Internal ultraviolet therapy

Abstract

An ultraviolet (UV) delivery device for performing in vivo UV therapy is provided. The device includes an elongated body separated at a proximal and distal end. The device also includes a cooling tube and a UV light source configured to be received at a receiving space. In some examples, the UV light source is configured to emit light with a wavelength having a desired intensity between 320 nm and 410 nm and is used in conjunction with an endotracheal tube or nasopharyngeal airway.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to U.S. Provisional Application No. 62 / 992,861, filed March 20, 2020, entitled "Internal Ultraviolet Therapy"; U.S. Provisional Application No. 62 / 993,595, filed March 23, 2020, entitled "Internal Ultraviolet Therapy"; U.S. Provisional Application No. 63 / 000,788, filed March 27, 2020, entitled "Internal Ultraviolet Therapy"; U.S. Provisional Application No. 63 / 012,727, filed April 20, 2020, entitled "Internal Ultraviolet Therapy"; and U.S. Provisional Application No. 63 / 158,350, filed March 8, 2021, entitled "Internal Ultraviolet Therapy", the entire contents of which are incorporated herein by reference. Technical Field

[0003] This invention relates to systems and methods for in vivo ultraviolet therapy. Background Technology

[0004] The following description includes information that may help in understanding the invention. This is not an admission that any information provided herein is prior art or related to the currently claimed invention, or an admission that any publication explicitly or implicitly referenced is prior art.

[0005] Infectious diseases, immune-mediated diseases, and inflammatory diseases continue to pose a global challenge. Despite significant progress over the past few decades, treatment for these diseases remains unsatisfactory. For example, many patients on ventilators may develop upper respiratory tract infections and pneumonia, which can be fatal. Patients on ventilators, for instance, are intubated using an endotracheal tube (“ETT”) and may become infected through the ventilation system (e.g., potentially developing pneumonia). Therefore, there is a need to reduce the incidence of viral, bacterial, and other infections in patients’ respiratory and other bodily systems. Summary of the Invention

[0006] A system for performing in vivo ultraviolet therapy is provided. The system includes an endotracheal tube (ETT) and a light conduit configured to be located within the ETT. The light conduit may include a light delivery section comprising a set of light-emitting diodes (LEDs) positioned to emit light outwardly along a circumference. Furthermore, the light conduit may include a cooling tube including at least one opening. The light conduit may also include an ETT connector configured for connection to the ETT.

[0007] The group of LEDs can be placed around the cooling tube, such that a portion of each LED in the group of LEDs is in direct contact with the cooling tube. Furthermore, within the cooling tube, cooling gas can flow in a first direction toward and out of the at least one opening, and can flow backward within the light guide tube in a second direction opposite to the first direction.

[0008] In some examples, each LED in the LED group may include a heat sink. In further examples, the heat sink may include one or more copper plates.

[0009] The group of LEDs emits a peak wavelength in the range of 340nm-349nm. In some examples, the peak wavelength may be in the range of 343nm to 345nm.

[0010] In some examples, the ETT connector includes a valve. The system may also include a compressor system comprising: one or more processors; an air compressor; and a dual connector comprising one or more air connectors and an electrical connector.

[0011] In some examples, the system further includes an umbilical cable comprising: at least one air passage; one or more electrical conductors; a light guide connector configured to connect to the light guide; and a compressor connector configured to connect to the compressor system.

[0012] A method for deploying a light guide in a system for performing in vivo ultraviolet therapy is also disclosed. The method includes connecting the ETT connector to the ETT; and deploying the light guide into the ETT by advancing the light guide through the valve. Furthermore, the method may include providing instructions to the controller to supply power to the group of LEDs; and supplying power to the air compressor to pump air through the air passage into the cooling pipe and out from the at least one opening.

[0013] Furthermore, the temperature sensor can be in thermal contact with the light transmission section, and in response to a temperature indication from the temperature sensor, the flow rate of the coolant can be adjusted and / or the power supplied to the group of LEDs can be adjusted.

[0014] This article also discloses a treatment method for a patient suffering from a respiratory tract infection. The method may include intubating the patient using an ETT connected to a ventilator. Furthermore, a light conduit may be connected to the ETT via an ETT connector. The light conduit includes a plurality of LEDs and cooling channels within the light conduit. While ventilating the patient, the plurality of LEDs may radiate UV-A light outwards from the light conduit along approximately the length of the light conduit from the set of LEDs to treat the patient's infection.

[0015] In one example, the light guide tube can be advanced via the ETT connector, allowing the light guide tube of the desired length to be placed within the ETT. As the light guide tube is advanced into the ETT, the control unit can instruct the light guide tube to power the group of LEDs and / or activate coolant flow to allow coolant to flow through the coolant tube. The coolant can flow out through at least one opening toward the sealed proximal end of the light guide tube (opposite to the distal end connected to the ETT) and push backward along the length of the group of LEDs, thereby cooling the LEDs. Warm air can then be returned to the control unit or vented to the atmosphere via a warm air duct.

[0016] Additional features and advantages of the invention will be set forth in the following description and will be apparent in part from the description; or may be learned by practicing the principles disclosed herein. The features and advantages of the invention can be realized and obtained by the means and combinations particularly pointed out in the appended claims. These and other features of the invention will become fully apparent from the following description and the appended claims, or may be learned by practicing the principles set forth herein. Attached Figure Description

[0017] To illustrate how the above-described invention, its advantages, and features can be obtained, a more specific explanation of the above principles will be given with reference to specific examples shown in the accompanying drawings. These drawings illustrate only exemplary aspects of the invention and should not be considered as limiting its scope. These principles are explained and illustrated in more detail using the following drawings:

[0018] Figure 1A A cross-sectional view of an exemplary UV emitting device inserted into a patient's colon according to the principles of the present invention is shown;

[0019] Figure 1B A cross-sectional view of an exemplary UV emitting device inserted into a patient's vagina according to the principles of the present invention is shown;

[0020] Figure 1C A cross-sectional view of an exemplary UV emitting device inserted into a patient's trachea according to the principles of the present invention is shown;

[0021] Figure 1DA cross-sectional view of an exemplary UV emitting device inserted into a patient's nasopharynx according to the principles of the present invention is shown;

[0022] Figure 1E A front view of an exemplary UV emitting device inserted into a patient's trachea according to an embodiment of the present invention is shown;

[0023] Figure 1F It shows Figure 1E The amplified portion;

[0024] Figure 2 A schematic diagram of an exemplary UV emitting device incorporating an LED according to the principles of the present invention is shown;

[0025] Figure 3 A schematic diagram of an exemplary UV emitting device including a cold cathode according to the principles of the present invention is shown;

[0026] Figure 4 A schematic diagram of a UV spectrum according to the principles of the present invention is shown;

[0027] Figure 5 A cross-sectional view of an exemplary UV emitting device inserted into the rectum and sigmoid colon of a patient according to the principles of the present invention is shown;

[0028] Figure 6 A cross-sectional view of an exemplary UV emitting device inserted into a patient's colon according to the principles of the present invention is shown;

[0029] Figure 7 A cross-sectional view of a UV emitting device inserted into a patient's esophagus and stomach according to the principles of the present invention is shown.

[0030] Figure 8 A cross-sectional view of an exemplary UV emitting device passing through a patient's digestive system according to the principles of the present invention is shown;

[0031] Figure 9 A side view of an exemplary light source accessory according to the principles of the present invention is shown;

[0032] Figure 10 An exemplary UV emitting device according to the principles of the present invention is shown;

[0033] Figure 11 An exemplary Foley conduit including an exemplary UV emitting device is shown according to the principles of the present invention;

[0034] Figure 12A The growth curves of E. coli are shown when implementing the exemplary UV emitting device of the present invention;

[0035] Figure 12B The growth curves of E. coli are shown when implementing the exemplary UV emitting device of the present invention;

[0036] Figure 13 An exemplary UV emitting device implemented in the mouse colon according to the principles of the present invention is shown;

[0037] Figure 14A and Figure 14B An exemplary UV emitting device of the present invention, inserted into the vaginal cavity of a mouse according to the principles of the present invention, is shown;

[0038] Figure 15A Growth curves of a liquid culture containing E. coli are shown when implementing an exemplary UV emitting device of the present invention;

[0039] Figure 15B An exemplary UV emitting device of the present invention implemented on a liquid culture containing E. coli is shown;

[0040] Figure 16 Growth curves of a liquid culture containing E. coli are shown when implementing an exemplary UV emitting device of the present invention;

[0041] Figure 17A and Figure 17B Growth curves of a liquid culture containing E. coli are shown when implementing an exemplary UV emitting device of the present invention;

[0042] Figure 18 Growth curves of a liquid culture containing E. coli are shown when implementing an exemplary UV emitting device of the present invention;

[0043] Figure 19 Growth curves of a liquid culture containing E. coli are shown when implementing an exemplary UV emitting device of the present invention;

[0044] Figure 20 Growth curves of a liquid culture containing E. coli are shown when implementing an exemplary UV emitting device of the present invention;

[0045] Figure 21A and Figure 21B Growth curves of liquid cultures containing E. coli are shown when implementing an exemplary UV emitting device of the present invention.

[0046] Figure 22 An exemplary UV emitting device according to an embodiment of the present invention is shown;

[0047] Figure 23 This illustrates the mounting to the gripping element 200 according to an embodiment of the invention. Figure 22 Exemplary UV emitting device;

[0048] Figure 24An exemplary UV emitting device according to an embodiment of the present invention is shown;

[0049] Figure 25 An exemplary UV emitting device according to an embodiment of the present invention is shown;

[0050] Figure 26 An exemplary UV emitting device according to an embodiment of the present invention is shown;

[0051] Figure 27 An exemplary UV emitting device according to an embodiment of the present invention is shown;

[0052] Figure 28 An exemplary UV emitting device according to an embodiment of the present invention is shown;

[0053] Figure 29 An exemplary UV emitting device according to an embodiment of the present invention is shown; and

[0054] Figure 30 An exemplary process for performing in vivo ultraviolet therapy according to an embodiment of the present invention is shown.

[0055] Figure 31 An exemplary procedure for performing in vivo ultraviolet therapy in relation to ETT according to an embodiment of the present invention is shown.

[0056] Figure 32 A schematic diagram of a chip-on-board (COB) mini bar used as a UV LED light source according to an embodiment of the present invention is shown;

[0057] Figure 33 A schematic diagram of an example of a UV light guide tube comprising one or more COB mini-rods contained within an outer tube, according to an embodiment of the present invention, is shown.

[0058] Figure 34A A schematic diagram of an optical fiber system connected to a UV LED light source according to an embodiment of the present invention is shown;

[0059] Figure 34B and Figure 34C A schematic diagram of multiple UV LED light sources for implanted fiber optic systems according to an embodiment of the present invention is shown;

[0060] Figure 35A Planar and tubular configurations of flexible printed circuit boards (PCBs) used in conjunction with one or more UV LED light sources are shown according to embodiments of the present invention.

[0061] Figure 35B An example UV light guide comprising one or more flexible PCBs according to an embodiment of the present invention is shown;

[0062] Figure 35C An embodiment of the invention is shown in, for example, Figure 35B Exemplary heat sinks implemented in UV light guides, such as UV light guides;

[0063] Figure 36A An exemplary UV light guide including a plurality of LEDs and a plurality of linear reflectors is shown according to an embodiment of the present invention;

[0064] Figure 36B An exemplary configuration of a plurality of LEDs and a plurality of linear reflectors according to an embodiment of the present invention is shown;

[0065] Figure 36C The invention illustrates embodiments in, for example, Figure 36B Exemplary heat sinks implemented in UV light guides, such as UV light guides;

[0066] Figure 36D An exemplary light distribution in an exemplary UV LED light source comprising a plurality of LEDs and a plurality of linear reflectors, according to an embodiment of the present invention, is shown;

[0067] Figure 37 An exemplary beam angle of a UV LED light source according to an embodiment of the present invention is shown;

[0068] Figure 38 A block diagram illustrating an exemplary safety assessment process using human cell lines according to an embodiment of the present invention is shown;

[0069] Figure 39 and Figure 40 Bar graphs illustrating cell growth of HeLa cells and alveolar cells after exposure to UVA light using an exemplary system according to the present invention are shown respectively.

[0070] Figure 41 A block diagram illustrating an exemplary safety assessment process for HeLa cell lines at higher UVA doses according to an embodiment of the present invention is shown;

[0071] Figure 42 A bar graph illustrating cell growth of HeLa cells after exposure to UVA light at a high dose using an exemplary system according to the present invention is shown.

[0072] Figure 43 A block diagram illustrating an example procedure for evaluating fluorescently labeled Coxsackie virus pretreatment prior to infection of HeLa cell lines, according to an embodiment of the present invention, is shown.

[0073] Figure 44A and Figure 44BFluorescence images of HeLa cells transfected with fluorescently labeled Coxsackievirus using an exemplary system according to the present invention are shown. The fluorescently labeled Coxsackievirus was pretreated with UVA prior to transfection of the HeLa cells.

[0074] Figure 45 A block diagram illustrating an exemplary evaluation of HeLa cell lines pretreated with UVA prior to transfection with Coxsackievirus, according to an embodiment of the present invention, is shown.

[0075] Figure 46A and Figure 46B Exemplary fluorescence images of HeLa cells transfected with fluorescently labeled Coxsackievirus using an exemplary system according to the present invention are shown. The HeLa cells were pretreated with UVA prior to Coxsackievirus transfection.

[0076] Figure 47 A block diagram illustrating an example procedure for evaluating the efficacy of UVA phototherapy on Coxsackievirus-transfected alveolar cells is shown.

[0077] Figure 48 Fluorescent images of the effects of Coxsackievirus-transfected alveolar cells and UVA treatment on the transfected alveolar cells according to an embodiment of the present invention are shown.

[0078] Figure 49 A block diagram illustrating an example procedure for evaluating the effect of UVA phototherapy on Coxsackievirus-transfected HeLa cells is shown.

[0079] Figure 50 A bar graph illustrating the effect of UVA treatment according to an embodiment of the present invention on the survival of Coxsackievirus-transfected HeLa cells is shown;

[0080] Figure 51 The images show a phase comparison of UVA-treated and untreated ciliated tracheal epithelial cells (HTeC) transfected with coronavirus 229E according to an embodiment of the present invention.

[0081] Figure 52 , Figure 53 and Figure 54 A bar graph illustrating the survival rate of ciliated tracheal epithelial cells depending on coronavirus 229E transfection and UVA light treatment according to an embodiment of the present invention is shown.

[0082] Figure 55 The figure shows a table illustrating the intensity and exposure duration of UVA light applied to a bacterial culture in one example.

[0083] Figure 56The illustration shows a table illustrating bacterial counts over time during UV light exposure, as in one example.

[0084] Figure 57 Growth curves showing bacterial counts over time during UV light exposure using an exemplary system according to the invention are illustrated.

[0085] Figure 58A Images of bacterial culture dishes exposed to UV light over time are shown compared to a control group.

[0086] Figures 58B-56 The figures illustrate growth curves showing the counts of E. coli bacteria exposed to various intensities of UV light using an exemplary system according to the invention over time.

[0087] Figure 58F (deliberately omitted).

[0088] Figures 58G-58J The illustrations show growth curves that illustrate the counts of Pseudomonas aeruginosa bacteria over time when exposed to UV light of various intensities using an exemplary system according to the invention.

