Patent Application
20220241139
The present invention relates to a device for treating vaginal atrophy. Also contemplated are methods of treating vaginal atrophy/dryness.
Vulva and/or Vaginal Atrophy (VVA/VA) is a chronic & progressive condition because of a reduction or absence of oestrogen. Vaginal Atrophy (VA) is a chronic and progressive condition that affects approximately 80% of women because of hormonal changes at some point during their lifetime. It results from reduced oestrogen levels that cause the vagina and surrounding tissue to become dry, thin and inflamed. Symptoms include chronic dryness, itching, irritation and pain. Studies have shown it impairs a woman's quality of life, affects intimate relationships and makes it uncomfortable to sit, stand, exercise, urinate or even work. VA is a prevalent condition and is most common in women in the menopausal age range and Breast Cancer Survivors (BCSs). It is estimated that by 2020, there will be 50 million menopausal women in the US and by 2025 there will be 1.1 billion women in the menopausal range across the world suffering from VA. Additionally, there are 3.1 million BCSs suffering with VA. There is currently no affordable, safe, non-hormonal and effective treatment for VA. The present disclosure seeks to address this clinical need.
When a woman experiences the menopause, oestrogen production is decreased by 70%. With VA, the tissues of a woman's vagina no longer work in their normal, healthy way. The lining of the vagina begins to shrink, and walls become thinner and drier that makes for an uncomfortable dry sensation that affects a woman's quality of life. The vaginal epithelium becomes thinner, elasticity is reduced, vaginal secretions decrease and blood flow is reduced.
More than 70% of BCSs become postmenopausal after chemotherapy and radiation treatment and consequently BCSs experience VA. The chemotherapy and radiation cause a reduction in oestrogen hence inducing early menopause. Additionally, the cancer blocker and endocrine drugs that women take to remain cancer free, further exacerbate the symptoms of VA owing to the oestrogen suppression effect of these therapies that worsens the symptoms of itchiness, pain and dryness around the vagina area. Additionally, VA is often the most poorly addressed side effect for BCSs on adjuvant endocrine therapy.
It is an object of the invention to overcome at least one of the above-referenced problems.
The present invention addresses the need for a treatment of vaginal atrophy that does not involve side effects, can be self-administered, is suitable for use with all women, not just postmenopausal or breast cancer survivor women, and that addresses the underlying cause of the indication without causing irreversible or serious damage to the vaginal epithelium. The solution is based on a device configured to be inserted into the vagina and actuated to cause a mechanical microtrauma to the wall of the vagina. Mechanical microtrauma refers to small deformations to the vaginal wall due to physical interaction between the device and wall that are sufficient to cause inflammation-induced angiogenesis and stimulate proliferation of new endothelial cells and/or generation of collagen matrix. The micro-deformations may include micro tears, punctures, holes, stretches, and cracks in the vaginal wall. Various methods of applying mechanical microtrauma to the wall of the vagina using an insertable device are described herein.
In a first aspect, the present application provides a device to treat vaginal atrophy comprising a treatment module configured for insertion into the vagina and having a microtrauma module configured to deliver negative pressure mechanical microtrauma therapy to a wall of the vagina when inserted, wherein the microtrauma module comprises a plurality of apertures in fluidic connection with a vacuum pump, the device being arranged to generate, in use, a negative pressure at the apertures.
The device delivers an array of microtraumas to the wall of the vagina to provide VA treatment. The microtraumas provide a controlled mechanical insult generated using a vacuum to apply negative pressure to the vaginal tissue. The suctioned tissue is strained by the pressure, causing an array of microtraumas that in turn leads to a healing response in the vaginal tissue. The mechanical microtrauma generated in this way produces an inflammatory response that stimulates the production of Hyaluronic Acid (HA).
Known devices include that described in US2018/0296383 A1, which discloses a device that combines ultrasound energy, electrical energy, light, and vacuum to improve the general health function of the penis and the vagina. US2018/0296383 does not disclose that the use of the vacuum therapy can be used to provide effective VA treatment, especially by stimulating angiogenesis as is provided for by the device of the present application. US2018/0296383 A1 discloses only promotion of health function by stimulation of blood flow and sensory nerves. Any use of pressure in US2018/0296383 A1 is merely to physically exercise the muscles of the vagina (paragraph [0051]) and which does not provide microtrauma within the meaning of the present application, and so cannot provide effective VA.
