vulva, labia minora, labia majora, clitoris, or surrounding area to the genitalia (e.g., perineum, rectum, etc.) as shown in
In general, the devices described herein are configured to provide ultrasound energy. While typically ultrasound energy may range anywhere between 20 kHz and 20 MHz, the ultrasound energy delivered from the handheld ultrasound device is approximately between 80 kHz and 3 MHz. At the range of 1 MHz and 3 MHz, optimal energy deposition occurs at more shallow tissue depths. In some instances, the user may vary the handheld ultrasound device's output for optimal energy deposition at more shallow tissue depths. The device may include features that provide for optimal energy deposition to all or a portion of the vaginal vestibule, vaginal canal, introitus, vulva, labia minora, labia majora, clitoris, or surrounding area to the genitalia (e.g., perineum, rectum, etc.).
In some instances, the ultrasound energy may be delivered at an intensity range of 0.1 W/cm2 to 5.0 W/cm2. More practically, the handheld ultrasound device is adapted to provide ultrasound intensity between approximately 0.25 W/cm2 to approximately 2.5 W/cm2. The intensity of the ultrasound energy is the acoustic ultrasound power over the area of the transducer.
The ultrasound output from the handheld devices may increase the temperature of the tissue being treated. In some instances, the ultrasound output may be designed to heat tissue to a minimum of 37° C., but no greater than 44° C., so as not to cause damage to the target or surrounding tissue. The increase in temperature from 37° C. to its upper limit may be increased stepwise or ramped up in a continuous fashion. Where the duty cycle of the ultrasound output is less than 100%, the increase in temperature may be coordinated with when the ultrasound beam is on or off. In other instances, the ultrasound output may be designed not to heat the tissue at all above the average core body temperature of 37° C. in order to induce only non-thermal effects in the tissue from ultrasound.
In some instances, the handheld ultrasound device may include an automatic duty cycle adjustment feature. The automatic duty cycle feature may be an open-loop (requiring action by the user) or closed-loop (not requiring action by the user) treatment algorithm. An automatic duty cycle adjustment feature is useful to ensure appropriate overall energy delivery to the tissue while maintaining user safety thereby providing optimal treatment for desired outcome. In some examples, the device may be highly customizable by the user to modify the treatment (e.g., delivery method, duration, and quantity of ultrasonic energy delivered to the vulvovaginal or surrounding tissue).
The handheld ultrasound device may have a duty cycle of anywhere between 20% and 100%. The term duty cycle refers to the percentage of time that a pulsed ultrasound wave is on (e.g., a 50% duty cycle means that a pulsed wave is on 50% of the time). At a duty cycle of 100% (also called a continuous duty cycle), the pulsed wave is on 100% of the time. The intensity and duty cycle can either be individually set for each treatment or set once for all subsequent treatments. In some embodiments, the intensity and duty cycle can be set by a trained physician, the user, or an advocate for the user. The intensity and duty cycle may be automatically set as a feature pre-programmed into the device and may or may not change. In some embodiments, the intensity and duty cycle settings are changed based on previous treatment duration and results.
The methods disclosed herein for using the handheld ultrasound devices may improve one or more indicators of vulvovaginal tissue health including: elasticity, type and amount of vaginal fluid present at rest (unaroused state), type and amount of vaginal fluid present during arousal, vaginal pH, friability of vaginal mucosa, amount of vaginal moisture present, and degree of inflammation. In some instances, the amount of vaginal fluid may also be measured during an aroused state. These parameters may be measured by the Vaginal Health Index (VHI) (e.g., by trained observer, by computer imaging). The device may also improve the distribution of cell types present in the vaginal epithelium, as measured by the Vaginal Maturation Index (VMI) and reflective of the maturity and health of the vaginal epithelium. The cell types measured in this index are parabasal, intermediate, and superficial squamous cells. The methods and devices of the invention may improve the distribution of each of these types of epithelial cells towards a healthier tissue state.
More specifically, the methods associated with the handheld ultrasound devices may result in one or more of the following effects on vulvovaginal tissue: increase cellular calcium uptake, increase cellular activity, increase cell metabolism, increase protein synthesis by fibroblasts, promote collagen synthesis and deposition, promote cell proliferation, promote cell degranulation, increase synthesis of non-collagenous protein (NCP), increase production and signaling of Vascular Endothelial Growth Factor (VEGF), stimulate the formation of endothelial cells, stimulate the release of endothelial growth factors, promote angiogenesis, increase in angiogenesis-related chemokines or cytokines (e.g., Interleukin 8, IL-8, or basic Fibroblast Growth Factor, bFGF, or TNF-alpha).
A study was conducted with 9 subjects to evaluate the ultrasound devices and methods of the invention. The results indicate that there is a local increase in blood flow and temperature, as described in PCT Publication No. WO2015/116512, expressly incorporated by reference herein.