[0089] Figure 58K-Figure 58L The growth curves showing logarithmic reduction at various intensities at 20 minutes and 40 minutes respectively using an exemplary system according to the invention are shown.

[0090] Figure 58M Growth curves showing the reduction in E. coli colony diameter at various intensities and treatment times using an exemplary system according to the invention are illustrated.

[0091] Figure 58N Growth curves showing the reduction in Pseudomonas aeruginosa colony diameter at various intensities and treatment times using an exemplary system according to the present invention are illustrated.

[0092] Figure 59A The illustration shows a bar graph depicting cell growth during exposure to UVA light using an exemplary system according to the present invention.

[0093] Figure 59B The illustration shows a bar graph depicting cell growth during exposure to UVA light using an exemplary system according to the present invention.

[0094] Figure 59C The illustration shows a bar graph depicting cell growth during exposure to UVA light using an exemplary system according to the present invention.

[0095] Figure 59DThe illustration shows a bar graph demonstrating that no DNA damage to cells occurred during exposure to UVA light using an exemplary system according to the present invention.

[0096] Figure 59E The illustration shows a bar graph demonstrating that no DNA damage to cells occurred during exposure to UVA light using an exemplary system according to the present invention.

[0097] Figure 59F The illustration shows a bar graph demonstrating that no DNA damage to cells occurred during exposure to UVA light using an exemplary system according to the present invention.

[0098] Figure 60 Fluorescent images illustrating the effect of UVA exposure on group B Coxsackievirus pretreated with UVA using an exemplary system according to the present invention are shown.

[0099] Figure 61 Fluorescent images illustrating the effect of narrow-band (NB)-UVA exposure using an exemplary system according to the present invention on HeLa cells transfected with group B Coxsackievirus are shown.

[0100] Figure 62 A bar graph illustrating the growth of virus-transfected cells during exposure to UV light using an exemplary system according to the present invention is shown.

[0101] Figure 63 The figure shows a bar graph illustrating the cell count of transfected cells 72 hours after UV light application according to an exemplary system of the present invention, compared with the control group;

[0102] Figure 64 A schematic overview of a phototherapy system according to an embodiment of the present invention is shown;

[0103] Figure 65 A schematic diagram of a UV light guide tube according to an embodiment of the present invention is shown;

[0104] Figure 66 It shows Figure 65 A schematic diagram of the magnified portion of the UV light guide tube;

[0105] Figure 67 An embodiment of the present invention is shown, comprising one or more depth markers. Figure 65 A schematic diagram of a UV light guide tube;

[0106] Figure 68 The following is illustrated: a deployment configuration within an ETT according to an embodiment of the present invention. Figure 65 A schematic diagram of a UV light guide tube;

[0107] Figure 69 It shows Figure 68A schematic diagram of the magnified portion of the UV light guide tube;

[0108] Figure 70 A schematic diagram of the light-emitting portion of a UV light guide according to an embodiment of the present invention is shown;

[0109] Figure 71 A schematic diagram of the beam angle of a UV-LED in a UV light guide according to an embodiment of the present invention is shown;

[0110] Figure 72 A schematic diagram of the light-emitting portion of a UV light guide according to an embodiment of the present invention is shown;

[0111] Figure 73 A table depicting baseline characteristics of subjects in human studies of UVA treatment using an exemplary system according to the present invention is shown;

[0112] Figure 74 A graph depicting the change in intratracheal SARS-CoV-2 load during UVA treatment in a human study using an exemplary system according to the present invention is shown.

[0113] Figure 75 The diagram depicts baseline (day 0), day 5, and day 6 of UVA treatment. Figure 74 The table showing the corresponding viral load; and

[0114] Figure 76 It shows in Figure 73 and Figure 74 A summary of the timeline and key events of subjects in human studies. Detailed Implementation

[0115] definition

[0116] Unless otherwise defined, the 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 pertains. Szycher's Dictionary of Medical Devices, CRC Press, 1995, can provide useful guidance for many of the terms and phrases used herein. Those skilled in the art will recognize many methods and materials similar to or equivalent to those described herein, which can be used in the implementation of this invention. In fact, this invention is by no means limited to the methods and materials specifically described. For example, the figures illustrate the invention primarily in the gastrointestinal tract, but as shown throughout, the disclosed systems and methods can be used in other applications.

[0117] In some embodiments, characteristics such as size, shape, relative position, etc., used to illustrate and claim certain embodiments of the invention should be understood to be modified by the term "about".

[0118] As used in this article, “ETT” refers to an endotracheal tube, which is a flexible tube that is placed through the patient’s mouth into the airway to help the patient breathe when connected to a ventilator.

[0119] As used in this article, “NPA” refers to the nasopharyngeal airway, which is a flexible tube placed through the nasal passage and terminates at the base of the tongue to help maintain an open airway.

[0120] As used herein, the term "LED" refers to a light-emitting diode, a semiconductor light source that emits light across a wide range of visible and invisible spectra. LEDs typically have an emission spectrum comprising a set of wavelengths whose intensity varies across the range of their emission spectrum and generally follows a bell-shaped or similar intensity curve within that wavelength range. A particular LED is usually described using the wavelength of its peak emission intensity, or the wavelength at which the LED emits its highest radiant intensity.

[0121] Therefore, LEDs typically emit light within a wavelength range, and this range of wavelengths emitted at a threshold intensity (in some examples, a percentage of the LED's maximum intensity) can also be used to describe a particular LED. For example, a given LED may emit light with at least 10% of its maximum emission intensity only between wavelengths of 335 nm and 345 nm. Below 335 nm and above 345 nm, the LED's emission intensity may be less than 10% of the LED's peak intensity emission wavelength ("peak wavelength" in this context), and in some cases, the emission intensity may be too low to be therapeutically relevant. Therefore, for many therapeutic applications, only wavelengths between 335 nm and 345 nm will have a therapeutic effect on a particular LED.

[0122] Therefore, the wavelength range described herein can be a range of wavelengths that are therapeutically effective or significantly effective for a specific therapeutic application, duration, and emission intensity, as delivered by an LED to the treatment site (or based on the emission power emitted by the LED). In some examples, the wavelength range can be a range of wavelengths emitted by an LED having an intensity of 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 emission intensity.

[0123] Therefore, this paper discloses the emission spectral ranges of various LED light sources, which correspond to the range of threshold intensity percentages of the LED's maximum emission intensity. Examples of various LED spectral emission ranges and peak emission intensity wavelengths for commercially available LEDs are described in Filippo et al.'s "LEDs: Sources and Intrinsically Bandwidth-Limited Detectors," the entire contents of which are incorporated herein by reference.

[0124] Various examples of the invention will now be described. The following description provides specific details for a thorough understanding and implementation of these examples. However, those skilled in the art will understand that the invention can be practiced without many of these details. Similarly, those skilled in the art will understand that the invention may include many other obvious features not described in detail herein. Furthermore, some well-known structures or functions may not be shown or described in detail below to avoid unnecessarily obscuring the related description.

[0125] Even when used in conjunction with the detailed description of certain specific examples of the invention, the terminology used below should be interpreted in its broadest and most reasonable manner. In fact, some terms may even be emphasized below; however, any term intended to be interpreted in any limiting manner will be disclosed and explicitly defined in this detailed description section.

[0126] While this specification contains numerous specific implementation details, these should not be construed as limiting the scope of any invention or what may be claimed, but rather as descriptions of features specific to particular embodiments of a particular invention. Certain features described in the context of individual embodiments in this specification 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 separately in multiple embodiments or in any suitable sub-combination. Furthermore, although features may be described above as functioning in certain combinations, and even initially so stated in the claims, in some cases one or more features from a claimed combination may be removed from said combination, and the claimed combination may be for sub-combinations or variations thereof.

[0127] Similarly, while operations may be illustrated in a specific order in the accompanying drawings, this should not be construed as requiring such operations to be performed in the specific order shown or sequentially, or to perform all of the shown operations to achieve the desired result. In some cases, multitasking and parallel processing may be advantageous. Furthermore, the separation of various system components in the above embodiments should not be construed as requiring such separation in all embodiments, and it should be understood that the program components and systems can typically be integrated together in a single software product or packaged into multiple software products.

[0128] Overview

[0129] While UV light in the UVA and UVB range is commonly used to treat skin conditions, its application in the broader treatment of infections or inflammation within the human body has not yet been developed. This invention describes a system for emitting therapeutic doses of UV light via catheters, capsules, endoscopes, tubes, or ports, which can be used to control internal infections and inflammatory conditions within a patient. The UV light sources disclosed herein are intended to provide a safe and effective alternative to antibiotics and anti-inflammatory / immunosuppressive drugs for various internal tubes in patients (e.g., colon, vagina, trachea).

[0130] In some examples, for certain indications and treatments, only UVA light or only UVB light may be emitted. For example, the UV light source may have wavelengths centered at or near 335 nm, 340 nm, or 345 nm as disclosed herein. In other embodiments, the UV light source may emit wavelengths between 320 nm and 410 nm, and / or have peak emission intensity within this range. It should be understood that a variety of wavelengths can be provided using these systems and methods. In some examples, the wavelength range provided may be the highest possible wavelength that is effective for treatment at a given application intensity and duration.

[0131] Figure 1A An example of a UV light management system is shown, including a delivery tube 100, several UV light sources 150, and a power supply 120 to power the system. Thus, as shown, a caregiver (e.g., a physician) can guide the delivery tube 100 to the patient's colon. Once guided to the patient's intended treatment target, the power supply 120 can be powered to emit UV light from the light sources 150 onto the treatment target (e.g., the colon).

[0132] Figure 1B An example of a UV light management system including a delivery tube 100, several UV light sources 150, and a power supply 120 is shown. Thus, a caregiver (e.g., a physician) can guide the delivery tube 100 into the patient's vagina. Once guided into the patient's vagina, the delivery tube 100 can be energized by the power supply 120 to emit therapeutic light (e.g., UV light) into the vaginal cavity. The UV light sources disclosed herein are intended to provide a safe and effective alternative to antibiotics and anti-inflammatory / immunosuppressive drugs for the colonic and / or vaginal regions.

[0133] Figure 1CAn example of a UV light management system is shown, including a delivery tube 100, a UV light source 150, a power supply 120, and a control system. The control system provides power and controls the duration and / or intensity of the treatment. Thus, as shown, a caregiver (e.g., a physician) can guide the delivery tube 100 into the patient's trachea during ventilation. Once guided into the patient's trachea, the power supply 120 can be energized to deliver power to the light source 150 through the delivery tube 100 (e.g., via a wired connection), thereby emitting therapeutic light (e.g., UV light) into the trachea and / or other airways.

[0134] For example, systems and methods for providing internal ultraviolet therapy have been developed in conjunction with the endotracheal tube (ETT) disclosed herein. Thus, the delivery tube 100 can be guided within the ETT during patient ventilation. In other examples, the delivery tube 100 may be connected to or built into the ETT, or the ETT may have a light source 150 housed within the ETT. Thus, the light source 150 can be placed within the tube and / or the ETT such that the UV light source 150 radiates respiratory tissues in the tracheal airway surrounding the ETT.

[0135] Figure 1D An example of a UV light management system is shown, including a delivery tube 100, a UV light source 150, a power supply 120, and a control system. The control system provides power and controls the duration and / or intensity of the treatment. Thus, as shown, a caregiver (e.g., a physician) can guide the delivery tube 100 into the patient's nasopharynx. Once guided into the patient's nasopharynx, the power supply 120 can be energized to deliver power to the light source 150 through the delivery tube 100 (e.g., via a wired connection), thereby emitting therapeutic light (e.g., UV light) into the nasopharynx and / or other airways.

[0136] For example, systems and methods have been developed to provide internal ultraviolet therapy by incorporating a nasopharyngeal airway (NPA), as described herein. Thus, a delivery tube 100 can be guided within the patient's NPA. In other examples, the delivery tube 100 can be connected to or built into an NPS, or the NPA can have a light source 150 housed within it. Therefore, the light source 150 can be placed within the tube and / or the NPA, such that the UV light source 150 radiates respiratory tissues in the nasopharynx surrounding the NPA.

[0137] Figure 1E A front view of a UV light management system comprising multiple light sources 150 within the patient's trachea is shown. Figure 1F yes Figure 1E The magnified portion shows how the UV light intensity changes with increasing distance from the light source (150°). Therefore, in some examples, the power supplied to each LED can be individually controlled based on the distance from the tissue to be irradiated.

[0138] Conveying system

[0139] A delivery tube / rod 100 is provided for delivering therapeutic UV light to various parts of the body. The delivery tube / rod may include at least one UV light source 150. The delivery tube / rod 100 may be a catheter, endoscope, capsule (for swallowing or suppository), or any other medical device configured to receive the UV light source 150.

[0140] In some examples, the UV delivery tube 100 may be configured as a catheter and guided within the ETT or NPA during the patient's breathing or other treatment. In some embodiments, the UV delivery tube / rod 100 is configured as an endoscope inserted transrectally or orally and guided to an appropriate area to deliver anti-inflammatory or other therapeutic doses of UV light. In another embodiment, the UV delivery tube / rod 100 may be configured as a catheter inserted into an artery, urethra, vagina and urinary tract, ear canal, airway, etc. In yet another embodiment, the UV delivery tube / rod 100 is configured as an indwelling catheter inserted into the patient's bladder. In some embodiments, the inflatable balloon catheter may include a UV light source 150 to emit UV light within an internal organ with a passage (e.g., vagina, rectum, gastroesophageal junction, stomach, bile duct, etc.) or other suitable passage. In some embodiments, the UV light source 150 may be configured as a caregiver's glove. This configuration may facilitate the emission of UV light into the patient's orifice (e.g., mouth, rectum, vagina, or others) for shorter treatment duration.

[0141] In some embodiments, the UV light source 150 is permanently mounted on the delivery tube / rod 100. In other embodiments, the delivery tube / rod 100 is configured such that the UV light source 150 is configurable and can be installed and removed according to the physician's preference. The delivery tube / rod 100 may include a hollow interior to allow electrical connection to the UV light source 150. In alternative embodiments, the UV light source 150 may be wireless and capable of coupling to the delivery tube / rod 100.

[0142] light source

[0143] Depending on the delivery pipe 100 or other delivery device, various light sources 150 capable of emitting UV light can be used. For example, Figure 2 An embodiment of a flexible delivery tube 100 (e.g., catheter, endoscope, etc.) including strings of LED light sources 150 distributed along the tube 100 is shown. In other examples, other suitable light sources 150 capable of emitting UV light may be used. The light sources 150 are attached together by electrical connections and connected to a power supply 120. LED light sources 150 may be advantageous because their small size and low power requirements allow them to be placed along the delivery tube 100.

[0144] Therefore, if the light source 150 is positioned along the delivery tube 100, the light source 150 can deliver UV light to a large delivery area within the patient's body. Thus, the target treatment area can be relatively large to treat inflammatory diseases that may affect a large portion of the colon.

[0145] Figure 3 An example of a delivery tube 100 utilizing a cold cathode-based light source 150 connected to a power supply 120 is shown. In this embodiment, the cold cathode light source 150 delivers light through a transparent, flexible delivery tube 100. This embodiment may include an inert gas filling the delivery tube (or vacuum tube) 100. The delivery tube 100 may include, for example, a cold cathode tube. The delivery tube 100 may include any cathode emitting element that is not electrically heated by a filament. For example, a cold cathode fluorescent lamp may utilize mercury vapor discharge to emit ultraviolet light.