Negative pressure therapy has been suggested previously as a treatment of wounds by Cipolla et al. (Negative pressure wound therapy: Unusual and innovative applications. OPUS, 2008, 12, 15-29) and Saxena et al. (Vacuum-assisted closure: Microdeformations of wounds and cell proliferation. Plastic and Reconstructive Surgery, 2004, 114(5), 1086-1096). The Applicants have discovered that negative pressure therapy is a particularly suitable method of causing mechanical microtrauma to the wall of the vagina. There has previously been nothing to suggest that negative pressure therapy for wound treatment could be used for this purpose. The inventors have found that application of negative pressure to the wall of the vagina stimulates proliferation of new endothelial cells and collagen matrix that will thicken the vaginal wall, reduce atrophy, promote angiogenesis and improve the moisture retaining ability of cells in the vaginal wall, reducing dryness. It is particularly applicable as a therapy for breast cancer patients and postmenopausal women, for whom vaginal atrophy is a recognised side-effect. A key molecule involved in skin and tissue moisture is Hyaluronic Acid (HA) that has a unique capacity in retaining water. HA is a natural polysaccharide, forms an important part of extra-cellular matrix of the vaginal tissue and is present naturally in the vaginal epithelium. It regulates several aspects of tissue repair and regeneration. The synthesis of HA increases in response to inflammation or trauma to the vagina tissue (i.e. the negative pressure will induce a controlled beneficial microtrauma). HA regulates several aspects of tissue repair including activation of inflammatory endothelial cells to enhance angiogenesis to form new blood vessels from existing ones, healing and hydration of damaged tissue. The synthesis of HA is decreased with aging which is associated to reduced oestrogen production. The synthesis of HA reduces after menopause due to reduced levels of oestrogen. The device of the present application will combat this effect by delivering a microtrauma to the wall of the vagina, which will in turn result in an inflammatory response and simulate the production of HA.
The microtrauma module may be arranged, in use, to draw tissue of the vaginal wall into the apertures to deliver the microtrauma. This allows microtrauma to be created by straining tissue drawn into each aperture which has been found to provide effective microtrauma for VA therapy. The microtrauma module is arranged, in use, to stimulate angiogenesis within the tissue of the vaginal wall to provide vaginal atrophy treatment.
The pressure generated at the apertures may be at least 50 mmHg and preferably greater than 100 mmHg. Pressures that are lower than this range would be unsuitable to provide effective treatment without excessive tissue damage. More specifically, the device may be arranged to generate a negative pressure of between 50 mmHg and 800 mmHg, or between 100 mmHg and 800 mmHg at the apertures.
More preferably, the device may be arranged to generate a negative pressure of between 50 mmHg and 600 mmHg. In a preferred embodiment, the device may be arranged to generate a negative pressure of between 200 mmHg and 600 mmHg. Testing performed by the inventors has shown that this provides effective VA treatment without causing excessive tissue damage.
In an even more preferred embodiment, the device may be arranged to generate a negative pressure of between 300 mmHg and 450 mmHg at the apertures. This has been found in testing carried out by the inventors to provide an optimal range for effective VA treatment.
The pressure and pressure ranges given herein are to be understood to be the pressure generated when the device is in use, e.g. when VA therapy is being applied by activation of the pump. The pressure generated at the apertures is considered to be the same as that generated by the pump.
The apertures may be formed by holes extending from an outer surface of the treatment module. The holes may extend a depth of at least 1 mm (and preferably less than 6 mm) from the outer surface. More preferably the holes may extend a depth of greater than 2 mm (and preferably less than 6 mm). This has been found by the inventors to provide effective treatment. The minimum depth of the holes has been found to be important in avoiding excessive tissue damage by reducing the risk of tissue extending out of the inner end of the hole.
The holes may extend a depth in the range between 3 mm and 4 mm. This has been found to provide a further improved balance of effective microtrauma and risk of tissue damage. This has been found to provide a suitable level of microtrauma to the tissue without causing excessive tissue damage. If the depth is less than this the tissue can extend out of the hole and mushroom on the inside surface of the treatment module causing tissue damage. A depth greater than this range may also result in excessive tissue strain. The holes may extend a depth of 3.5 mm. This has been found to provide optimal therapy.
The holes may have a maximum cross-sectional size of at least 0.5 mm (and preferably less than 4 mm). More preferably the holes may have a maximum cross-sectional size of greater than 1.0 mm (and preferably less than 3.5 mm). This has been found by the inventors to provide effective treatment. The inventors have found that the holes must a minimum size in order to draw enough tissue through the apertures to create adequate microtrauma and the desired therapeutic effect.
The holes may have a maximum cross-sectional size in the range between 2 mm and 3 mm. This has been found to provide a further improved balance of microtrauma and risk of tissue damage. The inventors have found that this provides a suitable level of microtrauma without excessive tissue damage. If hole sizes less than the above range are used, less tissue may be drawn into the hole due to the effects of friction which increase as the hole diameter decreases. This may result in an inadequate microtrauma effect required to provide VA therapy. Holes larger than the above range may result in more tissue entering each hole due to lower frictional forces. This results in larger tissue deformations leading to undesired tissue damage. Furthermore, the deformations and associated microtraumas are less concentrated with bigger hole diameters, leading to ineffective VA treatment. The holes may have a maximum cross-sectional size of 2.5 mm. This has been found to provide optimal therapeutic effect.
The portion of the treatment module adapted for insertion into the vagina may have a maximum cross-sectional size in the range between 20 mm and 30 mm. This has been found to provide an advantageous balance between stretching to the vagina during insertion providing additional microtrauma by circumferential stressing, while not making tissue too difficult to provide negative pressure therapy e.g. by making it more difficult for tissue to be deformed and drawn into the apertures.
The treatment module may comprise a support member. The support member may comprise an arrangement of passageways that are fluidly coupled to the vacuum pump. The treatment module may further comprise an outer tip member, the outer tip member comprising a plurality of holes forming the apertures of the treatment module. The outer tip member may be arranged to fit around a distal portion of the support member. The outer tip member and support member may be arranged to form an interlocking engagement (i.e. they have complimentary interlocking shapes) whereby the passageways of the support member are aligned relative to the holes of the outer tip member to form a fluidic connection between them. This aids alignment between the holes and passageways and aids assembly.
