Device for treating vaginal atrophy

Abstract

Device (1, 20, 100, 200) for the treatment of vaginal atrophy, the device comprising a treatment module (2, 21, 101, 201) configured for insertion into the vagina and having a microtrauma module. The microtrauma module is configured to deliver a negative pressure mechanical microtrauma treatment to the vaginal wall upon insertion. The microtrauma module comprises a plurality of pores (6, 106, 206) in fluid connection with a vacuum pump, the device being arranged to generate a negative pressure at the pores (6, 106).

Description

TECHNICAL FIELD

[0001] The present invention relates to a device for treating vaginal atrophy. Methods of treating vaginal atrophy / dryness are also contemplated. BACKGROUND

[0002] Vulvar and / or vaginal atrophy (VVA / VA) is a chronic and progressive condition that results from a decrease or lack of estrogen. It is due to a decrease in estrogen levels, which causes the vagina and surrounding tissues to become dry, thin, and inflamed. Symptoms include chronic dryness, itching, irritation, and pain. Studies show that it impairs a woman's quality of life, affects intimacy, and is uncomfortable to sit, stand, exercise, urinate, and even work. VA is a common condition, most commonly seen in women in the menopausal age range and breast cancer survivors (BCS). There is currently no affordable, safe, non-hormonal, and effective way to treat VA. The present disclosure seeks to address this clinical need.

[0003] With VA, the tissue of a woman's vagina no longer works in a normal, healthy way. The vaginal lining begins to shrink, and the vaginal walls become thinner and drier, creating an uncomfortable feeling of dryness that affects a woman's quality of life. The vaginal epithelium thins, elasticity decreases, vaginal secretions decrease, and blood flow decreases.

[0004] Chemotherapy and radiation therapy cause a decrease in estrogen, leading to early menopause. In addition, cancer blockers and endocrine drugs taken by women to prevent cancer can further exacerbate the symptoms of VA, as the inhibitory effect of these therapies on estrogen worsens the symptoms of itching, pain, and dryness around the vaginal area. Furthermore, VA is often the most difficult side effect for BCS to resolve in adjuvant endocrine therapy.

[0005] It is an object of the present invention to overcome at least one of the above problems. SUMMARY

[0006] The present invention addresses the need for a treatment for vaginal atrophy that does not involve side effects, can be self-administered, is suitable for use by all women, not just postmenopausal or breast cancer survivor women, and addresses the root cause of the indication without causing irreversible or severe damage to the vaginal epithelium. The solution is based on a device configured to be inserted into the vagina and actuated to cause mechanical microtrauma to the vaginal wall. Mechanical microtrauma refers to a small deformation of the vaginal wall resulting from a physical interaction between the device and the vaginal wall that is sufficient to induce inflammation-induced angiogenesis and stimulate the proliferation of new endothelial cells and / or the production of collagen matrix. The micro-deformation can include micro-tears, perforations, holes, stretches, and cracks on the vaginal wall. Various methods of applying mechanical microtrauma to the vaginal wall using an insertable device are described herein.

[0007] In a first aspect, the present application provides a device for treating vaginal atrophy, the device comprising a treatment module configured for insertion into the vagina, and having a microtrauma module configured for delivering a negative pressure mechanical microtrauma treatment to the vaginal wall upon insertion, wherein the microtrauma module comprises a plurality of pores in fluid connection with a vacuum pump, the device being arranged for generating a negative pressure at the pores when in use.

[0008] The device delivers a series of microtraumas to the vaginal wall to provide VA treatment. The microtraumas provide controlled mechanical injuries resulting from the application of negative pressure to the vaginal tissue using vacuum. The suctioned tissue is squeezed by the pressure, resulting in a series of microtraumas, which in turn results in a healing response of the vaginal tissue. The mechanical microtraumas created in this way result in an inflammatory response, stimulating the production of hyaluronic acid (HA).

[0009] Known devices include the device described in US2018 / 0296383A1, which discloses a device that combines ultrasound energy, electrical energy, light and vacuum to improve the overall health function of the penis and vagina. US2018 / 0296383 does not disclose that the use of vacuum therapy can be used to provide effective VA treatment, in particular by stimulating angiogenesis as provided by the device of the present application. US2018 / 0296383A1 only discloses the promotion of health function by stimulating blood flow and sensory nerves. The use of any pressure in US2018 / 0296383A1 is only for the physical exercise of the muscles of the vagina (paragraph

[0051] ) and does not provide microtraumas within the meaning of the present application and thus cannot provide effective VA treatment.

[0010] 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) have previously suggested negative pressure therapy as a method of treatment for wounds. The applicant has discovered that negative pressure therapy is a particularly suitable method of causing mechanical microtrauma to the vaginal wall. There has been no indication previously that negative pressure therapy for wound treatment could be used for this purpose. The inventors have discovered that the application of negative pressure to the vaginal wall can stimulate the proliferation of new endothelial cells and collagen matrix which will thicken the vaginal wall, reduce atrophy, promote angiogenesis and increase the moisture retention capacity of cells in the vaginal wall, reducing dryness. It is particularly suitable for the treatment of breast cancer patients and postmenopausal women for whom vaginal atrophy is a recognised side effect. A key molecule associated with skin and tissue hydration is hyaluronic acid (HA) which has a unique water-retaining capacity. HA is a natural polysaccharide and is an important component of the extracellular matrix of vaginal tissue and is naturally present in the vaginal epithelium. HA regulates multiple aspects of tissue repair and regeneration. The synthesis of HA increases in response to inflammation or trauma to the vaginal tissue (i.e. negative pressure will induce controlled beneficial microtrauma). HA regulates multiple aspects of tissue repair including activating inflammatory endothelial cells to enhance angiogenesis to form new blood vessels from existing ones, healing and hydrating damaged tissue. The synthesis of HA decreases with age which is linked to the reduction in production of oestrogen. As oestrogen levels decrease, the synthesis of HA decreases in postmenopausal women. The device of the present application will counteract this effect by delivering microtrauma to the vaginal wall which in turn leads to an inflammatory response and mimics the production of HA.

[0011] In use, the microtrauma module can be arranged to draw tissue of the vaginal wall into the apertures to deliver microtrauma. This allows microtrauma to be created by tensioning the 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 vaginal wall tissue to provide vaginal atrophy therapy.

[0012] The pressure generated at the aperture can be at least 50 mmHg, and preferably greater than 100 mmHg. Pressures below this range will not be suitable to provide effective treatment without excessive tissue damage. More particularly, the device can be arranged to generate a negative pressure at the aperture of between 50 mmHg and 800 mmHg, or between 100 mmHg and 800 mmHg.

[0013] More preferably, the device can be arranged to generate a negative pressure of between 50 mmHg and 600 mmHg. In preferred embodiments, the device can be arranged to generate a negative pressure of between 200 mmHg and 600 mmHg. Tests carried out by the inventors have shown that this provides effective VA treatment without causing excessive tissue damage. In even more preferred embodiments, the device can be arranged to generate a negative pressure at the aperture of between 300 mmHg and 450 mmHg. This has been found in tests carried out by the inventors to provide the optimum range for effective VA treatment.

[0014] The pressures and pressure ranges given herein are to be understood as the pressures generated when the device is in use, for example when VA treatment is being carried out by activating the pump. The pressure generated at the aperture is considered to be the same as the pressure generated by the pump.

[0015] The aperture can be formed by a hole extending from the outer surface of the treatment module. The hole can extend from the outer surface to a depth of at least 1 mm (and preferably less than 6 mm). More preferably, the hole can extend to a depth of greater than 2 mm (and preferably less than 6 mm). The inventors have found that this provides effective treatment. It has been found that a minimum depth of the hole is important to avoid excessive tissue damage by reducing the risk of tissue extending out of the inner end of the hole.

[0016] The hole can extend to a depth in the range 3 mm to 4 mm. It has been found that this provides a further improved balance between effective microtrauma and the risk of tissue damage. It has been found that this provides a suitable level of microtrauma to the tissue without causing excessive tissue damage. If the depth is less than this depth range, tissue can extend out of the hole and form a mushroom on the inner surface of the treatment module, causing tissue damage. A depth greater than this range can also result in excessive tissue strain. The hole can extend to a depth of 3.5 mm. It has been found that this provides optimum treatment.

[0017] The holes can have a maximum cross-sectional dimension of at least 0.5 mm (preferably less than 4 mm). More preferably, the holes can have a maximum cross-sectional dimension of greater than 1.0 mm (preferably less than 3.5 mm). The inventors have found that this provides effective treatment. The inventors have found that the holes must have a minimum size in order to draw sufficient tissue through the holes to create sufficient microtrauma and the desired therapeutic effect.