As described herein, the acoustic coupler or coupling pad is a sonolucent, deformable gel pad that physiologically conforms to the introitus (vaginal opening) and surrounding structures while gently ensuring consistent, safe therapy delivery. In order to ensure safe and effective energy delivery to the appropriate anatomical target, the coupling pad has several performance goals. First, it should ensure solid contact between the ultrasound device and the user's tissue to encourage loss-free ultrasound energy transmission. Second, to achieve intimate, consistent contact with a variety of anatomies, the coupling pad should be deformable. Finally, to maintain safety, the coupling pad can prevent burns by serving as a buffer between the ultrasound transducer and the user's skin.
To determine the ideal coupling pad design, three inter-related parameters were examined: 1) material, 2) size and shape (“Contour”), and 3) overall acoustic properties. Desired coupling pad characteristics were considered both from the perspectives of technical performance and commercialization. From a performance standpoint, the coupling pad should conform comfortably to the anatomy of the patient at the treatment site (introitus), be biocompatible with a mucosal membrane, minimize energy attenuation in order to maximize therapy delivery, and avoid unintended and unsafe beam focusing. From a commercialization standpoint, the coupling pad should be simple and cost-effective when manufactured at scale. The results of this research are summarized here.
Material selection has the largest effect on therapy efficacy and manufacturing costs and thus was investigated first. Based on experience, observation, and preliminary literature research, four candidate materials were selected based on their lubricity and sonolucent profiles. Lubricity can be key to maximizing energy delivery, as it decreases the acoustical impedance at the tissue interface by minimizing air gaps between the ultrasound device and the user's tissue. The candidate materials were either self-lubricating (hydrogels and agarose) or could easily be lubricated in a secondary manufacturing step (e.g. coated silicone rubber).
Sonolucence is also important to maximize energy delivery, and these materials were selected because they are similar to water (an ideal ultrasound coupling medium). The inventors have found that water as a coupling medium has demonstrated increases in vaginal blood flow and lubrication.
The four candidate materials were scored across five categories: Deformability, Cost of Materials, Biocompatibility, Manufacturability, and (degree of) Ultrasound Attenuation. These categories were weighted based on relative importance, and a total score was calculated to determine which candidate materials should be carried forward for the next stage of testing. Results are presented in the Decision Matrix in Table 1. Agarose and Silicone Rubber were found to be the two best materials. However, as described above and herein, other materials may also be used, in some embodiments.
Silicone and agarose were researched in further detail to determine the specific formulations that would meet the coupling pad performance goals of: 1) minimizing ultrasound attenuation, 2) having a high tear strength (durability), and 3) being non-sticky.
A range of silicone durometers were explored. Since silicone is not naturally lubricious, high deformability could be used to meet performance goal #1. Higher durometer silicones (Shore Hardness 30A and higher) were tested but did not deform to the female anatomy in some embodiments. Very low durometer silicones (Shore Hardness 00-20) demonstrated better deformation, but did not meet performance goal #3, as they stuck to hair and skin in initial testing. Silicone with a Shore 10A Hardness provided the right trade off between deformability, durability, and tackiness. It was selected as an optimal formulation.
Agarose concentrations of 0.5% to 5% (mass/volume of water) were examined. Agarose is naturally lubricious, and the lower the agarose concentration, the more lubricious the contact surface. Thus all concentrations explored met performance goal #1 and 3; however, the lower agarose concentrations did not meet performance goal #2 in some embodiments. The 2% agarose optimized the performance goals. While 2% agarose was found to be a preferred material, note that other concentrations of agarose (e.g., 0.5%-5%) can also be used.
Wattmeter tests were conducted to compare the ultrasound transmission characteristics of the selected silicone and agarose formulations. A Wattmeter was used to measure and compare the total acoustic power output through the two candidate materials. Materials with poor ultrasound conduction (high attenuation) will produce lower power output. For testing, each material was placed over a commercially available ultrasound transducer set to a fixed output (Intelect TranSport®, Chattanooga, with settings: 1 MHz, 0.8 W/cm2, 20% duty cycle).
Shore 10A silicone and 2% agarose were tested, and benchmarked against a bare ultrasound transducer (“No Coupling”) as well as a commercially available, ultrasound stand-off (AquaFlex® Ultrasound Gel Pad, Parker Laboratories, Inc.). The Aquaflex pads are specifically designed for use with therapeutic ultrasound and are currently being used by in a long-term (chronic) clinical trial. Wattmeter test results are listed in Table 2. Each material (including “No Coupling”) was measured 3 times and averaged.
Based on the wattmeter testing, it was clear that Shore 10A silicone attenuates ultrasound energy, while 2% agarose did not appear to attenuate ultrasound energy.