The outer tip member may be formed from an elastomeric material. The support member may be formed from a relatively rigid material. A friction fit may be provided between the support member and the outer tip member. This may allow welding or glue to be avoided, and aids manufacture. A seal is also provided between the outer tip and support member to reduce pressure leakage. The elastomeric material may be liquid silicone rubber (LSR) or thermoplastic elastomer (TPE). The support member may be made from a relatively more rigid polymeric material. A stretch fit of the outer tip member over the support member may be provided to aid sealing and coupling between them.
The VA device may further comprise a liquid (e.g. water) trap. The liquid trap may be provided upstream of the vacuum pump. The liquid trap may be arranged to trap liquid discharge drawn through the apertures. The liquid trap may trap water discharge before it gets to the pump. This may help reduce damage to the pump.
The VA device may further comprise a hydrophobic filter. The hydrophobic filter may be arranged to block contaminates drawn though the apertures from reaching the vacuum pump. The hydrophobic filter may comprise a filter module having a hydrophobic filter membrane (e.g. a PTFE membrane). The filter module may be provided in the treatment module, and may be arranged to block contaminates from passing along a flexible lead connecting the treatment module to the pump. The hydrophobic filter may be provided alternatively to the liquid trap.
The treatment module may comprise a proximal handle part and a distal treatment part. The distal treatment part may be adapted for insertion into the vagina during use. The apertures may be provided on the treatment part.
The treatment part may comprise a proximal sealing portion in which none of the apertures are located, and an aperture portion in which the apertures are located. The aperture portion may be located distally to the sealing portion. The sealing portion provides a region that is inserted during use that does not have apertures so that all of the apertures are within the vaginal canal during use. This provides sealing and prevents vacuum leakage during use.
In a second aspect, the present application provides a device to treat vaginal atrophy comprising a treatment module configured for insertion into the vagina and having a microtrauma module configured to deliver mechanical microtrauma therapy to a wall of the vagina when inserted.
In one embodiment, the microtrauma module is configured to deliver a mechanical microtrauma therapy to the wall of the vagina selected from negative pressure, needle puncture, clamping, heating, cooling, friction or rolling to the wall of the vagina.
In one embodiment, the microtrauma module is configured to deliver negative pressure therapy to the wall of the vagina as discussed above in connection with the first aspect.
In one embodiment, the microtrauma module of the second aspect comprises a plurality of small apertures in fluidic connection with a vacuum pump. The number and size of the apertures employed, and the arrangement of apertures on the microtrauma module, is variable. For example, the apertures may have a maximum dimension of 1 mm to 6 mm. The apertures may be arranged circumferentially around the microtrauma module, or arranged bilaterally in discrete arrays on the microtrauma module. Any number of apertures may be employed, for example at least 10, or 10-100.
Generally, when the device of the second aspect is configured to deliver mechanical microtrauma therapy by means of negative pressure therapy, the device will include a vacuum pump operatively connected to the microtrauma module to apply negative pressure to the wall of the vagina through the small apertures. The vacuum pump may be configured to generate a negative pressure of 50-800 mmHg during use and may be configured for user adjustment.
Any of the following statements may apply to the first or second aspect:
In one embodiment, the treatment module comprises a proximal handle part and a distal treatment part (e.g. the handle and treatment parts introduced above). The distal treatment part is dimensioned for insertion into the vagina, and delivery of mechanical microtrauma therapy to the wall of the vagina. The proximal handle part is configured for being held by a user during use. The treatment module is generally an elongated body in which the distal treatment part of the treatment module is optionally cranked with respect to the proximal handle part (for example by about 2-45 degrees).
In one embodiment, the distal treatment part is detachable from the proximal handle part. This allows the distal treatment part to be configured for single use, and disposed of after use, while retaining the handle part of multiple uses.
In one embodiment, the device comprises a pressure sensor configured to determine an operational pressure of the negative pressure therapy being applied to the wall of the vagina.
In one embodiment, the device comprises an actuation/controller module. This module may comprise actuation means for the microtrauma module (for example the vacuum pump in the case of negative pressure therapy, or a motor for actuation of microneedles). This module may also include one or more of a graphical user interface, a processor, and a sensor. The actuation/controller module may be located within the microtrauma module (for example the handle part), or it may be located remotely, in a separate base station.
In one embodiment, the actuation/controller module comprises a vacuum pump, a negative pressure sensor, and a processor configured to:
receive data relating to the operational pressure from the negative pressure sensor; compare the detected operational pressure with a reference pressure; and
modify the operational pressure to achieve a target pressure when a sub-optimal operational pressure is detected.
In one embodiment, the device comprises a graphical user interface operatively connected to the actuation/controller module, and configured to graphically display a parameter of the mechanical microtrauma therapy (for example the negative pressure being applied, the length of the treatment period, the time elapsed of the treatment period, the time remaining of the treatment period, etc).
In one embodiment, the device comprises a timer configured to switch off the device after a pre-defined treatment period.
In another embodiment, the graphical user interface may comprise a user adjustable timer interface. This may allow the user to set a treatment period. In other embodiments, the treatment period may be pre-programmed. This may reduce user input required, and aid ease of use.