[0018] The holes can have a maximum cross-sectional dimension in the range of 2 mm to 3 mm. The inventors have found that this provides a further improved balance of microtrauma and risk of tissue damage. The inventors have found that this provides an appropriate level of microtrauma without causing excessive tissue damage. If hole sizes smaller than the above range are used, less tissue can be drawn into the holes due to the increased friction effect as the hole diameter is reduced. This can result in insufficient microtrauma effect to provide the VA treatment required. Holes larger than the above range can result in more tissue entering each hole due to the lower friction force. This results in greater tissue deformation, leading to unwanted tissue damage. Furthermore, as the hole diameter is increased, the deformation and associated microtrauma is less localised, resulting in ineffective VA treatment. The holes can have a maximum cross-sectional dimension of 2.5 mm. The inventors have found that this provides the best treatment effect.

[0019] The portion of the treatment module adapted for insertion into the vagina can have a maximum cross-sectional dimension in the range of 20 mm and 30 mm. The inventors have found that this provides a beneficial balance between stretching of the vagina during insertion and providing additional microtrauma through circumferential stress, whilst not making it difficult for the tissue to provide negative pressure treatment, for example by making it more difficult for the tissue to deform and be drawn into the holes.

[0020] The treatment module can comprise a support member. The support member can comprise a channel arrangement fluidly connected to the vacuum pump. The treatment module can further comprise an outer tip member comprising a plurality of holes forming the holes of the treatment module. The outer tip member can be arranged to fit around a distal portion of the support member. The outer tip member and the support member can be arranged to form an interlocking engagement (i.e. they have complementary interlocking shapes), whereby the channels of the support member are aligned with respect to the holes of the outer tip member to form a fluid connection therebetween. This facilitates alignment between the holes and the channels and facilitates assembly.

[0021] The outer tip member can be formed of a resilient material. The support member can be formed of a relatively rigid material. A friction fit can be provided between the support member and the outer tip member. This can allow welding or gluing to be avoided and facilitate manufacture. A seal is also provided between the outer tip and the support member to reduce pressure leakage. The resilient material can be liquid silicone rubber (LSR) or thermoplastic elastomer (TPE). The support member can be made of a relatively more rigid polymeric material. A stretch fit of the outer tip member over the support member can be provided to facilitate sealing and connection therebetween.

[0022] The VA device can also include a liquid trap (e.g. water). The liquid trap can be provided upstream of the vacuum pump. The liquid trap can be provided to collect liquid discharge drawn through the hole. The liquid trap can collect the water discharge before it reaches the pump. This can help to reduce damage to the pump.

[0023] The VA device can also include a hydrophobic filter. The hydrophobic filter can be provided to prevent contaminants drawn through the hole from reaching the vacuum pump. The hydrophobic filter can include a filtration module having a hydrophobic filtration membrane (e.g. PTFE membrane). The filtration module can be provided in the treatment module and can be provided to prevent contaminants from passing along the flexible lead connecting the treatment module to the pump. The hydrophobic filter can be provided in place of the liquid trap.

[0024] The treatment module can include a proximal handle portion and a distal treatment portion. The distal treatment portion can be adapted to be inserted into the vagina during use. The hole can be provided on the treatment portion.

[0025] The treatment portion can include a proximal sealing portion on which the hole is not located and a hole portion on which the hole is located. The hole portion can be distal of the sealing portion. The sealing portion provides a region for insertion during use which is free of holes so that during use all of the holes are within the vaginal cavity. This provides a seal and prevents vacuum leakage during use.

[0026] In a second aspect, the application provides a device for treating vaginal atrophy, the device comprising a treatment module configured for insertion into the vagina and having a microtrauma module configured for delivering a mechanical microtrauma therapy to the vaginal wall when inserted.

[0027] In one embodiment, the microtrauma module is configured to deliver a mechanical microtrauma therapy to the vaginal wall, the therapy being selected from negative pressure, needle puncture, pinching, heating, cooling, rubbing or rolling of the vaginal wall.

[0028] In one embodiment, the microtrauma module is configured to deliver a negative pressure therapy to the vaginal wall, as described above in connection with the first aspect.

[0029] In one embodiment, the minimally invasive module of the second aspect comprises a plurality of small holes in fluid connection with a vacuum pump. The number and size of holes employed, and the arrangement of holes on the minimally invasive module, are variable. For example, the holes can have a maximum dimension of 1 mm to 6 mm. The holes can be arranged circumferentially around the minimally invasive module, or bilaterally in a discrete array on the minimally invasive module. Any number of holes can be used, for example at least 10 or 10-100.

[0030] Generally, when the device of the second aspect is configured to deliver mechanical minimally invasive therapy by negative pressure therapy, the device will comprise a vacuum pump operably connected to the minimally invasive module to apply negative pressure to the vaginal wall through the small holes. The vacuum pump can be configured to generate a negative pressure of 50-800 mmHg during use, and can be configured to be adjusted by a user.

[0031] Any of the following statements can apply to the first or second aspect:

[0032] In one embodiment, the therapy module comprises a proximal handle portion and a distal therapy portion (e.g. the handle and therapy portions introduced above). The distal therapy portion is sized to be inserted into the vagina and to deliver mechanical minimally invasive therapy to the vaginal wall. The proximal handle portion is configured to be held by a user during use. The therapy module is generally an elongate body, with the distal therapy portion of the therapy module optionally curved (e.g. by about 2-45 degrees) relative to the proximal handle portion.

[0033] In one embodiment, the distal therapy portion is detachable from the proximal handle portion. This allows the distal therapy portion to be configured for single use and to be discarded after use, while retaining the handle portion for multiple uses.

[0034] In one embodiment, the device comprises a pressure sensor configured to determine an operating pressure of the negative pressure therapy applied to the vaginal wall.

[0035] In one embodiment, the device comprises an actuation / controller module. This module can comprise an actuation mechanism for the minimally invasive module (e.g. a vacuum pump in the case of negative pressure therapy, or a motor for actuating microneedles). The module can also comprise one or more of a graphical user interface, a processor and a sensor. The actuation / controller module can be located within the minimally invasive module (e.g. the handle portion), or it can be remotely located in a separate base station.

[0036] In one embodiment, the actuation / controller module comprises a vacuum pump, a negative pressure sensor and a processor configured to:

[0037] receive data from the negative pressure sensor relating to the operating pressure; compare the detected operating pressure to a reference pressure; and

[0038] When a sub-optimal operating pressure is detected, the operating pressure is modified to achieve a target pressure.

[0039] In one embodiment, the device includes a graphical user interface operably connected to the actuation / controller module and configured to graphically display parameters of the mechanical microtrauma treatment (e.g., applied negative pressure, length of treatment cycle, time elapsed of treatment cycle, time remaining of treatment cycle, etc.).

[0040] In one embodiment, the device includes a timer configured to shut off the device after a predetermined treatment cycle.

[0041] In another embodiment, the graphical user interface can include a user-adjustable timer interface. This can allow the user to set the treatment cycle. In other embodiments, the treatment cycle can be pre-programmed. This can reduce the required user input and facilitate ease of use.

[0042] In one embodiment, the treatment module includes an imaging device (e.g., video or CCD camera) and optional illumination system configured to image the vaginal wall during use. The device can be configured to display the image from the imaging device on the graphical user interface.

[0043] In one embodiment, the treatment module includes a humidity sensor configured to sense vaginal wall humidity. In one embodiment, the device includes a processor configured to receive humidity data from the humidity sensor and process or store the data. The processor can be configured to display the humidity-related data on a graphical user interface forming part of the device, or to wirelessly relay the data to a remote computing device.

[0044] In a preferred embodiment, the actuation / controller module is a remote actuation / controller module (i.e., provided as a remote base station), operably connected to the treatment module, and including the actuation and / or control mechanisms for the microtrauma module. The actuation / controller module can be operably 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 the use of disposable treatment modules that can be detached from the remote actuation / controller module after use and disposed of.

[0045] The flexible lead can be detachable from the actuation / controller module, such that the flexible lead and the treatment module are detachable from the actuation / controller module and are disposable parts. The treatment module can be detachable from the flexible lead, such that the treatment module is a disposable part. This allows the treatment module or both the treatment module and the flexible lead to be disconnected and disposed of after use and replaced for subsequent uses.

[0046] The VA treatment device can also include a tamper-evident device. The tamper-evident device can be provided at the point of connection between the disposable and non-disposable parts of the device (e.g. at the proximal end of the flexible lead, which connects to the actuator / controller module, or at the treatment module, which connects to the flexible cable). The actuator / controller module can be provided to sense the tamper-evident device and determine, based on the tamper-evident device, whether the disposable part is being used for the first time, and prevent actuation of the vacuum pump if it is determined that the disposable part has been reused. The VA treatment device can be provided with a sensor in position to sense or read the tamper-evident device (e.g. at the actuation controller module, or at the distal end of the flexible cable).

