System and method of treating vaginal infections and inflammation

Abstract

Systems and methods are provided for treating vaginal infections. The system includes a body sized to be inserted to the vagina of a subject, and the body includes a wall with fenestrations to allow air flow to circulate from inside the body to outside the body. The system also includes a light emitter positioned within the body to emit light outward along a length of the body.

Description

SYSTEM AND METHOD OF TREATING VAGINAL INFECTIONS AND INFLAMMATIONSTATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0001] Not applicable.CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application is based on, claims priority to. and incorporates herein by reference for all purposes, U.S. Provisional Application Serial No. 63 / 633,637, filed April 12, 2024.BACKGROUND

[0003] Bacterial vaginosis, gonorrhea, and vaginal yeast infection are challenging conditions that affect women worldwide and can be very difficult to treat. While each of these conditions is traditionally treated with antibiotics, recurrence of the condition despite appropriate antibiotic use is very common, resulting in significant impact on quality of life as well as broader societal costs. Additionally, the extensive use of antibiotics has led to the increasing emergence of multi drug-resistant microbial strains.

[0004] For example, bacterial vaginosis (BV), characterized by a loss of healthy vaginal lactobacillus bacteria, impacts close to 30% of US women and is associated with higher risk for preterm birth, HIV acquisition, and HPV persistence. In addition, persistent, recurrent symptoms can have a significant impact on quality of life. Standard antibiotic treatment, e.g., metronidazole or clindamycin, has not changed in decades. However, recurrent (chronic) BV, characterized by failure of antibiotic therapy within 3-6 months of completion, affects 25% of women worldwide, with an estimated annual cost of $13 billion. While recurrence may be due to antimicrobial failure or to reinfection, there is increasing recognition that alteration of normal vaginal flora — which is not corrected and can even be exacerbated by antibiotics — plays a significant role in persistence of the condition.

[0005] As another example, gonorrhea is a sexually transmitted infection caused by the bacterium Neisseria gonorrhoeae, which can infect the genital tract, rectum, and throat. In women, gonorrhea can cause cervicitis, which is inflammation of the cervix, and can also spread to the uterus and fallopian tubes, leading to pelvic inflammatory disease (PID). Symptoms of gonorrhea in women may include vaginal discharge, pain or burning during urination, and vaginal bleeding between periods. Gonorrhea can also be asymptomatic in women. Treatment for gonorrhea typically involves antibiotics, but antibiotic-resistant strains of Neisseria gonorrhoeae have become a growing concern in recent years. The CDC considersantibiotic resistant gonorrhea to be an urgent threat. For example, the CDC estimates that 1.6 million new gonorrhea infections occur each year in the United States alone, and that half of those infections are resistant to at least one antibiotic. The cost per infection has been estimated to be $205 for treatment and $197 in lost productivity. This does not include the far greater costs of education, testing, treatment of pain, and sequelae of infection. The CDC has also classified drug-resistant gonorrhea as an urgent threat to public health and emphasizes the need for development of new treatments.

[0006] As yet another example, it is estimated that 75% of women will have a vaginal yeast infection at least once in their lifetime. Recurrent vaginal yeast infection, defined as having four or more infectious episodes per year, is estimated to occur in up to 35% of women. Vaginal yeast infection can be characterized by itch, pain, burning, malodorous discharge, and rash. Furthermore, recurrent vaginal yeast infection can also lead to the development of vulvodynia, which can cause persistent pain. The cause of vaginal yeast infection is primarily due to the overgrowth of the yeast Candida, specifically Candida albicans, in the vaginal area. However, other Candida species, which are less sensitive to currently marketed antifungals, can also cause vaginal yeast infections. Factors that may promote the development of vaginal yeast infection include pregnancy (particularly in the last months of gestation), stress, low socioeconomic status, poor hygiene or malnutrition, and the use of antimicrobial medication that destroys beneficial Lactobacillus bacteria of normal vaginal microbiota. Recurrent vaginal yeast infection can occur due to persistence of the yeast strain in the vaginal area despite appropriate use of antifungal medications, as well as re-infection from a sexual partner or a reservoir of yeasts in the gut. Additionally, Candida species other than C. cdbicans, which are less sensitive to currently marketed antifungals, can cause vaginal yeast infections, although the majority are still caused by C. albicans. Prolonged courses of antibacterial drugs, the use of vaginal douching, and diabetes mellitus are also factors that can contribute to the incidence and recurrence of vaginal yeast infection. The cost of Candida vaginitis in the US was estimated in 1995 to be $1.8 billion, and at the time was estimated to increase to $3.1 billion in 2014.

[0007] Given that these conditions continue to negatively affect women w orldw ide and are more often becoming resistant to, or even exacerbated by, traditional antibiotic use, there is a need for effective systems and methods for treating vaginal infections and corresponding symptoms.SUMMARY

[0008] In accordance with one aspect of the disclosure, a system for treating infection within a vagina of a subject is provided. The system includes a body sized to be inserted to the vagina of the subject, and the body includes a wall with fenestrations to allow air flow to circulate from inside the body to outside the body. The system also includes a light emitter positioned within the body to emit light outward along a length of the body.