In one embodiment, the treatment module includes an imaging device (for example a video or CCD camera) and optionally an illumination system, configured for imaging the wall of the vagina during use. The device may be configured to display images from the imaging device on the graphical user interface.
In one embodiment, the treatment module includes a moisture sensor configured to sense moisture of the vaginal wall. In one embodiment, the device comprises a processor configured to receive moisture data from the moisture sensor, and process or store the data. The processor may be configured to display data relating the moisture on a graphical user interface forming part of the device, or wirelessly relay the data to a remote computational device.
In one preferred embodiment, the actuation/controller module is a remote actuation/controller module (i.e. provided as a remote base station), operatively connectable to the treatment module and comprising actuating and/or controlling means for the microtrauma module. The actuation/controller module may be operatively connected to the treatment module by, for example, a flexible lead or tubing/conduit. In one embodiment, the treatment module is detachable from the remote actuation/controller module. This configuration allows for use of a disposable treatment module, which can be detached from the remote actuation/controller module after use and disposed of.
The flexible lead may be detachable from the actuation/controller module so that the flexible lead and the treatment module are detachable from the actuation/controller module and are disposable parts. The treatment module may be detachable from the flexible lead so that the treatment module is a disposable part. This allows either the treatment module, or both the treatment module and flexible lead, to be disconnected and disposed of after use and replaced for subsequent uses.
The VA treatment device may further comprise a tamper resistance device. The tamper resistance device may be provided at a connection point between disposable and non-disposable parts of the device (e.g. at a proximal end of the flexible lead where it connects to the actuation/controller module, or at the treatment module where it connects to the flexible cable). The actuator/controller module may be arranged to sense the tamper resistance device and to determine if the disposable parts are being used for the first time based on the tamper resistance device, and prevent activation of the vacuum pump if disposable parts are determined to have been reused. The VA treatment device may be provided with a sensor located in a suitable position to sense or read the tamper resistance device (e.g. at the actuation controller module, or at the distal end of the flexible cable).
The tamper resistance device may comprise a unique identifier, and the device further comprises a sensor arranged to read the unique identifier. The actuation/controller module may be arranged to determine if the flexible lead is being connected for the first time based on the unique identifier. The tamper resistance device may be arranged to be altered or removed during connection of the flexible lead for the first time. It may be a tamper proof cap, seal or foil. The sensor may be arranged to sense the presence or condition of the tamper resistance device, the actuation/controller module being arranged to determine whether the flexible lead is being connected for the first time based on the presence or condition of the tamper resistance device.
In one embodiment, the device (for example the processor) may include communication means for relaying data wirelessly to a remote computational device (for example a mobile phone) via a communication network. The communication network can be the internet, an intranet, or any wired or wireless communication network. For example, the communication network may include a mobile communications network such as a Global System for Mobile Communications (GSM) network, a Code Division Multiple Access (CDMA) network, 3rd Generation Partnership Project (GPP), an Internet Protocol (IP) network, a Wireless Application Protocol (WAP) network, a WiFi network, or an IEEE 802.11 standards network, as well as various communications thereof. Other conventional and/or later developed wired and wireless networks may also be used.
In one embodiment, the device, particularly the treatment module, and more particularly the distal treatment head (e.g. the outer tip member), is formed from a soft lubricious material.
In another aspect, the present application provides a method of treatment of vaginal atrophy in a mammal, especially a human, comprising the steps of administering mechanical microtrauma to a wall of the vagina of the mammal, optionally using an insertable device comprising a microtrauma module configured to deliver mechanical microtrauma therapy to a wall of the vagina when inserted. In one embodiment, the insertable device is the device of the first or second aspect, or any other embodiment described or claimed herein.
In one embodiment, the method comprises administering mechanical microtrauma therapy to the wall of the vagina for a treatment period. The duration of a treatment period may be 1-90, 1-60, 1-30, 5-90, 5-60, or 5-30 minutes. In one embodiment, the mammal is treated once every 1, 2, 3, 4, 5, 6 or 7 days weekly, fortnightly or monthly. In one embodiment, the mammal is suffering from vaginal atrophy. In one embodiment, the mammal is suffering from vaginal dryness.
In one embodiment, the method comprises the steps of positioning the treatment module at a first position in the vagina, and applying a first dose of mechanical microtrauma therapy, and then re-positioning the treatment module at a second position in the vagina, and applying a second dose of mechanical microtrauma therapy. In one embodiment, repositioning comprises rotating the device about a longitudinal axis. In another embodiment, re-positioning comprising adjusting the depth of the device.
Except where mutually exclusive, a feature or parameter described in relation to any one of the above aspects may be applied to any other aspect. As used herein, a range “from value X to value Y” or “between value X and value Y”, or the like, denotes an inclusive range; including the bounding values of X and Y.
Other aspects and preferred embodiments of the invention are defined and described in the other claims set out below.
All publications, patents, patent applications and other references mentioned herein are hereby incorporated by reference in their entireties for all purposes as if each individual publication, patent or patent application were specifically and individually indicated to be incorporated by reference and the content thereof recited in full.