The final contour determines the level of conformance to the anatomy as well as the ultrasound beam shape and efficacy.
The size of the contour can be key to ensuring the device will be placed correctly by the user and the therapy will reach the appropriate tissue. The target area of contact is the vaginal opening (introitus) and immediately surrounding tissue. Contact should be avoided with non-target, nearby tissue including: the clitoris, urethra, and anus.
Appropriate contour sizes were determined based on the typical range of vulva measurements. The mean labia minora width is reported as 20 mm on each side, and the mean length from the bottom of the urethra to the start of the perineum is 22-32 mm. [Lloyd 2005, Cao 2014]. Based on these measurements and initial testing with healthy volunteers, the base of the contour was designed to be 27 mm wide and 36 mm long. The contour was also given a taper to its top surface to fit well between the labia minora in a variety of women.
In order to determine the ideal contour, four prototypes were modeled and fit tested on four healthy volunteers (
The volunteers were given all four contours, instructed on proper placement, and were asked to report feedback based on comfort and ease of placement. The contours were ranked 1 to 4 (1=best, 4=worst) by each volunteer, and the average results are presented in Table 3.
All volunteers found the Oval Nub and Dome to be more comfortable than the Round Nub and Ridge. They also all considered the Ridge to be the least intuitive to place in the correct position. While the oval nub and dome were found to be more comfortable than the round nub and ridge contour shapes, the round nub and ridge contour shapes can be used, in some embodiments.
Contour prototypes were made from both Shore 10A silicone and 2% agarose in the three remaining Contour shapes with varying heights. These shapes and materials were again tested with four healthy volunteers for fit feedback. Bench testing was also completed with an anatomical model to visually examine the contact locations and level of conformance provided by each Contour prototype.
In addition, two independent gynecologists who regularly treat women with VVA were asked to evaluate the shape-height prototypes. Both physicians validated the volunteers' results, confirming that the prototype contours would conform well to a variety of female anatomies.
The top three shape-height combinations from the healthy volunteers' feedback were selected for further testing.
The coupling pad contours were tested by 7 post-menopausal women, 5 of whom were currently experiencing vulvovaginal dryness. As shown in Table 4 below, the short dome 1202 was reported to be the most comfortable contour.
The coupling pad allows ultrasound energy to pass through it without either (or only minimally) defocusing the beam (dispersing the energy) or inappropriately focusing the energy in an undesired location. Ultrasound pressure field maps (or Schlieren images) were recorded to examine how the prototype coupling pads affected the overall ultrasound beam profile at the desired ultrasound settings (1 MHz, 1.5 W/cm2 and 50% duty cycle) (see below for details on how ultrasound settings were determined).
Schlieren images were recorded using an OptiSon scanner (Onda Corporation, Sunnyvale, CA). The contours from
The images in
The Schlieren images shown in
As with
Hydrophone testing (AIMS III Hydrophone, Onda Corporation, Sunnyvale, CA) was conducted on a coupling pad design comprising 2% agarose and a flat top contour to gain a detailed understanding of the ultrasound field. The results are displayed as an intensity color map in
Hydrophone testing demonstrated that the ultrasound intensity is highest 40-60 mm from the transducer face (outlined in black), which aligns well with the vulvovaginal tissue target of the therapy. To find the exact location of maximum intensity, the hydrophone data was integrated over a 1 mm-wide cross section of the beam and plotted as a function of axial distance from the transducer face, as shown in
The data collected up to this point was collected with an off-the-shelf ultrasound transducer (Intelect TranSport, Chattanooga). Thus, the data need to be scaled to fit the current ultrasound device characteristics. The only difference between the off-the-shelf system and the current ultrasound device is the transducer head size (25 vs 20 mm diameter, respectively). Therefore, numerical simulations were performed with a 20 mm ultrasound transducer to determine the location and value of maximum acoustic intensity with this transducer size.
Matlab code (HIFU Simulator v1.2, Joshua Soneson, 2011) that simulates the acoustic intensity variations in different media was used for the numerical simulation. This code works by integrating the KZK-equation, which describes nonlinear wave propagation. The code was configured to run at the desired ultrasound settings (1 MHz, 1.5 W/cm2 and 50% duty cycle) with the incident ultrasound beam passing through two adjacent media to simulate the coupling pad and the vulvovaginal tissue. Both media were modeled as water because the body and 2% agarose are mostly water. To validate the code, coefficients were adjusted until the results with a 25 mm transducer head matched the experimental hydrophone data collected above.
There are four parameters that constitute the ultrasound settings. These are: treatment duration (in minutes), ultrasound frequency (in MHz), duty cycle (in % on-time) and acoustic intensity (in Watts/cm2). These settings have been informed by literature review, clinical studies, numerical simulation, and bench testing.
