Internal UV therapy

Abstract

One or more methods and systems are provided for performing intraluminal ultraviolet light therapy to treat and / or ameliorate inflammation and / or infection of the gastrointestinal tract. In one embodiment, a light delivery catheter can include a light-emitting portion and a non-illuminating portion, and the light-emitting portion can include one or more UV-transparent balloons. In some embodiments, the UV light source is configured to emit narrowband light having a wavelength in the range between 335 nm and 349 nm. TIFF2023539044000002.tif60164

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 065,167, filed August 13, 2020, entitled Internal Ultraviolet Light Therapy, the contents of which are incorporated herein by reference.

[0002] Field of the Disclosure The present invention relates to systems and methods for ultraviolet radiation therapy to treat patients, including for use in conjunction with the treatment of inflammatory diseases. [Background technology]

[0003] Background of the Disclosure The following description contains information that may be useful in understanding the present invention. No admission is made that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

[0004] Gastrointestinal (GI) disorders include diseases of the esophagus, stomach, small intestine, colon, and rectum. GI disorders are some of the most prevalent disorders, yet their symptoms are not effectively managed and in some cases, no effective treatment options are available. Among the disorders affecting the GI tract, one of the most prevalent conditions is inflammatory bowel disease (IBD).

[0005] Inflammatory bowel disease (IBD) is thought to arise from an abnormal host immune response against commensal flora in the gastrointestinal tract in genetically susceptible individuals. IBD has two major forms: ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD can face morbidity and severe productivity loss. Current trends indicate an increasing incidence and prevalence of IBD; however, effective long-term treatment options and / or cures have yet to be identified. As a result, IBD poses a significant financial burden to healthcare systems worldwide.

[0006] UC, a form of IBD, involves persistent inflammation of the colonic epithelium and affects various anatomical sites in the rectum and colon. Approximately 35% of UC patients have the rectum and sigmoid colon affected, 40% have the entire remaining colon affected, and 25% have widespread inflammation extending into the more proximal colon. Symptoms of UC include diarrhea, rectal bleeding, and abdominal pain and are associated with significant morbidity, cost, and impact on quality of life.

[0007] Currently approved therapies for UC involve immunosuppression or immunomodulation, with mesalamine for mild disease and broad-spectrum or targeted approaches with biologics and small molecules for moderate-to-severe disease. These treatments have the potential for adverse effects, including systemic infection, lymphoma, and immune-mediated reactions. Clinical trials of therapeutic agents in mild and moderate-to-severe UC have shown that the majority of patients do not achieve remission, even when dose-optimized biologic therapy is combined with immune-modulating agents. Currently approved therapies for moderate-to-severe ulcerative colitis are effective in only a minority of patients and are associated with risks of infection, malignancy, thrombosis, and immune-mediated reactions (depending on the drug class).

[0008] Thus, there is a significant unmet need for safe and effective treatments for GI tract disorders such as IBD, for both mildly affected and moderate-to-severely affected patients. Summary of the Invention

[0009] Summary of the Disclosure The present inventors have identified that manipulating the microbial flora using UV-A light emitted at wavelengths within the UV-A region may provide a safe and effective treatment for IBD. Furthermore, the present inventors have identified that UV-A light may be administered intraluminally along any length of the GI tract in a safe and effective manner. Thus, UV-A light may be used for effective microbiome-modifying and / or anti-inflammatory phototherapy for various infectious and / or inflammatory conditions of the GI tract, including IBD.

[0010] As disclosed herein, application of UV-A light has significant antimicrobial effects against a wide range of bacteria, viruses, and other organisms. Furthermore, UV-A light emitted at wavelengths between 335 nm and 348 nm offers a unique therapeutic window, targeting extracellular microorganisms and providing extracellular antimicrobial treatment (against microorganisms attached to cell surfaces). Furthermore, UV-A light emitted within the 335-349 nm range penetrates cells and enters the cytoplasm, triggering an effective intracellular antimicrobial response (against microorganisms that have invaded or are internalized within the cell) without causing UV-induced DNA damage. Therefore, UV-A light emitted at wavelengths between 335 nm and 348 nm can be safely and effectively used to treat, ameliorate, and / or prevent diseases affecting the GI tract by modifying the intestinal microbiome (i.e., providing extracellular and intracellular antimicrobial effects) and / or reducing inflammation within the lumen of the GI tract.

[0011] Accordingly, in one embodiment, a device for performing intraluminal phototherapy comprises a delivery tube having a light-emitting portion, the light-emitting portion including a plurality of light sources configured to emit narrowband light at wavelengths in the ultraviolet A (UV-A) range between 335 nm and 349 nm; and a plurality of inflatable balloons connected to the delivery tube at the light-emitting portion, each in fluid communication with a respective inflation port, each of the plurality of inflatable balloons being composed of a UV-transparent material.

[0012] In this manner, by using multiple balloons, the delivery device can be stabilized in place during UV light administration, which provides consistent UV exposure to the treatment area within the lumen. Additionally, the balloons can increase the uniformity of light distribution to the treatment site. As a result, the balloons increase the irradiance distribution at the treatment site.

[0013] Furthermore, when utilized for treatment within the GI tract, the balloon, in its inflated state, may stretch one or more folds and bulges of the colon, thereby increasing the surface area of ​​the colon during treatment. As a result, the balloon uniformly increases the amount of light exposure across the surface of the colon, which improves the efficiency and effectiveness of UV light treatment. Furthermore, inflation of the balloon also displaces obstructing stool / debris between the light source and the colonic epithelium. Furthermore, the balloon may help diffuse extraneous debris / biofilm that may act as a barrier between the delivery device and the colonic epithelium. Furthermore, the balloon also prevents stool from descending into the treatment segment. That is, the balloon does not allow proximal debris and feces to pass antegrade and block UV radiation to the colonic mucosa. Through at least these effects, the balloon improves both irradiance and irradiance distribution across the colonic epithelium, thereby increasing the efficiency and effectiveness of UV light treatment.

[0014] Furthermore, the multi-balloon approach may provide flexibility for the device as it passes through the hepatic and splenic flexures, and may also provide a customized approach, such as delivering light only to inflamed segments and reducing exposure to non-inflamed segments, through selective illumination of inflated segments in correlation with the individual's degree of disease.

[0015] Thus, multi-balloon internal UV-A phototherapy, as disclosed herein, may offer a safe and effective alternative to anti-inflammatory and immunosuppressive therapies for IBD and other gastrointestinal disorders. Thus, the antimicrobial and / or anti-inflammatory properties of UV-A light are utilized to manipulate the gut microbiome and / or reduce inflammation in IBD patients, while the multiple balloons are used to improve UV light distribution and irradiance, reduce obstruction caused by feces and biofilm formation, and stabilize the GI tract and delivery device during UV-A light treatment.

[0016] As described in the Detailed Description section below, in vitro and in vivo safety data indicate that UV-A can be safely applied to a variety of human cell types, even over short distances, without evidence of DNA damage, cell growth inhibition, or histological inflammation.

[0017] [The present invention 1001] a delivery tube with a light-emitting portion, the light-emitting portion including a plurality of light sources configured to emit narrowband light at wavelengths within the ultraviolet A (UV-A) range between 335 nm and 349 nm; a plurality of inflatable balloons connected to the delivery tube at the light emitting portion, each in fluid communication with a respective inflation port; Equipped with each of the plurality of inflatable balloons is composed of an ultraviolet (UV) transparent material; A light delivery device for performing intraluminal phototherapy. [The present invention 1002] The light delivery device of the present invention 1001, wherein each of the plurality of inflatable balloons is configured to increase the irradiance and / or irradiance distribution of light emitted from the plurality of light sources and delivered to a corresponding intraluminal treatment site. [The present invention 1003] The light delivery device of the present invention 1001, wherein the plurality of inflatable balloons are arranged in series along the length of the light emitting portion, and the separation between any two of the plurality of inflatable balloons is adjustable. [The present invention 1004] The light delivery device of the present invention 1003, wherein the light emitting portion comprises one or more segments not connected to the plurality of inflatable balloons, and the one or more segments include one or more light sources among the plurality of light sources. [The present invention 1005] The light delivery device of the present invention 1001, wherein the plurality of light sources are light emitting diodes (LEDs) electrically connected to a power source, and the plurality of light sources are configured to emit light outward from the delivery device. [The present invention 1006] The light delivery device of the present invention 1001, wherein the plurality of light sources are positioned on a cooling tube within the delivery device, and the cooling tube is configured to receive cooling air from a cooling system including a medical-grade compressor and a chiller. [The present invention 1007] 1001. The light delivery device of claim 10, wherein the plurality of light sources are configured to emit peak wavelengths within the UV-A region between 338 nm and 346 nm. [The present invention 1008] a balloon control unit configured to inflate and / or deflate each of the plurality of inflatable balloons via a respective balloon inflation port. The light delivery device of the present invention 1001 further comprises: [The present invention 1009] a guidewire channel within the delivery tube and extending the entire length of the delivery tube, the guidewire channel configured to pass the delivery device over a guidewire positioned within the patient's lumen; The light delivery device of the present invention 1001 further comprises: [The present invention 1010] 1001. The light delivery device of the present invention, wherein the UV transparent material is polyether block amide (PEBA), or cyclic olefin copolymer (COC), or silicone. [The present invention 1011] 1001. The light delivery device of claim 10, wherein said plurality of inflatable balloons comprises at least three balloons. [The present invention 1012] 1. A method for administering intraluminal ultraviolet (UV) therapy, comprising: a delivery tube comprising a plurality of light-emitting segments, each of the plurality of light-emitting segments including a plurality of light-emitting diodes (LEDs) configured to emit narrowband light having a wavelength in the ultraviolet A (UV-A) range between 338 nm and 346 nm; a plurality of inflatable balloons, each of the plurality of inflatable balloons coupled to one of the plurality of light segments and each of the plurality of inflatable balloons fluidly coupled to a respective inflation port coupled to a balloon control unit, the plurality of inflatable balloons being composed of a UV-transparent material; providing a UV light delivery device comprising: positioning the delivery tube within a lumen of a gastrointestinal (GI) tract of a patient with each of the plurality of inflatable balloons in a de-inflated state; selectively inflating the plurality of inflatable balloons via the balloon control unit; and energizing the plurality of LEDs at a threshold intensity for a threshold duration based on one or more of the type of GI tract disorder and overall severity. A method comprising: [The present invention 1013] 1011. The method of claim 10, wherein the step of positioning a delivery tube within a lumen includes juxtaposing one or more of said plurality of inflatable balloons with one or more diseased areas within said lumen. [The present invention 1014] The method of the present invention 1012, wherein the step of selectively inflating the plurality of inflatable balloons includes inflating the one or more inflatable balloons juxtaposed to the one or more diseased areas, while maintaining the remaining number of balloons juxtaposed to normal healthy tissue in a de-inflated state. [The present invention 1015] The method of claim 1012, wherein the step of selectively inflating the one or more inflatable balloons juxtaposed to the one or more affected areas includes pressurizing the one or more inflatable balloons to a threshold pressure at which the one or more inflatable balloons contact the epithelial layer of the lumen. [The present invention 1016] The method of claim 1014, wherein the threshold pressure is based on the diameter of the lumen. [The present invention 1017] and adjusting the magnitude of the light intensity for a given light emission segment based on the local severity of infection and / or inflammation in one or more target areas, where the one or more target areas have different severities of infection and / or inflammation during a condition. The method of the present invention 1011 further comprising: [The present invention 1018] the delivery tube includes a refrigerant tube configured to receive cooled air from the compressor; and the method further comprising monitoring the temperature of the delivery tube via a thermistor and adjusting the refrigerant flow rate through the refrigerant tube based on the temperature. The method of the present invention 1011. [The present invention 1019] The method of claim 1011, wherein the delivery tube is configured as an endoscope equipped with one or more cameras for visualizing the lumen. [The present invention 1020] The method of claim 1011, wherein the UV-transparent material comprises polyether block amide (PEBA), or cyclic olefin copolymer (COC), or silicone. [The present invention 1021] 1012. The method of claim 1011, wherein the step of positioning the delivery tube within the lumen comprises threading the delivery tube over a guidewire positioned within the lumen using an endoscope. [The present invention 1022] providing a delivery tube having a light-emitting portion including a set of light-emitting diodes (LEDs) and at least one inflatable balloon coupled to the light-emitting portion; guiding the delivery tube into a lumen of the patient's gastrointestinal tract, positioning the at least one inflatable balloon in juxtaposition with a target area within the lumen requiring ultraviolet (UV) light treatment; inflating the at least one inflatable balloon via a balloon inflation port fluidly coupled to the at least one inflatable balloon; and energizing the set of LEDs connected to the delivery tube and positioned within the at least one inflatable balloon for a duration and intensity sufficient to treat a gastrointestinal disorder. Including, The set of LEDs is configured to emit narrowband light having a wavelength in the UV region between 335 nm and 349 nm. A method for treating, ameliorating, and / or preventing gastrointestinal disorders in a patient. [The present invention 1023] 1021. The method of claim 1021, wherein said at least one inflatable balloon is composed of a UV-transparent material having a UV transmittance in the range of 8 percent to 100 percent. [The present invention 1024] 1021. The method of claim 1021, wherein said at least one inflatable balloon is constructed using a material comprising polyether block amide (PEBA), or cyclic olefin copolymer (COC), or silicone. [The present invention 1025] The method of claim 1021, wherein the step of inflating the at least one inflatable balloon comprises pressurizing the at least one inflatable balloon to a threshold pressure at which the at least one inflatable balloon comes into direct contact with a desired surface area of ​​the epithelial layer of the lumen. [The present invention 1026] The method of claim 1021, wherein the threshold pressure is based on the diameter of the lumen. [The present invention 1027] Intensity of at least 1,100 microwatts / cm 2 , 1,500 microwatts / cm 2 , 2,000 microwatts / cm 2 , 2,100 microwatts / cm 2 , 2,200 microwatts / cm 2 , 2,300 microwatts / cm 2 , 2,400 microwatts / cm 2 , 2,500 microwatts / cm 2 , 2,600 microwatts / cm 2 , 2,700 microwatts / cm 2 , 2,800 microwatts / cm 2 , 2,900 microwatts / cm 2 , 3,000 microwatts / cm 2 , or 4 milliwatts / cm 2 The method of the present invention 1021, comprising: [The present invention 1028] The method of claim 1021, wherein the gastrointestinal disorder is a form of inflammatory bowel disease. [The present invention 1029] The method of claim 1028, wherein the form of inflammatory bowel disease comprises ulcerative colitis and / or Crohn's disease. [The present invention 1030] 1021. The method of claim 1021, wherein the gastrointestinal disorder comprises at least one of ulcerative colitis, Crohn's disease, pouchitis, proctitis, fistula, inflammatory stricture, microscopic colitis, infectious diarrhea, refractory Helicobacter pylori, MALT lymphoma, colonic inertia, tropical sprue, celiac disease, small intestinal bacterial overgrowth, appendicitis, post-bone marrow transplant infection, pseudopolyps, radiation enteritis, refractory Clostridium difficile, gastrointestinal cancer, hepatobiliary infection, and / or mucosal and submucosal inflammation and cancer. Additional features and advantages disclosed herein will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the principles disclosed herein. The features and advantages disclosed herein may be realized and obtained by means of the instruments and combinations particularly pointed out in the appended claims. These and other features disclosed herein will become more fully apparent from the following description and the appended claims, or may be learned by practice of the principles set forth herein. [Brief explanation of the drawings]

[0018] To describe the above disclosure and the manner in which its advantages and features are obtained, a more particular description of the above principles will be made by reference to the illustrative examples shown in the accompanying drawings. These drawings are merely representative of exemplary embodiments disclosed herein and therefore should not be considered limiting of its scope. These principles will be described and explained with additional specificity and detail using the following drawings:

[0019] [Figure 1A] 1 shows a schematic block diagram depicting an overview of a light therapy system, in accordance with an embodiment of the present disclosure. [Figure 1B] 1B shows a simplified block diagram of the phototherapy system of FIG. 1A according to another embodiment of the present disclosure. [Figure 2A] 1 shows a schematic diagram of an optical catheter assembly with multiple balloons, according to an embodiment of the present disclosure. [Figure 2B] 1 shows a schematic diagram of an optical catheter assembly with a light emitting portion within a single balloon, according to an embodiment of the present disclosure. [Figure 3] 3A and 3B show schematic diagrams of an optical catheter assembly with multiple balloons in a de-inflated state and an inflated state, respectively, according to an embodiment of the present disclosure. [Figure 4] 4A and 4B show schematic diagrams of an exemplary UV light-emitting device with a single balloon element according to an embodiment of the present disclosure, and another exemplary UV light-emitting device with a single balloon element according to another embodiment of the present disclosure. [Figure 5A] 1 shows a flowchart illustrating an exemplary method for treating, ameliorating, and / or preventing GI tract disorders using a delivery device with multiple balloons, according to an embodiment of the present disclosure. [Figure 5B] 1 shows a flowchart illustrating an exemplary method for coordinating the operation of one or more balloons and UV LEDs while administering UV light using a delivery device with multiple balloons, according to an embodiment of the present disclosure. [Figure 6A] 6A-G show schematic diagrams depicting placement of an exemplary delivery device including multiple LEDs and multiple inflatable balloons within the lumen of the large intestine, according to an embodiment of the present disclosure. [Figure 6B] See legend to Figure 6A. [Figure 6C] See legend to Figure 6A. [Figure 6D] See legend to Figure 6A. [Figure 6E] See legend to Figure 6A. [Figure 6F] See legend to Figure 6A. [Figure 6G] See legend to Figure 6A. [Figure 7] 2B shows a schematic diagram of an enlarged portion of the UV light catheter of FIG. 2A. [Figure 8] 1 shows a schematic diagram of an exemplary UV light catheter with one or more chip-on-board (COB) miniature bars contained within a delivery tube, according to an embodiment of the present disclosure. [Figure 9] 9A shows a schematic diagram of a fiber optic system coupled to a UV LED light source, and FIGS. 9B and C show schematic diagrams of multiple UV LED light sources for embedding with a fiber optic system, according to embodiments of the present disclosure. [Figure 10] 10A illustrates flat and tubular configurations of a flexible printed circuit board (PCB) utilized in conjunction with one or more UV LED light sources, according to an embodiment of the present disclosure, and FIG. 10B illustrates a schematic diagram of an exemplary heat sink implemented in a UV light catheter, according to an embodiment of the present disclosure. [Figure 11] Figure 11A shows a schematic diagram of an example configuration of multiple LEDs and multiple linear reflectors according to an embodiment of the present disclosure, Figure 11B shows a schematic diagram of an example heat sink implemented in a UV light catheter according to an embodiment of the present disclosure, and Figure 11C shows a schematic diagram of an example light distribution in an example UV LED light source including multiple LEDs and multiple linear reflectors according to an embodiment of the present disclosure. [Figure 12A] 1 shows a growth curve of E. coli when an exemplary UV light-emitting device is implemented. [Figure 12B] 1 shows a growth curve of E. coli when an exemplary UV light-emitting device of the present disclosure is implemented. [Figure 13] FIG. 1 shows a schematic diagram of an exemplary UVA light-emitting device implemented in the colon of a mouse according to the principles of the present disclosure. [Figure 14] 14A and B show schematic diagrams of an exemplary UVA light-emitting device of the present disclosure inserted into the vaginal canal of a rat, in accordance with the principles of the present disclosure. [Figure 15] Figure 15A shows the growth curve of a liquid culture containing E. coli when an exemplary narrow-band UVA light-emitting device is implemented. Figure 15B shows an exemplary narrow-band UV-A light-emitting device implemented on a liquid culture containing E. coli. [Figure 16] 1 shows the growth curve of a liquid culture containing E. coli when an exemplary narrow band UV-A light emitting device is implemented. [Figure 17] 17A and B show the growth curves of a liquid culture containing E. coli when an exemplary narrow-band UV-A light-emitting device is implemented. [Figure 18] 1 shows the growth curve of a liquid culture containing E. coli when an exemplary UV light-emitting device is implemented. [Figure 19] 1 shows the growth curve of a liquid culture containing E. coli when an exemplary UV light-emitting device is implemented. [Figure 20] 1 shows the growth curve of a liquid culture containing E. coli when an exemplary UV light-emitting device is implemented. [Figure 21]21A and B show the growth curve of a liquid culture containing E. coli when an exemplary UV light-emitting device was implemented. [Figure 22] 1 shows a table illustrating the intensity and exposure duration of narrow-band UV-A light applied to bacterial cultures in one example. [Figure 23] 1 shows a table illustrating bacterial counts over time during narrowband UV-A light exposure in one example. [Figure 24] 1 shows a growth curve illustrating bacterial counts over time during narrow band UV-A light exposure using an exemplary system. [Figure 25-1] Figure 25A shows images over time of a petri dish containing bacteria exposed to narrowband UV-A light compared to a control, and Figure 25B shows images of a petri dish showing the effect of narrowband UV-A treatment of a liquid culture of E. coli when subsequently plated. [Figure 25-2] 25C-F show growth curves showing the number of E. coli bacteria over time exposed to various intensities of UV light using an exemplary system. [Figure 25-3] See description of Figure 25-2. [Figure 25-4] 25G-J show growth curves showing the number of P. aeruginosa bacteria over time exposed to various intensities of UV light using an exemplary system. [Figure 25-5] See description of Figure 25-4. [Figure 25-6] Figures 25K and L show growth curves comparing the logarithmic reduction at various intensities at 20 and 40 minutes, respectively, using an exemplary system. [Figure 25-7] Figure 25M shows growth curves demonstrating the reduction in E. coli colony diameter at various intensities and treatment times using an exemplary system. Figure 25N shows growth curves demonstrating the reduction in P. aeruginosa colony diameter at various intensities and treatment times using an exemplary system. [Figure 26-1] Figure 26A shows a bar graph illustrating cell proliferation during exposure to UV-A light using an exemplary system. Figure 26B shows a bar graph illustrating cell proliferation during exposure to UV-A light using an exemplary system. [Figure 26-2] Figure 26C shows a bar graph illustrating cell proliferation during exposure to UV-A light using an exemplary system, and Figure 26D shows a bar graph illustrating the absence of DNA damage to cells during exposure to UV-A light using an exemplary system. [Figure 26-3] Figure 26E shows a bar graph demonstrating the absence of DNA damage to cells during exposure to UV-A light using an exemplary system. Figure 26F shows a bar graph demonstrating the absence of DNA damage to cells during exposure to UV-A light using an exemplary system. [Figure 27] 1 shows a bar graph illustrating the growth of virus-infected cells during exposure to UV light using an exemplary system. [Figure 28] 1 shows a bar graph depicting cell number of infected cells after 72 hours of UV light application using an exemplary system compared to a control. [Figure 29] 1 shows a Western blot demonstrating intracellular detection of coronavirus 229E and levels of mitochondrial antiviral signaling protein (MAVS) at 96 hours in ciliated tracheal epithelial cells treated with NB-UVA light. [Figure 30] 1 shows fluorescence images of alveolar cells transfected with Coxsackievirus and the effect of UVA treatment on the transfected alveolar cells, according to embodiments of the present disclosure. [Figure 31] 1 shows a bar graph illustrating the effect of narrow band UV-A treatment on the survival of HeLa cells transfected with Coxsackievirus, according to an embodiment of the present disclosure. [Figure 32] 1 shows a bar graph illustrating the viability of ciliated tracheal epithelial cells in response to transfection with coronavirus 229E and treatment with narrow-band UV-A light, according to an embodiment of the present disclosure. [Figure 33] 1 shows a bar graph illustrating the viability of ciliated tracheal epithelial cells in response to transfection with coronavirus 229E and treatment with narrow-band UV-A light, according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0020] Detailed Description Unless otherwise defined, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Szycher's Dictionary of Medical Devices, CRC Press, 1995, can provide a useful guide to many of the terms and phrases used herein. Those skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. Indeed, the present invention is in no way limited to the specifically described methods and materials. For example, although the figures primarily depict the invention in the gastrointestinal tract, as shown throughout, the disclosed systems and methods can be used in other applications.

[0021] In some embodiments, characteristics such as dimensions, shapes, relative positions, and the like used to describe and claim particular embodiments of the present invention should be understood as being modified by the term "about."

[0022] Next, various embodiments of the present invention will be described. In the following description, specific details are provided to fully understand and enable description of these embodiments. However, those skilled in the art will understand that the present invention may be practiced without the need for many of these details. Likewise, those skilled in the art will also understand that the present invention may include many other obvious features not described in detail herein. Furthermore, in order to avoid unnecessarily obscuring the relevant description, some well-known structures or functions may not be shown or described in detail below.

[0023] The terms used below should be interpreted in their broadest reasonable manner, even when used in conjunction with detailed descriptions of certain specific embodiments of the present invention. Indeed, certain terms may even be emphasized below. However, terms intended to be interpreted in a restrictive manner are clearly and specifically defined as such in this Detailed Description section.

[0024] As used herein, the term "LED" refers to a light-emitting diode, which is a semiconductor light source that emits light across a range of visible and invisible light spectrums. LEDs typically have an emission spectrum that includes a set of wavelengths that vary in intensity over their emission spectrum, and typically follow a bell-shaped or similarly shaped intensity curve over their wavelength range. A particular LED is typically described using the wavelength of its peak emission intensity, or the wavelength at which the LED emits the most intense radiation.

[0025] Thus, LEDs typically emit light over a wavelength range, and a particular LED may be described in terms of the wavelength range at which it emits above a threshold intensity (in some embodiments, a percentage of the LED's maximum intensity). For example, a given LED may emit light at at least 10% of its maximum emission intensity only at wavelengths between 335 nm and 345 nm. The emission intensity of the LED below 335 nm and above 345 nm may be less than 10% of the LED's peak intensity emission wavelength (herein "peak wavelength"), and in some cases may be too low to be therapeutically relevant. Thus, for many therapeutic applications, only wavelengths between 335 nm and 345 nm for a particular LED are believed to have a therapeutic impact.

[0026] Thus, the wavelength ranges described herein can be wavelength ranges that are therapeutically effective or significant for a particular treatment application, duration, and intensity of emission delivered by the LED to a treatment site (or based on the power emitted by the LED). In some examples, the wavelength range can be a range of wavelengths emitted by the LED having an intensity that is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20% of the peak luminous intensity.

[0027] Thus, for various LED light sources, spectral emission regions corresponding to the region where the LED emits a threshold intensity percentage of its maximum intensity are disclosed herein. Examples of various LED spectral emission regions and peak intensity emission wavelengths for commercially available LEDs are described in Filippo, et al., "LEDs: Sources and Intrinsically Bandwidth-Limited Detectors," the entire contents of which are incorporated by reference.

[0028] Although many specific embodiment details are described herein, these should not be construed as limitations on the scope of any invention or what may be claimed, but rather as descriptions of features that are specific to particular embodiments of a particular invention. Certain features described herein in the context of separate embodiments may also be implemented in combination in a single embodiment. Conversely, various features described in the context of a single embodiment may also be implemented in multiple embodiments separately or in any suitable subcombination. Furthermore, while features may be described above as functioning in a particular combination and may even initially be claimed as such, one or more features from a claimed combination may, in some cases, be separated from that combination, and the claimed combination may be directed to a subcombination or variations of that subcombination.

[0029] Similarly, while operations may be depicted in the figures in a particular order, this should not be understood as requiring such operations to be performed in the particular order shown, or in a sequential order, or that all of the operations shown be performed, to achieve desirable results. In certain situations, multitasking and parallel processing may be advantageous. Furthermore, the separation of various system components in the above embodiments should not be understood as requiring such separation in all embodiments, and it should be understood that the program components and systems described may generally be integrated together in a single software product or packaged in multiple software products.

[0030] overview Methods and systems are provided for treating, ameliorating, and / or preventing inflammatory and / or infectious diseases affecting the gastrointestinal tract. Specifically, methods and systems are provided for improving the efficacy and safety of treating, ameliorating, and / or preventing inflammatory and / or infectious diseases affecting the gastrointestinal tract using narrowband light emitted at wavelengths within the ultraviolet A (UV-A) range. In some embodiments, the methods and systems described herein may be applied to the treatment of vaginal infection and / or inflammation. An exemplary UV light therapy system including a UV light catheter assembly with multiple UV light sources and multiple inflatable balloons is shown in FIGS. 1A and 1B. An example of a UV light catheter assembly including a delivery tube with a light-emitting portion including multiple light-emitting diodes (LEDs) and multiple inflatable balloons is shown in FIGS. 2A, 3A, and 3B. Additionally, a single-balloon device including a single balloon coupled to the light-emitting portion is shown in FIG. 2B. Further examples of single-balloon devices are shown in FIGS. 4A and 4B. FIG. 5A illustrates an exemplary method for treating, ameliorating, and / or preventing infectious and / or inflammatory conditions of the GI tract using a delivery device with multiple balloons. Additionally, FIG. 5B illustrates an exemplary method for controlling the operation of the balloons and the operation of the delivery device during UV light treatment. FIGS. 6A-6G illustrate exemplary positioning and placement of a multi-balloon UV light delivery device within the lumen of the large intestine. FIGS. 7-11C illustrate exemplary UV light sources that may be included within a delivery device to provide UV light treatment. FIGS. 12A-33 illustrate experimental data demonstrating the antimicrobial efficacy and safety of UV-A light against various microorganisms.

[0031] Technical advantages of using one or more balloons coupled to a UV light delivery device include improved efficacy of UV light treatment by improving UV light distribution, uniformity of light distribution, and irradiance at the treatment site through one or more of: increasing the surface area of ​​the treatment site by stretching folds and bulges at the contact area between the balloon and the colonic epithelium at the treatment site; uniform distance to the UV light source; displacing obstructing feces and / or debris (e.g., biofilm) at the treatment site; and preventing proximal feces and / or debris from descending to the treatment site. Another technical advantage of using a delivery device including one or more balloons includes selective treatment based on the number and / or location of treatment areas. The use of one or more balloons allows for customized UV light therapy through selectively operating and / or adjusting the balloons according to one or more of the location, severity, extent and pattern of spread of the infection and / or inflammation. Furthermore, when inflated to contact the colonic epithelium, the one or more balloons may stabilize the colon wall and the delivery device within the lumen, thereby reducing injury during placement of the delivery device and treatment. Furthermore, the one or more balloons may maintain a constant distance between the treatment site and the UV light source during light treatment, thereby providing uniform light delivery over the duration of the treatment. Furthermore, a delivery device including one or more balloons may be efficiently navigated through the lumen of the GI tract (e.g., through the hepatic flexure and / or splenic flexure), thereby potentially enabling delivery of UV light to any location within the GI tract.

[0032] UV Light Therapy System FIG. 1A illustrates an exemplary UV light therapy system 100. The UV light therapy system 100 may be configured to deliver UV light to one or more portions of the gastrointestinal (GI) tract to treat, ameliorate, reduce, and / or prevent infectious and / or inflammatory conditions. For example, the UV light therapy system may be configured to administer UV light intraluminally to one or more portions of the GI tract. The one or more portions of the GI tract may include, but are not limited to, one or more areas of the large intestine (e.g., rectum, sigmoid colon, descending colon, transverse colon, ascending colon), one or more areas of the small intestine (e.g., duodenum, jejunum, ileum), one or more areas of the stomach, and / or one or more areas within the esophagus. In some embodiments, the UV light therapy system 100 may be configured to treat vaginal infection and / or inflammation, as discussed with respect to FIGS. 4A and 4B. Additionally, the UV light therapy system 100 may be configured to evenly administer UV light onto a target area of ​​the GI tract (i.e., even distribution of UV light on the target area) to improve irradiance and irradiance distribution in the target area. The target area, alternatively referred to herein as a treatment area, includes an area within the GI tract affected by a GI tract pathology. In some embodiments, UV light therapy may be applied for preventative purposes, such that the target area may include an area more susceptible to infection and / or inflammation (e.g., an area adjacent to an area of ​​infection and / or inflammation) or an area suspected of having infection and / or inflammation. In other embodiments, UV light therapy may be applied to an area that has already been treated or healed to prevent recurrence of infection and / or inflammation. The target area may include a single intraluminal area within the GI tract, one or more adjacent intraluminal areas within the GI tract, or one or more non-adjacent intraluminal areas within the GI tract.

[0033] Additionally, the UV light therapy system 100 may be configured to selectively administer UV therapy within one or more portions of the GI tract. As a non-limiting example, the UV light therapy system 100 may be configured to deliver UV light to a portion of the sigmoid colon or to the entire sigmoid colon. In another non-limiting example, the UV light therapy system 100 may deliver UV light to a portion of the descending colon and a portion of the sigmoid colon. In yet another example, the UV light therapy system 100 may selectively deliver UV light to non-adjacent areas of the large intestine simultaneously (e.g., a portion of the sigmoid colon and a portion of the transverse colon). Thus, the UV light therapy system 100 may be configured to customize UV ​​therapy based on the target area (i.e., the infected and / or inflamed area), which may be a single area, one or more adjacent areas, one or more non-adjacent areas, or a combination thereof. Furthermore, in some examples, UV therapy may be administered simultaneously to improve the efficiency and speed of UV light therapy when targeting multiple target areas.

[0034] The UV light therapy system 100 includes a UV light catheter assembly 140 including one or more UV light sources 142, one or more balloons 144, and a cooling unit 146 configured to maintain the UV light catheter assembly within a desired temperature range and reduce overheating. In one embodiment, the one or more UV light sources 142 and the cooling unit 146 may be positioned within a delivery tube (e.g., a cylindrical flexible tube), while the one or more balloons may be disposed on the delivery tube along its length. The delivery tube is also referred to herein as a catheter or light catheter. In another embodiment, the one or more light sources 142 and the one or more balloons 144 may be positioned on the delivery tube, while the cooling unit is located within the housing catheter. In yet another embodiment, the cooling unit 146 may be positioned within a handle portion attached to a delivery catheter that includes the one or more light sources 142 positioned within or on or embedded in the housing catheter. In this embodiment, the one or more balloons 144 may be positioned on the delivery tube.

[0035] In one embodiment, a single balloon can be positioned in a distal portion of the housing catheter (e.g., the distal portion opposite the proximal portion that connects to the control unit 102, described below). A non-limiting example of a UV light catheter assembly including a single expandable balloon is shown in FIG. 2B. In some examples, a UV light catheter assembly for vaginal or rectal UV administration, such as the exemplary device shown in FIGS. 4A and 4B, can have a single balloon that can be deployed when positioned in vivo.

[0036] In another embodiment, the one or more balloons 144 can be positioned along the length of the delivery tube to treat infections at various locations throughout the entire length of the infected area (e.g., the entire length of the colon). One or more balloons 144 can be configured as UV-transparent balloons to allow transmission of UV light from the UV light source 142 to their respective target sites. The balloons can be constructed using a material that provides 100% UV transparency (i.e., a material with 100% UV transmission through it), or can be constructed using any material or combination of materials that provides UV transparency (i.e., a UV transmission rate ranging from 100% to 80%). In one embodiment, the UV-transparent balloon can be made from polyether block amide (PEBA). PEBA is partially UV-transparent (i.e., has a strength loss of approximately 15%). In another embodiment, the UV-transparent balloon can be constructed from cyclic olefin copolymer (COC), which is 100% UV-transparent. In yet another embodiment, the UV-transparent balloon can be composed of silicone. Additionally, the UV transparent material used to construct the one or more balloons 144 can be a medical grade material. Additionally, the UV transparent material (i.e., UV transmissive material) can also be UV stable.

[0037] The one or more balloons 144 may be utilized to securely secure the device in place during light administration, thereby reducing undesired movement of the housing catheter. Additionally, the one or more balloons 144 may be utilized to stretch folds within the GI tract to provide more uniform light exposure to the target area. Additionally, the one or more balloons 144 may be utilized to diffuse foreign debris / biofilm that may act as a barrier between the light catheter assembly 140 and the epithelium. Furthermore, the one or more balloons 144 may prevent stool from descending into the treatment segment, thereby increasing the effectiveness, efficiency, uniformity, and consistency of the UV light treatment delivered via the UV light treatment device.

[0038] In one embodiment, the one or more balloons 144 may be inflatable through one or more corresponding ports coupled to a fluid source (e.g., an air pump) so that they can be inflated when the UV light catheter assembly is navigated to a desired position in vivo before powering the UV light source. Furthermore, the one or more balloons 144 may be configured to allow the position of the one or more balloons to be adjusted. For example, the one or more balloons may have a modular configuration, thereby customizing the number and positioning of the balloons based on one or more of the pathology (e.g., ulcerative colitis, Crohn's disease), the location of the pathology (e.g., based on which area of ​​the colon is affected), and the progression of the pathology in the affected area. Furthermore, as described below with respect to FIG. 2A , in some embodiments, the degree of inflation of each of the one or more balloons may be adjusted based on the pathology, the location of the pathology, the diameter of the target area, and / or the degree of inflammation and / or infection in the affected area due to the identified pathology. For example, a first target area may have a smaller diameter than a second target area. That is, a first target area may be smaller than a second target area (e.g., due to a colonic stricture), and thus a first inflation amount of a first balloon used to deliver light to the first area may be less than a second inflation amount of a second balloon used to deliver light to a second target area having a larger diameter.

[0039] The one or more UV light sources 142 can be configured to deliver narrow-bandwidth UV light having wavelengths within the UV-A range. Light having wavelengths within the UV-A range has effective antimicrobial properties and is safe for internal administration over large areas within a patient's body (e.g., the entire sigmoid colon, or any large area within a patient's body). Furthermore, the inventors have identified that certain wavelengths within the UV-A range penetrate cells to activate antimicrobial responses without causing UV-induced DNA damage. In one example, the wavelength within the UV-A range can be between 335 nm and 349 nm. Furthermore, the wavelength within the UV-A range can have a peak wavelength between 335 nm and 349 nm, between 339 nm and 346 nm, between 338 nm and 342 nm, or between 338 nm and 346 nm.

[0040] In another embodiment, the one or more light sources 142 may emit light with wavelengths in the UV-A region between 338 nm and 342 nm or between 339 nm and 346 nm. Accordingly, the wavelengths may have peak wavelengths between 338 nm and 342 nm or between 339 nm and 346 nm. In some embodiments, the one or more light sources 142 may emit light with one or more peak wavelengths between 335 nm and 349 nm, between 338 nm and 342 nm, between 339 nm and 346 nm, or between 338 nm and 346 nm.

[0041] In one embodiment, the one or more light sources may be a plurality of light emitting diodes (LEDs), where each LED is configured to emit narrow-bandwidth light having a wavelength in the UV-A region. As noted above, the narrow-bandwidth light may have a wavelength between 335 nm and 349 nm, between 338 nm and 346 nm, between 338 nm and 342 nm, or between 339 nm and 346 nm.