[0009] In accordance with one aspect of the disclosure, a method of treating a vaginal infection is provided. The method includes inserting a device into a vagina of a subject, where the device includes a body and a light emitter positioned within the body to emit light outward along a length of the body, and causing the light emitter to emit light in a wavelength range between about 380 nanometers (nm) to about 500 nm. The method further includes circulating one of air, oxygen, or a cooling material through the body during light emission.

[0010] The foregoing and other aspects and advantages of the invention will appear in the following description. In the description, reference is made to the accompanying drawings, which form a part hereof, and in which a preferred embodiment of the invention is shown by way of illustration. Such embodiment does not necessarily represent the full scope of the invention, however, and reference is made therefore to the claims and herein for interpreting the scope of the invention.BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The foregoing and other aspects of the present disclosure will be apparent upon consideration of the following detailed description, taken in conjunction with the accompanying drawings, which reference characters refer to like parts throughout.

[0012] FIG. 1 is a block diagram of an exemplary system for treating vaginal infections, in accordance with embodiment of the present disclosure.

[0013] FIG. 2 is a partial view' of an example device of the system of FIG. 1, including a body and a light emitter within an internal lumen of the body.

[0014] FIG. 3 is a partial view of another example device of the system of FIG. 1, including a body with light diffusing patterns.

[0015] FIG. 4 is a partial view of another example device of the system of FIG. 1, including a body with fenestrations.

[0016] FIG. 5 is a partial view of another example device of the system of FIG. 1, including a body with a cup-shaped distal end.

[0017] FIG. 6 is a partial view of another example device of the system of FIG. 1 in acontracted and expanded configuration.

[0018] FIG. 7 is a partial view of another example device of the system of FIG. 1, including a body with dual walls and a light emitter within an internal pathway between the walls.

[0019] FIG. 8 is a partial view of another example device of the system of FIG. 1, including a body and a cooling material applied to an outer surface of the body.

[0020] FIG. 9 is a partial view of another example device of the system of FIG. 1, including a body with dual walls and a cooling material being circulated within an internal pathway between the walls.

[0021] FIG. 10 is a partial view of another example device of the system of FIG. 1, including a body and air being circulated around the body.

[0022] FIG. 11 is a partial view of another example device of the system of FIG. 1, including a body with fenestrations and air being directed through the body and out through the fenestrations.

[0023] FIG. 12 is a flow chart of an example method of treatment of vaginal infections using antibiotic blue light.

[0024] FIG. 13 is a graph illustrating results of a study of antibiotic blue light applied to various bacterial strains, shown as radiant exposure (in Joules per centimeter squared, J / cm2) versus logio of colony-forming unit reduction (CFU logio).DETAILED DESCRIPTION

[0025] Disclosed herein are systems and methods for delivering antimicrobial blue light (aBL) to the vagina for the purpose of treating difficult-to-treat infections such as, but not limited to, bacterial vaginosis (BV), gonorrhea, and yeast infections. Such systems can further deliver red and / or near infrared light to the vagina to produce anti-inflammatory, anti-dysbiosis, or other therapeutic effects. Generally, a device according to some examples is composed of a light emitter and an outer body or cage. The device is placed into the vagina for the purpose of killing bacteria or yeast. Examples of the devices described herein may vary, for example, in the type of light source, the geometry of the surrounding body, the presence or absence of cooling, and / or other features.

[0026] The device has the potential to treat vaginal infections that are common and are often recurrent despite the use of appropriate antibiotic therapy. For example, there are many potential advantages of antimicrobial blue light, including the ability to kill pathogenic microbes regardless of the drug resistance profiles of the microbes, faster onset of action than conventional antimicrobial drugs, synergistic effects with antibiotics, and apparent selectivityfor pathogenic organisms. For example, antimicrobial blue light can provide potent microbicidal effects and a high selectivity for bacteria over mammalian cells. In addition, since yeast are also killed by antimicrobial blue light, the risk of antibiotic-associated yeast infection is decreased when treating, for example, BV or gonorrhea using aBL.

[0027] Referring now to FIG. 1, a schematic view of an example system 10 is illustrated, which may be configured for delivering antimicrobial blue light to the vagina for the purpose of treating infections and / or delivering therapies. The system 10 can include a device 12 with a body 14 and a light emitter 16. In some examples, the device 12 can further include a handle 18 coupled to or integral with the body 14. Furthermore, the system 10 can include a control system 20 coupled to the device 12, either directly to the body 14 or via the handle 18. For example, the control system 20 can be coupled to the device 12 (e.g.. to the body 14 or the handle 18) via a connection line 22. In some embodiments, some or all of the control system 20 and / or the connection line 22 may instead be incorporated into the handle 18.

[0028] Generally, according to some embodiments, the body 14 can be sized to be inserted into a subject's vagina, allowing the light emitter 16 within the body 14 to deliver light to tissues within the vagina. The handle 18 can be used by an administrator (e.g., the subject or another user, such as medical personnel) to insert the body 14 into the subject’s vagina. The control system 20 can include a light source 24 for delivering light to the light emitter 16, a power management module 26 that selectively applies pow er from a pow er source 28, a cooling system 30, optionally in communication with a cooling source 32. that can apply cooling to the subject’s vagina through the device 12, and / or a user interface 34 that allow s the administrator to control, for example, light emission, cooling, powder management, and / or other functions of the device 12.