[0047] The tamper-evident device can comprise a unique identifier, and the device further comprises a sensor provided to read the unique identifier. The actuation / controller module can be provided to determine, based on the unique identifier, whether the flexible lead is being connected for the first time. The tamper-evident device can be provided to be altered or removed during the first connection of the flexible lead. It can be a tamper-evident cap, seal or foil. The sensor can be provided to sense the presence or condition of the tamper-evident device, the actuation / controller module being provided to determine, based on the presence or condition of the tamper-evident device, whether the flexible lead is being connected for the first time.

[0048] In one embodiment, the device (e.g. the processor) can include a communication mechanism for wirelessly relaying data to a remote computing device (e.g. 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 can include a mobile communication network such as a Global System for Mobile Communications (GSM) network, a Code Division Multiple Access (CDMA) network, a Third Generation Partnership Project (GPP), an Internet Protocol (IP) network, a Wireless Application Protocol (WAP) network, a WiFi network or an IEEE 802.11 standard network, and various communications thereof. Other conventional and / or later-developed wired and wireless networks can also be used.

[0049] In one embodiment, the device, in particular the treatment module, and more particularly the distal treatment head (e.g. the external tip member) is formed of a soft, lubricious material.

[0050] In another aspect, the application provides a method of treating vaginal atrophy in a mammal (particularly a human), comprising the step of applying mechanical microtrauma to the vaginal wall of the mammal, optionally using an insertable device comprising a microtrauma module configured to deliver mechanical microtrauma treatment to the vaginal wall 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.

[0051] In one embodiment, the method comprises applying mechanical microtrauma treatment to the vaginal wall for a treatment cycle. The duration of the treatment cycle can be 1-90 minutes, 1-60 minutes, 1-30 minutes, 5-90 minutes, 5-60 minutes, or 5-30 minutes. In one embodiment, the mammal is treated once every 1, 2, 3, 4, 5, 6, or 7 days (weekly), every two weeks, or monthly. In one embodiment, the mammal is suffering from vaginal atrophy. In one embodiment, the mammal is suffering from vaginal dryness.

[0052] In one embodiment, the method comprises the steps of positioning the treatment module at a first location in the vagina and applying a first dose of mechanical microtrauma treatment, and repositioning the treatment module at a second location in the vagina and applying a second dose of mechanical microtrauma treatment. In one embodiment, repositioning comprises rotating the device about the longitudinal axis. In another embodiment, repositioning comprises adjusting the depth of the device.

[0053] Except where mutually exclusive, features or parameters described in relation to any one aspect can be applicable to any other aspect. As used herein, the range "from X to Y" or "between X and Y" and the like means a range including the boundary values

[0054] Other aspects and preferred embodiments of the application are defined and described in the other claims below. BRIEF DESCRIPTION OF DRAWINGS

[0055] Figure 1 A device comprising a treatment module, a remote actuation / controller module, and a wire providing operational communication between the treatment module and the remote module is shown.

[0056] Figure 2 (A) of FIG. 1 is a block diagram showing the design of one embodiment of the device of the present application; Figure 2 (B) of FIG. 1 shows an alternative configuration of the portion of (A) in which the suction tube (flexible wire) is reusable and protected by a filter disposed in the treatment module.

[0057] Figure 3 A treatment module for vacuum therapy is shown in elevation (A) and plan (B).

[0058] Figure 4 A treatment module for vacuum therapy is shown in elevation: (A) the orifices are disposed in an array on opposite sides of the module wall; (B) the orifices are disposed in a single array circumferentially around the module wall; and (C) the orifices are disposed in a radial band of holes (the holes can be various shapes other than those shown, e.g., they can be circular, oval, or other shapes).

[0059] Figure 5Anatomy of the vagina and uterus is shown, with close-ups showing the inner layer (squamous), connective tissue, and muscle layers.

[0060] Figure 6 (A) insertion of a treatment module forming part of the device into the vagina and delivery of mechanical micro-abrasive therapy by deploying multiple needles into the vaginal wall; and (B) insertion of a treatment module into the vagina and delivery of mechanical micro-abrasive therapy by applying negative pressure therapy to the vaginal wall.

[0061] Figure 7A and 7B is a schematic of the device with the actuator / controller module and power source located in the handle.

[0062] Figure 8 is a schematic of a system comprising the device of the present application and a mobile phone.

[0063] Figure 9 The device of the present application is shown with a storage box resting on a bed-side storage cabinet.

[0064] Figure 10 A method of connecting flexible wires to the actuator / controller is shown.

[0065] Figure 11 The device of the present application is shown.

[0066] Figure 12 (A) to (C) in show information that can be shown graphically on an LCD screen.

[0067] Figure 13 An embodiment of an actuator / controller similar to that of Figure 12 is shown.

[0068] Figure 14 Plan and cross-sectional views of a treatment module according to another embodiment of the present application are shown.

[0069] Figures 15 to 17 Plan, cross-sectional, and close-up views of an embodiment of a treatment module having treatment portions of different shapes and cross-sectional dimensions are shown.

[0070] Figure 18A Plan and cross-sectional views of an embodiment of a treatment module having holes with rounded corners are shown.

[0071] Figure 18B In, (A) shows Figure 18A close-up views of an embodiment, and (B) use of rounded edge holes compared to sharp edge holes.

[0072] Figure 19A VA treatment device according to another embodiment is shown.

[0073] Figure 20 A treatment module of the device of Figure 19 is shown in an exploded view.

[0074] Figure 21 An external tip member of the treatment module of Figure 20 is shown in end view, top view, and side view.

[0075] Figure 22 and 23 First and second portions of a support member of the treatment module of Figure 20 are shown in front view, top view, rear view, and perspective view, respectively.

[0076] Figure 24 A control / actuation module of the device of Figure 19 is shown in an exploded view.

[0077] Figure 25A , 25B , 25C show experimental results using the device of the present application. DETAILED DESCRIPTION

[0078] All publications, patents, patent applications and other references mentioned herein are hereby incorporated by reference in their entirety for all purposes as if each individual publication, patent, patent application or other reference was specifically and individually indicated to be incorporated by reference for all purposes, and the contents of which are to be taken entirely of record herein.

[0079] Definitions and general preferences

[0080] As used herein, unless otherwise expressly specified, these terms are intended to have the meanings that can be normally ascribed to them by those of ordinary skill in the art, and that are used consistentily throughout the description:

[0081] The use of the singular herein shall be understood to include the plural, and vice versa, unless otherwise expressly stated. The use of the term "a" or "an" with respect to an entity shall be understood to mean one or more of that entity. Thus, the terms "a" (or "an"), "one or more", and "at least one" are used interchangeably herein.

[0082] As used herein, the term "comprise" or variations such as "comprises" or "comprising" shall mean include but not to the exclusion of any further integers (e.g. features, elements, characteristics, properties, method / process steps or limitations). As used herein, the term "comprising" is inclusive or open and does not exclude additional, unrecited integers or method / process steps.

[0083] 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, condition, malady or syndrome in which physiological function is impaired, regardless of etiological nature (or indeed whether an etiological basis for the disease has been established). It thus encompasses conditions arising from infection, trauma, injury, surgery, radioablation, poisoning or nutritional deficiency.

[0084] As used herein, the term "vaginal atrophy" refers to a chronic and progressive condition caused by a reduction or absence of oestrogen. It causes the vagina and the tissues near it to become dry, thin and inflamed. Vaginal atrophy is prevalent in postmenopausal women, but is more common in breast cancer survivors (BCS) who experience early menopause as a result of their cancer treatment. VA describes a range of symptoms, including vaginal dryness, irritation, pain and urinary incontinence, and affects a large proportion of postmenopausal women. This condition disproportionately affects BCS, who experience early menopause as a result of their cancer treatment. BCS who receive systemic endocrine therapy (e.g. aromatase inhibitors and tamoxifen) also experience more severe VA symptoms, due to the oestrogen-suppressing effects of these therapies. The devices and methods of the present invention are used to treat vaginal atrophy and vaginal dryness.

[0085] As used herein, the term "treatment" or "treating" refers to an intervention (e.g. administration of an agent to a subject) that cures, ameliorates or lessens symptoms of a disease or removes (or lessens the impact of) its cause. In this context, the term is used synonymously with the term "therapy". The treatment can be causal or symptomatic.

[0086] In addition, the term "treatment" or "treating" refers to an intervention (e.g. administration of an agent to a subject) that prevents or delays the onset or progression of a disease or reduces (or eradicates) its incidence in the treated population. In this context, the term treatment is used synonymously with the term "prevention".