[0042] In various embodiments, other types of light sources besides LEDs may be used, examples of which are described with respect to Figures 8-12.

[0043] The UV light catheter assembly 140 can be coupled to a control unit 102. In one embodiment, the control unit 102 includes a cooling system 108 for providing a refrigerant flow through a cooling unit 146 within the UV light catheter assembly 140 to regulate the temperature of the UV light assembly. The cooling system 108 includes a compressor 109 (e.g., a medical-grade compressor), an air cooler 111 (e.g., a medical-grade air cooler), a flow sensor (not shown) for the air returning from the cooling unit 146, a valve 106, and a pressure regulator 112 for starting and / or stopping the refrigerant flow and / or adjusting the refrigerant flow through the cooling tubes.

[0044] The control unit 102 includes a connector 110 that provides a connection interface (between the control unit 102 and the UV light assembly via one or more connectors or umbilicals, as described below) for mating with one or more of a high-temperature coolant connector 148, a low-temperature coolant connector 150, and an electrical connector 152. The high-temperature coolant connector 148 may be tubing for flowing high-temperature coolant from the UV light catheter assembly to the control unit 102, the low-temperature coolant connector 150 may be a second tubing through which low-temperature coolant from a cooling system may flow to the UV light catheter assembly, and the electrical connector 152 may provide an electrical coupling between the UV light catheter assembly and the control unit 102. In one embodiment, the connector 152 may be a wired or wireless connection, or a combination thereof. In one embodiment, the connector 152 may be used to send an electrical signal from the control unit 102 to power on or off the one or more light sources 142. In some embodiments, the intensity of the one or more light sources 142 and / or the duration of the one or more light sources 142 may be controlled via connector 152 .

[0045] In some embodiments, the UV light catheter assembly 140 may include one or more light segments, each light segment comprising multiple light sources. In some embodiments, the operation of each light segment (e.g., power-on time, power-off time, intensity adjustment, duration of operation, etc.) may be independently adjusted via the control unit 102. Accordingly, the control unit 102 may include one or more light segment control units (not shown) for adjusting various operations of the corresponding light segments. In some embodiments, the operation of all light segments may be adjusted in a synchronized manner (e.g., power-on time, power-off time, duration of operation, intensity, etc.). In some embodiments, some operations (e.g., power-on time) may be synchronized, while other operations (e.g., intensity, power-off time, duration, etc.) may be adjusted independently. As a non-limiting example, a first intensity of a first light segment delivering light to a first target area may differ from a second intensity of a second light segment delivering light to a second target area if the first target area has a different degree of infection and / or inflammation compared to the second target area.

[0046] The control unit 102 further includes a balloon control unit 120 for coordinating inflation and deflation of the one or more balloons 144. The balloon control unit 120 may be communicatively coupled to one or more pressure sensors 122 in fluid communication with the one or more balloons 146. In one embodiment, each of the one or more balloons may be coupled to a corresponding pressure sensor, and the pressure within each balloon may be individually monitored via a controller in the balloon control unit 120 and / or a controller 103 in the control unit 102. Additionally, pressure fluctuations within each balloon may be monitored via the controller to assess one or more of a leak condition and a temperature of the UV light assembly.

[0047] In some embodiments, balloon control unit 120 further includes a reservoir 130 for storing inflation fluid (e.g., air) that can be used to pressurize the one or more balloons 142 to a desired pressure and desired balloon volume during deployment of UV light therapy device 100. In one embodiment, one or more balloons 146 can be selectively pressurized with fluid from the reservoir via balloon control unit 120. Thus, in one embodiment, each of the one or more balloons can be fluidly coupled to one or more balloon inflation ports 124. Each balloon inflation port can be coupled to a reservoir 130 via balloon control unit 120. Thus, during pressurization of a selected balloon, fluid can flow from reservoir 130 to the respective balloon inflation port, through a channel or passageway within the UV light catheter assembly (between the balloon inflation port and the balloon), and then into the selected balloon.

[0048] Additionally, the balloon control unit 120 may be used to selectively depressurize the one or more balloons. For example, an inflated balloon may be de-inflated after completion of a treatment duration while the UV light treatment assembly is positioned within the patient's colon and before removing the UV light treatment assembly from the patient. In some embodiments, the balloon inflation port and passageway may also be used to remove fluid from the balloon during de-pressurization. In other embodiments, a separate balloon de-inflation port and passageway may be provided for de-inflating the balloons. Similar to pressurization, the one or more balloons may be selectively de-pressurized, or all inflated (i.e., pressurized) balloons may be simultaneously de-inflated (i.e., de-pressurized). Additionally, the balloon control unit may include one or more valves (not shown) for switching between pressurizing and de-pressurizing each balloon. In some embodiments, the balloon control unit 120 may include one or more pumps (not shown) for pressurizing and / or de-pressurizing the one or more balloons 144. In some embodiments, the one or more pumps may be coupled to the atmosphere, thereby using atmospheric air to pressurize the balloons. Similarly, during de-pressurization, air from the balloons may be released into the atmosphere. In some other embodiments, one or more filters may be provided (eg, at the pump inlet) to filter the air provided for pressurizing the balloon.

[0049] Additionally, one or more pressure sensors 130 may be coupled to the one or more balloon inflation ports to monitor and / or maintain a desired pressure within each of the one or more balloons 144. For example, during inflation, selected balloons may be inflated through their respective balloon inflation ports, and the pressure within the selected balloons may be monitored via respective pressure sensors fluidly coupled to the respective balloon inflation ports. The pressure sensors may transmit pressure signals to the balloon control unit 120. The control unit 120 may monitor the pressure signals within each balloon based on signals from the respective pressure sensors during operation of the UV light therapy system 100 and automatically adjust the inflation and / or depressurization of the one or more balloons based on the desired pressure. As a non-limiting example, a user may specify a respective desired pressure for each balloon via the control unit 120. Thus, one or more of the inflation amount, inflation rate, and de-inflation rate may be individually adjusted. In some embodiments, one or more of the inflation rate, inflation volume, and de-inflation rate may be adjusted in a synchronized manner for all balloons under operation (i.e., for a number of operating balloons less than or equal to the total number of balloons on the delivery device). An exemplary fluid flow for pressurizing one or more balloons is shown at 126, and an exemplary pressure signal via one or more pressure sensors 122 is shown at 128. Although shown separately in the figures, each pressure sensor may be coupled to a respective balloon inflation port to monitor the pressure inside the respective balloon.

[0050] In one embodiment, the therapeutic distance between the target area and the light source can be adjusted based on the amount of inflation of a balloon positioned within the target area. In other words, in some embodiments, the inflation amount of a given balloon can be adjusted based on the diameter of the lumen; the diameter of the lumen can be based on the anatomical characteristics of the patient's GI tract (e.g., small intestine or large intestine), the type of disease, and / or the severity of the disease affecting the target area. For example, if the target area has a larger diameter, the balloon can be pressurized to a higher first pressure to contact the target area and ensure consistent contact across the entire curved outer surface of the balloon, which can increase one or more of the irradiance of the administered UV light (e.g., by displacing stool, debris, or biofilm; preventing proximal stool from descending to the target area; widening folds to increase surface area; etc.), while improving the distribution of UV light irradiance on the target area. Furthermore, if the target area has a higher degree of inflammation and / or infection causing luminal narrowing, the balloon may be pressurized accordingly (e.g., inflated to a smaller volume) to provide the necessary contact with the epithelium and improve irradiance and / or irradiance distribution, as described above. Additionally, in some embodiments, light source parameters may be altered (e.g., adjusting current to increase or decrease intensity) based on the pathology for selective light therapy.

[0051] 1A and 1B show balloon control unit 120 and reservoir 130 integrated with control unit 102, it will be appreciated that balloon control unit 120 and / or reservoir 130 may be separate from control unit 102. Similarly, cooling system 108 may be integrated with control unit 102 (as shown) or may be separate from it.

[0052] The inflation fluid can be a UV-transparent fluid that allows UV light from the one or more light sources 142 to pass through effectively. Additionally, the one or more balloons 144 can be constructed using a UV-transparent material that allows UV-A light emitted from the one or more light sources 142 at wavelengths within the 335 nm to 350 nm range to be transmitted through the balloon 144 and reach the target tissue. Exemplary UV-transparent materials that can be used include, but are not limited to, polyether block amide (PEBA), cyclic olefin copolymer (COC), and silicone.

[0053] 1B, an umbilical assembly 131 may be utilized to couple the control unit 102 with the UV light catheter assembly 140. For example, a connector 110 may be used to couple with one or more of a high temperature refrigerant connector 134, a low temperature refrigerant connector 136, and an electrical connector 138 of the umbilical tube assembly 131 (located on the controller side 132 of the umbilical assembly 131).

[0054] An umbilical tube assembly 131 connects the control unit 102 with the UV light catheter assembly 140. The umbilical tube assembly 131 includes electrical connection wires for the LEDs in the UV light catheter assembly 140, electrical connection wires to the thermistor of the UV light catheter assembly, and an outer sheath within which one or more of the high-temperature and low-temperature coolant tubing are disposed. The electrical connection wires and the low-temperature and high-temperature coolant tubing pass along the length of the outer sheath. In some embodiments, the low-temperature coolant tubing may include additional insulation to reduce heat transfer from the environment.

[0055] At the UV light catheter side 141 of the umbilical tube assembly 131, the high and low temperature refrigerant tubing and the one or more electrical connection wires (leading to the thermistor and LED of the UV catheter assembly) exit as a high temperature refrigerant connector 152, a low temperature refrigerant connector 150, and an electrical connector 148, which are coupled to corresponding high temperature refrigerant connectors, low temperature refrigerant connectors, and electrical connectors of the UV light catheter assembly 140 via the catheter-umbilical connection interface 141.

[0056] In one embodiment, the umbilical tube assembly 131 may include one or more air passages (e.g., hot refrigerant tubing for returning warm air from the optical catheter assembly, cold refrigerant tubing for providing cooled refrigerant to the optical catheter assembly) and one or more electrical conductors (e.g., power conductors for providing power to the optical catheter assembly and / or a thermistor in the optical catheter assembly). Additionally, the one or more electrical conductors may also provide a temperature indication of the optical catheter assembly from the thermistor to the control unit. The control unit 102 may adjust one or more of the operation of the optical catheter assembly and the flow of refrigerant to the optical catheter assembly in response to the temperature. The umbilical tube assembly may further include an optical catheter connector configured to connect to the optical catheter assembly and a control unit connector (or compressor connector) configured to connect to the control unit (or compressor system).

[0057] The umbilical tube assembly 131 may be approximately 4, 5, or 6 feet long, or any other suitable length for connecting the UV light catheter assembly 140 to the control unit 102. The umbilical tube assembly 131 may be long enough to reach from the bedside cart containing the control unit 102 to the patient. As described above, the umbilical tube assembly 131 may include electrical wires for the LEDs, wires for the thermistor, and tubing for cool air to the light catheter assembly 140 and / or warm air return from the light catheter assembly 140. Thus, in one embodiment, the umbilical tube assembly 131 may connect the light catheter assembly 140 to the control unit 102 by functioning as a single hybrid connector for transmitting both gaseous refrigerant and electricity. For example, a central passageway may transmit air (e.g., cool air to the light catheter assembly 140 and, if applicable, warm air may be returned to the control unit 102 along a second passageway). Additionally, one or more electrical connectors / wires may be spaced around the periphery or in any configuration relative to the air passage.

[0058] In one embodiment, the coolant is air. Thus, cooled air from the cooling unit 108 can flow through the low-temperature coolant connector 136, the low-temperature coolant tubing in the umbilical sheath, and the low-temperature coolant connector 150 to enter the UV light catheter assembly 140. In one embodiment, air from the compressor 109 can be cooled by a chiller 111 (e.g., a thermoelectric cooler) and can flow into the low-temperature coolant connector 136. Furthermore, warm air from the UV light catheter can then flow through the high-temperature coolant connector 152, the high-temperature coolant tubing in the umbilical 131, and the high-temperature coolant connector 134 back to the control unit 102 for recycling, flow rate monitoring, leak monitoring, and / or venting to atmosphere. In some embodiments, the warm air can be vented at the connection interface between the umbilical assembly 131 and the optical catheter assembly 140 or through a valved opening in the umbilical assembly. Details of coolant flow when the UV light catheter is positioned in the GI lumen are discussed further below with reference to FIG. 7. In some embodiments, other gaseous refrigerants may be used and are within the scope of this disclosure.

[0059] The control unit 102 may include at least one processor (CPU) 103 and at least one memory 105, such as read-only memory ROM and / or random access memory RAM, comprising a computer-readable medium that may be operatively coupled to the processor. Thus, the at least one memory 105 may include system instructions that, when executed by the processor, perform one or more of the operations described herein, such as one or more of: cooling the UV light catheter during operation of the UV light catheter; operating the one or more balloons; and controlling operation of the UV light and / or one or more balloons according to the temperature of the UV light catheter and / or the pressure of the balloon. The processor 103 may receive one or more input signals from various sensory components (e.g., a thermistor coupled within the UV light catheter, a respective pressure sensor configured to sense pressure within each balloon) and may output one or more control signals to various control components described herein (e.g., to a cooling system 108 within the control unit to regulate the flow of coolant through cooling tubing of the UV light catheter, to a power source coupled to the UV light catheter, to a pump in the balloon control unit 120 to adjust pressurization of the one or more balloons, etc.) While this example illustrates an example configuration of the control unit 102, it will be appreciated that the control unit 102 may be implemented in other configurations.

[0060] As one non-limiting example, the control unit 102 may contain a medical-grade air compressor, such as the Timer PCS-414 by Allied, and may output 14 LPM of air at 50 psi or other suitable range. As described above, the control unit 102 may include a digital readout 104, a connector to the umbilical tubing (which may be a hybrid connector), user controls, and status indicators. Additionally, the cooling system 108 may include an air valve and a pressure regulator. The control unit 102 may also include a pressure sensor and flow control for the cooling air, and a flow sensor. In some embodiments, the control unit 102 may provide a closed feedback loop from a thermistor to determine the temperature and / or flow rate of the cooling air delivered to the optical catheter and through the cooling tubing.

[0061] Referring to Figure 2A, a schematic diagram of a UV light catheter assembly 200 is shown, which may be coupled to an umbilical assembly, such as umbilical 131 in Figure 1B, and a control unit, such as control unit 102 in Figure 1B, of a UV light therapy system, such as UV light therapy system 100 in Figure 1B; or may be coupled to a control unit without an umbilical assembly, as shown in Figure 1A. Furthermore, the UV light catheter assembly 200 may be an embodiment of the UV light catheter assembly 140 shown in Figures 1A and 1B. In this embodiment, the UV light catheter assembly 200 is shown in a released position, not stored within the protective sleeve 126. Prior to deployment (i.e., when the assembly 200 is not being prepared for deployment or not being deployed), the UV light catheter assembly 200 may be stored within the protective sleeve 126.

[0062] The UV light catheter assembly 200 includes a delivery tube 202 (also referred to herein as a housing catheter) with a light-emitting portion 204. The light-emitting portion 204 includes a plurality of LEDs 222. Additionally, the delivery tube 202 includes a plurality of balloons 230, 232, 234, and 236 in the light-emitting portion 204. While this example shows four balloons, the UV light catheter assembly may include fewer or more balloons. For example, the number of balloons may be one, two, three, four, five, six, or more. In some embodiments, the number of balloons may be more than two; that is, the minimum number of balloons may be three. For example, three or more balloons may be utilized in a delivery device configured for intraluminal administration of UV light within the colon.

[0063] In some embodiments, the number of balloons may be based on one or more of the total length of the UV light emitting portion, the total length of the delivery tube, and the axial length of each balloon along the length of the optical catheter (e.g., the major axis if the balloon is ellipsoidal in shape, or the diameter of the balloon if the balloon is spherical).

[0064] In some examples, each balloon 230, 232, 234, and 236 may be positioned only over light-emitting portion 204, while areas of delivery tube 202 without light-emitting portion 206 (i.e., without UV LEDs) may not include a balloon. Thus, each balloon may cover a light-emitting segment of light-emitting portion 206. This example shows each light-emitting segment having a length of 10 cm. In various embodiments, the light-emitting segment covered by each balloon may be 5, 6, 7, 9, 10, 11, 12, 13, 14, or 15 cm, or any other suitable length of the optical catheter.

[0065] In some embodiments, as shown in FIG. 2A , the balloons may be positioned back-to-back with a minimal distance between the distal end of first balloon 230 and the proximal end of second balloon 232 adjacent to the first balloon. However, in some embodiments, UV light catheter assembly 200 may be configured to allow the user to adjust the relative spacing between balloons on delivery tube 202. For example, a user may reposition balloon 236 and / or balloon 234 so that the distance between balloons 234 and 236 increases. Thus, in some embodiments, some light-emitting portions 206 may not be covered by the balloons. This adjustment of the spacing between balloons may allow a user to adjust the positioning of the balloons to target specific treatment areas. In particular, the spacing between balloons may be adjusted prior to insertion into a patient's body cavity and navigation to a target site. In other words, the balloon positions may be adjusted prior to deployment and when not during deployment when the delivery tube is within a lumen.

[0066] As a non-limiting example, if an inflammatory and / or infectious condition is present in a first area and a second area of ​​the colon that are not contiguous but are separated by healthy tissue, a user can adjust the positioning of the balloons so that the first balloon can be apposed to the first area and the second balloon can be apposed to the second area when the delivery tube 202 is positioned within the lumen of the colon. For example, the first target area, the second target area, and the separation between the first and second target areas can be identified by endoscopy. The balloon position can then be adjusted over the UV light-emitting portion. Furthermore, a portion of the light-emitting portion 206 of the delivery tube between the first and second balloons may not be enveloped by the balloons. Thus, when the UV LED is turned on, the infected and / or inflamed first and second areas are treated with a greater irradiance and irradiance distribution than the normal tissue between them. As described above, upon inflation, the curved outer surface of the balloon contacts the luminal epithelium, facilitating the removal of feces, debris, and / or biofilm on the epithelium, further assisting in stretching folds and / or bulges and preventing feces and / or debris outside the treatment area from interfering with the treatment. Thus, the balloon can improve the UV light distribution and irradiance on the target tissue (i.e., the first and second areas in this example). Thus, when the UV LED is turned on, the first and second areas (i.e., the inflamed and / or infected areas) can receive UV light emitted from the UV LED through the balloon, and through the balloon, the first and second areas can receive UV light with increased irradiance and irradiance distribution compared to the healthy tissue between them. In this manner, the balloon further enhances the antibacterial and / or anti-inflammatory effects provided by the UV light.

[0067] Furthermore, in some embodiments, the UV light catheter assembly can be configured so that only the UV LEDs present within the balloon area are selectively powered on during treatment, while UV LEDs not enclosed by the balloon do not have to be powered on. In this manner, the balloon can be utilized not only to provide uniform distribution and uniform intensity over the target area, but also to provide selective treatment within the GI lumen.