[0029] With further reference to the body 14, generally, the body 14 may serve the purpose of supporting the light emitter 16, diffusing light emitted by the light emitter 16, cooling the vaginal mucosa, and / or maintaining patency of the vagina during a treatment. As noted above, the body 14 can be sized to be inserted into a subject’s vagina, allowing the light emitter 16 within the body 14 to deliver light to tissues within the vagina. For example, FIG. 2 illustrates a subject’s anatomy, including a vagina 36, vaginal mucosa 38 (e.g., inner lining of the vagina 36), vaginal orifice 40, external os 42, lateral fornix 44, cervix 46, myometrium 48, and uterine cavity' 50. In some embodiments, the body 14 can be sized such that the entire body 14 or a portion of the body 14 extends into the subject’s vagina 36 when inserted through the vaginal orifice 40, such that a distal end 52 of the body 14 is adjacent to or reaches the external os 42. In one non-limiting example, the body 14 can have a substantially cylindrical shape, e.g., witha rounded distal end 52, similar to a vaginal ultrasound probe or to a tampon. In another example, the body 14 may be more egg-shaped.

[0030] In some embodiments, as shown in FIG. 2, the body 14 can be an optically transparent casing that surrounds the light emitter 16. For example, the body 14 can comprise glass, plastic, polymeric material, or another suitable material. As a result, light emitted by the light emitter 16 can be delivered through the body 14 to the vaginal mucosa 38 during a treatment.

[0031] In some embodiments, the body 14 can include an inner wall 54, an outer wall 56, and an internal lumen 58. In some embodiments, as shown in FIG. 2, the body 14 may comprise a singular wall 60, where the inner wall 54 is an inner wall surface of the singular w all 60, and the outer wall 56 is an outer wall surface of the singular wall 60. However, in other embodiments, the inner wall 54 and the outer wall 56 are separate, with an internal pathway 62 therebetween (as show n in FIGS. 7 and 9). Thus, reference to the wall 60 generally throughout the disclosure may refer to the singular wall 60, a separate inner w all 54, or a separate outer wall 56 unless otherwise specified. Accordingly, in some embodiments, the light emitter 16 may be positioned within the lumen 58, along the inner wall 54, along the outer wall 56, or within the internal pathw ay 62.

[0032] Additionally, in some embodiments, as shown in FIG. 3, the body 14 and, more specifically, the wall 60 can comprise a light diffusing material or special patterning 64 throughout the material to help more uniformly distribute light emitted from the light emitter 16. As another example, the inner wall surface 54 or the outer wall surface 56 may include special patterning details configured to help more uniformly distribute light emitted by the light emitter 16.

[0033] In some embodiments, as shown in FIG. 4, the body 14 can comprise fenestrations or openings 66 along the wall 60. In such embodiments, the body 14 may resemble a cage. The fenestrations 66 may assist to permit light transmission from the internal light emitter 16 to the vaginal mucosa 38. Additionally, in some embodiments, the fenestrations 66 can permit entry of outside air or oxygen to the vaginal mucosa 38 during treatment, as further described below. For example, the fenestrations 66 can allow air flow to circulate from inside the body 14 to outside the body 14, providing such air to the vagina 36. In embodiments where the body 14 comprises fenestrations 66, the wall 60 may still comprise an optically transparent material to enable light transmission through the wall 60 and through the fenestrations 66. Alternatively, in some embodiments, the wall 60 may comprise opaque material, such as opaque glass, plastic, polymeric material, metal, or another suitable material, where light transmission only occursthrough the fenestrations 66.

[0034] As noted above, the body 14 can be sized to be inserted into a subject's vagina 36, allowing the light emitter 16 within the body 14 to deliver light to tissues within the vagina 36. Furthermore, in some embodiments, the body 14 can be sized to come in contact with the vaginal mucosa 38 when inserted into the subject’s vagina 36. In some embodiments, the body 14 may comprise a flexible material and be sized to snugly fit into the vagina 36 to contact the vaginal mucosa 38. Accordingly, the body 14 may be flexible enough to conform to the inner walls of the vagina 36. Furthermore, in some embodiments, as shown in FIG. 5, the distal end 52 of the body 14 may have a pre-formed cup shape, allowing the body 14 to better conform to the vaginal fomices 44 around the external os 42 when inserted into the vagina 36.

[0035] Furthermore, in some embodiments, the body 14 may comprise a flexible material configured to expand when inserted into the vagina 36 in order to better contact the vaginal mucosa 38. For example, the wall 60 may be expanded mechanically, such as by filling the lumen 58 or the internal pathw ay 62 with a gas or liquid, or through another suitable method. For example, as shown in FIG. 6, the body 14 may be inserted into the vagina 36 in a first, or contraction configuration 67A, then mechanically expanded into a second, or expanded configuration 67B in order for the body 14 to better come into contact with the vaginal mucosa 38. For example, the control system 20 can include a pump or fan (not shown) that directs liquid or gas from a source (not shown) through the lumen 58 or internal pathway 62 to expand the body 14 after the body 14 has been inserted into the vagina 36. Alternatively, the cooling system 30 (e g., a pump or fan) may be used to circulate liquid or gas, e.g., from the cooling source 32 into the lumen 58 or the internal pathway 62 in order to expand the body 14. As another example, the lumen 58 or internal pathw ay 62 can include a mechanical expansion device (not shown) that can be controlled by the control system 20 to be expanded after the body 14 has been inserted into the vagina 36. These expansion mechanism examples can be activated, for example, by an administrator through the user interface 34 of the control system 20. That is, the user interface 34 can include buttons, dials, switches, or other suitable mechanisms that an administrator can actuate to activate the expansion mechanism.