[0146] However, in most implementations, for safety reasons, the gas used in the tube should be inert. For example, a 12-volt power supply can be used to energize neon vapor to generate sufficient UV light. In other examples, other power supplies with various voltages and / or currents will be used to generate sufficiently strong light at the current wavelength.

[0147] In some embodiments, the light source 150 can emit X-rays. For these embodiments, the system may include a vacuum tube or an X-ray tube.

[0148] Power supply 120 may include an on / off switch or other controls to turn light source 150 on and off. In some examples, the power supply will include the ability to turn on the UV light source at various intensities or to modulate the intensity over time depending on the therapeutic application. The power supply may differ for different types of UV light source 150. For example, the power requirements of an LED implementation may be less than those of a cold cathode implementation.

[0149] UV range

[0150] Figure 4 The disclosed apparatus and methods illustrate the UV ranges that can be implemented. For example, the light source may deliver light only in the UVA and UVB ranges, without delivering light in the UV-C range. In other examples, the system and methods may deliver light in all three UV ranges, or also deliver light in the visible spectrum. In some examples, for certain indications and treatments, only UVA light or only UVB light may be emitted. As described above, the light source may have a maximum intensity wavelength centered at or near 335 nm, 340 nm, or 345 nm. In other embodiments, the light source 150 may transmit light with wavelengths between 320 nm and 410 nm, 250 nm and 400 nm, or other suitable ranges described herein.

[0151] In some examples, the range of wavelengths applied can be (considering the intensity and duration of the therapeutic application) the longest wavelength range that is effective for a particular application. For example, the shorter the wavelength, the more likely the treatment is to damage the patient's body cells or tissues. Therefore, the longest effective wavelength would be the safest for application.

[0152] In some examples, a light source centered at 345 nm or 340 nm (or surrounding wavelengths) may be optimal, as lower / shorter wavelengths are more harmful closer to the UV-C range. For example, the shorter the wavelength, the more energy it possesses, and the more likely it is to damage the patient's tissues and DNA. In some examples, the longest wavelength that still provides sufficient antibacterial activity while remaining the safest wavelength to be effective may include one or more of the following: 335 nm, 336 nm, 337 nm, 338 nm, 339 nm, 340 nm, 341 nm, 342 nm, 344 nm, 345 nm, 346 nm, 347 nm, 348 nm, 349 nm, or 350 nm. Thus, the light source 150 disclosed herein is capable of emitting light with one or more of the aforementioned wavelengths at a therapeutically significant intensity. In some examples, the light source may emit UVA with a peak wavelength in the range of 343 nm to 345 nm, which can be used for phototherapy of patients inserted into an ETT connected to a ventilator. Example light guides may include a light source assembly that emits UVA light with a peak wavelength in the range of 343 nm to 345 nm. Furthermore, light can be emitted at 1000 μWatt / cm² via a light guide located within an ETT tube connected to a ventilator. 2 and 5000 μWatt / cm 2 Intensity transfer light therapy between them.

[0153] In some examples, the light source may be an LED with a peak wavelength of 335nm, 336nm, 337nm, 338nm, 339nm, 340nm, 341nm, 342nm, 343nm, 344nm, 345nm, 346nm, 347nm, 348nm, 349nm, 350nm, 351nm, 352nm, 353nm, 354nm, or 355nm. In some examples, the peak wavelength of the LED may have an error of + / -3nm, 2nm, or 1nm. In some examples, the LED may emit light with significant intensity in the range of + / -2nm, 3nm, 4nm, 5nm, or 6nm around its peak intensity emission wavelength. Therefore, in some examples, the wavelength range of the LED or other light source may be from 340nm to 350nm (e.g., including the wavelength range with significant emission intensity).

[0154] In some examples, the light source can be multiple LEDs, each of which emits a peak wavelength of 335nm, 336nm, 337nm, 338nm, 339nm, 340nm, 341nm, 342nm, 343nm, 344nm, 345nm, 346nm, 347nm, 348nm, 349nm, 350nm, 351nm, 352nm, 353nm, 354nm, or 355nm. In some examples, the LEDs can emit light with significant intensity in the range of + / - 2nm, 3nm, 4nm, 5nm, or 6nm around their peak intensity emission wavelength.

[0155] In some examples, each LED can emit light with a beam angle between 100 and 150 degrees. In one example, each LED can emit light with a beam angle between 120 and 135 degrees.

[0156] Treatment plan

[0157] The procedure described herein can be used to treat many different inflammatory and infectious diseases. Therefore, different amounts or durations of UV radiation doses can be administered based on factors such as: (1) disease type, (2) light source type, (3) light source power, (4) light source UV range, and (5) severity of infection or inflammation. For example, in some embodiments, the administration time will be determined by capsule digestibility, and other factors (e.g., light source power, UV range, etc.) can be manipulated to change the dose.

[0158] In other examples, light therapy 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 minute range between 10 and 160 minutes, or other suitable durations. Furthermore, the method of the present invention may include administering treatment 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. Depending on the application and other factors related to treatment efficacy, the light source intensity can be at least 1,000 μWatt / cm². 2 1,100 μWatt / cm 2 2,000 μWatt / cm 2 2,100 μWatt / cm 2 2,200 μWatt / cm 2 2,300 μWatt / cm 22,400 μWatt / cm 2 2,500 μWatt / cm 2 2,600 μWatt / cm 2 2,700 μWatt / cm 2 2,800 μWatt / cm 2 2,900 μWatt / cm 2 3,000 μWatt / cm 2 3100 μWatt / cm 2 3,200 μWatt / cm 2 1,000 to 5,000 μWatt / cm 2 Or other suitable strength. The inventors have demonstrated that at up to 5,000 μWatt / cm 2 At certain intensities, the application of UVA light is safe. In some examples, the light will be delivered continuously, and in others, the light will be incorporated into pulsed therapy.

[0159] Depending on the intensity and the target bacteria, the light source 150 can be positioned at varying distances from the target. For example, in some cases, the light source 150 may need to be within a range of 0 to 2 cm from E. coli in order to utilize 2000 μWatt / cm. 2 The intensity kills E. coli (but not at 2.8 cm or 3.5 cm). In some examples, the intensity can reach 1000 μWatt / cm. 2 Up to 5000 μWatt / cm 2 The distance to the target tissue can be 0cm to 1cm, 0cm to 1.5cm, 0cm to 2cm, 0cm to 2.5cm, 0cm to 3.0cm, 0cm to 3.5cm, 0cm to 4.0cm, or other similar and suitable ranges, depending on the light intensity and the target pathogen. In other examples, the time, distance, wavelength, and intensity required for viruses and other targets may differ.

[0160] Example

[0161] The following embodiments are provided to better illustrate the claimed invention and are not intended to be construed as limiting the scope of the invention. References to specific materials or steps are for illustrative purposes only and are not intended to limit the invention. Those skilled in the art can develop equivalent methods or reactants without exercising inventive capacity and without departing from the scope of the invention.

[0162] Gastrointestinal tract

[0163] Figure 5 and Figure 6Example applications for treating diseases of the colon and / or rectum are shown. For example, Figure 5 The illustration shows a delivery tube 100, including a light source 150, that can be inserted into the colon by a caregiver through the anus. The delivery tube 100 can then be guided to a treatment site, such as the colon, a portion or majority of the intestine (see, for example...). Figure 6 ) or via the mouth to the stomach (see, for example) Figure 7 Then, the power supply (or light source) 120 can be turned on to irradiate the treatment area with UV light.

[0164] In some instances, this can be used to treat a variety of inflammatory diseases, including ulcerative colitis and Crohn's colitis, IBD, infectious diseases, and other diseases described more fully in this article. As shown, depending on the size, location, and type of the disease, the delivery tube 100 may include a different number of light sources 150, which may be embedded in or contained within certain portions or lengths of the delivery tube 100.

[0165] Figure 7 An embodiment in which an endoscope or other delivery tube 100 is inserted into the stomach via the esophagus through the mouth is shown. In this example, an infection or inflammatory disease in the stomach can be treated with a UV light source 150.

[0166] colonoscopy

[0167] Figure 13 An example of a UV emitting device used in a mouse colonoscopy is shown. The colonoscopy and UV application were performed safely. Parameters included 1,100 μWatt / cm². 2 A normal colonoscopy is performed 72 hours after 10 minutes and 30 minutes of UV exposure.

[0168] GI therapy can include the following exemplary applications:

[0169] 1. Treatment of ulcerative colitis, Crohn's disease, acute / chronic pouchitis, and other chronic inflammatory bowel diseases (IBD).

[0170] 2. Treatment of non-IBD-related proctitis

[0171] 3. Treatment of fistulas related to IBD or non-IBD

[0172] 4. Treatment of inflammatory stenosis

[0173] 5. Treatment of colitis under a microscope

[0174] 6. Treatment of infectious diarrhea with UV-luminescent capsules

[0175] 7. Treatment of refractory Helicobacter pylori and MALT lymphoma

[0176] 8. Treatment of esophageal lichen planus and pemphigus vulgaris

[0177] 9. Treatment of refractory Clostridium difficile

[0178] 10. Treatment of colonic atony, tropical stomatitis-like diarrhea, gluten intolerance, small intestinal bacterial overgrowth, appendicitis following bone marrow transplantation infection, pseudopolyps (similar to nasal polyps), and radiation enteritis.

[0179] 11. Treatment of Barrett's esophagus with or without dysplasia

[0180] 12. Treatment of hepatic encephalopathy using daily UV light capsules

[0181] 13. Treatment of blind climbing syndrome in Roux-en-Y patients by placing an ILT (internal phototherapy) catheter through a PEG into the residual stomach.

[0182] 14. Treatment of perianal fistulas with transparent setons that emit UV light.

[0183] 15. Reduce the infection rate associated with percutaneous feeding tubes or straws.

[0184] 16. Treatment of gastrointestinal cancers limited to the mucosa and submucosa

[0185] 17. Treatment of hepatobiliary infections, inflammations, and cancers limited to the mucosa and submucosa.

[0186] capsule

[0187] In some embodiments, the delivery device is shaped as a capsule instead of a delivery tube / rod 100. In this embodiment, the capsule is inserted into the patient's body through the mouth or anus. The capsule is capable of emitting light for a period of time. For example, the capsule may include a smooth, clear or translucent polymer or other biocompatible coating to allow passage. In some examples, the capsule may include a light source 150 and a power source 120. The power source 120 may include, for example, a small battery. In some embodiments, the capsule can be configured and secured to internal organs to provide extended exposure time.

[0188] In some implementations, the capsule is configured such that UV light is positioned to emit light in all directions from the capsule. Therefore, as the capsule passes through the digestive system, it will emit UV light in all directions until the capsule is expelled from the body.

[0189] Figure 8An example of a system using a swallowable capsule 800 as a delivery device is shown. The capsule 800 may include a light source 150 and a power supply 120 for powering the light source 150. In some examples, the capsule will be made of a transparent material, or a portion thereof will be made of a transparent material to allow light to radiate through the capsule. The capsule may contain a tracking device to assess its position within the gastrointestinal tract. The capsule delivery system may be clamped in a hollow organ for continuous or intermittent controlled delivery.

[0190] In some examples, the capsule may be the size of a pill or smaller and may be orally edible. The capsule may include a timer for turning the UV light source on and off when the capsule reaches or is most likely to reach a specific part of the digestive tract. For example, the capsule may contain a simple timer to open the capsule after 30 minutes, one hour, or two hours. Alternatively, the capsule may not turn on the light source until it reaches the digestive tract to treat IBS or other infectious or inflammatory conditions.

[0191] Light guide tube

[0192] In some examples, the light source 150 may be placed inside the delivery tube 100 (e.g., an LED), and in other examples, the light source 150 may be placed externally or connected to the proximal end of the delivery tube 100 via an interface. Thus, in some examples, the delivery tube 100 may be made of optical fiber or other light-guiding material to propagate light from the light source 150 downwards along the delivery tube 100, thereby allowing it to be emitted to the treatment site.

[0193] For example, such as Figure 9 and Figure 10 As shown, the UV light management system may include a delivery rod 940, a UV light source 950, and a light source accessory 900, wherein the light source accessory 900 is configured to connect between the UV light source 950 and the delivery rod 940. The delivery rod 940 may include a borosilicate section 930, which omits UV-C from the spectrum, followed by a section made of pure silica (quartz), thereby extending the transmission distance of UV A / B with minimal loss.

[0194] For example, using only pure quartz segments has been shown to result in significant UV-C light emission (e.g., 4,300 μWatt / cm). 2 UV-C), while using a pure quartz rod with a short section of borosilicate (e.g., a borosilicate filter) between the UV light source 950 and the conveyor rod 940 will result in the same level of UVA and UVB detection without the borosilicate section and only 10 μWatt / cm at the top of the conveyor rod 940. 2The UV-C light is reflected back to the body of the conveyor rod 940, so that the UV light is uniformly delivered throughout the conveyor rod 940. The UV light source 950 can be configured to be connected to a power supply (not shown) that powers the UV light source 950.

[0195] The delivery rod 940 can be a fiber optic rod / conduit. In some example embodiments, the delivery rod 940 is made by using industrial diamond engraving, thereby using glass cutting oil and applying bilateral pressure to break it cleanly (rather than opaquely). The tip of the delivery rod 940 can be rounded using a drill bit (e.g., a 500 RPM drill bit) with high-quality diamond polishing pads (e.g., 120 to 200 grit) and sandpaper (e.g., 400 grit sandpaper). The body of the delivery rod 940 can then be polished with a 120 to 200 grit high-quality diamond polishing pad so that UV-C-free light (e.g., UVA and UVB) can penetrate and be emitted through the body of the delivery rod 940. Alternative chemical opacification can be used for custom opacification of the rod.

[0196] The light source accessory 900 may include a body 920 and a fastening mechanism for connecting the body 920 to a housing (e.g., a rod, conduit, handle, etc.). The body 920 may include a front end hole 970 configured to connect to a light source (or power supply) and a rear end hole 980 configured to connect to a rod (or conduit).

[0197] The light source accessory 900 may be made of aluminum for heat conduction and to reduce light intensity degradation. The diameters of the front aperture 970 and the rear aperture 980 can be varied to suit, for example, specific conduits, tubes, rods, etc. The light source accessory 900 may also include a convex lens 930 between the front aperture 970 and the rear aperture 980, which is configured to reduce light loss. The convex lens may include a semi-convex heat-resistant lens to reduce light loss and focus the light.

[0198] catheter

[0199] In some examples, the delivery device may be a catheter 100 that can be inserted into an artery, urethra, or other part of a patient's body. For example, the catheter 100 may include a hollow portion through which a guidewire can pass. Thus, a caregiver can guide the guidewire to the treatment site and then pass the catheter through the guidewire to guide the catheter to or across the treatment site.

[0200] Similar to endoscopic implementations, catheter 100 may then include any type of light source 150 suitable for UV treatment of the artery interior. In some examples, this implementation may use a smaller light source 150 such as an LED.

[0201] In another example of the invention, the delivery device may be a catheter 100 capable of being inserted into the bladder as an indwelling catheter (e.g., as shown in the original text). Figure 11(As shown), thus using UV light to kill bacteria in urinary tract infections. In another example, the delivery device may be part of a balloon inserted into the rectum to treat the rectum with UV light.