[0087] As used herein, an effective amount or therapeutically effective amount of negative pressure therapy defines a dose 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 that is sufficient to provide the desired effect, e.g., treatment or prevention as evidenced by permanent or temporary improvement of the subject’s condition. The dosage (pressure and / or treatment time) will vary from subject to subject depending on the age and general condition of the individual, the mode of administration and other factors. Thus, while it is not possible to specify an exact effective amount, one of ordinary skill in the art will be able to determine an appropriate “effective” amount in any individual case using routine experimentation and background knowledge. Therapeutic outcomes in this context include eradication or reduction of symptoms, reduction of pain or discomfort, prolongation of survival, improvement in mobility, and other markers of clinical improvement. Therapeutic outcomes need not be complete cure.

[0088] In the context of treatment and effective amounts as defined above, the term subject, which where the context permits is understood to include “individual,” “animal,” “patient,” or “mammal,” defines any subject in need of treatment, particularly a mammalian female subject. 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, cows, dairy cows; primates, such as apes, monkeys, chimpanzees, and gorillas; canids, such as dogs and wolves; felines, 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.

[0089] “Therapeutic module” refers to a portion of the device of the present invention that is configured to be inserted at least partially into the vagina and includes a microtrauma module to deliver mechanical microtrauma therapy to the vaginal wall when inserted. The module (or at least the portion that is inserted into the vagina) will generally have a smooth, non-traumatic shape, and the surface of the microtrauma module is configured to abut the vaginal wall when inserted. The therapeutic module can have a distal (transvaginal) portion configured to be inserted into the vagina (“distal therapeutic portion”), and a proximal portion configured to be held by the user during use (“proximal handle portion”).

[0090] “Microtrauma module” means a portion of the therapeutic module that is configured to deliver mechanical microtrauma therapy to the vaginal wall when the therapeutic module is inserted into the vagina.

[0091] "Mechanical microtrauma" refers to a slight deformation of the vaginal wall resulting from the physical interaction between the microtrauma module and the wall that is sufficient to induce inflammation-induced angiogenesis and stimulate new endothelial cell proliferation and / or production of collagen matrix. The microdeformation can include microtears, punctures, holes, stretches, and cracks in the vaginal wall. One 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 vaginal wall are also contemplated. For example, the microtrauma module can include needles (or more preferably, microneedles) configured for deployment during use to create microabrasions in the vaginal wall. The microneedles can be actuated for deployment from a retracted delivery position within the device to a deployed position in which the microneedles penetrate the vaginal wall during use. In another embodiment, the microtrauma module can include a mechanism for stretching the vaginal wall to create microtears or cracks in the wall, such as a mechanism for grasping a portion of the wall at each end of a cross-section and then stretching the wall. In another embodiment, the use of heating or cooling can be employed to create mechanical microtrauma in the vaginal wall. In another embodiment, the mechanical microtrauma module can include a mechanism for applying abrasion or mechanical deformation (rolling) to the vaginal wall.

[0092] "Negative pressure therapy" refers to the process of creating microdeformation in the vaginal wall by applying a vacuum to the vaginal wall, where the microdeformation is sufficient to stimulate the proliferation of new endothelial cells and collagen matrix, which will thicken the vaginal wall, reduce atrophy, and increase the moisture retention capacity of the cells in the vaginal wall, reducing dryness. One embodiment of the device of the present invention applies negative pressure therapy to an area of the vaginal wall through a plurality of small holes, typically a small, tightly packed array of holes, which are in fluid connection with a vacuum pump in the device. The use of negative pressure therapy in 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 promotes healing by increasing the rate of angiogenesis, endothelial proliferation, capillary blood flow, and reduction of interstitial edema, among other things. This approach is applicable to the vaginal wall, where it causes similar beneficial microtrauma effects. Negative pressure creates controlled, beneficial microtrauma to the vaginal wall to induce the beneficial inflammatory cascade of angiogenesis and neo-collagen generation (collagen turnover), which is a well-recognized molecular pathway. The literature supports that negative pressure therapy can induce angiogenesis and endothelial proliferation, which are the mechanisms needed to regenerate the vaginal wall to address vaginal atrophy. Vaginal lubrication is derived from the lamina propria, which contains elastic fibers, blood vessels, lymph, and nerves, as well as glands that secrete mucus and serous fluid. The lamina propria of an atrophic vagina has reduced extracellular matrix components, decreased vascularization, and water retention capacity. The device and method of the present invention induce angiogenesis of the lamina propria to produce microvascularization and neovascularization. This in turn will produce moisture and lubrication effects, while collagen remodels the connective tissue and elastin fibers of the vaginal wall, restoring the vaginal mucosa and rehydrating the vaginal wall. HA synthesis increases in response to inflammation or trauma to vaginal tissue (i.e., the tip with perforations will induce controlled, beneficial microtrauma). HA modulates multiple aspects of tissue repair, including activating inflammatory endothelial cells to enhance angiogenesis, thereby forming new blood vessels from existing ones. HA synthesis decreases with age, which is associated with decreased estrogen production.

[0093] A "pore" is to be understood as a hole that is small enough to deliver a negative pressure to the vaginal wall. 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, but holes of other shapes can be employed, for example square or rectangular, as long as they are small enough.

[0094] A "remote actuator / controller module" refers to an actuator / controller module that is separate from the therapeutic module and is typically connected by a connecting lead. It is also referred to herein as a remote "base station". The remote actuator / controller module typically includes mechanisms for actuating the mechanical microtrauma module, such as a pump, a motor, a heater, a graphical user interface, and a processor for receiving data related to the operation of the therapeutic module or treatment.

[0095] Examples

[0096] The application will now be described with reference to specific examples. These are merely exemplary and for illustrative purposes only: they are not intended to limit the scope of the patent protection or the described invention in any way. The examples constitute the best mode presently envisaged for carrying the invention into practice.

[0097] With reference to the drawings, reference will first be made to Figures 1 to 3 , which shows one embodiment of the device of the application, generally indicated by reference numeral 1. In this embodiment, the device is configured to deliver a mechanical microabrasive treatment by means of negative pressure therapy. The device 1 comprises a therapeutic (or treatment) module 2, a remote actuator / controller module 3, and a flexible lead 4 providing operational communication between the therapeutic module 2 and the remote module 3. The therapeutic module 2 comprises a distal therapeutic portion 5 having a curved atraumatic shape; and a microtrauma module provided in the form of two rows of pores 6, the pores 6 being disposed on opposite sides of the sidewall of the distal portion; and a proximal portion 7 configured to be held by a user during use of the device. The actuator / controller module 3 comprises a vacuum pump 8, a pressure transducer 10 configured to detect in real time the vacuum drawn by the pump 8, and a processor 11 configured to receive pressure data from the pressure transducer 10, the pump 8 being fluidically connected to the array of pores 6 and an exhaust 9 by the lead 4. A power supply 12 is operably connected to the processor, pump and pressure transducer, which can be mains electricity or a battery (not shown). The processor is configured to receive pressure data from the transducer 10 and process the data. The processor can be pre-programmed to apply a certain level of negative pressure therapy and can be configured to adjust the pump to adjust the pressure in accordance with pressure readings received from the pressure transducer. The processor can be operably connected to a graphical user interface (GUI) to display pressure readings on the GUI.

[0098] In any of the embodiments described herein, the treatment module 2, or both the treatment module 2 and the flexible lead 4, can be detachable from the actuator / controller module 3. Once detached, one or both of the treatment module 2 and the flexible lead 4 can be disposable.

[0099] In Figure 2 In the embodiment shown in part (A) of the figure, the flexible lead 4 is detachable from the actuator / controller module 3. Thus, the flexible lead 4 and the treatment module 2 are disposable and can be replaced for further use (i.e. they are consumables). In the embodiment shown in part (B) of the figure, the flexible lead 4 is detachable from the treatment module 2, so only the treatment module is disposable. In this embodiment, the treatment module 2 comprises a filter 5 (e.g. a hydrophobic filter module, described later) arranged to prevent contaminants drawn in through the flexible lead 4 from reaching the vacuum pump 8. Figure 2

[0100] In any of the embodiments described herein, the VA treatment device can further comprise a tamper-evident device arranged to prevent re-use of any disposable components. In Figure 2 In the embodiment of part (A) of the figure, the proximal end of the flexible lead 4 (i.e. the lead connected to the actuator / controller module 3) has a tamper-evident device 4a. The actuator / controller module comprises a sensor 4b arranged to sense the tamper-evident device to determine whether the flexible lead has been used before, or whether it is being used for the first time. The actuator / controller module 3 is arranged to prevent actuation of the treatment if the flexible lead 4 is determined to have been connected before.