Where used herein and unless specifically indicated otherwise, the following terms are intended to have the following meanings in addition to any broader (or narrower) meanings the terms might enjoy in the art:
Unless otherwise required by context, the use herein of the singular is to be read to include the plural and vice versa. The term “a” or “an” used in relation to an entity is to be read to refer to one or more of that entity. As such, the terms “a” (or “an”), “one or more,” and “at least one” are used interchangeably herein.
As used herein, the term “comprise,” or variations thereof such as “comprises” or “comprising,” are to be read to indicate the inclusion of any recited integer (e.g. a feature, element, characteristic, property, method/process step or limitation) or group of integers (e.g. features, element, characteristics, properties, method/process steps or limitations) but not the exclusion of any other integer or group of integers. Thus, as used herein the term “comprising” is inclusive or open-ended and does not exclude additional, unrecited integers or method/process steps.
As used herein, the term “disease” is used to define any abnormal condition that impairs physiological function and is associated with specific symptoms. The term is used broadly to encompass any disorder, illness, abnormality, pathology, sickness, condition or syndrome in which physiological function is impaired irrespective of the nature of the aetiology (or indeed whether the aetiological basis for the disease is established). It therefore encompasses conditions arising from infection, trauma, injury, surgery, radiological ablation, poisoning or nutritional deficiencies.
As used herein, the term “vaginal atrophy” refers to the chronic & progressive condition caused by a reduction or absence of oestrogen. It causes the vagina and tissue near it to become dry, thin & inflamed. Vaginal atrophy is prevalent in menopausal women, but more so in postmenopausal Breast Cancer Survivors (BCSs). VA describes a range of symptoms including vaginal dryness, irritation, pain & urinary incontinence & affects a large percentage of menopausal women. This condition disproportionately affects BCSs who experience premature menopause as a result of their cancer treatments. BCSs who receive systemic endocrine therapy (e.g. aromatase inhibitors and Tamoxifen) also experience more severe VA symptoms owing to the oestrogen suppression effect of these therapies. The device and methods of the invention are to treat vaginal atrophy and vaginal dryness.
As used herein, the term “treatment” or “treating” refers to an intervention (e.g. the administration of an agent to a subject) which cures, ameliorates or lessens the symptoms of a disease or removes (or lessens the impact of) its cause(s). In this case, the term is used synonymously with the term “therapy”. The treatment may be causal or symptomatic.
Additionally, the terms “treatment” or “treating” refers to an intervention (e.g. the administration of an agent to a subject) which prevents or delays the onset or progression of a disease or reduces (or eradicates) its incidence within a treated population. In this case, the term treatment is used synonymously with the term “prophylaxis”.
As used herein, an effective amount or a therapeutically effective amount of a negative pressure treatment defines an amount that can be administered to a subject without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio, but one that is sufficient to provide the desired effect, e.g. the treatment or prophylaxis manifested by a permanent or temporary improvement in the subject's condition. The amount (pressure and/or length of treatment) will vary from subject to subject, depending on the age and general condition of the individual, mode of administration and other factors. Thus, while it is not possible to specify an exact effective amount, those skilled in the art will be able to determine an appropriate “effective” amount in any individual case using routine experimentation and background general knowledge. A therapeutic result in this context includes eradication or lessening of symptoms, reduced pain or discomfort, prolonged survival, improved mobility and other markers of clinical improvement. A therapeutic result need not be a complete cure.
In the context of treatment and effective amounts as defined above, the term subject (which is to be read to include “individual”, “animal”, “patient” or “mammal” where context permits) defines any subject, particularly a mammalian female subject, for whom treatment is indicated. Mammalian subjects include, but are not limited to, humans, domestic animals, farm animals, zoo animals, sport animals, pet animals such as dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, cows; primates such as apes, monkeys, orangutans, and chimpanzees; canids such as dogs and wolves; felids such as cats, lions, and tigers; equids such as horses, donkeys, and zebras; food animals such as cows, pigs, and sheep; ungulates such as deer and giraffes; and rodents such as mice, rats, hamsters and guinea pigs. In preferred embodiments, the subject is a human.
“Treatment module” refers to a part of the device of the invention that is configured for at least partial insertion into the vagina and includes a microtrauma module to deliver mechanical microtrauma therapy to a wall of the vagina when inserted. The module (or at least the part that is inserted into the vagina) will generally have a smooth, atraumatic shape, and a surface comprising the microtrauma module configured to abut the wall of the vagina when inserted. The treatment module may have a distal (transvaginal) part configured for insertion into the vagina (“distal treatment part”), and a proximal part configured for being held by a user during use (“proximal handle part”).
“Microtrauma module” means part of the treatment module that is configured to deliver mechanical microtrauma therapy to a wall of the vagina, when the treatment module is inserted into the vagina.