Treatment duration was initially set to about 5-10 minutes or about 8 minutes, based on literature review demonstrating 5-10 minutes of ultrasound could have a profound impact on tissue blood-flow. [Baker and Bell, 1991, Dalecki, 2004] Further, clinical work has demonstrated this is a sufficient length of time to promote increases in vaginal blood-flow. This duration also meets therapy use requirements (generated through prospective user interviews) to balance benefit and total time required in order to promote user compliance.
The frequency of the ultrasound waveform delivered by the device can be about 0.5-2 MHz, or about 1 MHz, as this frequency has been shown in the literature to penetrate tissue to a depth of 3-5 cm before attenuation.
Duty cycle is the proportion of “on-time” of the ultrasound signal. (For example, a duty cycle of 50% means the ultrasound is pulsed and ‘on’ only 50% of the time.) According to the literature, pulsed ultrasound therapy (i.e. duty cycles of 20% and 50%) may have a greater effect on tissue healing than continuous wave ultrasound (duty cycle=100%), as a duty cycle less than 100% may heighten the non-thermal biological effects.
Literature review was used to determine initial ultrasound intensities. The goal of the ultrasound therapy is to increase local vaginal blood flow 3-5 cm deep in the vaginal canal. Thus, the initial intensities to be tested were chosen based on those shown to increase blood flow at tissue depths greater than 3 cm. The acoustic intensity has been the primary parameter of interest in bench and clinical work to date.
A series of bench-top experiments on tissue surrogates were run using three candidate acoustic intensities of 1.5, 2.0 and 2.2 W/cm2 to observe the overall tissue temperature rise expected. The female pelvic floor tissue (including the vaginal wall tissue) is heterogeneous (predominantly composed of muscle and fat), as is the orientation of the substructure (degree of anisotropy) of each tissue component. As a rough proxy for the overall tissue response (i.e. heating), notably without the effects of blood flow that would normally be found in perfused tissue, excised pig (TS1, shown in
The tissue was cut to an appropriate size to represent the vaginal opening (shown in
The results of these tests are depicted in
As with the ultrasound settings, the transducer configuration for the ultrasound therapy has been influenced by previous and ongoing clinical studies. Efficacy of the chosen transducer to create the desired therapeutic effect was paramount, but business considerations regarding the price of different types of transducers (e.g. curved versus flat) were also considered.
The shape of the ultrasound transducer dictates the form of the emitted ultrasound beam, and thus both curved and flat transducers were considered. Curved transducers are designed to precisely focus an ultrasound beam at a therapy target. Though this transducer shape showed initial promise, it may be impractical, in some embodiments, for a home-use therapy. It was determined that, in some embodiments, the curved transducer could easily deposit too much energy in one location of the vaginal canal if used outside of a well-controlled environment. Furthermore, the clinical work has demonstrated that a diffuse application of ultrasound can, in some embodiments, provide better therapy by vasodilating as much of the vascular bed of the vaginal canal as possible.
Flat, disc-type transducers were considered and proved appropriate for the therapy application, as they can achieve the desired therapy effect and are cost-effective. Flat transducers are characterized by a ‘natural focal length,’ which is a function of the transducer size and ultrasound frequency. At this focal length acoustic intensity reaches a global maximum as the ultrasound beam transitions from a near-field signal (characterized by intensity turbulence) to a far-field, smooth and predictable signal. As the therapy can be a fixed frequency (e.g., 1 MHz) in some embodiments, the natural focal length for the transducer can be tuned by adjusting the transducer size. Thus, a flat, disc-type ultrasound transducer can be used.
As described, a flat disc-type transducer's region of maximum intensity is driven by its size, and thus the next step is to determine the diameter that can yield both the desired natural focal length of 3 to 6 cm (our target zone) and can be driven at a resonant 1 MHz frequency. The clinical studies to date have largely used a 25 mm flat disc-type diameter transducer with an effective radiating area (ERA) of 5 cm2. Based on literature review and user interview research, it has been determined that this size may be slightly too large, in some embodiments. Therefore, a slightly smaller transducer (diameter 20 mm, with an ERA of 3.14 cm2) was investigated.
The computational model validated above (HIFU Simulator v1.2, Joshua Soneson, 2011) was used to model and compare the following three transducer diameters:
The results are presented in
In order to achieve adequate acoustic effect in our target axial distance of 3 to 5 cm, hydrophone experiments showed that a simple flat, disc-type transducer worked sufficiently well. Although these flat transducers are not intended for focusing the ultrasound energy, they do have a ‘natural focal length’ where the cleanest waveform and maximum intensity are achieved. The flat disc-type transducers were appropriate for producing a more diffuse spread of energy in the near-field axial region (from the transducer face). Further, from a business model perspective, these single disc transducers are more cost effective to manufacture and implement (i.e. their driving electronics are simpler) than any array could be.