[0036] Turning now to the light emitter 16, as noted above, the light emitter 16 can be configured to emit light through the body 14 to apply light treatment to the vagina 36. In some embodiments, the light emitter 16 can be configured to emit antimicrobial blue light (aBL), such as in the range of about 380 nanometers (nm) to about 500 nm, or from about 400 to about 470 nm, or at about 405 nm (plus / minus 5 nm). For example, multiple strains of antibioticresistant gonorrhea have been shown to be sensitive to antimicrobial blue light. Additionally,antimicrobial blue light has demonstrated excellent efficacy against C. albicans in vitro and in vivo. Furthermore, as discussed further below, antimicrobial blue light may be effective at killing organisms commonly implicated in the pathogenesis of BV while preserving good bacteria and, thus, may be effective at renormalizing the microbiome of the vagina 36.

[0037] Additionally, in some embodiments, the light emitter 16 can be configured to emit light in other wavelength ranges such as, but not limited to, red light (e.g., wavelength range of about 620 nm to about 750 nm) and / or near infrared light (NIR. e.g., wavelength range of about 780 nm to about 1300 nm). In one example, the light emitter 16 may be further configured to emit light with a wavelength range of about 620 nm to about 1300 nm, or about 630 nm to about 850 nm, or another range therebetween. Light in these red light and NIR wavelength ranges, e.g., ‘"red light treatment,” has trophic effects on epithelium through a photobiomodulation effect and, thus, may help modulate the vaginal microbiome dysbiosis that may occur after antimicrobial blue light treatment (e.g., by promoting growth of “normal” or “good” vaginal bacteria) and / or help reduce inflammation.

[0038] Generally, the light emitter 16 can be any type of light emitting mechanism capable of emitting target light wavelengths, such as the blue light, red light, and / or NIR light wavelength ranges discussed above. In some embodiments, the light emitter 16 itself can be a light source positioned within or on the body 14, such as one or more light emitting diodes (LEDs) or lasers. For example, in some embodiments, referring back to FIG. 2, LEDs 68 may be positioned within the lumen 58, e.g.. along one or more supports 69, to emit light through the body 14 into the vagina 36. The LEDs 68 may be arranged within the lumen 58 to emit light out the distal end 52 of the body 14 as well as along a length of the body 14. The LEDs 68 may be configured to emit a single wavelength, or may be configured to emit multiple wavelengths. Alternatively, a first portion of LEDs 68 may be configured to emit a first wavelength (e.g., antimicrobial blue light) and a second portion of LEDs 68 may be configured to emit a second wavelength (e.g., red or NIR light). In another example, the light emitter 16 can include materials capable of promoting chemiluminescent reactions in order to emit light at the wavelengths indicated above.

[0039] According to yet another example, the light emitter 16 can be configured to emit light from a remote light source, such as the light source 24 located within the control system 20, as show n in FIG. 1. For example, with reference to FIG. 1, in some embodiments, the light emitter 16 may be an optical fiber, connected to the light source 24 through the connection line 22. Additionally, in such embodiments, with reference to FIG. 7, the light emitter 16 may be a side-emitting optical fiber routed along or through the wall 60, or through the internal pathway62 between the inner and outer walls 54, 56, allowing light to be emitted from the distal end 52 as well as along the length of the body 14. Furthermore, in some embodiments, the optical fiber light source 16 (e.g., a side-emitting optical fiber) may be positioned within the lumen 58, e.g., as a stand-alone component or supported by a support 69. Alternatively, in other embodiments, the light emitter 16 may be an optical fiber that emits light from the tip of the fiber. In yet another example, in some embodiments the light emitter 16 can be configured to emit light from a remote light source, such as the light source 24 in the control system 20. via simple radiation rather than an optical fiber, and out through the support 69 or through the internal pathway 62.

[0040] In some embodiments, light emitted by the light emitter 16 can be controlled by control system 20. In one example, light emitted by the light emitter 16 can be activated by connecting the device 12 to the control system 20, e.g., by placing the light emitter 16 in communication with the light source 24. In another example, light emitted by the light emitter 16 can be activated by a user actuating a button (or switch, dial, etc.) on the user interface 34 to power the light emitter 16 or the light source 24. That is, the light emitter 16 or the light source 24 may be powered by the power source 28, e.g., via the power management module 26. When the user actuates the user interface 34, the power management module 26 can allow power from the power source 28 to power the light source 24 and / or the light emitter 16. In yet another example, light emitted by the light emitter 16 can be activated by a user connecting the control system 20 to the power source 28. such that power is automatically provided from the power source 28 to the light source 24 and / or the light emitter 16 when such connection is made.