[0202] vaginal

[0203] In yet another example, the delivery device can be incorporated into a vaginal bar to treat an infection in a patient's vagina.

[0204] Figure 22 An exemplary UV emitting device according to an embodiment of the present invention is shown, which in some examples can be used to deliver UV light to the vagina. The UV emitting device may include a delivery tube / rod 100. In some examples, the delivery tube / rod 100 includes a four-sided elongated body 101. The four-sided elongated body 101 may include a UV light source on each of the four sides. UV light sources 150 may be staggered on the sides of the delivery tube / rod 100. The delivery tube / rod 100 may include a proximal end 102 and a distal end 103. The four sides of the elongated body 101 converge toward the distal end 103 to form a guide surface 105. As described above, the distal end 103 of the delivery tube / rod 100 is configured for insertion into a patient. Conversely, the proximal end 102 is configured for the operability of the delivery tube / rod 100.

[0205] Figure 23 A gripping element 200 is shown. Figure 22 Examples of UV emitting devices. The gripping element 200 may be configured as a handle. The gripping element 200 may be connected to the delivery tube / rod 100 at its proximal end 102. The gripping element 200 may be designed to be ergonomically adequate for the needs of a physician or healthcare provider. The gripping element 200 may also include an input component 201 configured to receive user input. The input component 201 may be connected to an internal processor that modifies the functions of the delivery tube / rod 100 and the UV light source 150. In some embodiments, the delivery tube / rod 100 includes 2 to 20 UV light sources. The delivery tube / rod 100 shown herein includes three UV light sources 150 on each of its four sides, for a total of twelve (12) UV light sources 150. It should be understood that other configurations incorporating the features disclosed herein are feasible.

[0206] Figure 24An exemplary UV emitting device 300 according to an embodiment of the present invention is shown. The UV emitting device 300 may include a gripping element 350. The gripping element 350 may be designed to be ergonomically adequate to meet the needs of a physician or healthcare provider. The gripping element 350 may also include an input component 351 configured to receive user input. The input component 351 may be connected to an internal processor that modifies the functions of the delivery tube / rod 300 and the UV light source 330. The delivery tube / rod 300 shown herein includes two UV light sources 330 on each of its four sides, for a total of eight (8) UV light sources 330. It should be understood that other configurations incorporating the features disclosed herein are feasible.

[0207] In some embodiments, the delivery tube / rod 100 may include a rotating base at its distal end 103. The rotating base allows the delivery tube / rod 100 to rotate, resulting in uniform light emission from the UV light source 150. Uniform UV emission may aid in the treatment of bacterial growth when a patient is treated with the rotating delivery tube / rod 100. In some examples, the delivery tube / rod 100 also includes a stepper motor. The stepper motor enables the rotating base to rotate.

[0208] In some implementations, the UV light source 150 is distributed along the entire length of the delivery tube / rod 100 and at the distal end 103 to enable a wider range of applications for the UV light source 150.

[0209] In some embodiments, the delivery tube / rod 100 is configured to emit light uniformly and transmit UV light throughout. In some embodiments, the delivery tube / rod 100 is configured to emit light waves only in the UVA and / or UVB range, and not in the UV-C range. For example, the peak wavelength of the UV light source 150 may include 340 nm. In other, more extensive embodiments, the delivery tube / rod 100 (and the light source 150) may deliver wavelengths between 320 nm and 410 nm. It should be understood that various wavelengths and combinations of wavelengths can be provided using the disclosed delivery tube / rod 100. Other wavelength ranges may include, for example, 250 nm to 400 nm. In some embodiments, the vertical irradiation length extends 8 cm to 10 cm around the delivery tube / rod 100.

[0210] The delivery tube / rod 100 can be made of any suitable construction (e.g., rigid or flexible), including various polymers that are biocompatible or have a biocompatible coating. Figure 25An exemplary UV emitting device 400 according to an embodiment of the present invention is shown. In some embodiments, the delivery tube / rod 100 may include an outer layer of transparent material such that UV light from the light source 430 radiates outward from the delivery tube / rod 100. In some embodiments, the delivery tube / rod 100 may include an outer surface made of, for example, silicon, silica, polyurethane, polyethylene, polytetrafluoroethylene / PTFE, borosilicate, or other suitable materials. In some embodiments, the delivery tube / rod 100 is constructed of copper with a borosilicate outer layer. To optimize cooling, exposure area, and uniformity, the delivery tube / rod 100 may include a plurality of light-emitting diodes (LEDs) arranged in an alternating pattern on a copper strip. In some examples, eight (8) LEDs may be arranged on the delivery tube / rod. The spacing of the light sources 430 enables an optimal vertical illumination length. In some embodiments, the vertical illumination length extends 8 cm to 10 cm around the delivery tube / rod 100.

[0211] By using copper to construct the body of the delivery tube / rod 100, the delivery tube / rod 100 can withstand relatively high temperature levels. Using copper as a heat sink prevents the delivery tube / rod 100 from reaching uncomfortable temperatures. The applicant also proposes operating the light source 150 with a specific current to optimize the temperature of the delivery tube / rod 100. In some examples, the light source 150 is operated in the range of 60mA to 100mA. Within the proposed range, the temperature of the delivery tube / rod 100 will not rise above 40°C, thus achieving the goal of implementing an appropriate cooling scheme.

[0212] Figures 26-29 Various examples of UV light delivery systems with controller 450 are shown. Controller 450 may include more than one processor, memory, and a battery or other power source. The memory may contain instructions with various treatment protocols that can be applied using various intensities and / or durations as disclosed herein. For example, the memory may contain data structures that, when executed by the processor, supply power to the light source 150 at a given intensity or timing. The controller can be used in any implementation of the UV light delivery device disclosed herein, including vaginal, GI, and ETT.

[0213] Reference Figure 30 A procedure for performing in vivo ultraviolet (UV) therapy is provided. The procedure includes providing a UV light delivery device in step 2501. The UV light delivery device includes an elongated body comprising a proximal end and a distal end. The elongated body includes a receiving space. The UV light delivery device may also include a UV light source configured to be connected to the receiving space. In some examples, the method further includes rotating the elongated body in step 2503 such that two UV light sources are configured to emit UV light outward in a uniform manner.

[0214] The process may also include, in step 2504, emitting wavelengths between 320 nm and 410 nm from the two UV light sources, with peak wavelengths of 340 nm, 341 nm, 342 nm, 343 nm, 344 nm, 345 nm, and 346 nm. In some examples, the process also includes radiating outwards from the two UV light sources from the elongated body. In some examples, the elongated body includes four sides. Each of the four sides of the elongated body includes a receiving space, such that the corresponding UV light sources 150 are staggered on the elongated body.

[0215] The elongated body includes a receiving space at the proximal end and a corresponding UV light source. The elongated body is partially coated with borosilicate glass. In some examples, the elongated body is made of copper.

[0216] Respiratory system

[0217] In some examples, the systems and methods disclosed herein can be used to deliver UV light into the internal channels of a patient's respiratory system. For example, in some examples, the delivery tube 150 can be guided into an endotracheal tube (ETT) while the patient is receiving air. Alternatively, the delivery tube 150 can be guided into a patient's nasopharyngeal airway (NPA). These applications can be used to treat or prevent infections, including viral, bacterial, pneumonia, and other infections.

[0218] In some examples, the delivery tube 100 can be inserted into the ETT during inhalation. In other examples, the system and method described herein can be used to improve the treatment of emphysema by equipping a chest tube with a delivery tube to deliver internal phototherapy.

[0219] For example, the systems and methods disclosed herein have been developed to deliver internal ultraviolet therapy in conjunction with an endotracheal tube (ETT). Thus, during patient ventilation, the delivery tube 100 can be guided within the ETT. In other examples, the delivery tube 100 may be connected to or built into the ETT, or the ETT may have a light source 150 incorporated into the ETT. Therefore, the light source 150 can be placed within the tube 150 and / or the ETT such that the UV light source 150 radiates respiratory tissues in the tracheal airway surrounding the ETT.

[0220] For example, the systems and methods disclosed herein have been developed to provide internal ultraviolet therapy in conjunction with a nasopharyngeal airway (NPA). Thus, the delivery tube 100 can be guided within the patient's NPA. In other examples, the delivery tube 100 can be connected to or constructed into the NPA, or the NPA can have a light source 150 incorporated into the NPA. Therefore, the light source 150 can be placed within the tube 150 and / or the NPA such that the UV light source 150 radiates respiratory tissues within the nasopharyngeal airway surrounding the NPA.

[0221] In some examples, the UV light source 150 of the delivery tube 100 may be a string of LEDs. For example, the delivery tube 100 may be a flexible catheter connected to an ETT or NPA and may have LEDs placed on or inside the catheter to emit UV light outward from the delivery tube 100 to treat the patient's airway and / or the interior of the ETT or NPA. The LEDs may be connected to a power source via a wired connection. In other examples, the light source 150 may be any suitable light source other than LEDs.

[0222] In this example, the LED may have a maximum emission intensity wavelength of 335nm, 336nm, 337nm, 338nm, 339nm, 340nm, 341nm, 342nm, 343nm, 344nm, 345nm, 346nm, 347nm, 348nm, 349nm, or 350nm, or any wavelength range between 335nm and 350nm. In other embodiments, the LED may deliver wavelengths between 320nm and 410nm, 250nm and 400nm, or other suitable ranges described herein. In some examples, the LED may have a peak wavelength in the range from 343nm to 345nm.

[0223] Figure 31 A flowchart illustrating an example of a treatment protocol for treating a patient's respiratory tract and surrounding tissues with UV light is shown. For example, in step 3100, a light conduit or other delivery tube 150 with a UV light source may be provided and guided into the ETT in step 3102. In one example, a light conduit assembly including the light conduit or another delivery tube assembly including the delivery tube 150 is connected to the ETT via an ETT connector portion of the light conduit assembly. See below for reference. Figures 64-70 An example of a light guide assembly is discussed. Before being guided into the ETT, the light guide is encapsulated in a protective sleeve of the light guide assembly. After the light guide assembly is connected to the ETT, the light guide is guided through a valve (e.g., a valve valve) located in the ETT connector. The light guide is guided into the ETT via the valve such that the light-emitting portion of the light guide is positioned at the desired depth within the ETT. In other words, to deploy the light guide into the ETT, it is pushed through the valve and into the ETT until the desired depth is reached. Once the desired depth is reached, an auxiliary seal configured within the ETT connector and surrounding the light guide prevents air from the ventilator from being pushed into the protective sleeve. In one example, the auxiliary seal makes coplanar contact with the wall of the ETT connector and the light guide.

[0224] Then, in step 3104, the UV light source can be powered on for various treatments. For example, a processor of a control unit of an LED communicatively connected to the light guide can provide a signal to power the LED. In some examples, selected LEDs can be powered to emit light through a light guide of a desired length. For example, LEDs can be supplied along a first length of the light guide (e.g., 10 cm), however, LEDs within a second length (e.g., 5 cm) shorter than the first length can be powered to treat smaller areas. Furthermore, in some examples, a first number of LEDs can be powered to output a greater intensity than the remaining number of LEDs, and vice versa.

[0225] In some examples, a delivery conduit for an LED with a maximum emission intensity wavelength centered at 339 nm, 340 nm, 341 nm, 342 nm, 343 nm, 344 nm, 345 nm, or 346 nm may be energized once, twice, or three times daily 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 (or other suitable time ranges within or outside these ranges). Depending on the LED power and the distance from the LED light source to the trachea or other respiratory tissue, the applied intensity may be 1500 μW / cm². 2 1600uW / cm 2 1700uW / cm 2 1800uW / cm 2 1900uW / cm 2 2000uW / cm 2 2100uW / cm 2 2200uW / cm 2 2300uW / cm 2 2400uW / cm 2 2500uW / cm 2 2600uW / cm 2 2700uW / cm 2 2800uW / cm 2 2900uW / cm 2 3000uW / cm 2 3100uW / cm 2 3200uW / cm 2 3300uW / cm 2 Or other suitable strengths between or outside these ranges.

[0226] Furthermore, in some examples, the temperature of the light guide tube can be monitored via a temperature sensor connected to the light guide tube. In one example, the temperature sensor can be placed at at least one LED to monitor the LED temperature, providing an indication of the light guide tube temperature. As a non-limiting example, the temperature sensor can be placed at the last LED, positioned in the opposite direction to the end of the light guide tube. In some examples, more than one temperature sensor can be used, each located at a different position along the light-emitting portion of the light guide tube. In response to a light guide tube temperature exceeding a threshold temperature, in one example, the intensity output of the LED can be reduced or the power supply to the LED can be turned off via a processor. In another example, in response to a light guide tube temperature exceeding a threshold temperature, in addition to adjusting the LED output, or as an alternative to adjusting the LED output, the amount of cool airflow through the cooling pipe of the light guide tube can be adjusted. For example, in response to a light guide tube temperature exceeding a threshold temperature, the airflow velocity through the cooling pipe can be increased. Although the above examples are illustrated with a single threshold, multiple thresholds can be used to adjust the LED output and / or the cooling airflow through the light guide tube.

[0227] Figure 32 , Figure 33 , Figures 34A to 34C , Figures 35A to 35C , Figures 36A to 36D and Figure 37 Several different implementations of light guides that can be used within an ETT are shown. For example... Figure 32 and Figure 33 As shown, this can include one or more on-board chip-on-board (COB) mini-bars that can be connected to or inserted into the ETT 3302. The ETT 3302 may include a balloon 3308 that can reduce the intensity of UV radiation reaching the tissue, and thus, individual COB mini-bars can be selectively operated at different intensities to account for radiation loss due to the ET balloon 3308. For example, a COB mini-bar 3306 inside the ET balloon 3308 can operate at a greater intensity than a COB mini-bar outside the ET balloon 3308. The entire system can be connected to a flexible metal rod 3304, which can be connected to a power supply unit (not shown). This example with more than one COB mini-bar shows a UV irradiation area with a length of 10 cm. It should be understood that, depending on the application, the length may be less than or greater than 10 cm. In some examples, one or more additional COB mini-bars may be included in addition to mini-bars 3305 and 3306 to cover a greater length of the ETT 3302.

[0228] Figures 34A-34CAn example fiber optic solution with a COB light engine 3412 is shown, which can be integrated with (or connected to) an ETT 3410 for phototherapy. In this example, a single LED ( Figure 34A 3404) or multiple LEDs Figure 34B and Figure 34C A fiber optic cable 3408 is connected (e.g., via coupling 3406) to transmit light to the UV radiation region, and the fiber is configured or processed such that it radiates light in that portion of the tube. Furthermore, in some examples, such as Figure 34C As shown, the collimating lens 3414 can be used to focus and guide light through the fiber optic cable 3408. As described above, the fiber optic cable 3408 can be configured to emit light over the desired length of the ETT 3410.

[0229] Figures 35A to 35C A heat sink including LED 3510 is shown. Figure 35C An example of a flexible printed circuit board (PCB) 3504 is provided. In one example, the flexible PCB can be formed in a tube 3505, such that LEDs 3510 are placed around the circumference of the tube 3505. Due to the large surface area of ​​the flexible PCB, this implementation facilitates heat dissipation. Furthermore, more than one vent 3508 can be provided to further improve the cooling of the flexible PCB tube. Figure 35B Tube 3505 is shown inside ETT.