“Mechanical microtrauma” refers to small deformations to the vaginal wall due to physical interaction between the microtrauma module and wall that are sufficient to cause inflammation-induced angiogenesis and stimulate proliferation of new endothelial cells and/or generation of collagen matrix. The micro-deformations may include micro tears, punctures, holes, stretches, and cracks in the vaginal wall. On embodiment of mechanical microtrauma employs negative pressure therapy which is described in more detail below. However, other methods of delivering mechanical microtrauma therapy to the wall of the vagina are envisaged. For example, the microtrauma module may comprise needles (or more preferably microneedles) configured for deployment during use, to create microabrasions in the vaginal wall. The microneedles may be actuated for deployment from a retracted delivery position within the device to a deployed position during use where the microneedles penetrate the wall of the vagina. In another embodiment, the microtrauma module may comprise means for stretching the wall of the vagina to create micro tears or fissures in the wall, for example means for gripping a section of the wall at each end of the section, and then stretching the wall. In another embodiment, the use of heating or cooling may be employed to generate mechanical microtrauma in the wall of the vagina. In another embodiment, the mechanical microtrauma module may comprise means for applying friction or mechanical deformation (rolling) to the wall of the vagina.
“Negative pressure therapy” refers to the process of forming micro-deformations in the wall of the vagina by the application of a vacuum to the wall of the vagina, where the micro-deformations are sufficient to stimulate proliferation of new endothelial cells and collagen matrix that will thicken the vaginal wall, reduce atrophy and improve the moisture retaining ability of cells in the vaginal wall, reducing dryness. One embodiment of the device of the invention applies negative pressure therapy to an area of the wall of the vagina by means of a plurality of small apertures, typically an array of small, closely packed apertures, that are fluidically connected to a vacuum pump in the device. The application of negative pressure therapy to wound healing is described in the literature, for example Cipolla et al. (Negative pressure wound therapy: Unusual and innovative applications. OPUS, 2008, 12, 15-29) and Saxena et al. (Vacuum-assisted closure: Microdeformations of wounds and cell proliferation. Plastic and Reconstructive Surgery, 2004, 114(5), 1086-1096). Negative pressure wound therapy facilitates healing by improving the rate of angiogenesis, endothelial proliferation, capillary blood flow and decreasing interstitial edema (amongst other things) This approach is applicable to the vaginal wall where it causes a similar beneficial microtrauma effect. The negative pressure produces a controlled, beneficial microtrauma to the vaginal wall to induce a beneficial inflammation cascade of angiogenesis and neo-collagenesis (collagen renewal) which is a recognised molecular pathway. Negative pressure therapy is supported by literature to induce angiogenesis & endothelial proliferation that are the mechanisms of action required to rejuvenate the vaginal wall to address vaginal atrophy. Vaginal lubrication originates from the lamina propria, which contains elastic fibres, blood vessels, lymphatic & nerves, as well as glands that secrete mucus and serous fluids. The lamina propria of the atrophic vagina has decreased extracellular matrix components, reduced vascularization & water-retaining capacity. The device and methods of the invention induce angiogenesis of the lamina propria to create micro-vascularization & new vessel formation. This in turn will produce moisture & lubrication, simultaneously collagen remodelling of the connective tissue & elastin fibres of the vaginal wall & restoring the vaginal mucosa & rehydrating the vaginal walls. The synthesis of HA increases in response to inflammation or trauma to the vagina tissue (i.e. the tip with the perforations will induce a controlled beneficial microtrauma). HA regulates several aspects of tissue repair including activation of inflammatory endothelial cells to enhance angiogenesis to form new blood vessels from existing ones. The synthesis of HA is decreased with aging which is associated with reduced oestrogen production.
“Small apertures” should be understood to mean holes that are sufficiently small to deliver effective negative pressure to the wall of the vagina. Typically, the holes have a maximum diameter of about 1-3 mm, 2-3 mm, or preferably about 2.5 mm. Typically the holes are circular or oval, although other shapes of holes may be employed, for example square or rectangular, provided that they are sufficiently small.
“Remote actuation/controller module” refers to an actuation/controller module that is separate from the treatment module and generally connected by a connecting lead. It is also referred to herein as a remote “base station”. The remote actuation/controller module generally includes means for actuating the mechanical microtrauma module, for example a pump, motor, heater, a graphical user interface, and a processor for receiving data relating the operation of the treatment module or the treatment.
The invention will now be described with reference to specific Examples. These are merely exemplary and for illustrative purposes only: they are not intended to be limiting in any way to the scope of the monopoly claimed or to the invention described. These examples constitute the best mode currently contemplated for practicing the invention.
Referring to the drawings, and initially to
In any embodiment described herein, both the treatment module 2, or both the treatment module 2 and the flexible lead 4 may be detachable from the actuator controller module 3. One or both of the treatment module 2 and the flexible lead 4 may then be disposable once detached.
In the embodiment shown in
In any embodiment described herein, the VA treatment device may further comprise a tamper resistance device arranged to prevent repeated use of any components that are disposable. In the embodiment of
In one embodiment, the tamper resistant device 4a comprises a unique identifier that can be read by a sensor 4b provided at the actuation/controller module 3. The actuation/controller module 3 is arranged to determine if the flexible lead has been used before based on the unique identifier. For example, the actuation/controller module 3 may record the unique identifier in a memory when the flexible lead 4 is connected. The actuation/controller module 3 may then compare subsequently read unique identifiers to those read during previous uses in order to determine if the flexible lead/treatment module are being reused or are being connected for the first time. The unique identifier may take the form of a printed ID code (e.g. barcode, QR-code) or may be stored on a chip or magnetic strip or the like.