[0041] With reference back to FIG. 1, the power management module 26 can provide power from the power source 28 to the light source 24, the light emitter 16. and / or the cooling system 30. For example, in some embodiments, the power management module 26 can be a switching device that selectively applies or blocks power from the power source 28, or facilitates connection of the control system 20 to the power source 28. In other embodiments, the power management module 26 may comprise a controller including a processor and nonvolatile computer-readable memory storing instructions that, when carried out by the processor, causes the power management module 26 to selectively apply or block power from the power source 28 to control components of the control system 20, such as in response to input from the user interface 34. As such, the user interface 34 can be in communication with the power management module 26.

[0042] It should be noted that, while the power source 28 is illustrated in FIG. 1 as beingseparate from the control system 20, in some embodiments, the power source 28 may be incorporated into the control system 20. For example, in such embodiments, the power source 28 may be a battery. However, in other embodiments, the power source 28 may be an external AC or DC power source to which the control system 20 is connected.

[0043] Furthermore, as noted above, any or all components of the control system 20 may be incorporated into the handle 18 of the device 12. For example, the user interface 34 can include a plurality of buttons, switches, dials, of other suitable actuation mechanisms along the handle 18. Additionally or alternatively, a remote user interface (not shown) may be in communication with the control system 20, allowing an administrator to remotely control the light source 24, the light emitter 16, the power management module 26, and / or the cooling system 30.

[0044] Turning now to the cooling system 30, in some embodiments, the system 10 can include a cooling system 30. However, in other embodiments, the system 10 may incorporate passive cooling methods or techniques rather than a physical cooling system. For example, vaginal mucosae are rich in blood vessels, and hemoglobin in blood is a competing chromophore. As such, absorption of antibiotic blue light emitted by the device 12 by blood circulating through the vaginal mucosae 38 may result in undesirable heating of the vaginal wall. Thus, incorporating active or passive cooling methods into the system 10 can allow for shorter and more effective treatments, e.g., because treatment intensity may be less limited by tissue heating.

[0045] In some embodiments, cooling methods can include using a pre-cooled material along the body 14 in order to cool the vagina 36 during a treatment. For example, with reference to FIG. 8, in some embodiments, a cooling material 70, such as a pre-cooled gel or liquid, can be applied to an outer surface of the body 14 prior to insertion into the vagina 36. Alternatively, in some embodiments, the cooling material 70 can be pre-cooled and applied within the body 14 (e.g., within the lumen 58 or the internal pathway 62).

[0046] In addition or alternatively to this passive cooling, in some embodiments, the cooling material 70 can be circulated through the body 14. For example, the cooling system 30 can include a circulating pump that circulates the cooling material 70 from a cooling source 32 through the body 14 (e.g., via the connection line 22). As shown in FIG. 9, the cooling material 70 can be circulated, e.g., via the cooling system 30, through the internal pathway 62 of the body 14. However, in some embodiments, the cooling system 30 can circulating the cooling material 70 through the lumen 58 as well.

[0047] As another example, cooling methods can include convective cooling methods.That is. in some embodiments, as shown in FIG. 10, air, such as ambient air or pre-cooled air from a cooling source 32, may be circulated around the body 14 by the cooling system 32 (e.g., a fan) or, alternatively, through the internal pathway 62 or the lumen 58. As another example, as shown in FIG. 11, the air can be circulated through the lumen 58 by the cooling system 32 (e.g., a fan) and released through the fenestrations 66. In this manner, the fenestrations 66 allow air (or oxygen) flow to circulate from inside the body 14 to outside the body 14.

[0048] In view of the above. FIG. 12 illustrates an example method 80 of use of the system 10 according to some embodiments. Generally, in use, the device 12 can be inserted into the subject’s vagina 36 (step 82) and antimicrobial blue light can be emitted from the light emitter 16 at a predetermined intensity and / or for a predetermined time period to help normalize the microbiome of the vagina 36 (step 84). That is, as discussed above, the light emitter 16 can be positioned within or along the body 14 to emit light outward along a length of the body 14 towards the vaginal mucosa 38 at the predetermined intensity and / or for a predetermined time period. In some embodiments, the predetermined intensity and / or the predetermined time period can be controlled by the power management module 26. For example, the power management module 26 (e.g., the processor executing instructions stored in memory) can control application of power from the power source 28 to the light source 24 and / or the light emitter 1 to control the “on time,” intensity, and / or color of the emitted light. Additional or alternatively, such intensity, color, and / or time period can be controlled manually by a user via the user interface 34. In some embodiments, the time period may be between about 1 minute and about 30 minutes, between about 5 minutes and about 20 minutes, or another time period. In some embodiments, the light may be emitted with an irradiance around 60 mW / cm2, though other irradiance levels may be contemplated in other embodiments.