[0068] In addition to adjusting the position of the balloons, the amount of balloon pressure can be adjusted to provide selective treatment based on the area affected by the disease and / or the degree of disease progression. For example, if moderate ulcerative colitis is observed only in the sigmoid colon, balloons 230, 232, 234, and 236 can be positioned with minimal spacing between them, and after guiding delivery tube 224 to the desired target area (e.g., so that light-delivery portion 206 and balloons are juxtaposed with the desired target area), all balloons can be pressurized to a desired pressure, and the UV LEDs can be powered at a desired intensity and for a desired duration to treat the desired target area for moderate ulcerative colitis. However, during some conditions, each balloon can be adjusted to its desired pressure based on one or more parameters of the target area, including the diameter of the lumen within the target area and / or the degree of spread (i.e., the area affected by infection within the target area). In some embodiments, the lumen diameter can be based on the degree of inflammation and / or infection within the target area.

[0069] Additionally, in some embodiments, the area between two balloons may not include LEDs, as shown in Figures 3A and 3B. Referring to Figures 3A and 3B, a delivery tube 324 is shown with light-emitting segments 330, 332, 334, and 336 within balloons 230, 232, 234, and 236. Figure 3A shows balloons 230, 232, 234, and 236 in a depressurized (i.e., de-inflated) state, while Figure 3B shows delivery tube 324 with balloons 230, 232, 234, and 236 in a fully pressurized (i.e., fully inflated) state. Between the balloons, one or more areas 310 correspond to non-illuminated areas where no LEDs are positioned.

[0070] Further, as described above with respect to FIG. 1A , each of balloons 230, 232, 234, and 236 can be pressurized to a desired pressure via a balloon control unit (e.g., balloon control unit 120 in FIG. 1A or FIG. 1B ), which can be a pressure between the de-inflated pressure in a de-pressurized state and the fully inflated pressure in a fully pressurized state. The desired pressure can be set based on, for example, the diameter of the lumen in the target area and the extent of infection and / or inflammation in the target area. Furthermore, in some embodiments, the desired pressure can be different for each balloon based on one or more parameters of the target area, as described above, including the diameter of the target area and the extent of inflammation and / or infection. Furthermore, in some other embodiments, the desired pressure can be set to the same pressure for all balloons (e.g., for similar diameters and similar target areas).

[0071] 2A, balloons 230, 232, 234, and 236 provide a uniform distribution of UV light emitted by UV LED 222 over each target area, as indicated by dotted arrow 212. Additionally, proximal end 218 of optical catheter is not encased within a balloon. In some embodiments, proximal end 218 of optical catheter may be positioned within proximal balloon 230, as shown in FIGS. 3A and 3B.

[0072] 2A, each balloon 230, 232, 234, and 236 may be fluidly coupled to a respective inflation port 231, 233, 235, and 237 that is coupled to a balloon control unit, such as balloon control unit 120 discussed with respect to FIG. 1A or 1B. This allows for selective inflation, deflation, inflation rate, deflation rate, and / or pressure adjustment for each balloon during deployment.

[0073] Additionally, the distal end 221 of the optical catheter assembly 200 is coupled to the high-temperature coolant connector, low-temperature coolant connector, and electrical connector of the umbilical (e.g., umbilical 131) via connection ports 216 to the catheter's high-temperature coolant connector (e.g., connector 152), catheter's low-temperature coolant connector (e.g., connector 150), and catheter electrical connector (e.g., 148), respectively, which may be embodiments of connection port 154. In this manner, the umbilical provides coolant for cooling and power to the UV optical catheter assembly's LEDs (via electrical connector 148) and thermistor 228. The UV optical catheter assembly 200 includes a light-emitting portion 206 in its proximal portion, which is shown enlarged in FIG. 7 and described in more detail below.

[0074] Referring now to FIG. 2B, a single-balloon embodiment of a UV light catheter assembly is shown. In this example, a single balloon 210 encases a light-emitting portion with multiple LEDs 222. In some examples, the single-balloon device can be utilized to treat gynecological conditions, including, but not limited to, bacterial or fungal vaginal disease, rectovaginal / colovesical fistulas, and / or mucosal and submucosal cancers. In further examples, the single-balloon device can be coupled to a non-illuminated portion of a delivery tube, and depending on the overall length of the delivery tube, the single-balloon device can be navigated to a distal target site, such as the rectum. The single-balloon device can be used to facilitate navigation to a distal target (e.g., the rectum or vagina) without the need for colonoscopy or sedation, and can be performed in a physician's office. In other examples, a single-balloon device with a sufficient length of non-illuminated portion can be used to navigate to a single proximal target site, such as the ascending colon, and treat localized infections and / or inflammation far from the distal insertion site.

[0075] Additionally, as described above with respect to FIG. 2A where the delivery tube includes multiple balloons, the amount of pressure inside the single balloon 210 can be adjusted via balloon inflation port 204, which can be coupled to a balloon control unit, such as balloon control unit 120 of FIG. 1A.

[0076] Another embodiment of a single balloon device is shown in FIGS. 4A and 4B. Specifically, FIGS. 4A and 4B illustrate exemplary UV-emitting devices 400 and 450, respectively, which may be utilized for vaginal or rectal delivery of UV light in some embodiments. Referring to both FIGS. 4A and 4B, the UV-emitting devices 400, 450 may include a delivery tube / rod 402. In some embodiments, the delivery tube / rod 402 includes a four-sided elongated body including a UV light source 422 (e.g., a UV LED) on each of the four sides. In other embodiments, the delivery tube / rod 402 may have a cylindrical body, and the UV light source 422 may be positioned on a curved surface of the cylindrical body to deliver UV light along the circumference of the delivery tube throughout the entire length of the delivery tube. When the delivery tube is configured as a four-sided elongated body, the UV light source 422 may be positioned on the delivery tube / rod 402. 402 The UV light sources 422 may be staggered on each side of the delivery tube / rod. While exemplary devices 400 and 450 show a delivery tube with four sides, the number of sides may be three, five, six, seven, or eight. In some embodiments, the UV light source 422 may be staggered on each side of the delivery tube / rod. 402 distributed along the entire length of the 409 This allows for wider application of the UV light source 422 in the

[0077] In some embodiments, the delivery tube / rod 402 is configured to illuminate and transmit UV light homogeneously throughout the entire delivery tube / rod 402. 402is configured to emit light waves only in the UV-A region and not in the UV-B or UV-C or visible regions. For example, UV light source 422 may be configured to emit narrow-bandwidth UV light between 335 nm and 349 nm, between 338 nm and 342 nm, or between 339 nm and 346 nm. Furthermore, the peak wavelength of UV light source 422 may include 340 nm and may be within the range of 335 nm to 349 nm, 338 nm to 342 nm, or 339 nm to 346 nm. In other broader embodiments, light source 422 may be configured to deliver UV light having a wavelength between 320 nm and 410 nm. In some embodiments, the vertical illumination length of the delivery tube / rod 402 It extends for between 8 and 10 cm around the

[0078] The delivery tube / rod 402 may be made of any suitable construction (e.g., rigid or flexible, etc.), including various polymers that are biocompatible or have biocompatible coatings. In some embodiments, UV light from the light source 422 illuminates the delivery tube / rod. 402 The delivery tube / rod 402 may include an outer layer of UV transparent material 424 so that the UV radiation can be emitted outward from the delivery tube / rod 402. In some embodiments, the delivery tube / rod 402 may be made of a material such as silicon, silica, polyurethane, polyethylene, Teflon, or the like. (registered trademark) The delivery tube / rod 402 may have an outer surface made from a material such as PTFE, borosilicate, or other suitable material. In some embodiments, the delivery tube / rod 402 is constructed using copper with a borosilicate outer layer. For optimal cooling, exposure area, and uniformity, the delivery tube / rod 402 may include multiple light emitting diodes (LEDs) staggered on a copper bar. Light Source 402The spacing between the light sources 422 allows for optimal vertical lighting length. Fabricating the body of the delivery tube / rod 422 using copper allows the delivery tube / rod 402 to withstand high temperatures. The copper acts as a heat sink, preventing the delivery tube / rod 402 from reaching uncomfortable temperatures. In some embodiments, the light source 422 may be operated at a specific current to optimize the temperature of the delivery tube / rod 402. In some embodiments, the light source 422 may be operated in the range of 60-100 mA. In this range, the temperature of the delivery tube / rod 402 may not rise above 40°C, thus achieving the goal of implementing an adequate cooling solution. In some embodiments, the base 412 and / or handle 430 may additionally or alternatively be configured to include one or more fans to dissipate heat from the delivery tube / rod.

[0079] Additionally, each UV-emitting device 400, 450 may include an inflatable balloon 410 along the entire length of the delivery rod / tube 402. When inflated, the balloon 410 may provide a more uniform distribution of UV light over the target area within the patient. Additionally, in some embodiments, the balloon 410 may increase irradiance and provide a more uniform irradiance distribution over the target area. Additionally, the balloon may facilitate obstructing extraneous debris / biofilm that may act as a barrier between the optical catheter and the epithelial layer, thereby improving the delivery and distribution of UV light in the target tissue. The balloon 410 may be made of any suitable material that is expandable, UV-transparent, and improves UV irradiation distribution, and in some embodiments, the material may increase irradiance over the target area. Exemplary materials may be composed of PEBA, COC, or silicone.

[0080] The balloon 410 may be coupled to an inflation port 404, which is coupled to a balloon control unit 420. The balloon control unit 420 may be configured to pressurize and depressurize the balloon during deployment. The balloon control unit 420 is similar to the balloon control unit 120 described with respect to FIG. 1A, and for the sake of brevity, the description thereof will not be repeated. Briefly, the balloon control unit 420 may include a pressure sensor for monitoring the pressure within the balloon 410. Additionally, the balloon control unit 420 may include a pump system (e.g., a syringe-based pump system or a motor-based pump system) for pressurizing and depressurizing the balloon. Furthermore, the balloon control unit 420 may be used to maintain a constant or near-constant pressure and volume of the balloon 410 during deployment of the delivery rod within the patient's body and during delivery of the UV light therapy. Additionally, the balloon control unit 420 may use input from the pressure sensor to prevent pressurization of the balloon 410 beyond threshold limits. In some embodiments, prior to insertion and positioning within the patient, the balloon 410 may be inflated via the balloon control unit 420 to a smaller, first volume, which may facilitate insertion and positioning of the delivery rod / tube 402. Once navigated to the desired location within the patient, the balloon 410 may be inflated to a larger, second volume, which may allow the balloon to expand further. Subsequently, the UV light source 422 may be powered on to deliver UV light. During treatment, when UV light is being delivered to the patient, the balloon volume and pressure may be maintained constant by the balloon control unit 420. Thus, via the balloon control unit 420, one or more balloon parameters, including volume, pressure, and temperature, may be monitored and adjusted to maintain the desired expansion.

[0081] The delivery tube / rod 402 has a proximal end 408 and a distal end 409 The four sides of the elongated body 402 converge toward the distal end 409 to form a rounded surface. toThe distal end 409 of the delivery tube / rod 402 is configured for insertion into a patient's body, as described above. In contrast, the opposing proximal end 408 is configured to facilitate steering the delivery tube / rod 402 via a gripping element. In one example, the proximal end of the delivery tube / rod 402 can be coupled to a gripping element configured as a handle 430 ( FIG. 4A ). Referring to FIG. 4A , the handle 430 can be attached to the proximal end 408 of the delivery tube / rod 402 via the base 412. The handle 430 can be configured to be ergonomically sufficient for a physician or healthcare provider. The handle 430 can also include one or more input components 432 configured to receive user input (e.g., a power on / off button, an intensity selection button, a duration selection button, etc.). The input component 432 can be connected to an internal processor that alters the functionality of the delivery tube / rod 402 and the UV light source 422. In some embodiments, the delivery tube / rod 402 includes between 2 and 20 UV light sources. The delivery tube / rod 402 shown herein includes three UV light sources 422 on each of four sides, for a total of twelve (12) UV light sources 422. It should be understood that other configurations incorporating the features disclosed herein are possible.

[0082] In some embodiments, the handle 430 may include a rotating base (not shown) at the proximal end opposite the end that couples to the delivery tube / rod. The rotating base may allow the delivery tube / rod 402 to rotate so that the light emitted from the UV light source 422 is uniform. Rotating Delivery Tube / Rod 402 When treating a patient with a UV irradiance, uniform UV emission is likely to aid in the treatment of microbial growth. In some embodiments, the delivery tube / rod 402 or rotating base may also include a stepper motor to enable rotation of the rotating base.

[0083] 4B , an exemplary UV light delivery system 450 includes a controller 460 coupled to a base 412. In this example, the base 412 may be configured to function as a handle. The controller 460 may include one or more processors, a memory, and a battery or other power source. The memory may include instructions with various therapy regimens that may be applied using various intensities and / or durations as disclosed herein. For example, the memory may include a data structure that, when executed by the processor, provides power to the light source 422 at a given intensity or timing. The controller may be utilized in any of the embodiments disclosed herein, including vaginal and GI tract-based UV light delivery devices.

[0084] Next, Figure 5A shows a flowchart illustrating a high-level method 500 for treating, preventing, and / or ameliorating an infectious and / or inflammatory condition using a UV light catheter assembly. Specifically, method 500 may be performed using a UV light therapy system, such as UV light therapy system 100 described with reference to Figures 1A or 1B, the UV light catheter assembly described with reference to Figures 2A, 2B, 3A, or 3B, or the UV light-emitting device described with reference to Figures 4A or 4B. Although method 500 is described with reference to Figures 1A, 1B, 2A, 2B, 3A, or 3B, it will be recognized that method 500 may be applied to other similar UV light therapy systems without departing from the scope of the present disclosure.

[0085] Method 500 includes assessing the health of the GI tract, at 502. Assessing the health of the GI tract may be performed by a healthcare provider based on one or more of symptoms, endoscopic procedures such as colonoscopy with or without biopsy, blood analysis, and stool analysis, among other diagnostic procedures.

[0086] The step of assessing the health of the GI tract may include determining the type of inflammatory and / or infectious condition of the GI tract. Exemplary GI tract inflammatory and / or infectious conditions may include ulcerative colitis, Crohn's disease, and other chronic inflammatory diseases, non-IBD-related proctitis, IBD-related or non-IBD-related fistulas, inflammatory strictures, microscopic colitis, infectious diarrhea, refractory Helicobacter pylori and MALT lymphoma, esophageal lichen planus and pemphigus vulgaris, refractory Clostridium difficile, colonic inertia, tropical sprue, celiac disease, small intestinal bacterial overgrowth, appendicitis, post-bone marrow transplant infections, pseudopolyps (resembling nasal polyps) and radiation enteritis, Barrett's esophagus with or without dysplasia, hepatic encephalopathy, Roux-en-Y blind loop syndrome, perianal fistulas, gastrointestinal cancer, hepatobiliary infection, inflammation, and cancer.

[0087] Additionally, while method 500 is further described below with respect to inflammatory bowel disease (IBD) in the form of ulcerative colitis and Crohn's disease, it will be recognized that method 500 may be performed to treat, ameliorate, and / or prevent any inflammatory and / or infectious condition of the GI tract without departing from the scope of the present disclosure. In some embodiments, method 500 may be applied to reduce the rate of infection associated with percutaneous feeding or suction tubes. In other embodiments, method 500 may be performed using a UV light-emitting device configured for vaginal and / or rectal use, such as the exemplary systems shown in FIGS. 5A and 5B.

[0088] Additionally, assessing the health of the GI tract may include determining the progression of the inflammatory and / or infectious condition. For example, the progression may be determined based on a suitable scale based on the disease (e.g., mild, moderate, severe, etc.). In some embodiments, assessing the health of the GI tract may further include determining which layers of GI tract tissue are affected. For example, method 500 may include, when assessing the patient's colon, determining whether the inflammatory and / or infectious condition is in one or more of the mucosal layer, submucosa layer, muscular layer, and serosal layer.

[0089] Further, method 500 includes identifying one or more target areas requiring UV light treatment at 504. For example, when evaluating the colon for ulcerative colitis, imaging approaches such as colonoscopy may be used to identify which areas of the bowel are affected. In some embodiments, based on symptoms and one or more non-invasive or minimally invasive tests, a portion of the colon may be evaluated (e.g., via sigmoidoscopy to examine the rectum and lower portion of the colon), or the entire colon may be evaluated (e.g., via colonoscopy).

[0090] Next, method 500 includes positioning, at 506, a delivery tube of a UV light catheter assembly including multiple light sources (e.g., UV-LEDs) and multiple balloons, such as delivery tube 202 in FIG. 2A or delivery tube 324 in FIG. 3A, to treat the one or more target areas with UV light. An exemplary method for positioning a delivery tube within the large intestine is shown and described with respect to FIGS. 6A-6G. In one embodiment, placement of the delivery tube may be performed via colonoscopy using a guidewire based on the Seldinger technique.

[0091] 6A-6G, these figures show schematic diagrams illustrating cross sections of a large intestine 610 during various stages of placement of a delivery tube of a UV light catheter assembly. FIG. 6A shows the large intestine 610, including the lumen 602, prior to beginning the placement procedure. FIG. 6B shows a colonoscope view of the large intestine 610 up to the ascending colon 620. 612For example, during placement of the delivery tube, a colonoscope is inserted through the lumen of the colon 610 to a desired location within the lumen of the colon to view the colon and subsequently position a guidewire prior to inserting and positioning the delivery tube. 612 Figure 6B shows the colonoscope. 612 Although the colonoscope is shown inserted into the lumen of the ascending colon 620 up to the proximal region 630 of the ascending colon 620, the colonoscope may be inserted to any location within the lumen of the large intestine 610, such as any location within the ascending colon 620, the transverse colon 622, the descending colon 624, the sigmoid colon 626, or the rectum 628.

[0092] Next, once the colonoscope 612 has been inserted and positioned, a guidewire 614 is inserted through the channel of the colonoscope 612 (FIG. 6C). The guidewire 614 passes through the channel of the colonoscope 612 and exits an aperture at the end of the colonoscope 612, which in this embodiment is located in the ascending colon. The colonoscope is thus used to visualize the lumen and also to position the guidewire 614 at the desired location to facilitate final positioning of the UV light catheter. Once the guidewire 614 has been inserted, the colonoscope 612 is withdrawn from the lumen (indicated by arrow 615) as shown in FIG. 6C. In this manner, the colonoscope 612 is utilized to position the guidewire 614 within the lumen of the large intestine 610. In this embodiment shown in FIG. 6C, the colonoscope 612is used to position the guidewire 614 within the ascending colon 620. It will be appreciated that the guidewire 614 may be positioned anywhere within the lumen of the large intestine 610. FIG. 6D shows the guidewire 614 positioned through the colonoscope 612 and within the lumen of the large intestine 610, such that the proximal end 642 of the guidewire is positioned within the ascending colon 620. As discussed above, the guidewire 614 may be positioned anywhere within the lumen of the large intestine 610 based on the location and / or extent of the infection and / or inflammation. As a non-limiting example, if the patient has been diagnosed with ulcerative colitis in the left half of the colon (left-sided colitis), the guidewire 614 may be positioned such that the proximal end 642 of the guidewire 614 is positioned where the transverse colon 622 begins (the portion where the descending colon begins adjacent to the descending colon) or where the descending colon 624 ends (the portion where the descending colon ends adjacent to the transverse colon). As another non-limiting example, for a patient diagnosed with pockets of inflammation separated by healthy tissue, including inflammation in a portion of the transverse colon and a portion of the descending colon, guidewire 614 may be positioned so that it passes through the rectum, descending colon, and transverse colon and the proximal end of guidewire 614 terminates downstream (downstream in the direction from the descending colon to the ascending colon) at or beyond the area of ​​inflammation in the transverse colon.