[0101] In one embodiment, the tamper-evident device 4a comprises a unique identifier that can be read by the sensor 4b provided at the actuator / controller module 3. The actuator / controller module 3 is arranged to determine whether the flexible lead has been used before based on the unique identifier. For example, the actuator / controller module 3 can record the unique identifier in a memory when the flexible lead 4 is connected. The actuator / controller module 3 can then compare the unique identifier subsequently read with the unique identifier read during a previous use in order to determine whether the flexible lead / treatment module is being used again or is being connected for the first time. The unique identifier can take the form of a printed ID code (e.g. a bar code, a QR code), or can be stored on a chip or a magnetic strip, etc.

[0102] ​In other embodiments, the tamper-proof device 4a is configured to be altered or removed during the connection process of the flexible wire 4. For example, the tamper-proof device 4a may include a tamper-proof cap, a seal, or a foil, which is destroyed / removed when the flexible wire 4 is first connected. The actuation / controller module 3 is configured to sense the presence or status of the tamper-proof device 4a via a suitable sensor located at the connection point to determine whether the flexible wire 4 is being reused.

[0103] Although the tamper-proof device 4a is shown near the end of the flexible cable 4, it can be located in other locations within the device. For example, the tamper-proof device 4a can be located in the treatment module 3, with the corresponding sensor located in a connector at the end of the flexible wire 4. This arrangement is suitable for cases where only the treatment module is disposable.

[0104] Figure 4 Three embodiments of the treatment module are shown, in which the orifices are arranged in an array on opposite sides of the wall of module (A), and in a single array around the wall of module (B). (C) shows an embodiment with radially distributed orifices. It should be understood that the orifices can be arranged in other ways, including multiple orifice arrays.

[0105] Figure 5 and Figure 6 The use of the device of the present invention is shown, wherein Figure 5 The anatomical structure of the female human uterus and vagina is shown, and Figure 6 The distal treatment section of the treatment module of a device inserted into the vagina and actuated to administer mechanical microinvasive treatment is shown. Figure 6 In (B) (right figure), the device includes a circumferential array of orifices configured to deliver negative pressure therapy to the vaginal wall in contact with the orifices. Figure 6 In (A) (left figure), the device includes an array of deployable needles 25 configured to deploy into the vaginal wall. In both cases, the treatment results in microdeformations in the vaginal wall sufficient to induce angiogenesis and stimulate the proliferation of new endothelial cells and / or the production of collagen matrix, thereby treating vaginal atrophy.

[0106] refer to Figure 7A and 7B, showing an alternative embodiment of the device of the invention, in which parts identified with reference to the preceding embodiments are given the same reference numerals. In this embodiment, indicated by reference numeral 20, the device is provided as a single elongate body having a distal treatment portion 21 with an array of apertures 5 and a proximal handle portion 22, which portions are configured for disassembly. The handle portion 22 includes a vacuum pump, a processor, a pressure sensor, a battery (not shown) and an on / off button 23. The distal treatment portion is a single-use disposable portion which can be discarded after use. This embodiment of the device can be provided in modular form, comprising a single handle portion and a plurality of disposable distal treatment portions.

[0107] Reference is made to Figure 8 , showing a device of the invention, in which parts identified with reference to the preceding embodiments are given the same reference numerals. The device includes a treatment module 2 and a remote actuator controller 3 connected by a lead 4, as previously described. The actuator / controller is configured to relay data to a mobile phone 30, and the phone includes downloadable software (i.e. an "app") configured to receive and process data received from the actuator / controller and to display information on the phone screen 31 relating to the operation and treatment of the device. In this illustration, the phone provides information relating to the status of the treatment (i.e. treatment in progress) and the time remaining for the treatment.

[0108] Reference is made to Figure 9 , showing a device of the invention and a storage case resting on a bedside cabinet. The device includes a remote reusable actuator / controller, a disposable treatment module and a flexible lead. A storage case for the actuator controller is provided, as well as a storage case for the treatment module and flexible lead.

[0109] Reference is made to Figure 10 , showing a method of how to connect a flexible lead to an actuator / controller, the method having a friction fit "click to close" connection mechanism and a quick release mechanism to allow easy and quick disconnection of the lead and actuator controller.

[0110] Reference is made to Figure 11 , showing a device of the invention, showing an end face of the actuator / controller having a port for receiving a flexible lead, a pump exhaust port and a power adapter port. Also shown is a flexible lead including a woven sheath which helps to avoid kinking or crushing of the lead.

[0111] Reference is made to Figure 12 (A) to (C), showing information which can be graphically illustrated on an LCD screen, including information relating to the treatment cycle (A), information relating to the operational status of the device (B), and information relating to the remaining battery charge of the device (C).

[0112] Referring to Figure 13 , an embodiment of an actuator / controller similar to that of Figure 12 is shown, wherein the actuator / controller comprises a graphical display (in this case a strip of illuminated LEDs 40) disposed on one side of the actuator, which can indicate the status of the device at a glance.

[0113] Another embodiment of a VA treatment device 100 is shown in Figure 14 . In this embodiment, the treatment device 100 is configured to deliver mechanical microtrauma treatment to the vaginal wall in the form of negative pressure therapy.

[0114] As can be seen from Figure 14 , the device 100 comprises a treatment module 101 configured to be inserted into the vagina. The treatment module 101 has a distal treatment portion 105 insertable into the vagina and a proximal handle portion 107 through which a user can manipulate the treatment module 101, similar to other embodiments described herein. Corresponding reference numerals are used for parts common to other embodiments to aid explanation. Any features described in connection with other embodiments can be applied to the embodiment of Figure 14 .

[0115] The treatment module 101 comprises a plurality of apertures 106 in an array on at least a portion of an outer surface 108 of the treatment portion 105. Figure 14 The apertures 106 shown in are evenly disposed around the entire circumference of the treatment portion 105. In other embodiments, the apertures 106 can be disposed in a discrete array, can have a non-uniform distribution, or can be arranged around only a partial circumference.

[0116] Figure 14 The distal treatment portion 105 of the treatment module 101 comprises a sealed portion 105a shown) which is the axial portion of the device portion inserted into the vagina during use, but which does not include any aperture array 106. The apertures are only located in an aperture portion 105b distal to the sealed portion. As shown, the sealed portion is located distal to the treatment portion. By forming a region without apertures, the sealed region helps to ensure that all of the apertures are in contact with the vaginal wall when the treatment portion is inserted, and that no vacuum pressure leaks occur when vacuum pressure is applied, as the apertures are not in the vaginal cavity during use.

[0117] Figure 14 The treatment module 101 comprises an elongate hollow member (as shown in Figures 15 to 17 and 18, which can be straight; or as shown in Figure 14As can be seen in the cross-section shown, the hole 106 is formed by a through-hole 110 extending through the wall 112 of the treatment module 101, which leads to the inner cavity 114 within the hollow component. The cavity 114 is connected to the vacuum pump (…). Figure 14 (Not shown) fluid communication is provided to generate negative pressure within cavity 114 and at orifice 106. In this embodiment, device 100 also includes an actuation / controller module as described with respect to other embodiments. Figure 14 (Not shown in the image). The vacuum pump is located within the actuation module and is fluidly connected to the treatment module via flexible wires, such as in combination. Figure 1 The flexible lead takes the form of a flexible-length conduit connecting the treatment module and the actuation / controller module. However, as combined with... Figure 7A and 7B The vacuum pump may be located within the treatment module 101 (e.g., within the handle portion 107).

[0118] Figure 14 The VA treatment device 100 of the illustrated embodiment is configured to deliver mechanical microtrauma treatment by pulling tissue into and through orifices 106. In use, a negative pressure provided at the orifices 106 causes adjacent tissue near or in contact with the outer surface 108 of the treatment module 101 to be pulled into and through the orifices 106, causing the tissue to elongate within the holes 110. Thus, the mechanical microtrauma is generated by the strain of the tissue pulled into each orifice 106.

[0119] To draw tissue into the orifice, a negative pressure (i.e., a pressure less than ambient atmospheric pressure) is generated at the orifice by a vacuum pump. In various embodiments, the pressure generated at the orifice by the pump is at least about 50 mmHg, and preferably less than 800 mmHg. In other embodiments, it is greater than about 100 mmHg, and preferably less than 800 mmHg. In some embodiments, the pressure can be in the range between 50 mmHg and 600 mmHg. The pressure range in this paragraph is generally suitable for providing negative pressure at vaginal tissue without causing tissue damage. Other pressure ranges defined elsewhere herein may be used.

[0120] In the preferred embodiment described herein, a pressure between approximately 200 mmHg and 600 mmHg is generated during use. The inventors have discovered that when this pressure is applied to the vaginal wall, it provides a favorable level of tissue microtrauma, which in turn provides the desired VA treatment.