[0230] Figures 36A to 36D Various components of another embodiment of the light guide are shown, which includes a series of linear reflectors and LEDs. Similar to the embodiment described above, the light guide can be guided by an ETT 3602. Figure 36C As shown, the light guide includes a string of LED units aimed at a nearby reflector. Each LED unit includes an LED 3618, a reflector 3610, and a substrate 3614. An example distance between two LEDs 3618 can be 9 mm, and the distance between an LED 3618 and the end of the reflector 3610 that receives light from the LED can be 2 mm. For example, the distance between the LED and the end of the reflector can be small enough that the reflector can receive and disperse the light. In this way, a larger light distribution is achieved while improving the uniformity of light distribution. Figure 36C It shows the use of Figure 36A and Figure 36B An exemplary heat sink can be implemented using the above implementation scheme. Figure 37 It shows in Figure 36A and Figure 36B An exemplary beam angle of a narrow-band (e.g., 343nm-345nm) LED that can be used in the light guide shown.

[0231] UV light therapy system

[0232] Figure 64 An overview of an exemplary UV light therapy system 6400 is shown. In this example, the UV light therapy system 6400 is configured to connect a light conduit assembly 6440 to an endotracheal tube (ETT) of a ventilator and to guide the UV light conduit into the ETT while connecting the ETT to the light conduit assembly 6440 and the ventilator.

[0233] The UV light therapy system 6400 includes a control unit 6402, an umbilical cord cable assembly 6430, and a UV light conduit assembly 6440. The control unit 6402 includes a compressor 6408 for providing coolant flow through cooling pipes within the UV light conduit assembly 6440 to regulate the temperature of the UV light assembly. The control unit 6402 also includes a valve 6406 and a pressure regulator 6412 for initiating and / or stopping coolant flow, and / or for regulating the coolant flow rate through the cooling pipes.

[0234] The control unit 6402 includes a connector 6410, which is provided with a connection interface for connecting to one or more of the warm coolant connector 6434, the cold coolant connector 6436, and the electrical connector 6438 of the umbilical cable assembly 6430 (at the controller side 6432 of the umbilical cable assembly 6430).

[0235] The umbilical cable assembly 6430 connects the control unit 6402 to the UV light guide assembly 6440. The umbilical cable assembly 6430 includes an outer sheath within which are disposed one or more electrical connection wires for LEDs within the UV light guide assembly 6440, electrical connection wires to a temperature sensor of the UV light guide assembly, and a cooling / heating refrigerant pipe. The electrical connection wires and the cooling / heating refrigerant pipe extend laterally along the length of the outer sheath. In some examples, the cooling / heating refrigerant pipe may include additional insulation to reduce heat transfer from the environment.

[0236] On the UV light guide tube side 6442 of the umbilical cable assembly 6430, warm and cold coolant tubes and one or more electrical connection wires (to the temperature sensor and LED of the UV guide tube assembly) are led out via the guide tube-umbilical connection interface 6447 as corresponding warm coolant, cold coolant, and electrical connectors connected to the UV light guide tube assembly 6440. (The details will be provided below.) Figures 65-69 The details of the UV light guide assembly 6440 are explained here.

[0237] In one example, the umbilical cable assembly may include one or more air passages (e.g., a warm coolant pipe for returning warm air from the light duct assembly, and a cold coolant pipe for supplying cold coolant to the light duct assembly) and one or more electrical conductors (e.g., a power conductor for supplying power to the light duct assembly and / or a temperature sensor of the light duct assembly). Furthermore, one or more electrical conductors may also provide temperature indication of the light duct assembly from the temperature sensor to the control unit. In response to temperature, the control unit may regulate one or more operations of the light duct assembly and the coolant flow to the light duct assembly. The umbilical cable assembly may also include a light duct connector configured to connect to the light duct assembly and a control unit connector (or compressor connector) configured to connect to the control unit (or compressor system).

[0238] The umbilical cord assembly 6430 may be approximately 4 feet, 5 feet, or 6 feet long, or other suitable length, to connect a disposable light conduit to the controller. The umbilical cord assembly 6430 may be long enough to allow access from the bedside cart containing the control unit 6402 to the patient's ETT connector. As described above, the umbilical cord assembly 6430 may include electrical wiring for LEDs, wiring for temperature sensors, and conduits for cold air to the light conduit assembly 6440 and / or for warm air returning from the light conduit assembly 6440. Thus, in one example, the umbilical cord assembly 6430 can connect the light conduit assembly 6440 to the control unit 6402 via a single-hybrid connector used for transmitting gaseous coolant and power. For example, a central channel may transmit air (e.g., directing cooled air downwards to the light conduit assembly 6440 and, if applicable, returning warm air to the control unit 6402 along a second channel). Furthermore, one or more electrical connectors / wires may be spaced apart around the periphery or relative to any construction of the air channels.

[0239] In one example, the coolant is air. Therefore, cooled air from compressor 6408 can flow through cold coolant connector 6436, cold coolant tubing within the umbilical cable sheath, cold coolant connector 6446, and into UV light guide assembly 6440. In one example, air from the compressor can be cooled by a thermoelectric cooler and flow into the cold coolant connector. Furthermore, the heat-absorbed air from the UV light guide is then returned via warm coolant connector 6434, warm coolant tubing, and warm coolant connector 6434, and from there reaches control unit 6402 for recirculation, flow rate monitoring, leak monitoring, and / or venting to the atmosphere. In some examples, warm air can be discharged at the interface between umbilical cable assembly 6430 and light guide assembly 6440 or via a valve regulating opening within the umbilical cable assembly. (See below) Figure 69The details of coolant flow during UV light guide tube deployment within the ETT will be further described below. In some examples, other gaseous coolants may be used and are within the scope of this invention.

[0240] Control unit 6402 may include at least one processor (CPU) 6403 and at least one memory 6405, such as read-only memory (ROM) and / or random access memory (RAM), comprising a computer-readable medium operatively connected to the processor. Thus, at least one memory 6405 may contain system instructions that, when executed by the processor, perform one or more of the operations described herein, such as one or more control operations including cooling the UV light guide during operation of the UV light guide within the ETT and controlling UV light based on the temperature of the UV light guide. Processor 6403 may receive more than one input signal from various sensing components (e.g., a temperature sensor connected within the UV light guide) and may output more than one control signal to various control components described herein (e.g., output to compressor 6408 within the control unit to regulate the flow of coolant through the cooling pipes of the UV light guide, output to a power supply connected to the UV light guide). However, it should be understood that control unit 6402 may be implemented in other configurations.

[0241] In a non-limiting example, control unit 6402 may include a medical-grade air compressor (such as Allied's Timer PCS-414) and be able to output 14 LPM of air at 50 psi or other suitable range. As described above, control unit 6402 may include a digital readout, a connector (which may be a hybrid connector) for connection to the umbilical cord, and user controls and status indications. Furthermore, the compressor may include an air valve and a pressure regulator. Control unit 6402 may also include a pressure sensor and a flow controller for cooling air, as well as a flow sensor. In some examples, control unit 6402 may be configured with a closed feedback loop from a temperature sensor to determine the temperature and / or flow rate of the cooling air delivered to the light guide tube and through the cooling pipe.

[0242] Figure 65 An example of a UV light conduit assembly 6500 is shown. The UV light conduit assembly 6500 can be connected to the umbilical cable of a UV light therapy system, such as the umbilical cable 6430 of a UV light therapy system 6400. The UV light conduit assembly 6500 can be... Figure 64 An example of a UV light guide assembly 6440 is shown. Specifically, Figure 65 The UV light duct assembly 6500 is shown in its pre-deployment configuration. That is, its first configuration before being connected to and guided by the ETT.

[0243] The UV light guide assembly 6500 includes a guide 6506 (also referred to herein as a light guide), the guide 6506 including a light-emitting portion 6600. Figure 66 When not inserted into the ETT, the conduit 6506 is housed within the protective sleeve 6502. The distal end 6508 of the light guide assembly 6500 is connected to the umbilical cable's warm coolant connector 6510, cold coolant connector 6512, and electrical connector 6514, respectively. In this way, the umbilical cable introduces cooling fluid and power to multiple LEDs and provides power to the UV light guide assembly's temperature sensor (via electrical connector 6514). At the proximal end 6520, the UV light guide assembly 6500 includes a light-emitting portion 6600 (also referred to herein as a light delivery portion), which... Figure 66 The image is enlarged and explained below.

[0244] Turning Figure 66 The proximal end 6520 includes an ETT connector 6649 that receives the proximal tip 6616 of the catheter. Furthermore, the ETT connector 6649 directly connects the UV light catheter assembly 6500 to an ETT connected to the ventilator. The ETT connector 6649 includes a valve, for example, to prevent air from the ventilator from flowing into the light catheter assembly 6500 when the catheter assembly 6500 is connected to the ETT but the catheter 6506 (including the light-emitting portion) is not deployed within the ETT. The proximal end 6520 also includes an auxiliary seal 6602 that prevents air from the ventilator from entering the protective sleeve 6502 when the catheter 6506 is positioned inside the ETT. In one example, this valve is configured as a valve valve. Other types of valves, such as check valves, that prevent air from flowing back from the ventilator into the protective sleeve 6502 may also be used.

[0245] The light-emitting unit 6600 includes a plurality of LEDs 6604 disposed inside a conduit 6506, and a cooling pipe 6610 also disposed inside the conduit 6506. In one example, as shown, the LEDs 6604 are positioned rotated 90 degrees relative to each other and facing the conduit 6506, such that when the LEDs are powered, they emit light outward from the conduit 6506 in a 360-degree pattern along the length of the conduit 6506. Furthermore, in this example, each adjacent LED is rotated 90 degrees. For example, the first LED is at a reference angle of zero degrees, and the second LED (i.e., the second LED immediately adjacent to the first LED) is rotated 90 degrees from the first LED along the length of the conduit 6506. Furthermore, the third LED adjacent to the second LED along the length of the conduit 6506 is rotated 90 degrees relative to the second LED (i.e., rotated 180 degrees relative to the first LED), and so on, such that the Nth LED adjacent to the (N-1)th LED is rotated 90 degrees relative to the (N-1)th LED, where N is any number depending on the required light emission length along the conduit 6506. Furthermore, in this example, the LEDs are arranged in an interleaved configuration, wherein each adjacent LED (placed longitudinally inside the conduit) is rotated 90 degrees.

[0246] In some examples, LEDs can be arranged in a circumferential configuration. For example, four LEDs can be arranged 90 degrees apart, such that the first and third LEDs are placed back-to-back, and the second and fourth LEDs are placed back-to-back, with the second LED located between the first and third LEDs and the fourth LED located between the third and first LEDs. The four LEDs do not intersect, and when energized, they emit light 360 degrees around the outer periphery of the conduit 6506. Another set of four LEDs can be placed at a short distance from these four LEDs to provide continuous, substantially uniform illumination along the desired length of the conduit. In this way, multiple sets of LEDs can be placed to cover the desired length of the conduit used for illumination. Other configurations of LEDs covering 360-degree illumination along the desired length of the conduit are feasible and within the scope of this invention. For example, fewer than four LEDs can be used to provide 360-degree illumination when using LEDs with a wider beam angle. As a non-limiting example, three LEDs can be used, rotated 120 degrees from each other, arranged in an alternating manner (i.e., adjacent to each other along the length of the tube) or in a circular manner (i.e., adjacent to each other around the circumference of the cooling tube). In this way, the group of three LEDs can provide 360-degree illumination.

[0247] Furthermore, a cooling pipe 6610 is disposed within a conduit 6506 and supplies cooling air to the conduit 6506. The cooling pipe 6610 has an open end 6615 facing the proximal end 6520 of the conduit, through which the cooling air flows out of the cooling pipe and circulates back towards the LED to cool the LED. The cooling pipe 6610 is centrally positioned relative to the LED 6604. Specifically, the LEDs 6604 are positioned such that a portion of each LED contacts the cooling pipe 6610. For example, the LEDs 6604 are positioned such that their backside (e.g., a portion of the LED substrate) contacts the cooling pipe 6610. In some examples, the LEDs 6604 may be disposed on an inner tube, which may include one or more cooling pipes within the inner tube.

[0248] Furthermore, the cooling tube 6610 is flexible and wound around the back of each LED, allowing the LEDs to be arranged in a compact manner. This reduces the diameter of the tube, which is advantageous when deployed within the ETT as it reduces any resistance to the ventilator airflow through the ETT to the intubated patient. In some examples, one or more additional openings may be provided for the cooling tube to allow cooling air to exit from one or more additional outlet points.

[0249] Furthermore, the light guide 6506 may include an LED emitting a peak wavelength primarily in the 340 nm to 350 nm range. Example peak wavelengths may be in the range of 343 nm to 345 nm. In some examples, each LED may emit peak wavelengths 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, and 355 nm. In some examples, the LED may emit light with a significant intensity within a range of + / - 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, or 6 nm near its peak intensity emission wavelength.

[0250] The catheter 6506 has a diameter smaller than that of the ETT. In a non-limiting example, the catheter diameter is approximately 5.4 mm, equal to or smaller than the diameter of an adult bronchoscope, and small enough to prevent airflow obstruction through the ETT. In some examples, the catheter may be smaller than 5.4 mm. Furthermore, the catheter 6506 is flexible and can follow the bends of the endotracheal tube when guided through the ETT. In some examples, the catheter 6506 can be sized to be at or below the diameter of a bronchoscope. For example, for adults, the catheter could be approximately 3 mm, 4 mm, 5 mm, 5.4 mm, 5.5 mm, 5.6 mm, or other suitable diameters. Additionally, the catheter diameter can be configured to prevent obstruction or interruption of airflow within the ETT. The helical staggered arrangement of the LEDs relative to the cooling tubes allows for a sufficiently small catheter diameter to provide effective cooling while reducing resistance to airflow through the ETT.

[0251] Furthermore, the arrangement of cooling pipes and LED lights can increase the duration of treatment. For example, the cooling of the LEDs is more effective due to the cooling pipes placed inside the light guide and the flow of cooling air within the light guide.

[0252] Furthermore, temperature sensor 6612 can be connected to the last LED facing the distal end of conduit 6506 to monitor the temperature of LED 6604. In some examples, more than one temperature sensor can be used. Additionally, temperature sensor 6612 can be connected to any LED 6604. Temperature sensor 6612 can send the temperature indication of LED 6604 to a control unit (e.g., control unit 6402). In one example, a threshold temperature can be used to adjust the operation of the LED. For example, a single threshold temperature can be used, and the LED can be inactive when the temperature of at least one LED is at or above the single threshold temperature. In some examples, when the temperature reaches the single threshold temperature, the control unit can reduce the power of the LED to output a lower radiant intensity. The control unit can continue to monitor the temperature and, when the temperature drops below the single threshold, can supply power to the LED or increase the power to a desired intensity. In some examples, while the LED is off, the coolant flow through cooling conduit 6610 can continue or be increased to accelerate the cooling of the LED.

[0253] In another example, multiple temperature thresholds can be used to adjust LED operation and / or coolant flow. As an example, when power is supplied to more than one LED within the conduit, during a first condition where the temperature of at least one LED is below a first lower threshold, cooling airflow may be withheld or supplied at a low rate. During a second condition where the temperature is at or above the first threshold but below a second higher threshold, the cooling airflow may be increased to a rate greater than the aforementioned low rate. Furthermore, in a third case where the temperature is at or above the second higher threshold, power may not be supplied to the LED (i.e., the LED may be turned off). Additionally, in some examples, coolant flow may continue when the temperature is at or above a second temperature threshold to allow for faster LED cooling.