Clear propagation of ultrasonic energy from the surface of the transducer through the coupling pad medium and into the target tissue can be dependent on the ultrasound waves encountering a minimized number of air gaps, bubbles, or defects, along the direction of travel. Each air gap or defect can cause incident energy to attenuate from scattering or absorption; thereby weakening the ultimate dose to the intended area.
The coupling pad can be molded onto a support ring configured to provide structure to the coupling pad component. The support ring and coupling pad can together form the disposable component of the handheld device. Early efforts at molding the coupling pad into the support ring produced a significant meniscus in the coupling pad, which resulted in an air gap at the interface of the assembled transducer and coupling pad. Liquid coupling pad material can be cured in a mold (e.g., 3D printed mold).
In order to minimize these deleterious effects, the following three molds were designed and fabricated.
To prevent the wall surface tension from forming a problem meniscus in an open-cavity mold, a top plate was added to the mold assembly. As shown in
Although the Ported Cover design effectively eliminated the problem meniscus, the two ports can leave small blemishes on the surface of the cured agarose that contacts the transducer face, as shown in
In the embodiment shown in
In mold 2600, the liquid coupling medium flows in through one port in the support ring 2604, fills the mold 2600, and flows out through the second vent hole when the mold cavity is full. This flow helps prevent air bubbles from being trapped in the cured coupling pad. This design consistently created bubble-free coupling pads more often than any previous mold design. A finished coupling pad/support ring assembly 2802 made using mold 2400 shown in
The top fill mold 3000 design, shown in
In some embodiments, the component packaging comprises separate packaging for each disposable portion (e.g., support ring and coupling pad). The individualized packaging can hold the disposable portion in a liquid medium to keep the coupling pad hydrated as it may dry out if exposed to air. In some embodiments, the hydrating solution comprises a bacteriostatic solution (e.g., 0.9% benzyl alcohol solution). The support ring comprises plastic, in some embodiments, and will not degrade in the hydrating solution. The support ring can also provide a strong, rigid support for the coupling pad.
In some embodiments, the component packaging can comprise a blister pack formed to the shape of the coupling pad component. The shelf life can be about 1-3 years (e.g., 1 year, 2 years, 3 years). The blister pack can provide an easy to open component packaging sealed to lock in a hydrating solution. The blister pack can be rigid enough to support the shape of the coupling pad. The blister pack can comprise a medical grade plastic with a backing of foil or foil lined paper. A flexible backing can help with ease of opening for the user while still trapping the coupling pad moisture in the package.
In some embodiments, the coupling pad must be disinfected, but does not require sterilization
An embodiment of component packaging is provided by the Stephen Gould Corporation. The packaging consists of a thermoformed tray that holds 8 gel pads shown in
The coupling pad component 3304 comprises a coupling pad 3306 and a support ring 3308. As described herein, the coupling pad 3306 can be formed from a coupling pad material (e.g., liquid medium). The support ring 3308 can provide structure to the coupling pad and aid in its formation. In some embodiments, the coupling pad component is disposable.
The main device portion 3302 comprises a handle portion 3310 and a head portion 3312. The handle portion 3310 can be configured to fit in a patient's hand. The handle portion 3310 may comprise one or more controls or buttons.
Additional embodiments of ultrasound devices are provided below. It will be appreciated that the various embodiments devices can comprise features or combinations of features described herein with respect to other embodiments of devices.
As shown in
The handle portion 3310 can comprise one or more indicator lights. As shown in
As noted above, the handle portion 3302 can be configured to be held in a patient's hand during treatment. As such, the handle portion 3302 would be held near the front of the groin area. The controls and/or indicator lights can be positioned towards an end 3322 of the handle portion away from the head portion in order to provide a better view and easier access to the patient.
The control and/or indicator lights can be positioned in a recessed area 3324, as shown in
In some embodiments, the controls or indicators can comprise a user interface for user input of treatment parameters. In some embodiments, the device can be remotely controlled by a smartphone, dedicated device controller, computer, tablet, or the like. In some embodiments, the device comprises digital displays indicating battery status, therapy remaining status, or device status.
In some embodiments, the head portion 3312 of the device 3300 comprises an ultrasound head 3330, as shown in
The head portion 3312 also comprises attachment means for connecting to the coupling pad portion 3304. As shown in
As shown in
The following figures depict further embodiments of a coupling pad. It can be important for the coupling pad to maintain self-lubrication throughout the duration of the treatment. Maintained lubrication can prevent hot spots caused by ultrasound standing waves and can promote better acoustic coupling to the patient's tissue.
The following figures depict an additional coupling pad component embodiments. The coupling pad components shown below can allow for attachment to any ultrasound transducer head. Unless otherwise described, the coupling pad component can comprise one or a combination of features of other coupling pads and related coupling pad components described herein.