[0049] By helping normalize the microbiome of the vagina 36, the antimicrobial blue light can reduce infection-causing bacteria and / or yeast while maintaining or minimally reducing normal bacteria within the vagina 36. By way of example, antimicrobial blue light-mediated killing of bacteria (or yeast) may involve the photoexcitation of endogenous porphyrins, leading to the generation of intracellular reactive oxygen species (ROS) that cause membrane damage, DNA damage, lipid peroxidation, and more. However, as further discussed below, good bacteria within the vagina 36 may be less sensitive to the antimicrobial blue light and, thus, less affected by the light treatment. In this manner, rather than eliminating all kinds of bacteria, such as is done with antibiotic treatments (which can lead to an overgrowth of yeast and resulting yeast infections), the antimicrobial blue light treatment herein can help reset the subject’s natural balance of bacteria and yeast within the vagina 36.

[0050] With reference still to FIG. 12, in some embodiments, at step 86, additional treatment may be conducted in conjunction with the antimicrobial blue light therapy of step 84, e.g., either simultaneously with, before, or after step 84. Such additional treatment 86 can include, for example, adding oxygen to the environment (step 88), applying passing or active cooling (step 90), applying photodynamic therapy with exogenous photosensitizers (step 92), applying red light or NIR light therapy (step 94), and / or incorporating antibiotics or antifungal medicine (step 96).

[0051] More specifically, at step 88, steps may be taken to create a more oxygen-rich environment within the vagina 36 during antimicrobial blue light treatment. For example, as discussed above, since bacteria-killing mechanisms associated with antimicrobial blue light involve oxygen, and since such bacteria generally favor anaerobic environments, bringing in outside oxygen can help make light treatment more effective. In one example, step 88 may be accomplished using the cooling system 30, as described above. That is, the cooling system 30 (e.g., a fan), may circulate ambient or pre-cooled air into the vagina 36, as described above with respect to FIGS. 10 and 11. Furthermore, in some embodiments, the cooling source 32 may instead be an oxygen supply, and the cooling system 30 circulates oxygen from the oxygen supply (e.g., cooled or at ambient temperature) into the vagina 36. As another example, passive entry7of oxygen to the vagina 36 may be accomplished by the body design comprising fenestrations 66, as shown in FIG. 4. That is, the fenestrations 66 can increase exposure to outside air (i.e., including oxygen), by allowing for air to circulate from outside the vagina 36, through the lumen 58, and out the fenestrations 66 into the vagina 36.

[0052] As yet another example at step 88, according to some embodiments, the antimicrobial blue light treatment can be combined with a drug, such as hydrogen peroxide or another suitable composition, that can provide a source of oxygen to enable oxygen dependent killing. While hydrogen peroxide is itself bactericidal, the hydrogen peroxide can also help ensure a sufficiently oxygen-rich environment during the light treatment to increase the efficacy of the light treatment. For example, the hydrogen peroxide can be applied to the body- id prior to insertion into the vagina 36 or can be circulated into the lumen 58 after insertion and allowed to enter the vagina 36 through the fenestrations 66 (or other openings through the wall 60).

[0053] Referring now to step 90, active or passing cooling can be accomplished to help reduce unwanted affects of heating caused by the antimicrobial blue light treatment. For example, as described above with respect to FIG. 8. passive cooling may be accomplished via a cooling material 70 applied to the outside of the body 14. As described above with respect toFIG. 9, active cooling may be accomplished via a cooling material 70 (e.g., from cooling source 32) being circulated through the body 14 via the cooling system 30 (e.g., a pump). Additionally or alternatively, convective cooling can be accomplished by circulating air around or through the body 14, as shown in FIGS. 10 and 11, respectively, e.g., via the cooling system 30 (e.g., a fan).

[0054] Referring now to step 92 of FIG. 12, as yet another optional additional treatment step, a photo-sensitive medicine (photosensitizer) can be applied to the vaginal mucosae directly or to the outer surface of the body 14 and allowed to penetrate into the tissue and selectively bind to bacteria or yeasts. The light emitter 16 can then be caused to emit light at a wavelength that can be absorbed by the photosensitizer to activate it, such as blue light, red light, or NIR light, causing excitation of the photosensitizer and resulting damage to bound bacteria. Accordingly, in such embodiments, the system 10 can be used as a combination of antimicrobial blue light therapy and antimicrobial photodynamic therapy (aPDT) system.

[0055] Furthermore, referring to step 94, as discussed above, the light emitter 16 can further be configured to emit red light or NIR light. For example, such red or NIR light emission can provide anti-inflammatory effects, anti-dysbiosis effects, and / or additional beneficial effects to help rebalance the microbiome of the vagina 36. In some embodiments, red or NIR light emission can be applied for a predetermined time period and / or at a predetermined intensity, as controlled via stored instructions carried out by the processor of the power management module 26. and / or can be controlled manually via the user interface 34.

[0056] Referring now to step 96, in some embodiments, antimicrobial light therapy via the system 10 may be used in conjunction with traditional medical interventions, such as antibiotics or antifungal medications. For example, blue light can be synergistic with antibiotics. Thus, bacteria that are resistant to a given antibiotic, or that require high concentrations of an antibiotic for successful treatment, can be made sensitive to the antibiotic in the presence of antimicrobial blue light. As such, the system 10 can be used in combination with antibiotics for improved effect. For example, metronidazole and clindamycin, which are used in topical or oral forms to treat bacterial vaginosis, can be combined with the system 10 so that the antibiotic is delivered to the vaginal mucosa by the device 12 itself (e.g., by being applied to an outer surface of the body 14 prior to insertion into the vagina 36). Similarly, vaginal yeast infections are often treated with antifungals applied as a cream, gel, ointment, or suppository, to the vaginal mucosa. Such antifungal medications could also be combined with the device 12 for synergistic effect. Alternatively. aBL therapy may be used in conjunction with oral antibiotic treatments as well.