[0093] Once the guidewire 614 is positioned and the colonoscope is withdrawn, the delivery tube 652 of the UV light catheter assembly is inserted into the lumen of the intestine using the guidewire 614. FIG. 6E shows the delivery tube 652 positioned over the guidewire 614 (not shown in FIG. 6E ). The delivery tube 652 is one example of the delivery tube 202 or delivery tube 324 described above. The delivery tube 652 may include a guidewire channel (e.g., guidewire channel 160 in FIG. 1A ) through which the guidewire passes. After the guidewire 614 is positioned, the delivery tube 652, which includes multiple UV LEDs 656 and multiple balloons 658, is guided through the lumen of the colon 610 by threading the delivery tube's guidewire channel over the guidewire 614 positioned within the colon 610. In one example, all of the multiple balloons, such as balloon 232, may be in a deflated state while the delivery tube is being guided into the lumen. In some embodiments, a first balloon at the end of delivery tube 652 (first entering the lumen) may be partially inflated via its corresponding balloon inflation port coupled to control unit 660 to facilitate movement of delivery tube 652, while the remaining balloons may remain de-inflated during navigation of delivery tube 652. As a non-limiting example, when delivery tube 652 is navigated through a large portion of the colon and the end is positioned in the ascending colon (e.g., to treat and / or ameliorate extensive colitis throughout the colon), a first balloon at or near end 659 of delivery tube 652 may be partially inflated, while the remaining balloons may remain de-inflated during navigation and positioning. In some embodiments, more than one balloon may be partially inflated during deployment, for example, to facilitate passage through the hepatic flexure and / or splenic flexure.

[0094] 1A , and thus may include a balloon control unit for monitoring and / or regulating the pressurization and depressurization of the plurality of balloons 658. Also as discussed with respect to FIG. 1A , the control unit 660 may regulate the operation of the UV LEDs 656 (e.g., power on / off, selectively energizing one or more UV LED segments corresponding to the treatment area and / or balloon placement, adjusting UV light intensity, cycling UV light intensity, etc.) and may provide temperature control of the delivery tube 654 during placement and treatment (e.g., temperature regulation using refrigerant flow from the control unit compressor to a cooling tube in the delivery tube based on UV LED temperature from one or more thermistors positioned in the light-emitting portion).

[0095] Although the above-described examples illustrate positioning the delivery device using a colonoscope and guidewire, in some embodiments, the delivery tube may be configured as an endoscope (e.g., a colonoscope) equipped with one or more cameras for visualizing the interior of the lumen.

[0096] Returning to FIG. 5A , after positioning the delivery tube (i.e., UV light catheter) within the lumen such that one or more balloons are apposed to the treatment site, method 500 proceeds to 510. At 510, method 500 includes inflating the one or more balloons. In one embodiment, the number of balloons inflated may be based on the treatment area. For example, only balloons apposed to infected and / or inflamed areas requiring UV light treatment may be inflated, while other balloons apposed to normal tissue may not be inflated. However, in some embodiments, depending on the extent of insertion of the delivery device into the colon, one or more additional balloons apposed to normal tissue may also be inflated to stabilize the colon and potentially reduce undesired reflex movement of the colon, as well as to stabilize the delivery device, thereby reducing undesired movement of the delivery device. For example, if a delivery device with multiple balloons is navigated to the ascending colon and the treatment sites are in the ascending colon and transverse colon, in addition to inflating the balloons apposed to the treatment sites in the ascending colon and transverse colon, one or more balloons apposed to normal tissue may be inflated if further stabilization of the delivery device is desired. In such cases, the amount of inflation may be reduced (e.g., less inflation of the balloons apposed to normal, healthy tissue areas).

[0097] In one embodiment, inflating the one or more inflatable balloons includes pressurizing each of the one or more inflatable balloons to a threshold pressure at which each of the one or more inflatable balloons directly contacts a desired surface area of ​​the epithelial layer of the lumen. In one embodiment, the threshold pressure may be based on the diameter of the lumen at the target site. In one embodiment, the desired surface area is based on the extent of infection. In one embodiment, the threshold pressure is sufficient to displace one or more of debris, feces, and biofilm on the surface of the epithelial layer of the lumen.

[0098] In some embodiments, in addition to selectively inflating one or more balloons, method 500 may include selectively adjusting the intensity of light within each balloon (described below at 514) based on the progression of disease in the treatment area. Specifically, the intensity of the emitted UV light may be increased as the severity of infection and / or inflammation in the treatment area increases. As a result, the amount of irradiance at the target area increases with increasing disease severity.

[0099] Referring to FIG. 6F, this figure shows all balloons 658 after inflation. Specifically, once delivery tube 652 is positioned over the guidewire, the plurality of balloons 658 are inflated by providing inflation fluid (e.g., air) to balloons 658 via their respective balloon inflation ports and balloon control unit 660. While the present example in FIG. 6F shows all balloons inflated, in some embodiments, one or more balloons 658 may be selectively inflated based on the treatment area. As a non-limiting example, if the treatment area is in the ascending colon and transverse colon but not the descending colon, a first balloon in ascending colon 620 and a second balloon in transverse colon 622 may be inflated, while a third balloon in descending colon 624 and a fourth balloon in sigmoid colon 626 may not be inflated or may be inflated less than the first and second balloons (e.g., for stabilization of the delivery device).

[0100] Additionally, in some embodiments, as shown in FIG. 6F, all balloons 658 are inflated to the same pressure via their respective balloon inflation ports (not shown) and using balloon control unit 660.

[0101] In some other embodiments, the inflation amount may be adjusted independently for each balloon. In one embodiment, the inflation amount may be based on the diameter and / or extent of infection and / or inflammation in the treatment area.

[0102] In summary, one or more balloons may be selectively pressurized (i.e., one or more balloons may be pressurized while the remaining balloons are not pressurized) based on the number and / or location of the treatment areas. Additionally or alternatively, during inflation, the amount of expansion of each inflated balloon (whether all balloons are inflated or one or more balloons are selectively inflated) may be selectively adjusted (e.g., by adjusting the amount of expansion via a balloon control unit) based on one or more of the diameter and extent of the treatment area. Furthermore, in addition to selective balloon inflation, one or more UV light parameters may be adjusted during deployment, as described in more detail below. In this manner, UV phototherapy may be customized through selective operation and / or adjustment of the balloons depending on one or more of the location, severity, extent and pattern of spread of the infection and / or inflammation.

[0103] Returning to FIG. 5A , at 514, method 500 includes providing UV light therapy after inflating the one or more balloons. Providing UV light therapy includes adjusting one or more of the intensity of UV light emitted from the UV LEDs in the delivery device and the duration of the UV light emitted from the UV LEDs. In one example, adjusting one or more of the intensity and duration of the UV light emitted from the UV LEDs may include adjusting one or more of the intensity and duration for each balloon based on the degree and / or severity of inflammation and / or infection in the corresponding treatment area (step 516). For example, the duration and / or intensity of light output from the UV LEDs may be increased in one or more segments of the delivery device treating a more severe condition compared to segments of the delivery device treating a less severe infection and / or inflammation. The intensity and duration adjustments may be made in addition to, or as an alternative to, adjusting the amount of inflation in the corresponding balloons on the segments delivering UV light to the treatment area.

[0104] In some embodiments, all LEDs within a light emitting portion may be operated at the same intensity and / or duration based on the overall severity of the condition.

[0105] In some embodiments, UV wavelengths that provide sufficient antimicrobial efficacy without causing UV-associated DNA damage include 335, 336, 337, 338, 339, 340, 341, 342, 343 , 344, 345, 346, 347, 348, 349, or 350 nm. Thus, the UV LEDs disclosed herein can emit light with one or more of the foregoing wavelengths at therapeutically significant intensities. Furthermore, by using a balloon to improve UV light distribution and increase irradiance in the target area, the effectiveness of UV light therapy is further improved while still being safe for treatment over large areas within the patient's GI tract (e.g., the entire colon).

[0106] In some embodiments, the length of the GI lumen treated with the UV light catheter assembly can range between 5 cm and 45 cm, and in some embodiments, treatment sites having lengths greater than 40 cm can be treated with the delivery device.

[0107] In some embodiments, a delivery tube equipped with an LED emitting light having a wavelength of maximum emission intensity centered at 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, or 349 nm can be energized for at least 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 60, 80, or 90 minutes. Repeated treatments can be based on disease progression, symptoms, and / or other assessments performed by the healthcare provider. The applied intensities are based on the severity of the infection and are: 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300 uW / cm 2 , or any other suitable intensity between these ranges.

[0108] In some embodiments, each of the plurality of UV LEDs may emit a peak wavelength of 335 nm, 336 nm, 337 nm, 338 nm, 339 nm, 340 nm, 341 nm, 342 nm, 343 nm, 344 nm, 345 nm, 346 nm, 347 nm, 348 nm, 349 nm, 350 nm, 351 nm, 352 nm, 353 nm, 354 nm, 355 nm. In some embodiments, the LED may emit light with significant intensity within a range of + / - 2, 3, 4, 5, or 6 nm around its peak intensity emission wavelength.

[0109] In some embodiments, each of the LEDs may emit light at a beam angle between 100 and 150 degrees. In one embodiment, each of the LEDs may emit light at a beam angle between 120 and 135 degrees.

[0110] In other examples, phototherapy can be delivered by a caregiver for 10, 15, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 60, 90, 120, or 160 minutes, any range between 10 and 160 minutes, or other suitable time periods. Additionally, methods of the present invention can include administering therapy for a threshold duration of at least 10, 15, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 60 minutes. Light source intensity can be at least 1,000 microwatts / cm, depending on the application and other factors related to therapeutic efficacy. 2 , 1,100 microwatts / cm 2 , 2,000 microwatts / cm 2 , 2,100 microwatts / cm 2 , 2,200 microwatts / cm 2 , 2,300 microwatts / cm 2 , 2,400 microwatts / cm 2 , 2,500 microwatts / cm 2 , 2,600 microwatts / cm 2 , 2,700 microwatts / cm 2, 2,800 microwatts / cm 2 , 2,900 microwatts / cm 2 , 3,000 microwatts / cm 2 , 3100 microwatts / cm 2 , 3,200 microwatts / cm 2 , 1,000 to 5,000 microwatts / cm 2 or other suitable intensity. We have used UV-A light at up to 5,000 microwatts / cm 2 In some embodiments, the light will be emitted continuously, while in other embodiments, the light will be incorporated into a pulsed regimen.

[0111] An exemplary operation of providing UV light into the lumen of the large intestine is described below with respect to FIG. 6G.

[0112] FIG. 6G shows the delivery tube 654 containing the UV LEDs powered on. Prior to the initiation of UV light treatment, the one or more balloons are inflated and the guidewire is removed. Next, one or more balloons 658 are inflated and the UV LEDs are powered on to illuminate the treatment site through the corresponding balloon. Additionally, in some embodiments, UV LEDs not covered by the balloon may also be powered on, thereby illuminating the area adjacent to the balloon. UV light emitted by the UV LEDs is transmitted through the inflated balloon 658 to the treatment site. As indicated by the bold line 670, the balloons increase the irradiance at the treatment site and additionally improve the UV light distribution at the treatment site. Furthermore, when the balloons 658 are inflated and in contact with the mucosa, they reduce folds and promote the diffusion of biofilm or foreign debris that may form on the colonic epithelium, reducing barriers that may prevent UV light from effectively reaching the colonic epithelium. Additionally, the balloons 658 may reduce the passage of stool down to the treatment area.

[0113] In this manner, the balloon-equipped UV light catheter assembly improves the efficiency and effectiveness of UV light treatment within the GI tract. Furthermore, the balloons 658, when inflated into contact with the colonic epithelium, may stabilize the colon wall and also stabilize the delivery device within the lumen, reducing injury caused during placement of the delivery device and treatment.

[0114] 5B depicts a high-level flowchart illustrating an exemplary method 550 for adjusting one or more of balloon inflation volume and UV light intensity during UV light treatment delivered into a lumen of a patient's GI tract using a UV light catheter assembly, such as the UV light catheter assembly discussed with respect to FIGURES 1A, 2A, or 3A. In some examples, method 550 may be performed by a controller, such as controller 103, based on executable instructions stored in a memory, such as non-transitory memory 105, of a control unit, such as control unit 102, in conjunction with a balloon control unit, such as balloon control unit 120, and one or more sensors (e.g., thermistors) coupled to the UV light catheter assembly upon energizing a UV LED in the UV light catheter assembly.

[0115] Method 500 includes, at 552, providing UV light therapy to the patient, as described above with respect to FIG. 5A. Next, method 500 includes, at 554, determining whether the treatment regimen is complete. For example, a user may set a treatment regimen that includes providing UV light therapy for 20 minutes with UV light of a desired intensity emitted from the plurality of LEDs (e.g., LEDs 222 in FIG. 2A). A controller may monitor the duration of the light therapy, and treatment may be determined to be complete in response to a timer monitoring the duration reaching a zero value. If the treatment regimen is complete, method 550 proceeds to 562. At 562, method 550 includes de-energizing the LEDs, followed by de-inflating one or more inflated balloons at 564. In one embodiment, the one or more balloons may be fully de-inflated. In another example, such as when the delivery tube is navigated through the hepatic flexure and / or splenic flexure during removal of the delivery tube from the patient, the one or more inflated balloons may be partially de-inflated to maintain the one or more inflated balloons at a smaller volume to facilitate passage of the delivery tube through the lumen of the GI tract and to reduce contact between the delivery tube and the colonic epithelium, thereby reducing potential injury from the delivery tube providing light therapy. Once the one or more balloons are de-inflated (partially or fully), the user may remove the delivery tube from the lumen.

[0116] Returning to 554, if the answer at 554 is "no," UV light treatment continues, and method 550 proceeds to 556 to continue providing UV light. This includes monitoring one or more of the temperature of the delivery tube and the pressure inside each of the one or more balloons at 558. The temperature of the delivery tube may be monitored based on a signal from a thermistor, such as thermistor 228, positioned within the delivery tube and outputting the delivery tube temperature. In one embodiment, as shown in FIG. 2A, thermistor 228 may be positioned at the end of the light-emitting portion; however, it will be appreciated that thermistor 228 may be positioned anywhere within the light-emitting portion of the delivery tube. In some embodiments, each light-emitting segment (of the light-emitting portion) coupled to a balloon may include a thermistor to monitor the temperature corresponding to each light-emitting segment enclosed by the balloon. For example, each light emitting segment 330, 332, 334, 336 in FIG. 3A may include a respective thermistor to monitor the temperature within the respective light emitting segment within the balloon 230, 232, 234, and 236.

[0117] Additionally, the pressure within each balloon can be monitored via a pressure sensor in fluid communication with the respective inflation port. That is, each balloon inflation port can be fluidly connected to a respective pressure sensor, and pressure signals from each pressure sensor can be received and monitored via the balloon control unit and / or controller. Through the pressure sensors, the controller can monitor leakage from the balloon. Additionally, in some embodiments, pressure sensors can be used in conjunction with thermistors to monitor the temperature within individual light segments corresponding to the balloons.

[0118] The method 550 further includes, at 560, adjusting one or more of the UV light intensity, duration, and / or balloon inflation amount based on one or more of the delivery tube temperature and the respective pressure within each balloon. For example, when the temperature within the balloon increases, the pressure within the balloon may increase due to the resulting expansion of air. In response to one or more of the temperature increase above a threshold and the pressure increase above a threshold pressure, the controller may adjust the actuator to increase refrigerant flow and / or decompress such that the pressure within the balloon is within the threshold pressure (e.g., to ensure desired contact between the balloon and the epithelium without excessive pressure). In some embodiments, the threshold pressure may be different for balloons treating treatment areas of different diameters. For example, the threshold pressure may be higher for balloons treating target areas of larger diameters.

[0119] In some embodiments, the UV light intensity or duration may additionally or alternatively be adjusted via a controller.

[0120] The method 550 then returns to 554 .

[0121] As one non-limiting example, narrowband UV light therapy through the one or more balloons may be provided to treat inflammatory and / or infectious conditions affecting only the mucosal and / or submucosal layers of the gastrointestinal tract. In another example, narrowband UV light therapy through the one or more balloons may be provided in addition to or as an alternative to treating inflammatory and / or infectious conditions affecting one or more deeper layers that are more distal to the intestinal lumen than the mucosa and / or submucosa. The one or more deeper layers may include the muscularis propria and / or serosa.

[0122] Referring to FIG. 7 , a schematic diagram of the light-emitting portion 206 of the delivery tube is shown, including exemplary positioning of the LEDs 222 and cooling tubes 224 within the delivery tube 202, along with a representation of the coolant flow. A balloon is not shown in this example. Specifically, the light-emitting portion 206 includes a plurality of LEDs 222 disposed within the delivery tube 202 and cooling tubes 224 also disposed within the delivery tube 202. In one example, as shown, the LEDs 222 are positioned rotated 90 degrees from each other and facing the delivery tube 202 such that when the LEDs 222 are powered, the LEDs 222 emit light in a 360-degree pattern along the length of the delivery tube 202 and outward from the delivery tube 202. Additionally, in this example, adjacent LEDs are rotated 90 degrees. For example, a first LED is at a reference angle of zero degrees, and a second LED positioned adjacent to the first LED along the length of the delivery tube 202 (i.e., the second LED immediately next to the first LED) is rotated 90 degrees from the first LED. Further, a third LED adjacent to the second LED along the length of the delivery tube 202 is rotated 90 degrees relative to the second LED (i.e., 180 degrees relative to the first LED), and so on, with the Nth LED adjacent to the (N-1)th LED being rotated 90 degrees relative to the second LED (i.e., 180 degrees relative to the first LED), and so on. ( N -1) 1 LED is rotated 90 degrees relative to the 1st LED; where N is any number depending on the desired length of light emission along the delivery tube 202.

[0123] In some embodiments, the LEDs may be arranged in a circumferential configuration. For example, the first and third LEDs may be positioned back-to-back, the second and fourth LEDs may be back-to-back, the second LED may be between the first and third LEDs, and the fourth LED may be between the third and first LEDs; the four LEDs may not be staggered; and the four LEDs may be arranged 90 degrees from each other such that, when powered, the four LEDs emit light 360 degrees around the delivery tube 202. Another set of four LEDs may be positioned a short distance from the first four LEDs to provide continuous, substantially uniform illumination along the desired length of the delivery tube 202. Multiple sets of LEDs may be positioned in this manner to cover the desired length of the catheter tube for illumination. Other configurations of LEDs that cover 360 degrees of illumination along the desired length of the catheter tube are possible and are within the scope of the present disclosure. For example, when LEDs with wider beam angles are used, fewer than four LEDs may be used to provide 360 ​​degrees of illumination. As a non-limiting example, three LEDs arranged in a staggered fashion (positioned next to each other along the length of the tube) or a circumferential fashion (side-by-side around the circumference of the cooling tube), each rotated 120 degrees from each other, may be utilized. In this manner, several sets of three LEDs may provide 360-degree illumination.