To assemble the coupling pad component, a user can place a top surface of a coupling pad through a top opening of a top portion of the coupling pad holder. The bottom surface of the coupling pad should be flush with the bottom edge of the top portion of the holder. This positioning can ensure good contact with the ultrasound transducer. The user can then connect the bottom portion of the holder to the top portion using an attachment mechanism, such as magnets shown in
A method of using a device as described herein follows. A user ensures the device is sufficiently charged to initiate a therapy session. The user can remove a coupling pad portion from its packaging and attach it to the head portion of the device. Attaching can be performed using magnets, a threaded connection, or as otherwise described herein. Once the device is assembled, the user holds the handle portion and positions the device so the coupling pad is in contact with her introitus (vaginal opening). The user then activates the device. Activating the device can comprise pressing down a button on the handle portion. In some embodiments, the button is held down to turn the device on or off. For example, the button can be depressed for about 1, 2, 3, or more seconds. During treatment pressing the same button can pause and resume treatment. Pressing the button can activate the device for the desired duration and at the desired settings.
In some embodiments, the ultrasound settings comprise a frequency of about 1 MHz. The intensity can be about 1.5 W/cm2. The duty cycle can be about 50%. In some embodiments, the frequency can be 0.5 MHz-3 MHz, 1.5 MHz, 2 MHz, or 2.5 MHz. In some embodiments, the intensity can be bout 1-2.5 W/cm2, 1 W/cm2, 1.5 W/cm2, 2 W/cm2, 2.2 W/cm2, or 2.5 W/cm2. In some embodiments, the duty cycle can be between about 20%-80%, about 30%, about 40%, about 60%, about 70%, about 80%, about 90%, or about 100%.
In some embodiments, the device is used daily for eight minutes per day. As described herein, in other embodiments, the device can be used multiple times a day, weekly, bi-weekly, monthly, etc. The device can be used for different durations. For example, durations of 5, 6, 7, 9, 10, or 10-15 minutes are contemplated.
Two acute and one chronic (ongoing) IRB-approved clinical studies have been conducted at Stanford University Hospital. The goal of the first study (Acute Study #1) was to determine therapy safety, as therapeutic ultrasound had never been used in this part of the body for this purpose with this patient population.
Safety was demonstrated by Acute Study #1. The results showed that the energy used may be too low and therefore attenuated before reaching the target depth of 3 cm to 6 cm. Hence, a second acute clinical study (Acute Study #2) was conducted at increased ultrasound intensities (See Table 6), still deemed to be safe based on numerical and benchtop temperature simulations (not shown). The data from this study showed a significant (3×) increase in vaginal tissue blood flow and temperature (about 2.5°) (data not shown), demonstrating the current device mechanism of action. Results from Acute Study #1 are partly shown in
Patient symptoms, as recorded by surveys, also showed improvements in both Acute Study #1 and #2. 68% of participants reported an increased level of vulvovaginal lubrication after treatment for 24 hours or more after the study visit.
To determine if repeated use of the current ultrasound therapy will lead to improvements in VVA, a third clinical study (Chronic Study, Table 6) is currently being conducted. In this investigation, participants use a ultrasound treatment prototype at home, daily for 8 minutes a day. For this study, the Ultrasound Settings were modified slightly from Acute Study #2. Duty cycle was reduced from 100% to 50%. Intensity was decreased to 1.5 W/cm2 for the first seven patients. After it was clear this energy level was well tolerated (no complaints or adverse events), the dose was escalated to 2.0 W/cm2 for all subsequent pts.
Currently, approximately 90% of medical device waste consists of disposable, one-time-use products or components. The move to reduce the volume of disposable component waste can be constrained by the need to maintain safety standards. The risks associated with hazardous medical waste and biological contamination, as well as the high cost of product sterilization and reprocessing, have prevented businesses from moving away from disposable products towards something more sustainable.
To address this problem, embodiments of coupling pads reducing or eliminating the use of plastic are described below. Such configurations can reduce the volume of waste generated by each coupling pad and can make more of the product biodegradable.
In embodiments of coupling pads described herein, a plastic portion of the coupling pad (e.g., plastic support ring) can provide some support or structure to the softer material of the coupling pad. A plastic portion of the coupling pad can also help provide the attachment means to attach the coupling pad to the device. In the following embodiments, a coupling pad can comprise a gel pad having two or more kinds of gel.
In some embodiments, a harder gel can be used to provide more structural functionality, and a softer gel can be used to provide the conformability and deformability for engaging tissue. It will be appreciated that portions of either gel may perform either function, for example, at boundaries of the different parts.
In some embodiments, the coupling pad comprises an agarose hydrogel. In such embodiments, a first portion of the coupling pad can comprise a softer hydrogel, and a second portion of the coupling pad can comprise a harder hydrogel.