[0121] 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 vaginal tissue is limited, thus creating minimal strain. This results in a small microtrauma being created. This can be insufficient to create the desired healing response and associated vaginal tissue regeneration. At high vacuum pressures, the tissue is drawn deeply into each hole. This can create excessive elongation of the tissue, resulting in unwanted tearing and / or bleeding. Furthermore, if the tissue is elongated excessively within the hole, it can protrude over the inner surface of the treatment portion, creating a mushroom-like effect. This can again result in tearing and / or bleeding of the vaginal tissue. Tearing and bleeding can result in negative clinical outcomes, including scarring or ulceration.

[0122] In other embodiments, the pressure can be in the range between 300 mmHg and 450 mmHg. This has been found to provide a more optimal treatment effect.

[0123] In the presently described embodiments, the holes have a cross-sectional dimension (e.g. maximum diameter) as indicated by P in Figs. 17 and 18. The inventors have found that, in addition to pressure and other factors, the behaviour of the tissue drawn into each hole is influenced by the hole entrance dimension. Thus, the cross-sectional dimension of the hole has a significant effect on the microtrauma, and the corresponding clinical efficacy and safety. In various embodiments, the maximum cross-sectional dimension of the hole is at least 0.5 mm, and preferably less than 4 mm. In other embodiments, the maximum cross-sectional dimension of the hole is greater than 1.0 mm, and preferably less than 4 mm. Figure 14 In the presently described preferred embodiments, the hole diameter is in the range between 2 mm and 3 mm. This has been found to provide a more optimal microtrauma. In other embodiments, an optimal diameter of approximately 2.5 mm can be used. The inventors have found that this provides an optimal treatment. The inventors have found that a diameter of the hole in the range of approximately 2 mm to 3 mm provides an optimal hole diameter which maximises the level of microtrauma without the risk of complications such as tissue tearing and associated bleeding. If a hole size less than the above range is used, the result can be that less tissue is drawn into the hole due to the increased friction effect as the diameter of the hole is reduced. This can result in an insufficient microtrauma effect being provided to deliver the VA treatment. A hole larger than the above range can result in more tissue being drawn into each hole due to the lower frictional forces. This results in greater tissue deformation, leading to unwanted tissue damage. Furthermore, as the diameter of the hole is increased, the deformation and associated microtrauma is less localised, resulting in an ineffective VA treatment. The inventors have found that the range of cross-sectional dimensions of the hole provides advantageous results, particularly in combination with the pressure range defined herein.

[0124] In the presently described preferred embodiments, the hole diameter is in the range between 2 mm and 3 mm. This has been found to provide a more optimal microtrauma. In other embodiments, an optimal diameter of approximately 2.5 mm can be used. The inventors have found that this provides an optimal treatment. The inventors have found that a diameter of the hole in the range of approximately 2 mm to 3 mm provides an optimal hole diameter which maximises the level of microtrauma without the risk of complications such as tissue tearing and associated bleeding. If a hole size less than the above range is used, the result can be that less tissue is drawn into the hole due to the increased friction effect as the diameter of the hole is reduced. This can result in an insufficient microtrauma effect being provided to deliver the VA treatment. A hole larger than the above range can result in more tissue being drawn into each hole due to the lower frictional forces. This results in greater tissue deformation, leading to unwanted tissue damage. Furthermore, as the diameter of the hole is increased, the deformation and associated microtrauma is less localised, resulting in an ineffective VA treatment. The inventors have found that the range of cross-sectional dimensions of the hole provides advantageous results, particularly in combination with the pressure range defined herein.

[0125] Figure 14 ​In the illustrated embodiments, the holes are generally cylindrical and have a constant diameter along their length. In other embodiments, the holes can have other shapes, for example their cross-sectional shape can be oval. In other embodiments, the diameter of the holes can vary along their length. In such embodiments, the diameter of the hole is measured in the plane of the aperture (i.e. not including any larger or rounded portion of the aperture at the outer wall of the treatment portion as shown in Figure 18). The cross-sectional dimensions of the aperture given herein are measured for the hole or channel forming the aperture, as shown at the plane of the aperture in the inset of Figure 18.

[0126] With reference to Figure 14 The holes 110 forming the apertures 106 have a length or depth, labelled L, by which they extend from the outer surface 108 of the treatment model through the wall 112. The length L is measured along the axial centre line of the hole, from a point level with the outer surface 108 of the wall 112 of the treatment portion 105 to a point level with the inner surface of the wall 112 at which the hole 110 opens into the lumen 114. In various embodiments, the holes extend a depth of at least about 1 mm (preferably less than 6 mm). In other embodiments, the holes extend a depth of greater than about 2 mm (preferably less than 6 mm). The inventors have found that the depth of the hole also has an effect on the microtrauma created. The inventors have found that a hole depth less than the above ranges risks the tissue reaching the inner surface of the hollow member too quickly, at which point the tissue can be pulled out by the vacuum, creating a mushroom effect on the inner surface. This can lead to excessive deformation of the vaginal tissue and associated complications.

[0127] In the presently described preferred embodiments, the depth of the hole is between 3 mm and 4 mm. The inventors have found that this provides a more optimised level of microtrauma suitable for VA treatment. In other embodiments, a hole depth of 3.5 mm is provided. The inventors have found that this provides optimal treatment. The inventors have found that a hole depth greater than the above ranges can cause excessive damage, i.e. can tear the tissue. The inventors have found that the ranges of hole depth defined in this paragraph and the above paragraph provide advantageous results, particularly in combination with the pressure ranges defined herein.

[0128] In other embodiments, different hole geometries can be provided. The depth of the hole is defined as the length of the channel created by the hole in which elongation of the contained tissue can occur. In other words, the hole depth is the distance that the tissue can extend from the outer surface 110 before it is no longer contained by the inner wall of the hole (e.g. by opening into a cavity) or by contact with the end wall of the hole.

[0129] Figures 15 to 17 Embodiments of the device 100 are shown with treatment portions 105 having various different shapes. In these embodiments, the treatment portion 105 has a curved shape, rather thanFigure 14 a straight line shape.

[0130] In Figures 15 to 17 various cross-sectional dimensions of the treatment portion 105 are shown. The maximum cross-sectional dimension D of the treatment portion can be in the range of 20 mm and 30 mm. The inventors have found that a larger diameter (e.g., greater than 30 mm) will result in circumferential stretching of the vaginal wall. This in turn makes it more difficult to deform the tissue and pull it into each hole such that negative pressure therapy can be properly provided. However, a larger diameter means that the tissue will have been circumferentially compressed by the treatment module used as a dilator, and thus, some degree of trauma is delivered to the tissue. Accordingly, a small diameter (e.g., less than 20 mm) will not sufficiently circumferentially stretch the vaginal canal, and the tissue will easily be pulled into each hole because there is no resistance from the tissue being under tension. If the tissue is not under tension, it is more easily pulled into the hole because nothing can resist it. If the diameter is too narrow, the negative pressure can not be sufficiently applied to the tissue surface, and it can not be able to pull the tissue into the hole at all. The inventors have found that a cross-sectional dimension in the range of 20 mm to 30 mm provides a favorable balance of these factors (e.g., for a human subject). However, for other applications, other dimensions can be envisioned.

[0131] In Figures 14 to 17 In the illustrated embodiment, the cross-section of the treatment portion is circular. In other embodiments, the cross-section can be non-circular. In some embodiments, the cross-sectional dimension (or shape) can vary along the length of the treatment portion 105, as Figure 16 illustrated. The cross-sectional dimension of the treatment portion 105 is considered to be the maximum cross-sectional dimension at any point along the insertable tip portion length (e.g., the length of the treatment portion configured for insertion during use).

[0132] Another embodiment of a VA treatment device is shown in Figure 18A and Figure 18BThe holes 110 forming the apertures have rounded edges 116 where they meet the outer surface of the treatment portion. In the illustrated embodiment, all of the entrances of the holes 106 have rounded edges. However, in some embodiments, only some of the holes 106 have rounded edges at locations where they pose a greater risk of causing greater damage to tissue as they are passed through. The inventors have found that the entrance geometry of each hole at the outer surface 108 of the treatment portion 105 will also have an impact on how tissue is drawn into each hole. The rounding of the entrance of each hole 106 reduces the mechanical load on the tissue as it is drawn into the hole 106, and the entrance lengthens as the tissue is drawn down the passage of the hole. The rounding helps to reduce the friction and strain in the vaginal tissue as it is drawn in through the edge of the hole. This reduces the risk of tearing of the tissue. The cross-sectional dimensions of the apertures given herein are measured for the holes or passages forming the apertures, as shown in Figure 18B The holes are shown without rounded edges in the plane of the apertures.