[0124] Additionally, cooling tubes 224 are positioned within the delivery tube 202 to provide cooling air to the delivery tube 202. The delivery tube 202 has an open end 704 toward the catheter tube proximal end 218, through which cooling air exits the cooling tube and circulates back toward the LEDs to cool them (cooling air flow indicated by arrows 702). The cooling tubes 224 may be configured to receive cooling air from a compressor, such as compressor 108 in FIG. 1A. The cooling tubes 224 are centered relative to the LEDs 222. Specifically, the LEDs 222 are positioned such that a portion of each LED contacts the cooling tube 224. For example, the LEDs 222 are arranged such that a rear portion (e.g., a portion of the LED substrate) contacts the cooling tube 224. In some embodiments, the LEDs 222 may be positioned on an inner tube (e.g., tube 324 in FIGS. 3A and 3B), which may include one or more cooling tubes within the inner tube.

[0125] Additionally, the cooling tube 224 is flexible and bends through the rear portion of each LED, which allows the LEDs to be arranged in a compact manner. In some embodiments, one or more additional apertures may be provided in the cooling tube to allow cooling air to exit through one or more additional exit points.

[0126] FIGS. 8, 9A-9C, 10A-10B, 11A-11C, and 12 illustrate several different embodiments that can be used for the light-emitting portion of the delivery tube, which can be coupled to one or more balloons. This can include one or more chip-on-board (COB) mini-bars that can be connected to delivery tube 802, as shown in FIG. 8. The delivery tube can include balloon 808, which can improve UV distribution and increase irradiance at the target tissue. The entire system can be connected to a flexible metal rod 804, which can be connected to a power supply unit (not shown). This example with one or more COB mini-bars shows a UV irradiation area having a length of 10 cm. It will be appreciated that the length can be less than or greater than 10 cm depending on the application. In some embodiments, one or more additional COB mini-bars can be included in addition to mini-bars 805 and 806 to cover a longer length of delivery tube 802.

[0127] An exemplary fiber optic solution with a COB light engine 902 that can be integrated with a delivery tube to spread light therapy is shown in Figures 9A-9C. In this example, a single LED (904 in Figure 9A) or multiple LEDs (Figures 9B and 9C) are connected (e.g., via coupling 906) to a fiber optic cable 908 that transmits light to the UV-emitting area, the fiber optic being constructed or treated to emit light in that portion of the tube. Additionally, in some examples, a collimating lens 914 can be utilized to focus and direct the light through the fiber optic cable 908, as shown in Figure 9C. As discussed above, the fiber optic cable 908 can be configured to emit light over the desired length of the delivery tube.

[0128] 10A-10B show one example of a flexible printed circuit board (PCB) 1004 with a heat sink (FIG. 10B) containing LEDs 1010. In one example, the flexible PCB can be formed into the tube 1005 so that the LEDs 1010 are positioned around the tube 1005. This embodiment helps dissipate heat due to the large surface area of ​​the flexible PCB. Additionally, one or more air holes 1008 can be provided to allow for improved cooling of the flexible PCB tube.

[0129] 11A-11C illustrate various components of another embodiment of a delivery tube including a series of linear reflectors and LEDs. As shown in FIG. 11B, the delivery tube includes a series of LED units directed toward a nearby reflector. Each LED unit includes an LED 1108, a reflector 1110, and a substrate 1114. An exemplary distance between two LEDs 1108 may be 9 mm, and the distance between the LED 1108 and the end of the reflector 1110 that receives the light from the LED may be 2 mm. For example, the distance between the LED and the end of the reflector may be small enough so that the reflector can receive and spread the light. In this manner, a greater light distribution is achieved while improving the uniformity of the delivery tube. FIG. 11B illustrates an exemplary heat sink that can be implemented in the embodiment of FIG. 11A. Furthermore, an exemplary beam angle of a narrow-band (e.g., 343-345 nm) LED that may be utilized in the delivery tube shown in FIG. 11A may be 135 degrees. [Example]

[0130] The following set of experimental data is provided to better illustrate the presently claimed invention and is not intended to be construed as limiting its scope.

[0131] Example 1: Escherichia coli 12A and 12B show experimental data illustrating an example in which a UV light-emitting device disclosed herein is used to prevent the growth of E. coli. As shown, the control group to which no UV light was applied continued to grow, while the test group to which UV light was applied by the UV light-emitting device showed a continuous decrease in E. coli counts over time. UV light has been shown to prevent E. coli growth and kill the bacteria over time.

[0132] Figure 15B shows an example in which a UV-light-emitting device disclosed herein is used with a liquid culture containing E. coli. Results of this experiment and similar experiments with other bacteria and the fungus Candida albicans are shown, for example, in Figure 15A, as well as in Figures 16, 17A-17B, 18-20, 21A, and 21B. All results demonstrate a significant reduction in the growth of E. coli and other infectious pathogens in liquid samples where UVA and UVB light was emitted onto the liquid sample by a UV-light-emitting device disclosed herein.

[0133] Example 2: Bacteria In another example, two exemplary devices according to the present disclosure were used in UVA experiments to treat bacteria. The first device was a borosilicate rod (3 mm outer diameter) that was repeatedly etched with a mixture of dilute sulfuric acid, sodium bifluoride, barium sulfate, and ammonium bifluoride, and a reflective coating was added to the end of the rod, allowing UVA to be emitted from the side. This process resulted in a side-emitting rod with UVA (peak wavelength 345 nm), as confirmed by a spectrometer (Ocean Optics; Extech). The second device incorporated a narrowband LED with a peak wavelength (345 nm).

[0134] The UVA rod was inserted into the liquid medium. A mercury lamp (Asahi Max 303, Asahi Spectra Co., Tokyo, Japan) was used as the light source. The second UVA-emitting device was a small light-emitting diode (LED) array (peak wavelength 345 nm) attached to a heat sink (Seoul Viosys, Gyeonggi-Do, Korea). This device was used in the plating experiments described below.

[0135] Stock cultures of Escherichia coli, E. coli GFP, Pseudomonas aeruginosa, Streptococcus pyogenes, Staphylococcus epidermis, Klebsiella pneumoniae, Enterococcus faecalis, Proteus mirabilis, Clostridioides difficile, and Candida albicans were grown in the appropriate liquid media and conditions as indicated in the table shown in Figure 22. American Type Culture Collection (ATCC) strains and one clinical isolate were grown in the appropriate solid and liquid media according to the instructions suggested by ATCC for each organism (Manassas, VA, USA). Using sterile technique, the vial containing the microbial strain was opened and the entire pellet was rehydrated with approximately 500 μL of liquid broth.

[0136] The resuspended pellet was aseptically transferred to a tube containing 56 mL of the same liquid broth used to resuspend the cells. A few drops from the primary broth tube were used to inoculate solid microbial agar to isolate single colony forming units (CFU). The liquid and solid cultures were incubated at the specified temperatures, atmospheric conditions, and times as described in Figure 22.

[0137] First, liquid cultures were prepared from a single CFU of each microorganism to ensure strain purity during UVA treatment. Only fresh, pure liquid cultures were used throughout the experiment. One single colony was added to a 10 mL sterile tube containing 5 mL of liquid medium, followed by thorough vortexing to homogenize the microbial cells. The liquid cultures, shown in Figure 22, were incubated until a McFarland turbidimetric assay of 0.5 was achieved. After reaching the standard turbidity, the microbial cultures were thoroughly mixed for 1 minute, and 1000 μL of the liquid culture was transferred to two 1.7 mL sterile microcentrifuge tubes to serve as treatment and control. 100 μL aliquots from each tube were serially diluted and plated on solid microbiological media to determine baseline CFU / mL counts, as shown in Figure 23.

[0138] Prior to UVA phototherapy, several sterile 1.7 mL tube caps were prepared by using a heated glass rod to poke a small hole in the top, the shape and size of the rod that would be used to transmit the UVA light.

[0139] The original caps from the liquid cultures in the 1.7 mL tubes were aseptically replaced with sterile caps with holes. A UV light-transmitting rod (sterilized with 70% ethanol) was placed in the hole created in the top of each cap. An identical rod was also placed in the control tube. Light was transmitted through a glass rod inserted into the tube using a MAX-303 xenon light source (Asahi Spectra USA, Inc., Torrance, CA). UV bandwidth and irradiance peak were assessed (Flame UV-VIS fiber optic spectrometer, Ocean Optics). UV intensity was measured with SDL470 and UV510 UV light meters (Extech, NH, USA). The absence of UVC was confirmed using an SDL470 UV light meter (Extech, NH, USA). Figure 22 describes the intensity and exposure duration of UVA light applied to bacterial cultures.

[0140] At the end of the treatment period, the rods were removed from the treatment and control tubes, and new sterile caps without holes were used to close the liquid cultures. Both the treatment and control groups were homogenized by vortexing. A 100 μL aliquot of each tube was then serially diluted and plated on solid microbial media to determine the number of CFU / mL after UVA treatment, as shown in the table in Figure 23. This process was repeated until all time points listed in Figure 23 were achieved.

[0141] After each time point (baseline and post-UVA treatment), 100 μL of liquid microbial culture (treated and control) was serially diluted with sterile 1x PBS (EMD Millipore, Billerica, MA). The final serial dilutions were 1:10 (100 μL microbial culture + 900 μL sterile 1x PBS), 1:100, 1:1000, 1:10,000, and 1:100,000. 100 μL of each dilution was plated in duplicate on solid agar plates and incubated for the time, temperature, and atmospheric conditions described in Figure 22. After incubation, colonies were counted using a Scan 300 automated colony counter (Interscience, Woburn, MA, USA), and the number of CFU / mL was defined by correcting for volume and dilution.

[0142] The second device used in these experiments incorporated a small light-emitting diode (LED) array (peak wavelength 345 nm, bandwidth 10 nm) mounted on an aluminum heat sink (Seoul Viosys, Gyeonggi-Do, Korea). In the first experiment, the system was placed 1 cm above the surface of a culture plate with a thick lawn of E. coli, generating approximately 2000 μW / cm. 2 This light source was then placed in a separate experiment at 10 2 CFU / mL was applied to liquid cultures of Escherichia coli and Pseudomonas aeruginosa.

[0143] In both conditions, UVA was irradiated at 500, 1000, 2000, and 3000 μW / cm 2In a separate series of experiments, dose-response curves were generated by testing at 1 cm for 20 and 40 minutes at different intensities. After incubation, colonies were counted using a Scan 300 automated colony counter (Interscience), and colony size was measured and corrected for volume and dilution to define the number of CFU / mL.

[0144] result Exposure to UVA was associated with a significant reduction in various pathogenic microorganisms, including Candida albicans (P = 0.007) and Clostridium difficile (P = 0.01), as shown in the table in Figure 23. UVA light exposure times of 20 min (intensity 1300–3500 μW / cm) were significantly longer than those of 100 min (intensity 1300–3500 μW / cm). 2 ) showed a reduction in most microorganisms compared to the control group (P<0.05), except for Klebsiella pneumoniae (P=0.17), Enterococcus faecalis (P=0.1), and Streptococcus pyogenes (P=0.64). When compared to the untreated control, UVA light exposure times of 40 and 60 minutes were effective against all microorganisms tested (P<0.05, Figure 33). Notably, the bactericidal and fungicidal effects showed a dose-dependent response to UVA light, with greater microbial reductions associated with longer exposure times, as shown in Figure 23.

[0145] UVA light therapy was also applied to a clinically isolated strain of E. coli obtained from the human urinary tract. UVA light was tested in a set of five consecutive experiments, exposing the bacterial culture to 1100–1300 μW / cm for 20, 40, 60, and 80 minutes. 2 Compared to baseline, the number of CFU / mL observed in bacterial cultures exposed to UVA light was reduced at all time points evaluated, including 20 minutes (P=0.03), 40 minutes (P=0.0002), 60 minutes (P<0.0001), and 80 minutes (P<0.0001), as shown in Figure 24.

[0146] Finally, we conducted experiments to test the effects of LED-based narrow-band UVA (peak wavelength of 345 nm) on E. coli and P. aeruginosa. In these experiments, this particular wavelength of UVA resulted in a significant reduction in bacterial cells, as shown in Figures 25A-25N. For example, Figure 25A shows a photograph of bacterial colonies in a Petri dish and the pattern of colony disappearance around the site of LED light application at 20 and 40 minutes. Figure 25B shows the effect of UVA treatment on E. coli liquid cultures when subsequently plated. E. coli liquid cultures were treated with 3000 W / cm² for 20 minutes (right) or left untreated as a control (left) and then plated on solid media. A significant reduction in the number and size of E. coli colonies after UVA treatment was observed (right plate).

[0147] Figures 25C-25F show graphs showing the time course of colony-forming units (CFU) of E. coli when exposed to various intensities of UVA light with a peak wavelength of 345 nm. As shown, most bacteria were eliminated by 40 minutes at an intensity of 2000 uW (Figure 25E), and most bacteria were eliminated by 20 minutes at an intensity of 3000 uW (Figure 25F). When the same light was applied at intensities of 500 uW and 1000 uW, a significant reduction in CFU was observed by 40 minutes, but only by about half (Figures 25C and 25D).

[0148] Figures 25G-25J show graphs showing the time course of colony-forming units (CFU) of P. aeruginosa when exposed to various intensities of UVA light with a peak wavelength of 345 nm. As shown, treatments at 1000 uW, 2000 uW, and 3000 uW intensities showed significantly greater reductions in CFU compared to the control (Figures 25H, 25I, and 25J), and by 20 minutes at 2000 uW and 3000 uW intensities, most bacteria were eliminated (Figures 25I and 25J).

[0149] Figures 25K-25L show growth curves comparing the log reduction of P. aeruginosa at various intensities at 20 and 40 minutes, respectively. Figure 25M shows growth curves illustrating the reduction in E. coli colony diameter at various intensities and treatment times. Figure 25N shows growth curves illustrating the reduction in P. aeruginosa colony diameter at various intensities and treatment times.

[0150] When examining the effect of light intensity on the reduction of E. coli and P. aeruginosa, a dose-response effect was observed for both bacterial load and colony size (Figures 25B-25N). The ideal UVA intensity to affect bacteria appears to be 2000-3000 μW / cm2 using narrowband LEDs with a peak wavelength of 345 nm, and in some examples may depend on the type and species of bacteria or pathogen, as well as other factors disclosed herein.

[0151] Example 3: Safety Data Three experiments were performed to evaluate the safety of UVA for mammalian cells. In the first experiment, HeLa cells in culture were exposed to UVA. HeLa cells were plated in 60x15mm cell culture dishes (Falcon) in DMEM cell culture medium (Gibco, Waltham, MA) plus 10% bovine serum (Omega Scientific, Tarzana, CA) and 1x antibiotic-antimycotic (100x Gibco) and grown at 37°C (5% CO2) for 24 hours to reach a cell density of 1,000,000–1,800,000 cells per plate. At this point, the cells were exposed to UVA LED light (1800 μW / cm2). 2 ) for 0 (control), 10, or 20 minutes. After 24 hours, cells were removed with 0.05% trypsin-EDTA (1x) (Gibco), stained with trypan blue (trypan blue 0.4% ready-to-use (1:1) (Gibco)), and quantified using an automated cell counter (Biorad T20, Hercules, CA). In a similar experiment, LED UVA light was applied at a higher intensity (5000 μW / cm). 2 ) for 20 minutes. Again, HeLa cells were quantified 24 hours after UVA exposure.

[0152] The safety of UVA was also investigated in two human respiratory cell types. These included alveolar (ATCC A549) and primary ciliated tracheal epithelial cells (HTEpC) (PromoCell, Heidelberg, Germany). For each cell line, 250,000 cells were plated and grown in DMEM for 48 hours until there were approximately 750,000 cells per plate. At this point, the cells were exposed to UVA (2000 μW / cm). 2 ) for 0 minutes (control) or 20 minutes (treatment), and cell counts were obtained 24 hours later.

[0153] The level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA from UVA-treated cells was also analyzed. 8-OHdG is widely accepted as a sensitive marker of oxidative DNA damage and oxidative stress. DNA was extracted using the AllPrep DNA / RNA / Protein Mini Kit (Qiagen) according to the manufacturer's instructions. 8-OHdG levels were detected using the EpiQuik™ 8-OHdG DNA Damage Quantification Direct Kit according to the manufacturer's instructions (Epigentek, Farmingdale, NY). For optimal quantification, the input DNA amount was 300 ng, as basal 8-OHdG typically accounts for less than 0.01% of total DNA (Epigentek, Farmingdale, NY).

[0154] For UVA photosafety testing, wild-type 129S6 / SvEv mice (n = 20, 10 females) and BALB / cJ mice (n = 10, 5 females) were used. All animals were anesthetized before treatment. Prior to UVA phototherapy, animals were placed in an induction chamber containing isoflurane anesthetic gas (1–5%). The carrier gas for isoflurane was compressed oxygen (100% oxygen). Once the breathing rate slowed (approximately 1 breath per second), the animals were removed from the induction chamber and maintained under sedation using nose cone anesthesia (1–2% isoflurane). The depth of anesthesia was confirmed by the lack of response to toe pinch.

[0155] Under anesthesia, a customized rod (D = 4 mm, L = 40 mm) was introduced from the anus to the splenic flexure. The control group underwent the same procedure using an identical but unlit rod. The light source and measurement equipment were the same as those described for the liquid culture experiments.

[0156] In the first experiment, five BALB / cJ mice were given a 30-minute colonic UVA exposure (2,000 μW / cm 2 ) and compared with five mice treated with the same technique but without the optical rod.

[0157] In the second experiment, 10 129S6 / SvEv mice received 20 min of colonic UVA exposure (3,000–3,500 μW / cm) per day. 2 ) was performed on two consecutive days and compared with 10 mice (5 males) treated with unlit rods.

[0158] Colonoscopy before and after UVA phototherapy A rigid pediatric cystoscope (Olympus A37027A) was used to evaluate the intestinal mucosa before and after 7 days of UVA exposure. Endoscopy was performed in anesthetized animals. Sedation was as previously described.

[0159] The anus was first lubricated with an aqueous gel (Astroglide®, BioFilm, Inc., Vista, CA, USA). The endoscope was then inserted to the splenic flexure, and the colon was insufflated using room air injected through the endoscope port. All endoscopic examinations were recorded and interpreted blindly by two gastroenterologists experienced in animal model endoscopy. Endoscopic images were analyzed based on perianal examination, bowel wall clarity, mucosal bleeding, and focal lesions.

[0160] On day 14, control and treated mice were euthanized, and whole-colon Swiss-roll preparations were prepared as proposed by Bialkowska et al. Briefly, the entire colon was removed and rinsed in modified Bouin's fixative (50% ethanol / 5% acetic acid in dH2O). Using scissors, the colon was opened longitudinally along the mesenteric line and briefly rinsed in a Petri dish containing 1x PBS. The luminal side was identified, and Swiss-rolling of the open tissue was performed. Once the entire length of the colon was rolled, the colon was carefully transferred to a tissue processing / embedding cassette. The cassette was placed in 10% buffered formalin overnight at room temperature, after which paraffin sections of the colon were cut, stained with hematoxylin and eosin (H&E), and evaluated by a blinded pathologist (SS).

[0161] Because bacterial count data between groups were not normally distributed, they were compared using a nonparametric test (Mann-Whitney U test). Other quantitative data were compared by t-test using GraphPad Prism 7 (GraphPad, San Diego, CA).