In some embodiments, the hydrogel comprises a combination of agarose, water, glycerin, and an antimicrobial agent.
The hardness of the hydrogel can be adjusted by varying the amount of agarose in the gel. In some embodiments, the harder hydrogel comprises about 4 times as much agarose as the softer hydrogel. In some embodiments, the harder hydrogel can comprise about 5% agarose (or about 5-10% agarose, or about 4-6% agarose, or about 5-7% agarose, etc.). In some embodiments, the softer hydrogel can comprise about 1.25% agarose (or about 1-2% agarose, or about 1-1.5% agarose, or about 1-3% agarose, etc.).
Referring now to
The coupling pad 5000 comprise a detachable connection to an ultrasound device. For example, the coupling pad 5000 can comprise one or more metal components 5006 that can help provide a magnetic connection between the coupling pad and a handheld ultrasound device. Other connections are also contemplated. For example, the coupling pad may connect to a handheld ultrasound device using an interference fit between one or more features on the coupling pad and one or more features on the handheld ultrasound device.
The first part 5002 of the coupling pad can comprise a rounded or dome shape, as described herein.
In some embodiments, the metal components comprise stainless steel (e.g., grade 430).
The metal components may comprise a size large enough to provide sufficient magnetic force to maintain coupling between the ultrasound device and the coupling pad. In some embodiments, the metal component comprises a width of about 4 mm (or about 3-5 mm). The metal component can comprise a length of about 11 mm (or about 10-12 mm or about 9-13 mm). The metal component can comprise a thickness of about 3 mm (or about 2-4 mm).
As shown in the cross section of
The molded first part can be transferred from the first mold 5010 to the second mold 5020. The top portion 5022 of the mold 5020 can be placed onto the mold 5020. The higher durometer material (e.g., gel) can be poured over the first part into the second mold 5020 and allowed to harden.
The top portion 5022 can be removed and the finished coupling pad can be retrieved from the mold.
The second part 5104 defines a lip portion 5106 around a depression 5108 configured to receive a transducer face of the ultrasound device. The second part 5104 can be formed so that is configured to snap onto the face of the ultrasound device. The hydrogel forming the second part 5104 can be sufficiently hard to provide structural integrity to the lip portion configured to snap onto the device.
As a first step, referring to
In some embodiments, the second part comprises a material hard enough to provide a secure attachment to the ultrasound device, but also pliable enough to fit over a mating feature (e.g., lip) on the device. The right balance of these properties may also be selected based on the specific dimensions of the mating feature (e.g., lip) from the ultrasound device. In some embodiments, using the snap feature to couple a first portion of the coupling pad and then engaging the snap feature along the remaining portions of the coupling pad can cause a first portion of the coupling pad to contact the transducer face first, while contact is made between the transducer face and the remaining portions of the coupling pad gradually, starting with the portions closest to the first portion and ending with the portions farther from the first portion. This gradual contact can chase any air bubbles out from between the coupling pad and the transducer. In some embodiments, this effect may be enhanced by forming the snap feature (or other interference fit feature) to be tighter at a portion of the coupling pad, causing the looser portion of the snap feature to be connected first, thereby forcing a user to first contact only a portion of the coupling pad to the transducer face.
In some embodiments, the coupling pad can connect to the ultrasound device using a magnetic connection through the use of foil or wire in the coupling pad. Foil or wire can be a cheaper and more easily manufactured component than magnets or metal slugs, for example. In some embodiments, a foil and/or wire component can be used in addition to another metal component. In certain such embodiments, one or more of the components can use less material when being used in combination with other metal components.
Referring now to
In some embodiments, a support ring can comprise plastic, but comprises less plastic than those embodiments described above. For example, a support ring can comprise about 75% less plastic that the support rings previously described. A reduced material support ring can comprise holes (or grooves, slits, and/or undercuts) configured to help lock in the coupling pad (e.g., as the gel hardens in the holes during molding). In some embodiments, a reduced plastic support ring comprising holes or undercuts can be used in combination with a two-part coupling pad design (e.g., two part hydrogel design), having a softer part and a harder part.
A coupling pad comprises a device side surface configured to contact an ultrasound transducer of the ultrasound device. Lack of conformal contact can lead to air being trapped between the coupling pad and transducer, and non-optimal transmission of ultrasound energy. To address this issue, in some embodiments provided herein, this device side surface can be convex or perfectly flat to aid in conformal contact between the transducer and the coupling pad.
When molding the coupling pads described herein rounded or dome side down, the liquid material poured into the mold can cling to the surface of the mold, forming a meniscus in the material and a concave top surface. As it cures, the material can shrink down, further exaggerating the meniscus and concave shape. This concave shape at the device side surface of the coupling pad can cause lack of conformal contact with the transducer, and may result in bubble formation.