[0133] Although Figures 14 to 17 The illustrated embodiment has holes without rounded edges, but it will be appreciated that this is merely an example, and that rounded corners are provided in preferred embodiments. The inventors have found that it is desirable to eliminate sharp corners on the holes, which would be a potential source of trauma if the device or patient moves during treatment. In Figure 18B The use of rounded edges to the holes is shown in

[0134] In various embodiments, the outer surface of the treatment portion is formed of a material having any one or more of the following: a Shore hardness of 40A and a coefficient of sliding friction less than or equal to 0.4. Other material properties can be provided.

[0135] The inventors have found that the ranges of pressure, hole depth, aperture diameter and treatment module cross-section described above provide advantageous treatment effects. However, each of these factors can be used independently to provide advantageous effects, and not all are necessary to provide the desired mechanical microtrauma.

[0136] Figures 19 to 24 Another embodiment of a VA treatment device 200 is shown. The treatment device 200 includes a treatment module 201, an actuation / controller module 203 connected to the treatment module 201 by a flexible lead 204, as described in connection with other embodiments herein. The treatment module is shown in Figures 20 to 23 in more detail in Figure 24The treatment module 201 has a distal treatment portion 205 that is insertable into the vagina and a proximal handle portion 207, similar to other embodiments described herein, through which a user can manipulate the treatment module 201. The treatment portion includes a plurality of holes 206, similar to other embodiments described herein, that are in fluid connection with a vacuum source (e.g., a pump) provided within the actuation / controller module 203. Any of the features described in connection with other embodiments elsewhere herein can also be applied to Figures 19 to 24 embodiments described above in connection with Figures 14 to 1 8 can be applied to embodiments of Figures 19 to 24 , e.g., pressure ranges and hole placement, size, hole depth, and geometry, etc.). Reference is made to Figure 20 , the treatment module 201 includes a support member 220 (e.g., a support frame / scaffold) and an outer tip member 222 (e.g., an outer “sock / sleeve”). In this embodiment, the support member 220 is formed of two parts, a first part 221a and a second part 221b. The distal portion of the support member 220, together with the outer tip member, forms the inner portion of the distal treatment portion, and the proximal portion of the support member 220 forms the handle portion. The outer tip member 222 has an atraumatic elongate shape for insertion into the vagina, and can have a shape as described herein with respect to any other embodiment. The outer tip member 222 has a cavity extending along its axial length (as can be seen in Figure 21 ), which is open at its proximal end. The outer tip member 222 is arranged to fit over the distal portion of the support member, such that the support member is received within the cavity.

[0137] A friction fit is provided between the outer tip member 222 and the support member 220. This can be helpful for manufacturing, as no glue or welding is required to connect the components. The outer tip member 222 is formed of an elastomeric material, such as liquid silicone rubber (LSR) or thermoplastic elastomer (TPE). Other suitable elastomeric materials can be used. The use of an elastomeric material can improve the friction fit between the outer tip member 222 and the support member 220, as a tight fit can be provided. In some embodiments, a stretch fit of the outer tip member 222 over the support member 220 can be provided to aid in the seal and connection between them. The seal between them can also be provided by the use of an elastomeric material to reduce pressure loss or ingress of liquids. The distal portion of the support member 220 has a shape that corresponds to the shape of the outer tip member 222, such that it will retain its shape during use. The support member 220 is made of a relatively more rigid material compared to the outer tip member, to provide structural strength to the treatment portion, allowing for insertion.

[0138] Figure 21The external tip member 222 is shown separately. The external tip member includes a plurality of holes 206 through which microinvasive treatments are delivered. The holes are formed by through-holes extending through the wall 224 of the external tip member. As described elsewhere herein, the holes may have any size, shape, and depth.

[0139] Support member 220 in Figure 22 and 23 They are shown separately. Figure 22 and 23 The first portion 221a and the second portion 221b of the support member are shown in different views. The support member 220 includes a distal portion 220a adapted for insertion into the vagina during use, thus forming part of the treatment portion of the treatment module. The support member 220 also includes a proximal portion 220b forming the handle portion of the treatment module. Figure 20 As shown, the outer tip member 222 is fitted onto the distal portion 220a. In this embodiment, the support member 220 has a length C of approximately 160 mm. Other dimensions may be considered; this is given only as an example.

[0140] The support member includes an inner cavity 214. The inner cavity 214 is defined by a wall forming the distal portion 220a of the support member 220. The inner cavity 214 is in fluid communication with a vacuum pump provided in the actuator / controller module 203, and also with a hole 206 forming the outer tip member 222. Fluid communication between the inner cavity 214 and the vacuum pump is provided via an internal conduit 226 extending through the proximal portion 220b of the support member 220. The internal conduit 226 fluidly connects the inner cavity 214 and the flexible wire 204.

[0141] The support member 220 also includes a channel 228 that fluidly connects the inner cavity 214 to the opening of the outer tip member 222 forming the hole 206. In this embodiment, the channel 228 is formed by a combination of an opening 230 extending through the wall of the support member (which leads to the inner cavity 214) and a channel formed on the outer surface of the support member. When the outer tip member 222 is fitted onto the support member 220, its inner surface is spaced apart from a portion of the outer surface of the support member to define the channel therebetween. In this embodiment, the channel is formed by a ridge 232 defining a circumferential channel 230a. A cutout 234 in the ridge defines an axial channel to interconnect the circumferential channels along the length of the device, such that each circumferential channel does not require a corresponding opening 230. Other structural arrangements may be provided to form channels within the support member 220. For example, the cutout may be absent, providing an opening 230 for each circumferential channel.

[0142] The support member 220 is arranged to interlock with the external tip member such that the hole 206 of the external tip member is oriented with respect to the channel of the support member 220 and provides a fluid connection between the hole 206 and the support member 220. A keyed interlock arrangement is provided to ensure alignment and fluid connection. In the present embodiment, the hole of the external tip member 222 is aligned with the channel formed on the outer surface of the support member such that they are fluidly connected. This allows for easy assembly of the components of the device.

[0143] The treatment module 201 also includes a liquid trap 236 arranged to collect liquid (e.g. water) discharged from the vagina which can be drawn through the hole during use. The liquid trap 236 is arranged at a position upstream of the pump (along the fluid connection path between the pump and the hole 206) so as to collect any liquid drawn through the hole 206 before it reaches the pump. In the present embodiment, the liquid trap 236 is located within the handle portion 207 of the support member 220 such that it is located within the fluid communication path between the cavity 214 and the flexible conduit 204 (i.e. it is located at a point along the conduit 226). In other embodiments, the liquid trap 236 can be mounted elsewhere within the treatment module 201, or at the controller actuator module 203 or within the conduit 204. In other embodiments, it can be absent.

[0144] In various embodiments, the VA device 200 can include a hydrophobic filter. The hydrophobic filter can be provided in place of the liquid trap. The hydrophobic filter is arranged to prevent contaminants drawn through the hole 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 can be provided in the treatment module and can be arranged to prevent contaminants from passing along the flexible conduit or tubing connecting the treatment module to the pump. The filter module can alternatively be provided at any point on the fluid connection path upstream of the pump, for example at the connection point between the flexible conduit and the actuator / controller module.

[0145] Reference Figure 24The actuation / controller module 203 is shown in more detail. The actuation / controller module 203 includes a housing formed by a first (or top) portion 250 and a second (or bottom) portion 252. The first and second portions of the housing are connected by a bolt-type connection mechanism 254. In other embodiments, other connection mechanisms, such as adhesives, may be used. The controller actuation module 203 also includes a vacuum pump 256 mounted within the housing, which is fluidly connected to a flexible wire 204 via a conduit 258. The vacuum pump is configured to provide vacuum pressure at the orifice described above. The conduit 258 includes a connector 260 in the form of a T-connector. The T-connector is configured to split the pump output into a first output connected to a treatment module (e.g., via the flexible wire 204) and a second output connected to a sensor disposed within the actuation / controller module (e.g., via the flexible wire 204). Figure 2 As schematically shown, the sensor is located at controller 11. The second output and sensor provide a feedback loop to monitor pressure during use and allow for corresponding adjustment of pump operation. Actuation / controller module 203 also includes a microcontroller 262 operably in communication with pump 256 to provide control over treatment delivery. Microcontroller 262 is also operably in communication with a user interface including main control button 264 and LED panel 266. Actuation / controller module also includes a battery 268 and a power port 270 to provide electrical power. Various connectors 272, 274, 276, and 278 are provided to mount components within the housing. Connectors may be in the form of bolts as shown, although other types of components or connection mechanisms may also be provided.