[0162] result Overall, based on cell proliferation over time, LED UVA appeared to be safe in the mammalian cells tested (HeLa, alveolar A549, and primary tracheal cells). Cell proliferation continued in all plates despite UVA exposure, with the number of cells per plate reaching 1.5-2 times the control, indicating continued robust replication. In the case of HeLa cells, UVA had no effect on viable cell counts after 24 hours (approximately 2000 μW / cm) compared to unexposed controls, as shown in Figure 26A. 2 UVA for 10 and 20 minutes, P = 0.99 and P = 0.55, respectively. Higher intensity UVA (5000 μW / cm 2 ) did not affect HeLa cell proliferation, as shown in the bar graph depicted in Figure 26B. Similar findings were observed at 2000 μW / cm, as shown in Figure 26C. 2 , and alveolar cells at 20 min (P = 0.99). Finally, ciliated epithelial cell growth was also observed at UVA exposures of approximately 1000 μW / cm. 2and approximately 2000 μW / cm 2 After 20 minutes of exposure to light, the animals were unaffected.

[0163] Furthermore, UVA exposure did not cause DNA damage in any of the cell lines analyzed, and as shown in Figure 26D (HeLa cells), Figure 26E (alveolar cells), and Figure 26F (tracheal cells), the levels of 8-oxo-2'-deoxyguanosine (8-OHdG) in cells treated with narrowband LED UVA were similar to those of non-UVA exposed controls (P<0.05). Higher LED UVA intensities (5000 μW / cm) 2 ), levels of 8-OHdG appeared to be elevated ( P = 0.07), but the proportion of 8-OHdG remained well below the generally accepted threshold of 0.01% of total DNA.

[0164] UVA light exposure is not associated with endoscopic or histological damage To evaluate the safety of UVA therapy on internal organ cells and tissues, two different wild-type mouse strains were exposed to intracolonic broad-spectrum UVA light using an optical rod designed to uniformly laterally emit broad-spectrum UVA. Only the left side of the colon up to the splenic flexure was exposed to UVA light, so the unexposed right side served as an autologous control. In the first experiment, five anesthetized mice received a 30-minute colonic UVA exposure (2,000 μW / cm2) and were compared with five mice treated with the same procedure but without the optical rod.

[0165] In the second experiment, 10 mice (129S6 / SvEv, male = 5) received 20 min of colonic broad-spectrum UVA exposure (3,000–3,500 μW / cm) per day. 2 ) were performed on two consecutive days and compared with 10 mice (5 males) treated with unlit rods. No perforation, bleeding, or death was observed in any of the experiments. Colonoscopy images of the mice showed no changes before and after UVA exposure.

[0166] In both experiments, endoscopic evaluation of mice before and after UVA treatment revealed no macroscopic evidence of mucosal erythema, fractures, ulcers, or bleeding. As assessed by a blinded pathologist (SS), full-thickness colon specimens exposed to broad-spectrum UVA showed no chronic or acute inflammation, cystitis, crypt abscesses, granulomas, ulcers, or dysplasia compared with control and untreated colon segments.

[0167] RNA virus experiment data Furthermore, experimental data was obtained using the disclosed system and method to treat various RNA viruses with UVA light. The data demonstrated that UVA light emitted from an LED with a peak wavelength of 340 nm can kill RNA viruses, such as coxsackieviruses. For example, HeLa cells infected with coxsackieviruses survived when this UVA treatment was applied, but did not survive when UVA light treatment was not applied after infection. Furthermore, the experimental data showed that only 15% of the UVA light was lost after passing through the ET tube.

[0168] In late December 2019, an outbreak of novel coronavirus disease (SARS-CoV-2 or COVID-19, formerly known as 2019-nCoV) was reported in Wuhan, China. COVID-19 is a viral infection that replicates efficiently in the upper respiratory tract. As part of its mechanism of action, the virus infects ciliated tracheal epithelial cells, which then slough off, impairing alveolar function. Secondary bacterial infections have also been noted, and both of these processes can lead to further inflammation, acute respiratory distress syndrome (ARDS), and ultimately death. It is estimated that 10–15% of infected individuals will experience a severe clinical course, and approximately 5% will progress to a critical condition requiring mechanical ventilation due to respiratory or other organ failure. The case fatality rate for COVID-19 is estimated to range from 0.5% to 9.5%, although this estimate is confounded by the prioritization of testing for symptomatic patients and a lag time of up to 14 days before symptom onset. Deaths are thought to be due to respiratory failure in the setting of ARDS and / or secondary infections, including ventilator-associated pneumonia (VAP).

[0169] Ventilator-associated pneumonia (VAP) can develop in intensive care unit (ICU) patients receiving mechanical ventilation for at least 48 hours and is common in COVID-19 patients. The incidence of VAP ranges widely, from 5% to 67%, depending on the diagnostic criteria used and the patient population studied. Causative bacteria include Enterobacteriaceae (25%), Staphylococcus aureus (20%), Pseudomonas aeruginosa (20%), Haemophilus influenzae (10%), and Streptococcus pyogenes (13). Multidrug-resistant bacteria are more common in late-onset cases. Early-onset VAP has a mortality rate of approximately 6%, while late-onset VAP has a mortality rate of 10%.

[0170] There is currently no cure for COVID-19, and conventional measures to reduce secondary infections in mechanically ventilated patients have thus far proven insufficient. A safe and effective broad-spectrum antiviral and antibacterial approach for these patients should potentially reduce viral load, secondary infections and VAP, time on mechanical ventilation, and deaths from respiratory failure.

[0171] As disclosed herein, ultraviolet (UV) light has antibacterial properties. UVC (110–280 nm) light is widely used for industrial sterilization (16), but it has been shown to have deleterious effects on human DNA. External UVA (320–400 nm) and UVB (280–320 nm) devices have been approved by the FDA for the treatment of human diseases such as psoriasis, eczema, and cutaneous lymphoma. These wavelengths penetrate mucosal and submucosal tissues. Of the three spectrums, UVA appears to cause the least damage to mammalian cells. Currently, no studies have demonstrated the effectiveness of internal application of UVA light against bacterial or viral infections. Advances in light-emitting diodes (LEDs) are making it feasible to deliver narrow-band UVA light to internal organs.

[0172] Thus, experimental data are disclosed demonstrating the efficacy of broadband and / or narrowband UVA for the treatment of common bacterial pathogens known to be associated with VAP. Furthermore, data are disclosed demonstrating the efficacy of specific wavelengths of UVA against group B coxsackievirus and coronavirus 229E. Finally, additional data demonstrate the safety of UVA exposure to mammalian cells and epithelial cells in vivo.

[0173] Example 4: Coxsackievirus Obtaining coxsackievirus samples and infecting cells A recombinant Coxsackievirus B (pMKS1) expressing enhanced green fluorescent protein (EGFP-CVB) plasmid was linearized using the ClaI restriction enzyme (ER0142, Thermo Fisher Scientific). The linearized plasmid was purified using standard phenol / chloroform extraction and ethanol precipitation. Viral RNA was then generated using the mMessage mMachine T7 Transcription Kit (AM1344, Thermo Fisher Scientific). The viral RNA was then transfected into HeLa cells (approximately 80% confluency) using Lipofectamine 2000 (11668027, Thermo Fisher Scientific). When the cells showed approximately 50% cytopathic effect, the cells were scraped and the cell / media suspension was collected. This mixture was then subjected to three rounds of rapid freeze-thaw cycles and centrifuged at 1,000 x g for 10 minutes to clear the media of cell debris. The supernatant was used as the passage 1 virus stock. The passage 1 virus stock was then overlaid onto separate HeLa cells (approximately 80% confluency) to expand the stock to a passage 2 virus stock, which was used in subsequent experiments.

[0174] UVA treatment of HeLa cells infected with group B coxsackieviruses. HeLa cells were used in four different experiments using enhanced green fluorescent protein (EGFP)-expressing group B coxsackievirus (EGFP-CVB). In the first experiment, HeLa cells (253,000 per plate) (n = 12 plates) were cultured for 24 h. Half of the EGFP-CVB aliquot was irradiated with LED UVA (2000 μW / cm). 2 One plate was exposed to UVA (peak wavelength 340 nm) for 20 minutes, while the other was not. HeLa cells were then infected with either the UVA-exposed virus or the non-UVA-exposed virus (MOI = 0.1). After 6 hours, the supernatant was removed and the cells were washed twice with 1x sterile PBS (pH = 7.0). Fresh DMEM medium was added. The plate infected with the UVA-exposed virus was then exposed to UVA (2000 μW / cm) for an additional 20 minutes. 2) for 24 hours. Dead cells in the supernatant were collected and quantified. Six plates (three UVA-treated and three UVA-untreated) were evaluated for viable cells. Of the remaining six plates, three that were initially exposed to UVA with a peak wavelength of 340 nm were exposed to UVA (2000 μW / cm ) for an additional 20 minutes. 2 After another 24 hours, the remaining plates were counted for dead and live cells.

[0175] Pretreatment of HeLa cells with UVA against group B coxsackievirus infection In the second experiment, HeLa cells (235,000 cells) were plated and then incubated in DMEM for 24 hours. Plates were then treated with either an unexposed control (n=3) or LED UVA (2000 μW / cm 2 After 24 hours, all plates were infected with EGFP-CVB (MOI = 0.1). After another 24 hours, cells were counted as described above.

[0176] Pretreatment of group B coxsackievirus with UVA for infection of HeLa cells In the third experiment, HeLa cells were cultured for 24 h and then infected with EGFP-CVB (MOI = 0.1). Immediately before infection, half of the EGFP-CVB aliquot was irradiated with LED UVA (2000 µW / cm). 2 Half were exposed to a 300 nm (peak wavelength 340 nm) light, and the other half remained unexposed. After 24 hours, the viable cell count was taken.

[0177] Long-term UVA treatment of HeLa cells during ongoing infection with group B coxsackieviruses. In this experiment, 250,000 HeLa cells were plated. After 24 hours, the cells were divided into three groups. In the first group, the cells were infected with EGFP-CVB (MOI = 0.1). These cells served as a positive infection control. In group 2, HeLa cells were infected with EGFP-CVB (MOI = 0.1) treated with UVA (2000 μW / cm2, 20 minutes, peak wavelength 340 nm). After 6 hours, the infected cells were exposed to UVA (2000 μW / cm2). 2 After treatment with UVA (peak wavelength 340 nm) for 20 minutes, four additional treatments were performed: two 20-minute treatments at 8-hour intervals on day 2 and two 20-minute treatments at 8-hour intervals on day 3. Group 3 was not infected with EGFP-CVB but was treated with UVA five times at the same time points as group 2. This was an uninfected positive control to demonstrate the safety of UVA. Imaging and cell counts were obtained for all conditions.

[0178] UVA treatment of alveolar (A549) cells infected with group B coxsackievirus In preliminary experiments using alveolar cells, we determined that 48 hours post-infection was the ideal time point for cell death due to infection. In this study, 200,000 alveolar cells were plated and counted 48 hours later (754,000 cells). The alveolar cells were then infected with EGFP-CVB (MOI = 0.1). 24 hours after infection, the alveolar cell plates were exposed to LED UVA (2000 μW / cm). 2 The cells were exposed to UV light (peak wavelength 340 nm) for 0 minutes (control) or 20 minutes (treatment), and this was repeated every 24 hours for 3 days. Imaging and cell number were measured 96 hours after infection.

[0179] result Pretreatment of HeLa cells with group B coxsackieviruses with UVA alone prior to infection does not reduce infection. In this experiment, half of the plate containing HeLa cells was treated with EGFP-CVB, and the other half was treated with a peak wavelength of 340 nm and approximately 2000 μW / cm 2The mice were treated with group B coxsackievirus followed by 20 minutes of exposure to LED UVA light. The effect on infection rates at 24 hours did not differ between groups.

[0180] UVA pretreatment of HeLa cells prior to infection with group B coxsackievirus does not attenuate the virus's effects In this experiment, half of the plate containing HeLa cells was left untreated, while the other half was exposed to a peak wavelength of 340 nm and approximately 2000 μW / cm 2 HeLa cells were pre-treated with 1000kJ of LED UVA for 20 minutes without further UVA treatment. Both groups were spiked with EGFP-CVB. Both groups were equally infected, suggesting that treating HeLa cells prior to infection had no effect on infection rates.

[0181] UVA treatment after infection with group B coxsackievirus attenuated viral effects on HeLa cells. In this study, UVA was applied to HeLa cells after they were infected with EGFP-CVB. Treated cells received approximately 2000 μW / cm at a peak wavelength of 340 nm 6 hours after infection. 2 The cells were exposed to LED UVA light for 10 min at 48 h and then counted at 72 h postinfection and then exposed twice daily for two more days. This was compared to infected but untreated controls. In the treated group, UVA light prevented cell death from EGFP-CVB, increasing the cell count to 339,333 ± 60,781 at 72 h, as shown in the bar graph in Figure 27, whereas no viable cells remained on the plate in the untreated control group at 48 and 72 h. Importantly, a third group of HeLa cells, uninfected but exposed to UVA for the same time interval, showed normal cell proliferation with a cell count of 2,413,333 ± 403,773 at 72 h.

[0182] Further experimental data using GFP-tagged Coxsackievirus B (EGFP-CVB) Assessment of UVA treatment by fluorescence microscopy of alveolar cells infected with GFP-CVB (Figure 30). Alveolar cells cultured for 24 hours were transfected with GFP-CVB and observed under a fluorescent microscope 48 hours later to establish a baseline (image 3002). The transfected cells were then treated with UVA and imaged 24 hours (image 3006) and 48 hours (image 3010) after transfection. A control group included GFP-CVB transfected cells without UVA treatment. A control group without UVA treatment was also imaged 24 hours (image 3004) and 48 hours (image 3008) after transfection. As seen in the images in Figure 30, UVA treatment resulted in a reduction of approximately 70% of GFP-CVB infection after 24 hours and a reduction of approximately 90% of GFP-CVB infection after 48 hours. UVA treatment was performed for 20 minutes using a UV LED with a peak wavelength of 345 nm.

[0183] Assessment of UVA treatment by quantitative analysis of HeLa cells infected with GFP-CVB (Figure 31). HeLa cells cultured for 24 hours were counted before transfection with GFP-CVB (time point zero in Figure 31). After transfection, HeLa cells were cultured with GFP-CVB for 24 hours. At the 24-hour time point, one group was treated with UVA. The control group included GFP-CVB-transfected HeLa cells without UVA treatment. Final cell counts were performed on the UVA-treated and untreated GFP-CVB-transfected HeLa cells. As shown in Figure 31, the survival of HeLa cells was significantly increased by UVA treatment. Similar to the above experiment, UVA treatment was performed with a UV LED with a peak wavelength at 345 nm for a duration of 20 minutes.

[0184] Effect of UVA treatment on group B coxsackievirus-infected alveolar (A549) cells. In alveolar cells infected with EGFP-CVB, cell death was much less than that observed in HeLa cells. At 96 hours post-infection, clear and widespread infection was observed in control cells. Alveolar cells treated with LED UVA at a peak wavelength of 340 nm also showed infection, but visual assessment suggested a lower infection rate and far fewer cells emitting viral EGFP signals. Furthermore, the number of viable cells appeared to be higher in the UVA-treated group compared to the untreated group.

[0185] Example 5: Coronavirus In another example, coronavirus-infected ciliated tracheal epithelial cells (HTeCs) were treated with UV light as disclosed below.

[0186] Ciliated tracheal epithelial cells (Promocell, Heidelberg, Germany) were plated in three groups (135,000 cells per plate). One group was infected with coronavirus 229E (Cov-229E) (50 μL per plate). The other group was infected with coronavirus 229E at a peak wavelength of 340 nm (2000 μW / cm) immediately before infection. 2 The third group received neither infection nor UVA. After infection, the cells were treated daily with UVA (4 cm distance, 2000 μW / cm at the plate surface) for 20 min. 2 Plates were imaged at 16, 72, and 96 hours post-infection, and cell counts were obtained at 72 and 96 hours post-infection.

[0187] UVA to rescue ciliated tracheal epithelial cells already infected (by coronavirus 229E) In this experiment, plates of ciliated tracheal epithelial cells (HTeCs) were infected with Cov-229E as described above. After 24 hours, the plates were divided into two groups. Group 1 was allowed to continue the infection. Group 2 was exposed to UVA with a peak wavelength of 340 nm (4 cm distance, 2000 μW / cm at the plate surface). 2) for 20 minutes. After 48 hours, the plates were imaged and the viable cell count was determined.

[0188] UVA for short-range treatment of coronavirus-infected ciliated tracheal epithelial cells Another experiment, targeting an intratracheal device using UVA technology, was performed using a lower intensity light (1300 μW / cm at the surface of the plate from a distance of just 1 cm) for 20 minutes per day. 2 This was performed identically to the experiment described above using a ventilated tracheal tube (Fig. 1B). This is the expected distance between the tracheal tissue and the optical catheter in a patient ventilated from inside the endotracheal tube.

[0189] Coronavirus load in UVA-treated or non-UVA-treated cells Total protein was extracted from cell samples using the AllPrep DNA / RNA / Protein Mini Kit (Qiagen). Proteins were loaded onto a Bolt 4-12% Bis-Tris gel (NW04122, Thermo Fisher Scientific) and transferred onto a Biotrace NT nitrocellulose membrane (27376-991, VWR). Total proteins were stained with Ponceau S solution (P7170, Sigma-Aldrich). The membrane was then blocked with blocking solution (Tris-buffered saline containing 3% bovine serum albumin (A7030, Sigma-Aldrich) and 0.1% Tween 20 (P1379, Sigma-Aldrich)). The membrane was then incubated overnight at 4°C with rabbit anti-coronavirus spike protein antibody (1:1000; PA5-81777, Thermo Fisher Scientific) or mouse anti-MAVS (mitochondrial antiviral signaling) antibody (1:200; SC-166583, Santa Cruz Biotechnology) diluted in blocking solution. After washing with Tris-buffered saline + 0.1% Tween 20 (TBS-T), the membrane was overlaid with either horseradish peroxidase (HRP)-conjugated goat anti-rabbit IgG antibody (1:300; 95058-734, VWR) or HRP-conjugated goat anti-mouse IgG antibody (1:300; 5220-0286, SeraCare). The membrane was then washed with TBS-T and subsequently exposed to enhanced chemiluminescence solution (RPN2235, GE Healthcare). Immunoreactive protein bands were imaged using a ChemiDoc imaging system (Bio-Rad Laboratories, Hercules, CA USA).

[0190] LED UVA light preserves ciliated tracheal epithelial cells infected with coronavirus 229E Ciliated tracheal epithelial cells were pretreated with coronavirus 229E and exposed daily to LED UVA (2000 μW / cm 220-minute exposure to UVA (peak wavelength 340 nm) was compared with control cells (no UVA, no infection) and cells infected with coronavirus but without UVA exposure. Direct visualization showed clear changes in cell morphology (no UVA) associated with infection. However, control cells and infected cells treated daily with UVA displayed similar morphology. After 96 hours, the supernatant was removed and viable cells (adherent to the plate) were counted. There was no difference in tracheal cell numbers between control and UVA-treated infected cells. However, as shown in the bar graph in Figure 28, there was a significant decrease in viable cells among infected cells compared to UVA-treated cells (P=0.005).

[0191] Interestingly, infected cells treated with LED UVA showed a decrease in CoV-229E spike (S) protein (approximately 130 kDa) compared to untreated infected cells. Furthermore, CoV-229E-infected and UVA-treated cells showed elevated levels of MAVS compared to CoV-229E-infected but untreated cells (Figure 29). Columns 1, 2, and 3 in Figure 29 represent CoV-229E-infected cells; columns 4, 5, and 6 represent CoV-229E-infected and NB-UVA-treated cells. To check the amount of protein loaded on the gel, Ponceau S staining was used to reveal the overall protein band. Therefore, these experimental data confirm that UV-A light can kill coronavirus 229E after infection of lung epithelial tissue and validate the use of UV-A light to irradiate lung tissue in conjunction with ET tubes and other devices as a treatment for coronavirus-infected patients.