[0254] Furthermore, in some examples, the conduit 6506 of the UV light component can be disposable. That is, the conduit can be used on a single patient during treatment and then discarded.

[0255] The catheter 6506 also includes one or more depth indicators 6614 at the non-light-emitting portion of the catheter 6506. Figure 67 An exemplary indication 6614 is shown. Specifically, catheter 6506 includes one or more external depth markers indicating the distance to the proximal end of the catheter. Figure 67 In the example shown, the indication starts at 13cm and extends to 30cm. Furthermore, every 5cm between 15cm and 30cm is marked with a number, and intermediate distances are marked with dots. It should be understood that the above example is for illustrative purposes, and different types of indications (non-circular shapes, any geometry, etc.) and different distances (e.g., distance indications every 2cm, 3cm, 4cm, or 6cm, or any available intervals and / or distance markings) may be shown on the non-light-emitting portion of the conduit without departing from the scope of the invention.

[0256] Furthermore, this example illustrates a light-emitting portion (also referred to as a light delivery portion) with a length of 10 cm. It should be understood that the length of the light-emitting portion, including the LED, can be longer or shorter. As a non-limiting example, when the catheter is configured for use in children, the length of the light-emitting portion (i.e., the portion including the LED) can be shorter. Therefore, in one example, the length of the light-emitting portion can be based on the patient's age and / or height. Furthermore, the length of the light-emitting portion can vary depending on the application (e.g., ETT or NPA, etc.). In some examples, the light delivery portion can be 5 cm, 6 cm, 7 cm, 9 cm, 10 cm, 11 cm, 12 cm, 13 cm, 14 cm, or 15 cm, or other suitable lengths for catheter 6506.

[0257] In some examples, the conduit can be configured with more than one light-emitting element. For example, one or more light-emitting elements, each having a predetermined length, can be positioned along the length of the conduit, and the control unit can activate (i.e., by powering the LEDs) the required number of light-emitting elements based on the desired illumination distance. As an example, if a greater illumination distance is required, the control unit can activate more light-emitting elements, and vice versa. In some examples, LEDs can be selectively activated. For example, when a greater illumination distance is required, the number of activated LEDs may be greater. Furthermore, LEDs at different locations (e.g., proximal, distal, intermediate, etc.) can be selectively activated.

[0258] Figure 68 The catheter 6506 is shown in a deployment configuration within the ETT 6804. To deploy the catheter 6506 into the ETT 6804, the catheter 6506 is pushed past the valve and into the ETT 6804 until the desired depth is reached. Once the catheter 6506 is deployed, an auxiliary seal 6602 prevents ventilator air from being forced into the protective sleeve 6502. Furthermore, the proximal end 6616 of the catheter 6506 can be sealed and has multiple small blocks (nubs) (not shown) that help center the light conduit within the ETT 6804. This provides a more uniform light distribution within the trachea.

[0259] Figure 69 The coolant airflow is shown when deployed within the ETT 6804. A cooling tube 6610 within duct 6506 provides a steady flow of gaseous coolant toward the sealed end 6616 of the duct. The gaseous coolant (coolant flow indicated by arrow 6902) flows rearward over the LED, keeping the LED cooled. Warm air exits from the rear of duct 6506 toward the umbilical cable assembly. The warm air may be vented at the connection to the umbilical cable or may be carried back to a control unit that monitors the flow rate to detect system leaks and / or adjust the flow rate (e.g., increase the flow rate for greater cooling).

[0260] Figure 70 An example LED arrangement that can be implemented within a conduit (such as conduit 6506) of a UV light therapy system is shown. Here, each LED 7004 includes a substrate with copper pads 7006 serving as heat sinks. This example shows two copper pads 7006, but fewer or more copper electrical connections between the two LEDs are shown at 7008. The copper pads 7006 can be used to supplement or replace cooling pipes (e.g., cooling pipe 6610 described above). Figure 71 An exemplary radiation pattern 7102 of an LED (e.g., LED 7004) is shown. For example, radiation pattern 7102 has a corn kernel shape. Other radiation patterns may be used and are within the scope of this invention.

[0261] In some examples, LEDs are individually soldered to small PCBs connected in series, forming flexible LED chains. These chains can be segmented to create individually controllable sections; for example, a segment below the ETT airbag can emit a higher amount of light to compensate for additional light loss or attenuation from the airbag. Furthermore, VIAS thermally bond the front and back sides of the PCB, allowing heat to be transferred to the back of the PCB with additional exposed copper pads 7006. These pads dissipate the extra heat into cooling air to prevent the LEDs 7004 from overheating.

[0262] LEDs 7004 can be arranged in a spiral pattern within the light guide tube. In one embodiment of the spiral pattern, each LED is rotated 120 degrees relative to the next LED in the spiral and spaced 3.5 mm apart along the axis of the light guide tube to generate uniform 360-degree UVA light around the light guide tube.

[0263] In one example, LED 7004 is a 3.5mm square and 1.5mm high, with a flat quartz lens soldered to a metal housing. Each LED can produce... Figure 71 The light pattern shown is approximately 120 degrees. In some examples, the LED may have a beam angle between 120 and 135 degrees.

[0264] In this way, including the above in Figures 65-70 The UV light therapy system, comprising the UV light assembly, umbilical cable, and control unit, illustrates an example of the disclosed technique applied to an endotracheal tube to irradiate the patient's airway and surrounding internal tissues. This is advantageous for treating coronavirus infections, such as SARS-CoV-2 infection and illnesses caused by coronavirus infections (such as COVID-19), and also reduces the chance of primary SARS-CoV-2 or other viral infections in patients intubated for reasons other than COVID-19 treatment. Furthermore, these treatments can reduce the incidence of secondary infections caused by oral or ventilator-associated bacteria or fungi.

[0265] As described above, the light guide can be connected to an umbilical cable, which includes flexible power and air connectors between the light guide and the controller. In some examples, the umbilical cable is reusable. Therefore, the umbilical cable includes wiring and circuitry for powering LEDs in the light guide, as well as channels for delivering cooling air from the controller to the light guide.

[0266] exist Figure 72The image shows a portion of another exemplary light-emitting section of a light guide for a UV light therapy assembly that can be used for UVA therapy. In this example, a plurality of LEDs 7202 are disposed on an inner tube 7204, which may include one or more cooling tubes 7206. An outer tube (not shown) may surround the plurality of LEDs 7202, the inner tube 7204, and the one or more cooling tubes 7206.

[0267] Nasopharyngeal airway (NPA)

[0268] The device inserted into the nasopharynx is called a "nasopharyngeal airway" (NPA) (or nasal horn or nasal tube). The above-described examples of UV light therapy systems (including the control unit, umbilical cable and UV light conduit assembly, UVA LED structure) and UVA treatment parameters including the wavelength, intensity and duration described with respect to the endotracheal tube can also be applied to NPA applications without departing from the scope of the invention.

[0269] In one example, a nasal cannula, such as a catheter with a UV light source or other thin tube or guidewire as disclosed herein, can be guided through the nose to various locations in the respiratory tract. Therefore, for example, treatments applied before a patient requires ventilation due to a pneumonia-like infection can have an antibacterial effect in the nasopharynx.

[0270] Other respiratory applications

[0271] The disclosed systems and methods can be used for the following other respiratory applications:

[0272] 1. Insert an internal phototherapy (ILT) tube while using ETT to eliminate bacteria in the tube and bacteria that have accumulated in the throat and other tissues to prevent pneumonia.

[0273] 2. Construct an ETT with intermittent emission ILT performance.

[0274] 3. Improve the treatment of emphysema by equipping the chest tube with an ILT.

[0275] Other therapeutic applications and treatment regimens

[0276] The procedure described herein can be used to treat many different inflammatory and infectious diseases. Therefore, different amounts or time-duration doses of UV radiation can be administered depending on: (1) the type of disease, (2) the type of light source, (3) the power of the light source, (4) the UV range of the light source, and (5) the severity of the infection or inflammation. For example, in some embodiments, the administration time will be determined by the capsule digestibility, and other factors (e.g., light source power, UV range, etc.) can be manipulated to change the dose. In other examples, the endoscope can be delivered by a physician / surgeon for 1 hour, 30 minutes, 2 hours, or other suitable time.

[0277] The following are examples of treatment options and their applications. Therefore, the apparatus and methods disclosed herein can be applied to treat these different conditions.

[0278] Urology and Nephrology:

[0279] 1. During dialysis, blood from patients with known bacteremia, fungemia, or viremia is sterilized to eradicate or reduce bacterial load. Alternatively, a light needle can be placed in a fistula so that it can be opened even outside the dialysis window. Ex vivo sensitivity analysis will be performed for ILT at narrower but more intense wavelengths.

[0280] 2. Sterilize indwelling urinary catheters in patients with catheter dependence.

[0281] 3. Treatment of bladder and urethral cancers confined to the mucosa and submucosa.

[0282] 4. Treatment of refractory cystitis / urinary tract infection.

[0283] 5. Add UV phototherapy to the peritoneal dialysis catheter to reduce the risk of peritonitis or even long-term peritoneal sclerosis.

[0284] Cardiology

[0285] 1. Sterilize the blood of patients with known bacteremia, fungemia, or viremia to eradicate or reduce bacterial load. Alternatively, a photoneedle can be placed in a fistula that can be opened even outside the dialysis window. Ex vivo sensitivity analysis can be performed on narrower wavelength but more intense UV therapy.

[0286] 2. Direct UV light irradiation of the valves for the treatment of refractory bacterial and fungal endocarditis. In this case, a photosensitizer can be administered intravenously.

[0287] Dental

[0288] 1. Treatment of gingivitis.

[0289] 2. Treatment of leukoplakia and oral lichen planus.

[0290] 3. Treatment of cancers confined to the mucosa and submucosa.

[0291] Hematology / Oncology

[0292] 1. Treatment of intestinal graft-versus-host disease. In this case, X-ray wavelengths are emitted, causing lymphocyte death. This can be used for end-stage Crohn's disease patients awaiting small bowel transplantation or palliative care.

[0293] Otolaryngology

[0294] 1. Treatment of chronic sinusitis.

[0295] 2. Treatment of chronic otitis media.

[0296] 3. Treatment of acute otitis media in patients requiring tympanostomy.

[0297] 4. Treatment of nasal polyps.

[0298] 5. Treatment of halitosis.

[0299] 6. Treatment of recurrent tonsillitis / pharyngitis.

[0300] 7. Treatment of cancers confined to the mucosa and submucosa.

[0301] Operation

[0302] 1. Improve the treatment of abscesses by equipping drainage tubes with UV light technology.

[0303] 2. Use in conjunction with surgical drainage tubes to avoid reinfection.

[0304] 3. Accelerate the healing process of anastomosis.

[0305] 4. Helps prevent adhesion.

[0306] Neurosurgery

[0307] 1. Intrathecal fiber light delivery of UV light in the treatment of refractory meningitis.

[0308] 2. Treatment of refractory shunt infections.

[0309] 3. Treatment of prion diseases using intrathecal or subarachnoid UV therapy.

[0310] 4. Treat JC virus-associated progressive multifocal leukoencephalopathy by reducing viral load.

[0311] Gynecology

[0312] 1. Treatment of bacterial or fungal vaginitis.

[0313] 2. Treatment of rectovaginal / colovesical fistula.

[0314] 3. Treatment of cancers confined to the mucosa and submucosa

[0315] Rheumatism

[0316] 1. Intra-articular ILT for the treatment of inflammatory and infectious large joint arthritis.

[0317] Vaginal treatment

[0318] 1. Figure 14A , Figure 14B An example of a UV emitting device for vaginal treatment of mice is shown.

[0319] Experimental data

[0320] The following set of experimental data is provided to better illustrate the claimed invention and should not be construed as a limitation on the scope of protection.

[0321] Example 1: E. coli (Escherichia coli)

[0322] Figure 12A and Figure 12B Experimental data illustrating an example of the UV emitting device of the present invention for preventing the proliferation of E. coli are shown. As shown, the control group without UV light continued to grow, while the test group subjected to UV light by the UV emitting device showed a continuous decrease in the number of E. coli over time. Over time, UV light showed that it was able to both prevent the proliferation of E. coli and kill the bacteria.

[0323] Figure 15B An example of the UV emitting device of the present invention for use with liquid cultures containing E. coli is shown. For example, Figure 15A and Figure 16 , Figure 17A and Figure 17B , Figures 18-20 , Figure 21A and Figure 21B The results of this experiment and similar experiments with other bacteria and fungi, including C. albicans, are shown. All results demonstrate that when UVA and UVB light is emitted onto the liquid sample using the UV emitting device of this invention, the growth of E. coli and other infectious agents in the liquid sample is significantly reduced.

[0324] Example 2: Bacteria

[0325] In another example, two exemplary devices according to the invention were used in a UVA experiment to treat bacteria. The first device was a borosilicate rod (3 mm outer diameter) repeatedly etched with a mixture of dilute sulfuric acid, sodium bifluoride, barium sulfate, and ammonium bifluoride, with a reflective coating added to the end of the rod through which UVA was side-emitted. As confirmed by Ocean Optics (Extech), this process resulted in a side-emitting rod of UVA (peak wavelength 345 nm). The second device contained a narrowband LED with a peak wavelength of 345 nm.

[0326] The UVA lamp was inserted into the liquid medium. A mercury vapor lamp was used as the light source (Asahi Max 303, Asahi Spectra Co., Tokyo, Japan). The second UVA emitting device was a miniature array of light-emitting diodes (LEDs) (peak wavelength 345 nm) mounted on a heat sink (Seoul Viosys, Gyeonggi-Do, South Korea). This device was used for the planar culture experiments mentioned below.

[0327] Primary cultures of *Escherichia coli*, *Escherichia coli GFP*, *Pseudomonas aeruginosa*, *Streptococcus pyogenes*, *Staphylococcus epidermidis*, *Klebsiella pneumoniae*, *Enterococcus faecalis*, *Proteus mirabilis*, *Clostridium difficile*, and *Candida albicans* in, for example Figure 53 The appropriate liquid culture media and conditions are shown in the table. The American Type Culture Collection (ATCC) strain and a clinical isolate were grown in appropriate solid and liquid media according to the ATCC recommendations for each bacterium (Manassas, VA, USA). Using aseptic techniques, the vial containing the strain was opened, and the entire pellet was rehydrated with approximately 500 μL of liquid broth.

[0328] Aseptically, transfer the resuspended clumps to a tube containing 5 to 6 mL of the same liquid broth used to resuspend the cells. A few drops of the primary broth tube are used to inoculate solid microbial agar and isolate single colony-forming units (CFUs). Figure 53 Liquid and solid cultures were cultured under the specified temperature, atmospheric conditions, and time.

[0329] Initially, liquid cultures were prepared from individual CFUs of each microorganism to ensure the purity of the strains during UVA treatment. Only fresh, pure liquid cultures were used during the experiment. A single colony was added to a 10 mL sterile tube containing 5 mL of liquid culture medium, and then thoroughly vortexed to homogenize the microbial cells. Figure 53 The liquid cultures shown were incubated until they reached the McFarland standard of 0.5. 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 microcentrifuge tubes for use as treatment and control. 100 μL aliquots from each tube were serially diluted and plated on solid bacterial culture medium to determine the turbidity level. Figure 54 The CFU / mL number at the baseline is shown.