[0057] While various examples of additional treatments at step 86, e.g., steps 88-96, are described above to be used with the system 20. such steps 88-96 may be incorporated individually or in any combination with each other and antimicrobial blue light therapy of step 84 in some applications.

[0058] In view of the above, some embodiments provide a system, device, and associated methods for treating infections such as, but not limited to, bacterial vaginosis (BV), gonorrhea, and yeast infections, which are common and often recurrent despite the use of appropriate antibiotic therapies. Furthermore, the system, devices, and methods address issues posed by heating of the vaginal mucosa through blue light therapy as well as address the issue of oxygen delivery' to the tissues in order to further facilitate oxygen dependent killing, and are capable of providing combination therapies, e.g.. blue light therapy in combination with additional therapies. Such system, device, and methods not only can be used to treat such infections but also normalize the microbiome of the vagina, e.g., by allowing a rebalancing of normal vaginal bacteria and flora within the vagina.

[0059] With reference to BV in particular, BV is a type of dysbiosis marked by reduced Lactobacillus and an overgrowth of anaerobic species, including Gardnerella, Fannyhessea vaginae, and Prevotella. Many women experience high recurrence rates of BV, which leads to recurrent antibiotic use, which can lead to antibiotic resistance, and can lead to an inability' to reestablish healthy vaginal flora. For example, antibiotics, if effective, may kill all — both good and bad — bacteria in the vagina, making it difficult for a normal balance of bacteria to be reestablished. As a result, yeast may grow or, as bacteria starts to grow again, it does so in an unbalanced manner, potentially due to the inability' to reestablish dominance with the most beneficial Lactobacillus species after antibiotics. Furthermore, there is a risk of antibiotic resistance in BV-related pathogens due to frequent use, a concerning issue given the rising global antibiotic resistance and the high prevalence of BV. Approximately 20% of people treated with antibiotics will not achieve a microbiological cure, even if symptoms temporarily resolve, suggesting that antibiotics are insufficient to eliminate BV-associated microbes.

[0060] Antimicrobial blue light therapy may not only lead to less antibiotic use, e.g., as a "‘drug-free’7or “reduced-drug” approach, but also can help normalize the microbiome by targeting infection-causing bacteria, e.g., targeting anaerobic pathogens. For example, a study was performed by assessing antimicrobial blue light therapy on the following bacterial strains: Lactobacillus crispatus ATCC33197 , Lactobacillus iners ATCC55195. Gardnerella vaginalis GR34, ATCC14018 and ATCC49115, Fannyhessea vaginae BAA55, and Prevotella bivia DNF650. Agar plates and broths were prepared by using pre-sterilized media to support thegrowth of specific bacterial strains. Different media types were chosen to meet the specific growth requirements of each bacterial strain. Following bacterial inoculation, the agar plates were incubated at 37 °C in a Bactron anaerobic chamber for three days. Bacterial inocula were then collected using lOpL Fisherbrand™ Disposable Inoculating Loops and transferred to Coming™ Cell Culture Treated Flasks filled with broths for overnight cultures within the anaerobic chamber.

[0061] Overnight bacterial cultures were centrifuged at 18G for 10 minutes to separate bacterial cells from the culture medium. The pelleted bacterial cells were gently washed with phosphate-buffered saline (PBS) and resuspended in PBS to an optical density7(OD) at 600nm of 0.1. corresponding to a bacterial density' of 108colony-forming units (CFU) / mL. Subsequently, one milliliter of the bacterial suspension was added to Coming™ Costar™ Clear 12-Well Plates (with a 3.8 cm2culture area and 6.9 mL volume per well) for antimicrobial blue light (aBL) exposure. A light-emitting diode (LED) with peak emission at 405 nm (M405L2; Thorlabs, Newton, NJ) was used for irradiation, and an irradiance of 60 mW / cm2was used. After exposure to aBL at 60 mW / cm2for various time durations in the range of 2.5 to 30 minutes, aliquots of 30 pL were taken, and the viability of different strains was measured using serial 10-fold dilutions and agar plating.

[0062] The experiment was performed in three independent replicates for each condition. Plates were incubated at 37 °C in a Bactron anaerobic chamber for two days before counting of CFU. The CFU / mL averages for each condition were normalized in relation to the corresponding non-irradiated group (N0 / N). This step allows for a direct comparison of the irradiated groups to the control group, considering the impact of the treatment. To facilitate data analysis, the normalized CFU / mL values were converted into logio values. This transformation is often used to better represent changes over a wide range of values, making the data more suitable for statistical analysis. The mean logio CFU / mL value and the standard error of the mean (SEM) were calculated for each experimental condition.