In other embodiments, the tamper resistance device 4a is configured to be altered or removed during the process of the connection of the flexible lead 4. For example, the tamper resistance device 4a may comprise a tamper proof cap, seal or foil that is broken/removed when the flexible lead 4 is connected for the first time. The actuation/controller module 3 is arranged to sense the presence or condition of the tamper resistance device 4a to determine whether the flexible lead 4 is being reused via a suitable sensor provided at the connection point.
While the tamper resistance device 4a is shown at the proximal end of the flexible cable 4, it may be provided at other locations within the device. For example, the tamper resistance device 4a may be provided in the treatment module 3, with a corresponding sensor provided in a connector at the end of the flexible lead 4. This arrangement is suitable for where only the treatment module is disposable.
The use of the device of the invention is illustrated in
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Referring to
Referring to
Another embodiment of a VA treatment device 100 is illustrated in
As can be seen in
The treatment module 101 comprises a plurality of apertures 106 in an array over at least part of the outer surface 108 of the treatment part 105. The apertures 106 shown in
The distal treatment part 105 of the treatment module 101 comprises a sealing portion 105a (illustrated in
The treatment module 101 comprises an elongate hollow member having an atraumatic shape (that may be straight as shown in
The VA treatment device 100 of the embodiment shown in
In order to draw tissue into the apertures a negative pressure (i.e. a pressure less than the ambient atmospheric pressure) is generated at the apertures by the vacuum pump. In various embodiments the pressure generated by the pump at the apertures is at least about 50 mmHg, and preferably less than 800 mmHg. In yet other embodiments, it is greater than about 100 mmHg, and preferably less than 800 mmHg. In some embodiments the pressure may be in the range between 50 mmHg and 600 mmHg. The pressure ranges in this paragraph are generally suitable for providing negative pressure at the vaginal tissue, but without causing tissue damage. Other pressure ranges defined elsewhere herein may be used.
In the presently described preferred embodiment, a pressure of between about 200 mmHg and 600 mmHg is generated during use. This pressure has been found by the inventors to provide an advantageous level of tissue microtrauma when applied to the vagina wall which in turn provides the desired VA therapy.
The inventors have found that the operating pressure has a significant effect on the microtrauma created by the device 100. At low pressures the deformation of the vagina tissue is limited and therefore minimal strain is generated. This results in a small microtrauma being developed. This may not be significant enough to generate the desired healing response and associated rejuvenation of the vagina tissue. At high vacuum pressures the tissue is drawn deep into each aperture. This may produce excessive elongation of the tissue causing undesired tearing and or bleeding. Moreover, if the tissue is excessively elongated within the holes it may bulge out on the inner surface of the treatment part, creating a mushroom-like effect. This can again result in tearing of the vaginal tissue and/or bleeding. Tearing and bleeding can lead to negative clinical outcomes including scarring or ulcer formation.
In other embodiments, the pressure may be in the range between 300 and 450 mmHg. This has been found to provide a yet more optimal therapeutic effect.
In the presently described embodiment, the holes have a cross-sectional size (e.g. maximum diameter) labelled P in
In the described preferred embodiment, the hole diameter is in the range of between 2 mm and 3 mm. This has been found to provide more optimal microtrauma. In yet other embodiments, an optimal diameter of about 2.5 mm may be used. This has been found by the inventors to provide optimal treatment. The inventors have found that a range of between about 2 mm to 3 mm provides an optimal hole diameter which maximises the level of microtrauma without risking complications, for example tearing of the tissue and associated bleeding. If hole sizes less than the above range are used, the result may be less tissue being drawn into the hole due to the effects of friction which increase as the hole diameter decreases. This may result in an inadequate microtrauma effect required to provide VA therapy. Holes larger than the above range may result in more tissue entering each hole due to lower frictional forces. This results in larger tissue deformations leading to undesired tissue damage. Furthermore, the deformations and associated microtraumas are less concentrated with bigger hole diameters leading to ineffective VA treatment. The range of hole cross-sectional sizes has been found by the inventors to provide advantageous results, particularly in combination with the pressure ranges defined herein.
In the embodiment shown in
Referring to the cross-section shown in the insert of
In the presently described preferred embodiment the hole depth is between 3 mm and 4 mm. The inventors have found this to provide a more optimised level of microtrauma suitable for VA treatment. In yet other embodiments, a hole depth of 3.5 mm is provided. This has been found by the inventors to provide optimal treatment. The inventors have found that a hole depth greater than the above range may cause excessive damage, i.e. it may tear the tissue. The range of hole depth defined in this paragraph and the paragraph above have been found by the inventors to provide advantageous results, particularly in combination with the pressure ranges defined herein.
In other embodiments, different hole geometries may be provided. The depth of the holes is defined as the length of a channel created by the holes in which contained tissue elongation may occur. In other words, the hole depth is the distance that tissue may extend from the outer surface 110 before being no longer contained by the internal walls of the hole (e.g. by opening into the cavity) or by coming into contact with an end wall of the hole.
In
In the embodiments illustrated in
Another embodiment of the VA treatment device is illustrated in
Although the embodiments shown in
In various embodiments, the outer surface of the treatment part is formed from a material having any one or more of: a Shore hardness of 40 A and a frictional coefficient of sliding less than or equal to 0.4. Other material properties may be provided.