[0330] Prior to UVA light therapy, several sterile 1.7 mL tube caps are prepared by forming a small hole at the top using a heated glass rod. The hole is shaped and sized to accommodate the transmission of UVA light from the rod.

[0331] Aseptically, the original caps of the liquid cultures from the 1.7 mL tubes were replaced with sterile caps with perforations. UV light emitter rods (sterilized with 70% ethanol) were inserted into the holes created on the top of each cap. The same rods were also placed in the control tubes. Light was transmitted through the inserted glass rods using a MAX-303 Xenon light source (Asahi Spectra USA, Inc., Torrance, CA). UV bandwidth and irradiance peaks were assessed (Flame UV-VIS fiber optic spectrometer, Ocean Optics). UV intensity was measured using SDL470 and UV510 UV photometers (Extech, NH, USA). The absence of UVC was confirmed using an SDL470 UV photometer (Extech NH, USA). Figure 53 The intensity and exposure duration of UVA light applied to bacterial cultures were described.

[0332] After the treatment period, the tubes were removed from both the treated and control tubes, and the liquid cultures were sealed with new, sterile caps without pores. Both the treatment and control groups were homogenized by vortexing. Then, 100 μL aliquots from each tube were serially diluted and plated on solid bacterial culture medium to determine the effect of UVA treatment. Figure 54 The CFU / mL count at the baseline is shown. Repeat this process until complete. Figure 54 All the time points mentioned.

[0333] At each time point (baseline and after UVA treatment), 100 μL of liquid bacterial culture (treatment and control) was serially diluted in sterile 1x PBS (EMD Millipore, Billerica, MA). The final serial dilution ratios were 1:10 (100 μL bacterial culture and 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 onto solid agar plates and... Figure 53 Propagation was performed under the specified time, temperature, and atmospheric conditions. After propagation, colonies were counted using a Scan 300 automated colony counter (Interscience, Woburn, MA, USA), and the CFU / mL count was defined after adjusting for volume and dilution factor.

[0334] The second device used in these experiments incorporated a miniature light-emitting diode (LED) array (peak wavelength 345 nm, bandwidth 10 nm) mounted on an aluminum heat sink (Seoul Viosys, Gyeonggi-Do, South Korea). In the first experiment, the system was placed 1 cm from the surface of a culture plate with a thick E. coli mycelium, at approximately 2000 μWatt / cm².2 The intensity was maintained for 20 minutes. Subsequently, in a separate experiment, the light source was applied to 10... 2 Liquid cultures of E. coli and Pseudomonas aeruginosa at CFU / mL.

[0335] Under these two conditions, UVA at 500 μWatt / cm in different experimental groups 2 1000 μWatt / cm 2 2000 μWatt / cm 2 and 3000 μWatt / cm 2 The intensity was tested at 1 cm for 20 and 40 minutes to generate dose-response curves. After propagation, colonies were counted and colony size was measured using a Scan 300 automated colony counter (Interscience), and the number of CFU / mL was defined after correcting for volume and dilution factor.

[0336] result

[0337] like Figure 54 As shown in the table, UVA exposure was associated with a significant reduction in various pathogenic bacteria, including Candida albicans (P = 0.007) and Clostridium difficile (P = 0.01). This reduction was observed after 20 minutes of UVA light exposure (intensity range 1300–3500 μWatt / cm²) compared to the control group (P < 0.05). 2 This was the shortest effective duration for which reductions were observed in most tested bacteria (except for Klebsiella pneumoniae (P = 0.17), Enterococcus faecalis (P = 0.1), and Streptococcus pyogenes (P = 0.64)). Compared to the untreated control group (P < 0.05), this was the shortest effective duration. Figure 33 Compared to 40 minutes and 60 minutes of UVA light exposure, both were effective for all tested bacteria. In particular, as... Figure 54 As shown, the bactericidal and fungicidal effects exhibit a dose-dependent response to UVA light, with greater reduction in microorganisms associated with longer exposure times.

[0338] UVA light therapy has also been applied to clinically isolated strains of *E. coli* obtained from the human urinary tract. UVA light was tested in a series of five consecutive experiments, exposing the bacterial cultures to UVA for 20, 40, 60, and 80 minutes at 1100 to 1300 μWatt / cm². 2 Compared to the baseline, such as Figure 57As shown, the number of CFU / mL observed in bacterial cultures exposed to UVA light decreased at all time points assessed, including 20 min (P = 0.03), 40 min (P = 0.0002), 60 min (P < 0.0001), and 80 min (P < 0.0001).

[0339] Finally, experiments were conducted to test the effects of LED narrowband UVA (345nm peak wavelength) on *Escherichia coli* and *Pseudomonas aeruginosa*. In these experiments, such as... Figures 58A to 58N As shown, this specific wavelength of UVA leads to a significant reduction in bacterial cells. For example, Figure 58A Images of bacterial colonies in a petri dish are shown, along with patterns of colony disappearance around areas where LED lights were applied at 20 and 40 minutes.

[0340] Figure 58B-Figure 5 Figure 8F shows a graph illustrating the change in colony-forming units (CFU) of E. coli over time when UVA light with a peak wavelength of 345 nm was applied at various intensities. As shown, most bacteria were eliminated within 40 minutes at an intensity of 2000 uW. Figure 58D And most bacteria are eliminated within 20 minutes at an intensity of 3000uW. Figure 58E (and Figure 58F). When the same light intensity was applied at 500uW and 1000uW, the CFU significantly decreased by 40 minutes, but only by about half. Figure 58C and Figure 58B ).

[0341] Figures 58G to 58J The graph shows the change in colony-forming units (CFU) of Pseudomonas aeruginosa over time when UVA light with a peak wavelength of 345 nm was applied at various intensities. As shown in the figure, treatments at intensities of 1000 μW, 2000 μW, and 3000 μW showed a significant reduction in CFU compared to the control. Figure 58H , Figure 58I and Figure 58J ), and most bacteria were eliminated after 20 minutes at intensities of 2000 μW and 3000 μW. Figure 58I and Figure 58J ).

[0342] Figure 58K-Figure 58L The growth curves showing the logarithmic reduction of Pseudomonas aeruginosa at different intensities at 20 minutes and 40 minutes are shown respectively. Figure 58M The figure illustrates growth curves used to show the decrease in E. coli colony diameter at different intensities and treatment times. Figure 58N The figure shows growth curves used to illustrate the decrease in colony diameter of Pseudomonas aeruginosa under different intensities and treatment times.

[0343] Examination of the effect of light intensity on reducing E. coli and Pseudomonas aeruginosa revealed a dose-response effect in both bacterial levels and colony size. Figures 58B-58N When using a narrowband LED with a peak wavelength of 345 nm, the ideal UVA intensity affecting bacteria occurs at 2000 μWatt / cm². 2 and 3000 μWatt / cm 2 The exact number of cases varies, and in some examples may depend on the type and species of bacteria or pathogens, as well as other factors disclosed herein.

[0344] Example 3: Secure Data

[0345] To assess the safety of UVA for mammalian cells, three experiments were performed. The first involved exposing cultured HeLa cells to UVA. HeLa cells were added to DMEM cell culture medium (Gibco, Waltham, MA) in 60x15mm cell culture dishes (Falcon), along with 10% bovine serum (Omega Scientific, Tarzana, CA) and 1x antibiotic-antifungal agent (100x Gibco), and cultured at 37°C (5% CO2) for 24 hours to reach a cell density of 1,000,000 to 1,800,000 cells per plate. At this point, the cells were exposed to a UVA LED lamp (1800 μWatt / cm²). 2 Cells were incubated for 0 (control) minutes, 10 minutes, or 20 minutes. After 24 hours, cells were removed with 0.05% trypsin-EDTA (1x) (Gibco), stained with trypan blue 0.4% ready-to-use (1:1) (Gibco), and quantified using an automated cell counter (Biorad T20, Hercules, CA). In similar experiments, cells were incubated at a higher intensity (5000 μWatt / cm²). 2 Use an LED UVA lamp for 20 minutes. Again, quantify HeLa cells 24 hours after UVA exposure.

[0346] In addition, the safety of UVA was investigated in two human respiratory cell types: alveolar cells (ATCCA549) and primary ciliated tracheal epithelial cells (HTEpC) (PromoCell, Heidelberg, Germany). For each cell line, 250,000 cells were seeded and grown in DMEM for 48 hours until the cell count per plate was approximately 750,000. At this point, the cells were exposed to UVA (2000 μWatt / cm²). 2 Cell counts were obtained after 0 minutes (control) or 20 minutes (treatment) and after 24 hours.

[0347] The level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was analyzed in the DNA of cells treated with UVA. 8-OHdG is widely considered a sensitive biomarker 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. EpiQuik was used. TM The 8-OHdG DNA Damage Quantification Direct Kit was used to detect 8-OHdG levels according to the manufacturer's instructions (Epigentek, Farmingdale, NY). For optimal quantification, the input DNA volume was 300 ng, as baseline 8-OHdG is typically less than 0.01% of total DNA (Epigentek, Farmingdale, NY).

[0348] Wild-type 129S6 / SvEv mice (n=20, female=10) and BALB / cJ mice (n=10, female=5) were used for UVA photosafety testing. All animals were anesthetized prior to the procedure. Before UVA phototherapy, animals were placed in an inhalation chamber containing isoflurane anesthetic gas (1-5%). The carrier gas for isoflurane was compressed oxygen (100% oxygen). Once the respiratory rate slowed (approximately one breath per second), the animals were removed from the inhalation chamber and sedated using nasal cone anesthesia (1-2% isoflurane). Depth of anesthesia was determined by the absence of a response to toe pinching.

[0349] Under anesthesia, a custom-made rod (D=4mm, L=40mm) was inserted through the anus to the splenic flexure. The same procedure was applied to the control group using the same non-illuminated rod. The same light source and measuring equipment were used as described in the liquid culture experiment.

[0350] In the first experiment, five BALB / cJ mice were exposed to colonic UVA (2,000 μWatt / cm²). 2 )30 minutes, compared with 5 mice treated with the same technique without light rods.

[0351] In the second experiment, 10 129S6 / SvEv mice were exposed to colonic UVA for 20 minutes daily for two consecutive days (3,000 to 3,500 μWatt / cm). 2 ), compared with 10 mice (male = 5) treated without light rods.

[0352] Colonoscopy before and after UVA light therapy

[0353] A rigid pediatric cystoscope (Olympus A37027A) was used to evaluate the intestinal mucosa before and after 7 days of UVA exposure. Endoscopic examination was performed in anesthetized animals. Sedation was performed as described above.

[0354] First, use water-based gel ( BioFilm, Inc., Vista, CA, USA) lubricated the anus. The endoscope was then inserted into the splenic flexure, and chamber air injected through the endoscope port was blown into the colon. All endoscopic examinations were recorded and blindly read by two gastroenterologists with expertise in endoscopy of animal models. Endoscopic appearance was analyzed based on perianal examination, intestinal wall transparency, mucosal bleeding, and focal lesions.

[0355] On day 14, control and treatment mice were euthanized, and a Swiss-roll preparation of the entire colon was performed. Briefly, the entire colon was removed and rinsed in modified Bouin fixative (50% ethanol / 5% acetic acid in dH2O solution). Using scissors, the colon was longitudinally opened along the mesenteric line and briefly rinsed in a Petri dish containing 1x PBS. The luminal side was identified, and the Swiss-roll preparation of the opened tissue was performed. Once the entire length of the colon was rolled up, the colon was carefully transferred to a tissue processing / embedding cassette. The cassette was incubated overnight in 10% buffered formalin at room temperature, and then paraffin sections of the colon were excised, stained with hematoxylin and eosin (H&E), and evaluated by an uninformed pathologist (SS).

[0356] The bacterial count data between groups were not normally distributed, and therefore a nonparametric test (Mann-Whitney U test) was used for comparison. Other quantitative data were compared using a t-test with GraphPad Prism 7 (GraphPad, San Diego, CA).

[0357] result

[0358] Overall, based on cell growth over time, LED UVA showed safety in the tested mammalian cell types (HeLa, alveolar A549, and primary tracheal cells). All plates exhibited sustained cell growth regardless of UVA exposure, with 1.5 to 2 times more cells cultured per plate compared to the control, demonstrating robust and sustained replication capacity. In the case of HeLa cells, compared to the unexposed control (P = 0.99 and P = 0.55, respectively, at approximately 2000 μWatt / cm²), the growth was significantly lower. 2 Compared to UVA exposure for 10 minutes and 20 minutes, UVA does not affect the number of viable cells over 24 hours. Figure 59A As shown. Higher intensity UVA (5000 μWatt / cm²) 2 It does not affect the growth of HeLa cells, such as Figure 59B The bar chart shown is illustrated below. Figure 59CAs shown, at 2000 μWatt / cm 2 Similar findings were also observed in alveolar cells after 20 minutes (P = 0.99). Finally, ciliated epithelial cell growth was observed in cells exposed to approximately 1000 μWatt / cm². 2 and approximately 2000 μWatt / cm 2 The intensity was not affected by UVA after 20 minutes.

[0359] Furthermore, exposure to UVA did not cause DNA damage in any of the cell lines analyzed, and as... Figure 59D (HeLa cells) Figure 59E (alveolar cells) and Figure 59F (Tracheal cells) As shown, the level of 8-Oxo-2'-deoxyguanosine (8-OHdG) in cells treated with narrow-band LED UVA was similar to that in the control group not exposed to UVA (P<0.05). Higher intensity LED UVA (5000 μWatt / cm²) 2 The study showed an increase in 8-OHdG levels (P = 0.07), but the percentage of 8-OHdG remained well below the generally accepted threshold of 0.01% for total DNA.

[0360] UVA light exposure is not associated with endoscopy or tissue damage.

[0361] To assess the safety of UVA treatment on visceral cells and tissues, two different wild-type mouse strains were exposed to broad-spectrum UVA light in the colon using an optical rod designed for uniform, side-exposure of broad-spectrum UVA. Only the left colon up to the splenic flexure was exposed to UVA light; therefore, the unexposed right side served as a self-control. In the first experiment, five mice under anesthesia received colonic UVA exposure (2,000 μWatt / cm²). 2 For 30 minutes, five mice received the same lightless optical rod treatment as a control.

[0362] In the second experiment, 10 mice (129S6 / SvEv, male = 5) were exposed to 20 minutes of broad-spectrum UVA (3,000 μWatt / cm) in the colon daily for two consecutive days. 2 Up to 3,500 μWatt / cm 2 UVA exposure was performed, with 10 mice (5 males) treated without light for comparison. No perforation, hemorrhage, or death was observed in any experiment. Colonoscopy images of the mice showed no changes before and after UVA exposure.

[0363] In both experiments, endoscopic evaluation of mice before and after UVA administration showed no macroscopic evidence of mucosal erythema, fragility, ulceration, or hemorrhage. Evaluation by an uninformed pathologist (SS) revealed no chronic / acute inflammation, cystitis, crypt abscesses, granulomas, ulcers, or developmental abnormalities in examined full-thickness colon specimens exposed to broad-spectrum UVA, compared to the control and untreated colonic sections.