In some embodiments, to counteract this phenomenon, the coupling pad can be molded so that the rounded or dome portion of the coupling pad is at the top. In such embodiments, the device side surface is at the bottom of the mold, where formation of a meniscus is not an issue. Referring to
The first part 5502 goes on the bottom and is shown with a support ring 5508 of a coupling pad positioned on it. The support ring can attach to the metal slugs (e.g., using snap features). The slugs can be located within the first part 5502 be, for example, a depression in the first part 5502. Because the slugs are attached to the support ring, the locating feature (e.g., depression) can also locate the support ring. The support ring 5508, in some embodiments, comprises holes 5509 (e.g., allowing the support ring to comprise less plastic, be thinner).
The second part 5504 gets positioned above the first part 5502. The second part 5504 comprises a coupling pad portion 5505. A bottom portion 5510 of the coupling pad portion 5505 is shaped to correspond with the shape of the support ring. A top portion 5512 of the coupling pad portion 5505 comprises a rounded or dome shape. A port 5514 is positioned at or near the top of the top portion 5512. Liquid material for forming the coupling pad can pass through the port 5514 into the inside portion of the coupling pad portion 5505.
The third part 5506 is positioned to go above the second part 5504. The third part comprises an aperture 5516 configured to surround the coupling pad portion 5505 of the second part 5504. The second part 5504 and the third part 5506 of the mold comprise holes 5516, 5518 configured to interact with corresponding protrusion or tabs 5520 on the first part 5502. The holes 5516 are positioned away from the coupling pad portion and are configured to hold the various portions of the mold together and properly positioned.
The first part 5502 and the second part 5504 comprise holes 5522, 5524. The dimples created by the vacuum process will nest in the lower CP casting mold.
In some embodiments, as shown in
Referring to
As noted above, the convexity on either the transducer face or the coupling pad can help to prevent air from being trapped between the coupling pad and the transducer face. In such embodiments, the durometer of the coupling pad needs to be sufficiently low (i.e., sufficiently deformable) to conform to the transducer face without needing excessive retention force (e.g., using magnets or other techniques). At the same time, the durometer of the coupling pad needs to be high enough (i.e., sufficiently stiff) to be handled without falling apart.
When a feature or element is herein referred to as being “on” another feature or element, it can be directly on the other feature or element or intervening features and/or elements may also be present. In contrast, when a feature or element is referred to as being “directly on” another feature or element, there are no intervening features or elements present. It will also be understood that, when a feature or element is referred to as being “connected,” “attached” or “coupled” to another feature or element, it can be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being “directly connected,” “directly attached” or “directly coupled” to another feature or element, there are no intervening features or elements present. Although described or shown with respect to one embodiment, the features and elements so described or shown can apply to other embodiments. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.
Terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms “a,” “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “/”.
Spatially relative terms, such as “under,” “below,” “lower,” “over,” “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the exemplary term “under” can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms “upwardly,” “downwardly,” “vertical,” “horizontal” and the like are used herein for the purpose of explanation only unless specifically indicated otherwise.
Although the terms “first” and “second” may be used herein to describe various features/elements (including steps), these features/elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings of the present invention.
Throughout this specification and the claims that follow, unless the context requires otherwise, the word “comprise,” and variations such as “comprises” and “comprising” means various components can be co-jointly employed in the methods and articles (e.g., compositions and apparatuses including device and methods). For example, the term “comprising” will be understood to imply the inclusion of any stated elements or steps but not the exclusion of any other elements or steps.
As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word “about” or “approximately,” even if the term does not expressly appear. The phrase “about” or “approximately” may be used when describing magnitude and/or position to indicate that the value and/or position described is within a reasonable expected range of values and/or positions. For example, a numeric value may have a value that is +/−0.1% of the stated value (or range of values), +/−1% of the stated value (or range of values), +/−2% of the stated value (or range of values), +/−5% of the stated value (or range of values), +/−10% of the stated value (or range of values), etc. Any numerical range recited herein is intended to include all sub-ranges subsumed therein.
Although various illustrative embodiments are described above, any of a number of changes may be made to various embodiments without departing from the scope of the invention as described by the claims. For example, the order in which various described method steps are performed may often be changed in alternative embodiments, and in other alternative embodiments one or more method steps may be skipped altogether. Optional features of various device and system embodiments may be included in some embodiments and not in others. Therefore, the foregoing description is provided primarily for exemplary purposes and should not be interpreted to limit the scope of the invention as it is set forth in the claims.
The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. As mentioned, other embodiments may be utilized and derived there from, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one is, in fact, disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description.
This application claims the benefit of U.S. Provisional Patent Application No. 63/168,844, filed on Mar. 31, 2021, the entire disclosure of which is incorporated by reference herein.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2022/022863 | 3/31/2022 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63168844 | Mar 2021 | US |