[0192] Figures 32 and 33 are bar graphs showing the effect of UVA treatment on coronavirus 229E-transfected HTeC cells compared to untreated controls 48 and 72 hours after UVA treatment. As evidenced in Figures 33 and 34, UVA treatment increases cell viability of coronavirus 229E-transfected HTeC cells.

[0193] Further embodiments In one embodiment, an endoscope or other delivery tube, such as delivery tube 202, equipped with one or more balloons and one or more UV LEDs may be inserted through the oral cavity and esophagus into the stomach. In this example, an infection or inflammatory condition in the GI tract may be treated with UV light source 222 and one or more balloons selectively inflated to one or more target areas in the stomach and / or small intestine, including one or more of the duodenum, jejunum, and ileum.

[0194] In one embodiment, a light delivery device for performing intraluminal phototherapy is provided. The light delivery device includes: a delivery tube with a light-emitting portion, the light-emitting portion including a plurality of light sources configured to emit narrowband light at wavelengths within the ultraviolet A (UV-A) range between 335 nm and 349 nm; and a plurality of inflatable balloons connected to the delivery tube at the light-emitting portion, each of the plurality of inflatable balloons fluidly coupled to a respective inflation port, each of the plurality of inflatable balloons being composed of an ultraviolet (UV)-transparent material. In a first embodiment of the light delivery device, each of the plurality of inflatable balloons is configured to increase the irradiance and / or irradiance distribution of light emitted from the plurality of light sources and delivered to a corresponding intraluminal treatment site. In a second embodiment of the light delivery device, which may optionally include the first embodiment, the plurality of inflatable balloons are arranged in series along the length of the light-emitting portion; and the separation between any two of the plurality of inflatable balloons is adjustable. In a third embodiment of the light delivery device, which may optionally include one or both of the first and second embodiments, the light-emitting portion comprises one or more segments not connected to the plurality of inflatable balloons; and the one or more segments include one or more light sources of the plurality of light sources. In a fourth embodiment of the light delivery device, which may optionally include one or more of the first through third embodiments, the plurality of light sources are light-emitting diodes (LEDs) electrically connected to a power source and configured to emit light outward from the delivery device. In a fifth embodiment of the light delivery device, which may optionally include one or more of the first through fourth embodiments, the plurality of light sources are positioned on a cooling tube within the delivery device configured to receive cooled air from a cooling system including a medical-grade compressor and a chiller. In a sixth embodiment of the light delivery device, which may optionally include one or more of the first through fifth embodiments, the plurality of light sources are configured to emit a peak wavelength in the UV-A region between 338 nm and 346 nm.In a seventh embodiment of the light delivery device, which may optionally include one or more of the first through sixth embodiments, the light delivery device further comprises a balloon control unit configured to inflate and / or deflate each of the plurality of inflatable balloons via a respective balloon inflation port. In an eighth embodiment of the light delivery device, which may optionally include one or more of the first through seventh embodiments, the light delivery device further comprises a guidewire channel within the delivery tube and extending the entire length of the delivery tube, the guidewire channel configured to thread the delivery device over a guidewire positioned in the patient's lumen. In a ninth embodiment of the light delivery device, which may optionally include one or more of the first through eighth embodiments, the UV-transparent material is polyether block amide (PEBA), or cyclic olefin copolymer (COC), or silicone. In a tenth embodiment of the light delivery device, which may optionally include one or more of the first through ninth embodiments, the plurality of inflatable balloons comprises at least three balloons.

[0195] One embodiment relates to a method for performing intraluminal ultraviolet (UV) therapy, comprising: providing a UV light delivery device comprising: a delivery tube with a plurality of light-emitting segments, each of the plurality of light-emitting segments including a plurality of light-emitting diodes (LEDs) configured to emit narrowband light having a wavelength in the ultraviolet A (UV-A) range between 338 nm and 346 nm; and a plurality of inflatable balloons, each of the plurality of inflatable balloons coupled to one of the plurality of light segments and fluidly coupled to a respective inflation port coupled to a balloon control unit, the plurality of inflatable balloons being composed of a UV-transparent material; positioning the delivery tube within a lumen of a gastrointestinal (GI) tract of a patient with each of the plurality of inflatable balloons in a de-inflated state; selectively inflating the plurality of inflatable balloons via the balloon control unit; and energizing the plurality of LEDs at a threshold intensity for a threshold duration based on one or more of a type and overall severity of a GI tract disorder. In a first embodiment of the method, the step of positioning a delivery tube within a lumen comprises juxtaposing one or more of the plurality of inflatable balloons with one or more diseased areas within the lumen. In a second embodiment of the method, which may optionally include the first embodiment, the step of selectively inflating the plurality of inflatable balloons comprises inflating the one or more inflatable balloons juxtaposed with the one or more diseased areas, while maintaining the remaining balloons juxtaposed with normal, healthy tissue in a de-inflated state. In a third embodiment of the method, which may optionally include one or both of the first and second embodiments, the step of selectively inflating the one or more inflatable balloons juxtaposed with the one or more diseased areas comprises pressurizing the one or more inflatable balloons to a threshold pressure at which the one or more inflatable balloons contact the epithelial layer of the lumen. In a fourth embodiment of the method, which may optionally include one or more of the first through third embodiments, the threshold pressure is based on the diameter of the lumen.In a fifth embodiment of the method, which may optionally include the first through fourth embodiments, when one or more target areas have different severities of infection and / or inflammation during a condition, the magnitude of light intensity for a given light-emitting segment is adjusted based on the local severity of infection and / or inflammation in the one or more target areas. In a sixth embodiment of the method, which may optionally include the first through fifth embodiments, the delivery tube includes a refrigerant tube configured to receive cooled air from a compressor, and the method further includes monitoring the temperature of the delivery tube via a thermistor and adjusting the refrigerant flow rate through the refrigerant tube based on the temperature. In a seventh embodiment of the method, which may optionally include the first through sixth embodiments, the delivery tube is configured as an endoscope equipped with one or more cameras for visualizing the lumen. In an eighth embodiment of the method, which may optionally include the first through seventh embodiments, the UV-transparent material includes polyether block amide (PEBA), cyclic olefin copolymer (COC), or silicone. In a ninth embodiment of the method, which may optionally include the first through eighth embodiments, the step of positioning the delivery tube within the lumen includes passing the delivery tube over a guidewire positioned within the lumen using an endoscope.

[0196]

[0010] Another embodiment relates to a method for treating, ameliorating, and / or preventing gastrointestinal disorders in a patient, the method comprising: providing a delivery tube with a light-emitting portion including a set of light-emitting diodes (LEDs) and at least one inflatable balloon coupled to the light-emitting portion; guiding the delivery tube into a lumen of the patient's gastrointestinal tract and positioning the at least one inflatable balloon in juxtaposition with a target area within the lumen requiring ultraviolet (UV) light treatment; inflating the at least one inflatable balloon via a balloon inflation port fluidly coupled to the at least one inflatable balloon; and energizing a set of LEDs connected to the delivery tube and positioned within the at least one inflatable balloon at a duration and intensity sufficient to treat the gastrointestinal disorder, wherein the set of LEDs is configured to emit narrowband light having a wavelength in the UV range between 335 nm and 349 nm. A first embodiment of the method relates to a method for treating, ameliorating, and / or preventing gastrointestinal disorders in a patient, the method comprising: providing a delivery tube with a light-emitting portion including a set of light-emitting diodes (LEDs) and at least one inflatable balloon coupled to the light-emitting portion; guiding the delivery tube into a lumen of the patient's gastrointestinal tract and positioning the at least one inflatable balloon in juxtaposition with a target area within the lumen requiring ultraviolet (UV) light treatment; inflating the at least one inflatable balloon via a balloon inflation port fluidly coupled to the at least one inflatable balloon; and energizing a set of LEDs connected to the delivery tube and positioned within the at least one inflatable balloon at a duration and intensity sufficient to treat the gastrointestinal disorder, the set of LEDs being configured to emit narrowband light having a wavelength in the UV range between 335 nm and 349 nm. 0 In a second embodiment of the method, which may optionally include the first embodiment, the at least one inflatable balloon is constructed using a material including polyether block amide (PEBA), or cyclic olefin copolymer (COC), or silicone. In a third embodiment of the method, which may optionally include one or both of the first and second embodiments, inflating the at least one inflatable balloon includes pressurizing the at least one inflatable balloon to a threshold pressure at which the at least one inflatable balloon directly contacts a desired surface area of ​​the epithelial layer of the lumen. In a fourth embodiment of the method, which may optionally include one or more of the first through third embodiments, the threshold pressure is based on the diameter of the lumen. In a fifth embodiment of the method, which may optionally include one or more of the first through fourth embodiments, the intensity is at least 1,100 microwatts / cm. 2 , 1,500 microwatts / cm 2 , 2,000 microwatts / cm 2 , 2,100 microwatts / cm 2, 2,200 microwatts / cm 2 , 2,300 microwatts / cm 2 , 2,400 microwatts / cm 2 , 2,500 microwatts / cm 2 , 2,600 microwatts / cm 2 , 2,700 microwatts / cm 2 , 2,800 microwatts / cm 2 , 2,900 microwatts / cm 2 , 3,000 microwatts / cm 2 , or 2 milliwatts / cm 2 In a sixth embodiment of the method, which may optionally include one or more of the first through fifth embodiments, the gastrointestinal disorder comprises at least one of ulcerative colitis, Crohn's disease, pouchitis, proctitis, fistulas, inflammatory strictures, microscopic colitis, infectious diarrhea, refractory Helicobacter pylori, MALT lymphoma, colonic inertia, tropical sprue, celiac disease, small intestinal bacterial overgrowth, appendicitis, post-bone marrow transplant infection, pseudopolyps, radiation enteritis, refractory Clostridium difficile, gastrointestinal cancer, hepatobiliary infection, and mucosal and submucosal inflammation and cancer. In a seventh embodiment of the method, which may optionally include one or more of the first through sixth embodiments, the gastrointestinal disorder is a form of inflammatory bowel disease. In an eighth embodiment of the method, which may optionally include one or more of the first to sixth embodiments, said forms of IBD include ulcerative colitis and / or Crohn's disease.

[0197] In one embodiment, the UV light treatment assembly includes a UV light catheter comprising one or more balloons and one or more LEDs. As a non-limiting example, when configured as a single-balloon device, the UV light catheter can be approximately 15 cm in length, including a 10 cm segment containing an LED light and sheathed in a UV-transparent inflatable balloon. In another non-limiting example, when configured as a multi-balloon device, the UV light catheter can be approximately 100 cm in length and include four 10 cm segments of LED light, each sheathed in a UV-transparent inflatable balloon. The UV light can be wired on an electronic printed circuit board. Chilled air can be pumped into the catheter within cooling tubing wrapped between the LEDs and circulates around the LED light upon exiting the catheter. The catheter can be flexible to allow manipulation into the proximal colon using guidewire techniques. Additionally, the catheter includes a thermistor that detects heat and turns off the device if it exceeds body temperature. In some embodiments, the light catheter can be provided for single use. The UV light therapy system further includes a controller including a compressor and a cooler. The controller powers the LED light and includes a timer and a user interface / display. The controller also includes an air cooler / compressor configured to pump cooled air into the catheter to reduce the risk of thermal injury. Furthermore, in some embodiments, the controller and compressor / cooler may be stored on a mobile cart and may be reusable. The UV light therapy system further includes an umbilical assembly. The umbilical includes flexible tubing connecting the controller to the catheter. The flexible tubing may store necessary wiring and tubing to operate the catheter. The umbilical may be reusable.

[0198] Advantages of the UV-transparent balloon include securely holding the light delivery device in place during light administration; this in turn provides more uniform exposure to a wider diameter of the colon, dispersing foreign debris / biofilm that may act as a barrier between the light delivery device (i.e., optical catheter) and the colonic epithelium, and also preventing stool from descending into the treatment segment. Furthermore, the balloon provides a consistent distance between the light source and the target tissue, resulting in a uniform exposure dose. The multi-balloon approach also provides flexibility for the device as it passes through the hepatic and splenic flexures, potentially providing a customized method for delivering light only to inflamed segments without exposing non-inflamed segments through selective illumination of inflated segments in correlation with an individual's degree of disease.

[0199] conclusion The various methods and techniques described above provide multiple means for implementing the present invention. Of course, it should be understood that not all of the described objectives or advantages can necessarily be achieved in accordance with any particular embodiment described herein. Thus, for example, one skilled in the art will recognize that a method can be implemented to achieve or optimize one advantage or advantages taught herein without necessarily achieving other objectives or advantages taught or suggested herein. Various alternatives are mentioned herein. It should be understood that some embodiments specifically include one, another, or several features, while others specifically exclude one, another, or several features, and still others reduce a particular feature by including one, another, or several advantageous features.

[0200] Additionally, those skilled in the art will recognize the applicability of various features from different embodiments. Similarly, the various elements, features, and steps discussed above, as well as other known equivalents of each such element, feature, or step, can be used in various combinations by those skilled in the art to perform methods according to the principles described herein. Among the various elements, features, and steps, some are specifically included and others are specifically excluded in various embodiments.

[0201] Although the present application has been disclosed in the context of particular embodiments and examples, it will be understood by those skilled in the art that the embodiments of the present application extend beyond the specifically disclosed embodiments to other alternative embodiments and / or uses, as well as modifications and equivalents thereof.

[0202] In some embodiments, the terms "a," "an," and "the" and similar referents, when used in the context of describing particular embodiments of the present application (particularly in the specific context of the claims below), can be construed to cover both the singular and the plural. The recitation of ranges of values ​​herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each separate value is incorporated herein as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples or exemplary language (e.g., "etc.") provided with respect to specific embodiments herein is intended only to better illustrate the application and does not pose a limitation on the scope of the application as otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the application.

[0203] Certain embodiments of the present application are described herein. Variations on those embodiments will become apparent to those skilled in the art upon reading the foregoing description. It is contemplated that those skilled in the art will be able to employ such variations as appropriate and to practice the present application in ways other than as specifically described herein. Accordingly, many embodiments of the present application include all modifications and equivalents of the patient problems recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the present application unless otherwise indicated herein or clearly contradicted by context.

[0204] Specific embodiments of a patient's problem have been described. Other embodiments are within the scope of the following claims. In some cases, the actions recited in the claims can be performed in a different order and still achieve desirable results. Furthermore, the processes depicted in the accompanying figures do not necessarily require the particular order or sequential order shown to achieve desirable results.

[0205] All patents, patent applications, patent application publications, and other materials, such as articles, books, specifications, publications, documents, articles, and / or the like, referenced herein are incorporated by reference in their entirety and for all purposes, except for any associated prosecution file history, either of which is inconsistent or contradictory with this document, or which may have a limiting effect on the broadest scope of any claims now or in the future associated with this application document. By way of example, in the event of an inconsistency or contradiction between the explanation, definition, and / or use of a term associated with any of the incorporated materials and that associated with this document, the explanation, definition, and / or use of the term in this document shall control.

[0206] Finally, it should be understood that the embodiments of the present application disclosed herein are illustrative of the principles of the embodiments of the present application. Other modifications that may be employed may be within the scope of the present application. Thus, by way of example, and not of limitation, alternative configurations of the embodiments of the present application may be utilized in accordance with the teachings herein. Accordingly, the embodiments of the present application are not limited to those precisely as shown and described.

Claims

1. a delivery tube with a light-emitting portion, the light-emitting portion including a plurality of light-emitting segments, each of the plurality of light-emitting segments including a plurality of light sources configured to emit narrowband light at wavelengths in the ultraviolet A (UV-A) region between 335 nm and 349 nm or between 338 nm and 346 nm; a plurality of inflatable balloons connected to the delivery tube at the light emitting portion, each of the plurality of inflatable balloons covering a corresponding one of the plurality of light emitting segments and in fluid communication with a respective balloon inflation port; Equipped with each of the plurality of inflatable balloons is composed of an ultraviolet (UV) transparent material; A light delivery device for performing intraluminal phototherapy.

2. 10. The light delivery device of claim 1, wherein the plurality of inflatable balloons are configured to inflate to stabilize the light delivery device in position during UV-A light administration, provide consistent UV-A exposure to the endoluminal treatment site, and increase the uniformity of irradiance distribution to the endoluminal treatment site, thereby increasing the irradiance and / or irradiance distribution of UV-A light emitted from the plurality of light sources and delivered to the endoluminal treatment site.

3. 10. The light delivery device of claim 1, wherein the plurality of inflatable balloons are arranged in series along the length of the light emitting portion, and the distance or relative spacing between any two of the plurality of inflatable balloons is adjustable.

4. The light delivery device of claim 3 , wherein the light emitting portion comprises one or more segments that are not connected to the plurality of inflatable balloons, and the one or more segments correspond to non-illuminated areas where no light source is positioned.

5. 10. The light delivery device of claim 1, wherein the plurality of light sources are light emitting diodes (LEDs) electrically connected to a power source, and the plurality of light sources are configured to emit light outwardly from the delivery device.

6. The light delivery device of claim 1 , wherein the plurality of light sources are positioned on a cooling tube within the delivery device, the cooling tube configured to receive cooling air from a cooling system including a medical-grade compressor and a chiller.

7. a balloon control unit configured to inflate and / or deflate each of the plurality of inflatable balloons through a respective balloon inflation port. The light delivery device of claim 1 , further comprising:

8. a guidewire channel within the delivery tube and extending the entire length of the delivery tube, the guidewire channel configured to pass the light delivery device over a guidewire positioned within a lumen of a patient; The light delivery device of claim 1 , further comprising:

9. The light delivery device of claim 1 , wherein the UV transparent material is polyether block amide (PEBA), or cyclic olefin copolymer (COC), or silicone.

10. The light delivery device of claim 1 , wherein the plurality of inflatable balloons comprises at least three balloons.

11. The light source intensity is at least 1,000 microwatts / cm ２ , 1,100 microwatts / cm ２ , 2,000 microwatts / cm ２ , 2,100 microwatts / cm ２ , 2,200 microwatts / cm ２ , 2,300 microwatts / cm ２ , 2,400 microwatts / cm ２ , 2,500 microwatts / cm ２ , 2,600 microwatts / cm ２ , 2,700 microwatts / cm ２ , 2,800 microwatts / cm ２ , 2,900 microwatts / cm ２ , 3,000 microwatts / cm ２ , 3100 microwatts / cm ２ , 3,200 microwatts / cm ２ , or 1,000 to 5,000 microwatts / cm ２ 10. The light delivery device of claim 1, wherein:

12. The light delivery device of claim 1 , including a thermistor positioned within the delivery tube.

13. The light delivery device of claim 1 , wherein the delivery tube is configured as an endoscope equipped with one or more cameras for visualization of the lumen.

14. The light delivery device of claim 1 , wherein the ultraviolet (UV) transparent material provides UV transparency in a range of between 100% and 80%.

15. The light delivery device of claim 1, wherein the multiple light sources are configured to emit light only in the UV-A region and not in the UV-B or UV-C, or visible regions.

16. The light delivery device of claim 3, wherein each of the plurality of light-emitting segments covered by the inflatable balloon has a length of 5, 6, 7, 9, 10, 11, 12, 13, 14, or 15 cm.

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