[0146] Experimental test results

[0147] A series of experimental tests have been conducted on ex vivo and in vivo tissues to demonstrate the safety and efficacy of VA treatment. Figure 14 , 15 Preclinical testing of the device in sheep models, as illustrated in embodiment 16, showed that the microtrauma process and subsequent healing resulted in vaginal wall thickening, angiogenesis (i.e., blood vessel growth), and enhanced capillary flow. It has been found that minute vaginal hematomas (pinprick bleeding) do not cause any adverse bleeding or effusion because their mechanism of action only causes “microtrauma” to small blood vessels.

[0148] Figure 25A The above-described method is shown. Figure 14 , 15 The vaginal wall after treatment was delivered using a device of the type shown in Figure 16 (labeled “(a)”). Figure 25A A series of microtraumas induced in a sheep model by pulling tissue into a hole under negative pressure are shown (labeled "(b)"). Figure 25BHistological control images are shown demonstrating that the vaginal tissue was not exposed to inflammation-induced angiogenesis (indicated by the absence of endothelial cell proliferation or capillary remodeling, labeled "(c)"). Figure 25C Images obtained using histology are shown demonstrating angiogenesis and healing effects in the vaginal wall 3 weeks post-treatment. New remodeled capillaries are indicated by "(d)" and endothelial cell proliferation by "(e)".

[0149] Various modifications will be apparent to those skilled in the art without departing from the scope of the claims. Any feature disclosed in conjunction with an embodiment can be used with any and all embodiments. While the appended claims set forth particular combinations and sub-combinations of features, it is understood that off claims may, in fact, be directed to any novel feature or any novel combination of features disclosed herein. Each feature disclosed in this specification, and / or the recitation of any feature in any claim or accompanying description, should not be construed as being dedicated to the public whatever may be in fact.

[0150] Equivalents

[0151] The foregoing description details certain embodiments of the application. It will be appreciated, however, that numerous modifications can be made thereto without departing from the basic scope of the application. Such modifications are included within the scope of the following claims.

Claims

1. An apparatus for treating vaginal atrophy, comprising a treatment module configured for insertion into the vagina, at least a portion of the treatment module having an elongated, non-traumatic shape and an outer surface configured to abut against a vaginal wall upon insertion, the treatment module having a microtraumatic module configured to deliver negative pressure mechanical microtraumatic therapy to the vaginal wall upon insertion, wherein the microtraumatic module includes a plurality of holes formed by holes extending from a portion of the outer surface of the treatment module, the outer surface of the treatment module being configured to abut against the vaginal wall upon insertion, the holes being arranged on at least a portion of the outer surface of the treatment module and configured to deliver negative pressure therapy to the vaginal wall in contact with the holes, wherein the holes are fluidly connected to a vacuum pump, the apparatus being configured to generate negative pressure at the holes during use, thereby configuring the microtraumatic module to draw tissue of the vaginal wall into the holes during use to deliver microtraumatic therapy, stimulating angiogenesis within the tissue of the vaginal wall to provide treatment for vaginal atrophy, wherein the microtraumatic therapy is characterized by a series of injuries that persist on the vaginal wall after delivery of negative pressure mechanical microtraumatic therapy.

2. The apparatus according to claim 1, wherein: The device is configured to generate a pressure of at least 50 mmHg and less than 800 mmHg at the orifice; and The maximum cross-sectional dimension of the hole is at least 0.5 mm and less than 4 mm.

3. The apparatus according to claim 2, wherein: The maximum cross-sectional dimension of the portion of the treatment module suitable for insertion into the vagina is in the range of 20 mm to 30 mm.

4. The apparatus according to claim 2, wherein, The device is configured to generate a pressure at the orifice greater than 100 mmHg and less than 800 mmHg.

5. The apparatus according to claim 2, wherein, The device is configured to generate a pressure at the orifice in the range of 50 mmHg to 600 mmHg.

6. The apparatus according to claim 2, wherein, The device is configured to generate a pressure at the orifice in the range of 200 mmHg to 600 mmHg.

7. The apparatus according to claim 2, wherein, The device is configured to generate a pressure at the orifice in the range of 300 mmHg and 450 mmHg.

8. The device according to claim 2, wherein the maximum cross-sectional dimension of the hole is greater than 1.0 mm and less than 4 mm.

9. The device according to claim 8, wherein the maximum cross-sectional dimension of the hole is in the range of 2 mm and 3 mm.

10. The device of claim 1, wherein the hole extends to a depth of at least 1 mm.

11. The device of claim 10, wherein the depth of the hole extends in the range of 3 mm and 4 mm.

12. The apparatus of claim 1, wherein the apparatus includes a timer configured to turn off the apparatus after a predetermined treatment cycle, wherein the duration of the treatment cycle is 1-90 minutes.

13. The apparatus according to claim 1, wherein, The treatment module includes: A support member, the support member including a passage fluidly connected to the vacuum pump; An external tip component, the external tip component including a plurality of holes forming the orifice of the treatment module, The external tip member is configured to assemble around the distal portion of the support member, and the external tip member and the support member are configured to form an interlocking engagement, whereby the channel of the support member is aligned with the hole of the external tip member to form a fluid connection therebetween.

14. The apparatus of claim 13, wherein one or both of the following: a) The outer tip member is formed of an elastic material, and the support member is formed of a material that is relatively rigid compared to the outer tip member; and b) Provide a friction fit between the support member and the external tip member.

15. The apparatus according to claim 1, further comprising: a) A liquid collector, which is located upstream of the vacuum pump and configured to collect liquid discharge drawn in through the orifice; and / or b) A hydrophobic filter configured to block contaminants drawn in through the orifice from reaching the vacuum pump.

16. The apparatus according to claim 1, wherein, The treatment module includes a proximal handle portion and a distal treatment portion adapted for insertion into the vagina during use, wherein the orifice is provided on the treatment portion.

17. The apparatus according to claim 16, wherein, The treatment portion includes a proximal sealing portion without an orifice thereon and an orifice portion with an orifice thereon, the orifice portion being located at the distal end of the sealing portion.

18. The apparatus according to claim 16 or 17, wherein, The distal treatment portion is detachable from the proximal handle portion, and the distal treatment portion is disposable.

19. The apparatus according to claim 1, wherein, The device includes a remote actuation / controller module operatively connected to the treatment module and includes an actuation and / or control mechanism comprising a vacuum pump for the microtrauma module.

20. The apparatus according to claim 19, wherein, The treatment module is detachable from the remote actuation / controller module and is disposable.

21. The apparatus according to claim 20, wherein, The treatment module and the actuation / controller are connected by a flexible wire, wherein: the flexible wire can be detached from the actuation / controller module, so that the flexible wire and the treatment module can be detached from the actuation / controller module, and are disposable parts; or wherein the treatment module can be detached from the flexible wire, so that the treatment module is a disposable part.

22. The apparatus of claim 19, further comprising an anti-tampering device disposed at the connection point between the disposable and non-disposable parts of the apparatus, wherein the remote actuation / controller module is configured to: The anti-tampering device is sensed, and based on the anti-tampering device, it is determined whether the disposable portion is being used for the first time. If a disposable component is determined to have been reused, prevent the vacuum pump from being actuated.

23. The apparatus according to claim 22, wherein: a) The tamper-proof device includes a unique identifier, and the device further includes a sensor configured to read the unique identifier, the actuation / controller module being configured to determine whether the one-time portion is being connected for the first time based on a comparison of the unique identifier with a memory storing previously read unique identifiers; or b) The tamper-proof device is configured to be altered or removed during the initial connection of the disposable part, and the device further includes a sensor configured to sense the presence or condition of the tamper-proof device, and the actuation / controller module is configured to determine whether the disposable part is being connected for the first time based on the presence or condition of the tamper-proof device.

24. The apparatus according to any one of claims 19 to 23, wherein, The actuation / controller module includes a graphical user interface.

25. The apparatus according to claim 1, wherein, The treatment module includes a humidity sensor.

26. The apparatus according to claim 1, wherein, The plurality of holes are arranged circumferentially around the microtrauma module, or the plurality of holes are arranged on both sides of the microtrauma module in a discrete array.

27. The apparatus according to claim 1, wherein, The device includes a pressure sensor and a processor. The pressure sensor is configured to determine the operating pressure of the negative pressure treatment applied to the vaginal wall. The processor is configured to receive data related to the operating pressure from the pressure sensor, compare the detected operating pressure with a reference pressure, and modify the operating pressure to achieve a target pressure when a suboptimal operating pressure is detected.

28. The apparatus according to claim 1, wherein, The device includes a camera and an optional lighting system configured to image the vaginal wall during use.

29. The apparatus according to claim 1, wherein, The device is configured to relay data to a mobile user device and receive control data from the mobile user device to control the treatment.

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