The inventors have found that the ranges of pressure, hole depth, aperture diameter and treatment module cross-section described above provide an advantageous therapeutic effect. Each of these factors may however be used independently to provide an advantageous effect and are not all essential to provide the desired mechanical microtrauma.
A friction fit is provided between the outer tip member 222 and the support member 220. This may aid manufacture as glue or welding is not required to join the components. The outer tip member 222 is formed from an elastomeric material such as a Liquid Silicone Rubber (LSR) or Thermoplastic Elastomer (TPE). Other suitable elastomeric materials may be used. The use of an elastomeric material may improve the friction fit between the cover member 222 and the support member 220, as a tight fit may be provided. In some embodiments, a stretch fit of the outer tip member 222 over the support member 220 may be provided to aid sealing and coupling between them. A seal between them may also be provided by the use of the elastomeric material to reduce pressure loss or liquid ingress. The distal portion of the support member 220 has a shape corresponding to that of the outer tip member 222 so that it will keep its shape during use. The support member 220 is made from a relatively more rigid material compared to the outer tip member to provide structure strength of the treatment part to allow insertion.
The outer tip member 222 is illustrated separately in
The support member 220 is illustrated separately in
The support member comprises an internal cavity 214. The cavity 214 is defined by a wall forming the distal portion 220a of the support member 220. The cavity 214 is in fluid communication with the vacuum pump provided in the controller/actuation module 203 and is also in fluid communication with the holes forming the apertures 206 of the outer tip member 222. Fluid communication between the internal cavity 214 and the vacuum pump is provided via an internal conduit 226 running through the proximal portion 220b of the support member 220. The internal conduit 226 fluidly connects the internal cavity 214 and the flexible lead 204.
The support member 220 further comprises an arrangement of passageways 228 that fluidly connect the internal cavity 214 with the holes of the outer tip member 222 which form the apertures 206. In the present embodiment, the passageways 228 are formed by a combination of holes 230 extending through the wall of the support member (which open into the internal cavity 214) and channels formed on the outer surface of the support member. When the outer tip member 222 is fit over the support member 220 its inner surface is spaced apart from parts of the outer surface of the support member to define the channels therebetween. In the present embodiment, the channels are formed by ridges 232 that define circumferential channels 230a. Cut-outs 234 in the ridges define axial channels to interconnect the circumferential channels along the length of the device so that each circumferential channel does not require a corresponding hole 230. Other structural arrangements may be provided to form the passage ways within the support member 220. For example, the cut-outs may be absent, with a hole 230 provided for each circumferential channel.
The support member 220 is arranged to interlock with the outer tip member so that the holes 206 of the outer tip member are orientated relative to the passageways of the support member 220 and a fluid connection is provided between them. A keyed interlocking arrangement is provided to ensure alignment and fluidic connection. In the present embodiment, the holes of the outer tip member 222 are aligned with the channels formed on the outer surface of the support member so that they are fluidly connected. This allows easy assembly of the components of the device.
The treatment module 201 further comprises a liquid trap 236 arranged to trap liquid (e.g. water) discharge from the vagina that may be drawn through the apertures during use. The liquid trap 236 is provided at a position upstream of the pump (along the fluidic connection path between the pump and the apertures 206) so as to trap any liquid drawn through the apertures 206 before it reaches the pump. In the present embodiment, the liquid tap 236 is located within the handle portion 207 of the support member 220 so that it is within the fluid communication path between the cavity 214 and the flexible lead 204 (i.e. it is located at a point along the conduit 226). In other embodiments, the liquid trap 236 may be mounted elsewhere within the treatment module 201, or provided at the controller actuation module 203 or within the lead 204. In yet other embodiments it may be absent.
In various embodiments, the VA device 200 may comprise a hydrophobic filter. The hydrophobic filter may be provided instead of the liquid trap. The hydrophobic filter is arranged to block contaminates drawn though the apertures 206 from reaching the vacuum pump. The hydrophobic filter comprises a filter module having a hydrophobic filter membrane (e.g. a PTFE membrane). The filter module may be provided in the treatment module, and may be arranged to block contaminates from passing along flexible lead or tubing connecting the treatment module to the pump. The filter module may alternatively be provided at any point on the fluid connection path upstream of the pump, e.g. at the connection point between the flexible lead and the actuator/controller module.
Referring to
A series of experimental tests have been conducted with both ex vivo tissue and in vivo to demonstrate the safety and efficacy of the VA treatment. Preclinical testing of a device according to the embodiments shown in
Various modifications will be apparent to the skilled person without departing from the scope of the claims. Any feature disclosed in connection with one embodiment may be used in combination with the features of another embodiment. Although the appended claims are directed to particular combinations of features, it should be understood that the scope of the disclosure of the present invention also includes any novel feature or any novel combination of features disclosed herein either explicitly or implicitly or any generalisation thereof, whether or not it relates to the same invention as presently claimed in any claim and whether or not it mitigates any or all of the same technical problems as does the present invention.
The foregoing description details presently preferred embodiments of the present invention. Numerous modifications and variations in practice thereof are expected to occur to those skilled in the art upon consideration of these descriptions. Those modifications and variations are intended to be encompassed within the claims appended hereto.
| Number | Date | Country | Kind |
|---|---|---|---|
| 19185897.6 | Jul 2019 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/069668 | 7/10/2020 | WO | 00 |