[0063] FIG. 13 illustrates a chart 100 of the results of the above experiment, in terms of radiant exposure versus logio CFU reduction, showing that 405 nm aBL at an irradiance of 60 mW / cm2resulted in significant reductions in CFU for various bacterial strains. That is. G. vaginalis GR34 exhibited a 7.5-logio CFU reduction following exposure to aBL at 31.2 J / cm2(line 102). G. vaginalis ATCC14018 demonstrated a 6.2-logio CFU reduction with 62.4 J / cm2aBL irradiation (line 104). G. vaginalis ATCC49115 demonstrated a 3.2-logio CFU reduction with 104.0 J / cm2aBL irradiation (line 106). P. bivia DNF650 experienced a 6.3-logio CFU reduction after an exposure of 41.6 J / cm2of aBL treatment (line 108). F. vaginae BAA55exhibited a 5.2-logio CFU reduction with 41.6 J / cm2aBL exposure (line 110). L. inners ATCC55195 showed a 5.3-logio CFU reduction after 52.0 J / cm2aBL (line 112). Notably, L. crispatus ATCC33197 exhibited a significant 6.8-logio CFU reduction with aBL 135.2 J / cm2(line 114).

[0064] Accordingly, the above study illustrates the efficacy of 405-nrn aBL in killing organisms commonly implicated in the pathogenesis of BV. A time period of 25 minutes of irradiation (at an irradiance of 60 mW / cm2) with 405-nm aBL under in vitro conditions effectively killed all L. iners ATCC55195, G. vaginalis GR34, ATCC14018, ATCC49115, F. vaginae BAA55, P. bivia DNF650 cells while preserving approximately 78% of L. crispatus ATCC33197. These findings suggest that 405-nm aBL may be a potential antibiotic-sparing strategy for BV control.

[0065] Furthermore, 405 nm blue light has been identified as an effective alternative for managing candidal vulvovaginitis as well as for inactivating N. gonorrhea while preserving vaginal epithelial cells. Additionally, as discussed above, antimicrobial blue light therapy maybe used in conjunction with traditional antibiotics or antifungal drugs, increasing the effectiveness of such traditional therapies and / or reducing the overall dosage needed to treat infections while allowing the microbiome to be rebalanced.

[0066] The present invention has been described in terms of one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.

[0067] As used in the claims, the phrase "at least one of A, B, and C" or "at least one of A, B, or C" means at least one of A. at least one of B, and / or at least one of C, or any one of A, B, or C or combination of A, B, or C. A, B, and C are elements of a list, and A, B, and C may be anything contained in the specification.

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A system for treating infection within a vagina of a subject, the system comprising: a body sized to be inserted to the vagina of the subject, the body comprising a wall with fenestrations to allow air flow to circulate from inside the body to outside the body; and a light emitter positioned within the body to emit light outward along a length of the body.

2. The system of claim 1, further comprising a control system coupled to the body, the control system to control light emission by the light emitter.

3. The system of claim 2, further comprising a handle coupled to the body, wherein the control system is located within the handle.

4. The system of claim 2, wherein the control system includes a cooling system configured to circulate a cooling material through the body.

5. The system of claim 2, wherein the control system includes a cooling system configured to circulate air into the body.

6. The system of claim 2, wherein the light emitter is an optical fiber, and the control system includes a light source coupled to the optical fiber.

7. The system of claim 6, wherein the optical fiber is a side-emitting fiber optic cable.

8. The system of claim 2. wherein the light emitter comprises a plurality of lightemitting diodes.

9. The system of claim 1, wherein the body comprises a cup-shaped distal end.

10. The system of claim 1, wherein the light emitter is configured to emit light in a wavelength range of about 380 nanometers (nm) to about 500 nm.

11. The system of claim 10, wherein the light emitter is further configured to emit light in a wavelength range of about 620 nm to about 1300 nm.

12. A method of treating vaginal infection, the method comprising: inserting a device into a vagina of a subject, the device comprising a body and a light emitter positioned within the body to emit light outward along a length of the body; causing the light emitter to emit light in a wavelength range between about 380 nanometers (nm) to about 500 nm; and circulating one of air, oxygen, or a cooling material through the body during light emission.

13. The method of claim 12, wherein circulating one of the air, oxygen, or cooling material through the body includes providing the body with fenestrations that allow the air or oxygen to circulate from inside the body to outside the body.

14. The method of claim 12, wherein circulating one of the air, oxygen, or cooling material through the body includes circulating the air through the body via a fan.

15. The method of claim 12, wherein circulating one of the air, oxygen, or cooling material through the body includes circulating the cooling material from a cooling source through the body via a pump.

16. The method of claim 12, further comprising expanding the body of the device after inserting the device into the vagina so that the body contacts vaginal mucosa of the subject.

17. The method of claim 12, further comprising causing the light emitter to emit light in a wavelength range between about 620 nm to about 1300 nm.

18. The method of claim 12, further comprising applying an antibiotic or antifungal medicine to an outer surface of the body prior to inserting the device into the vagina.

19. The method of claim 12, further comprising applying hydrogen peroxide to an outer surface of the body prior to inserting the device into the vagina.

20. The method of claim 12, further comprising applying a photo-sensitive medicine to the vagina; and causing the light emitter to emit light in a wavelength range that causes excitation of the photo-sensitive medicine.

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