[0364] Additional security data and results

[0365] Turning Figure 38 HeLa cells were grown for 24 hours and then treated with UVA light (1800 μWatt / cm²). 2 -2100μWatt / cm 2 Treatment lasts up to 20 minutes and is quantified by cell counting. Similarly, as... Figure 38 As shown, alveolar cells grew for 72 hours under UVA light (1800 μWatt / cm²). 2 -2100μWatt / cm 2 Treatment lasts up to 20 minutes and is quantified by cell counting. Figure 39 and Figure 40 The HeLa cell count and alveolar cell count are shown. When treated with UVA light, HeLa cells and alveolar cells had 99%–100% and 92%–100% survival rates, respectively, comparable to control cells not treated with UVA light. Similarly, when tested on HeLa cells with higher intensity UVA light (5000 μWatt / cm²), the survival rate was significantly improved. 2 )hour( Figure 41 HeLa cells treated with UVA light showed a survival rate of 97%–100%, compared to 98%–100% in the control group (HeLa cells not treated with UVA). This further highlights the safety of UVA treatment, particularly given the strength, wavelength, and duration of the antiviral therapy.

[0366] RNA virus experimental data

[0367] Furthermore, the disclosed system and method were used to obtain experimental data on the treatment of various RNA viruses with UVA light. Therefore, the data show that UVA light with a peak wavelength of 340 nm emitted from an LED can kill RNA viruses such as coxsackievirus. For example, HeLa cells infected with coxsackievirus survived when treated with this UVA light, but did not survive without UVA light treatment after infection. Moreover, experimental data show that only 15% of the UVA light is lost once the light passes through the ETT (Extra-Transfer Therapy).

[0368] In late December 2019, media reported an outbreak of a novel coronavirus disease (SARS-CoV-2 or COVID-19; formerly known as 2019-nCoV). COVID-19 is a viral infection that replicates effectively in the upper respiratory tract. As part of its mechanism of action, the virus infects the ciliated tracheal epithelial cells, which then slough off and impair alveolar function. Secondary bacterial infections have also been noted, and both processes can lead to further inflammation, acute respiratory distress syndrome (ARDS), and ultimately death. It is estimated that 10–15% of infected individuals have a severe clinical course, and approximately 5% become critically ill, requiring mechanical ventilation to cope with respiratory and other organ system failure. The case fatality rate of COVID-19 has been estimated between 0.5% and 9.5%, although these estimates are confounded by the priority testing of symptomatic patients and the lag time of symptom presentation, which can be up to 14 days. Death is considered to be due to respiratory failure in the ARDS environment and / or secondary infections, including ventilator-associated pneumonia (VAP).

[0369] Ventilator-associated pneumonia (VAP) can occur in patients in the intensive care unit (ICU) who are mechanically ventilated for at least 48 hours, and this is common in COVID-19 patients. The incidence of VAP ranges from 5% to 67%, depending on the diagnostic criteria used and the patient population studied. Pathogenic bacteria include Enterobacteriaceae (25%), Staphylococcus aureus (20%), Pseudomonas aeruginosa (20%), Haemophilus influenzae (10%), and Streptococcus (13%). Multidrug-resistant bacteria are more common in late-onset cases. The mortality rate of early-onset VAP is estimated to be approximately 6%, while the mortality rate of late-onset VAP is 10%.

[0370] Currently, there is no treatment for COVID-19, and routine methods for reducing secondary infections in mechanically ventilated patients have proven insufficient to date. A safe and effective broad-spectrum antiviral and antimicrobial regimen for these patients may reduce viral load, secondary infections and VAP, duration of mechanical ventilation, and death due to respiratory failure.

[0371] As disclosed herein, ultraviolet (UV) light possesses antibacterial properties. UVC (110-280 nm) is widely used for industrial sterilization, but it has harmful effects on human DNA. External UVA (320-400 nm) and UVB (280-320 nm) devices have FDA-approved indications for the treatment of human diseases such as psoriasis, eczema, and cutaneous lymphoma. These wavelengths penetrate mucous membranes and submucosal tissues. Of these three wavelengths, UVA exhibits the least damage to mammalian cells. Currently, no studies have shown the effects of internal application of UVA light on bacterial or viral infections.

[0372] Therefore, experimental data demonstrating the efficacy of broadband and / or narrowband UVA in treating common bacterial pathogens known to be associated with VAP have been disclosed. Furthermore, data demonstrating the effects of specific wavelengths of UVA on group B Coxsackievirus and coronavirus 229E have been disclosed. Finally, further data demonstrate the safety of UVA exposure to mammalian cells and in vivo epithelial cells.

[0373] Example 4: Coxsackievirus

[0374] Obtaining Coxsackievirus Samples and Infecting Cells

[0375] The plasmid expressing enhanced green fluorescent protein (EGFP-CVB) (pMKS1) was linearized using the ClaI restriction enzyme (ER0142, Thermo Fisher), and 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). The viral RNA was then transfected into HeLa cells (approximately 80% confluence) using Lipofectamine 2000 (11668027, Thermo Fisher). Once the cells exhibited approximately 50% cytopathic effect, the cells were scraped off and the cell / culture medium suspension was collected. This mixture was then subjected to three rapid freeze-thaw cycles and centrifuged at 1000 x g for 10 min to clarify the culture medium containing cell debris. The supernatant was used as the first-generation viral stock solution. The first-generation viral stock solution was then used to amplify the stock solution into a second-generation viral stock solution for subsequent experiments by covering individual HeLa cells (approximately 80% confluence).

[0376] UVA therapy for HeLa cells infected with group B Coxsackievirus

[0377] HeLa cells were used in four different experiments to express group B Coxsackievirus (EGFP-CVB) with enhanced green fluorescent protein (EGFP). In the first experiment, HeLa cells (253,000 cells per plate) (n = 12 plates) were cultured for 24 hours. Half of the EGFP-CVB aliquots were exposed to LED UVA (2000 μWatt / cm²). 2 Half of the cells were exposed to UVA (peak wavelength 340 nm) for 20 minutes, while the other half remained unexposed. HeLa cells were then infected with either UVA-exposed or UVA-unexposed virus (MOI = 0.1). Six hours later, the supernatant was removed, and the cells were washed twice with 1x sterile PBS (pH = 7.0). Fresh DMEM medium was added. Plates infected with the UVA-exposed virus were then subjected to UVA (2000 μWatt / cm²) for another 20 minutes. 2 Exposure. Dead cells in the supernatant were collected and quantified after 24 hours. Viable cells were evaluated in six plates (3 for UVA and 3 for no UVA treatment). Of the remaining six plates, the three initially exposed to UVA at a peak wavelength of 340 nm were subsequently exposed to UVA (2000 μWatt / cm²) for 20 minutes. 2 After another 24 hours, dead and live cell counts were obtained from the remaining plate.

[0378] HeLa cells were pretreated with UVA and then infected with group B Coxsackievirus.

[0379] In the second experiment, HeLa cells (235,000 cells) were plated and cultured in DMEM for 24 hours. The plates were then divided into an unexposed control group (n=3) and a group exposed to LED UVA (2000 μWatt / cm²). 2 The peak wavelength was 340 nm for 20 minutes (n=3). After another 24 hours, all plates were infected with EGFP-CVB (MOI=0.1). After another 24 hours, the cells were counted as described above.

[0380] Group B Coxsackievirus Pretreated with UVA Infection of HeLa Cells

[0381] In the third experiment, HeLa cells were cultured for 24 hours and then infected with EGFP-CVB (MOI = 0.1). Just before infection, half of the EGFP-CVB aliquots were exposed to LED UVA (2000 μWatt / cm²). 2 The peak wavelength was 340 nm, and the other half was not exposed. After 24 hours, live cell counts were obtained.

[0382] Long-term UVA therapy of HeLa cells during ongoing group B Coxsackievirus infection

[0383] In this experiment, 250,000 HeLa cells were plated. After 24 hours, the cells were divided into three groups. In group 1, cells were infected with EGFP-CVB (MOI = 0.1). These cells served as a positive infection control group. In group 2, cells were treated with UVA (2000 μWatt / cm²). 2 HeLa cells were infected with EGFP-CVB (MOI = 0.1) for 20 minutes (peak wavelength 340 nm), and 6 hours later, they were treated with UVA (2000 μWatt / cm²). 2 Infected cells were treated with UVA for 20 minutes at a peak wavelength of 340 nm, followed by four additional treatments (two 20-minute treatments on day 2, with an 8-hour interval between each treatment; and two 20-minute treatments on day 3, with an 8-hour interval between each treatment). Group 3 was uninfected with EGFP-CVB but treated with UVA five times at the same time points as Group 2. This served as a positive control for uninfected cells, demonstrating the safety of UVA. Imaging and cell counts were obtained under all conditions.

[0384] UVA therapy on alveolar (A549) cells infected with group B Coxsackievirus

[0385] In preliminary experiments with alveolar cells, the ideal time point for cell death after infection was determined to be 48 hours post-infection. In this study, 200,000 alveolar cells were plated and counted at 48 hours (cell count: 754,000). The alveolar cells were then infected with EGFP-CVB (MOI = 0.1). 24 hours post-infection, the alveolar cell plate was exposed to LED UVA (2000 μWatt / cm²). 2 The peak wavelength was 340 nm. The treatment was administered for 0 minutes (control) or 20 minutes (treatment), and repeated every 24 hours for 3 days. Imaging and cell counting were performed 96 hours after infection.

[0386] result

[0387] UVA pretreatment of group B Coxsackievirus before HeLa cell infection alone does not reduce infection.

[0388] In this experiment, half of the HeLa cells were transfected with EGFP-CVB, and the other half were exposed to approximately 2000 μWatt / cm². 2 EGFP-CVB treatment with LED UVA light at a peak wavelength of 340 nm for 20 minutes was observed. There was no difference in the 24-hour infection rate among the groups. Figure 60 ).

[0389] Pretreatment of HeLa cells with UVA prior to group B Coxsackievirus infection did not reduce viral effects.

[0390] In this experiment, one half of the plates containing HeLa cells were untreated, and the other half were treated with approximately 2000 μWatt / cm². 2 LED UVA pretreatment; peak wavelength 340nm, duration 20 minutes, no further UVA treatment. Both groups received EGFP-CVB. The infection rates were the same in both groups, indicating that pretreatment of HeLa cells does not affect the infection rate.

[0391] UVA treatment following group B Coxsackievirus infection reduced the virus's impact on HeLa cells.

[0392] In this study, UVA was applied after HeLa cells were infected with EGFP-CVB. The treated cells were then exposed to approximately 2000 μWatt / cm² of UVA 6 hours post-infection. 2 The peak wavelength of the LED UVA was 340 nm, and cell counting was performed twice daily for two consecutive days at 72 hours post-infection. This was compared to an infected but untreated control group. In the treated group, UVA light prevented EGFP-CVB-induced cell death, as shown in the untreated control group where no live cells remained on the plate at 48 and 72 hours. Figure 62 (Also shown) Figure 61 As shown in the bar graph, the cell count increased to 339,333 ± 60,781 at 72 hours. Importantly, the third group of uninfected HeLa cells, which received UVA irradiation at the same time intervals, showed normal cell proliferation, with a cell count of 2,413,333 ± 403,773 at 72 hours.

[0393] Figure 61 The effects of NB-UVA exposure on HeLa cells transfected with group B Coxsackievirus are shown. Images 6102 and 6104 show cells 24 hours post-transfection: compared to the UVA-exposed plate (right plate 6104, percentage of dead cells in supernatant = 16.1 ± 5.8%) (P = 0.002), the number of adherent cells in the unexposed plate was reduced (left plate 6102, percentage of dead cells in supernatant = 67.5 ± 11.0%). (Magnification = 4x, green light and bright field overlay). Images 6112 and 6114 show cells 48 hours post-transfection (left image 6112 shows no remaining viable cells (unexposed to UVA)). Right image 6114 shows the survival rate of cells exposed to UVA (magnification = 4x, green light and bright field overlay).

[0394] Effects of UVA treatment on alveolar (A549) cells infected with group B Coxsackievirus

[0395] In alveolar cells infected with EGFP-CVB, cell death was significantly lower than observed in HeLa cells. At 96 hours post-infection, the control group exhibited significant and widespread cell infection. Alveolar cells treated with LED UVA at a peak wavelength of 340 nm also showed infection, but visual assessment indicated a lower infection rate and far fewer cells producing viral EGFP signals. Furthermore, the UVA-treated group showed a significantly higher viable cell count compared to the untreated group.

[0396] Other experimental data on GFP-labeled Coxsackievirus B (EGFP-CVB)

[0397] Reference Figure 43 Fluorescence microscopy analysis was performed on HeLa cells transfected with EGFP-CVB, in which EGFP-CVB was treated with UVA (20 min, 345 nm peak wavelength) before transfection. The control group consisted of HeLa cells transfected with untreated EGFP-CVB. Figure 44A and Figure 44B (Control) The results of fluorescence microscopy analysis are shown. UVA proved to have no significant effect on extracellular Coxsackievirus. That is, as demonstrated by GFP fluorescence imaging, pre-treated and untreated GFP-CVB showed similar HeLa cell infection rates.

[0398] In addition, such as Figure 45 As shown, in another experiment, HeLa cells were pretreated with UVA before transfection with GFP-CVB. The control group consisted of untreated HeLa cells. Fluorescence microscopy analysis was performed 48 hours after transfection. Figure 46A and Figure 46B As demonstrated by the combined bright-field and fluorescence images, UVA pretreatment of HeLa cells had no significant effect on infection rate compared to the control group (untreated HeLa cells).

[0399] Evaluation of UVA treatment using fluorescence microscopy analysis of GFP-CVB-infected alveolar cells ( Figure 47 and Figure 48 )

[0400] Alveolar cells cultured for 24 hours were transfected with GFP-CVB, and fluorescence microscopy was performed at 48 hours to establish a baseline (Image 4802). Transfected cells were then treated with UVA, and imaging was performed at 24 hours (Image 4806) and 48 hours post-transfection (Image 4810). The control group consisted of GFP-CVB-transfected cells but without UVA treatment. The untreated control group was also imaged at 24 hours (Image 4804) and 48 hours (Image 4808) post-transfection. Figure 48The images show that UVA treatment resulted in a reduction of approximately 70% in GFP-CVB infection at 24 hours and approximately 90% at 48 hours. UVA treatment was performed using a UV LED with a peak wavelength of 345 nm for 20 minutes.

[0401] Evaluation of UVA treatment by quantitative analysis of HeLa cells infected with GFP-CVB ( Figure 49 and Figure 50 )

[0402] Counting of HeLa cells cultured for 24 hours prior to transfection with GFP-CVB ( Figure 50 (Time zero). After transfection, HeLa cells were cultured with GFP-CVB for 24 hours. At 24 hours, one group was treated with UVA. The control group consisted of GFP-CVB-transfected HeLa cells that were not treated with UVA. Final cell counts were performed on the UVA-treated and untreated GFP-CVB-transfected HeLa cells. Figure 50 As shown, the survival rate of HeLa cells significantly increased after UVA treatment. Similar to the above experiment, UVA treatment was performed using a UV LED with a peak wavelength of 345 nm for 20 minutes.

[0403] Example 5: Coronavirus

[0404] In another example, UV light was used to treat coronavirus-infected ciliated tracheal epithelial cells (HTeC), as described below.

[0405] Ciliated tracheal epithelial cells (Promocell, Heidelberg, Germany) were plated (135,000 cells per plate) in three groups. One group was infected with coronavirus 229E (Cov-229E) (50 μL per plate). In another group, cells were pretreated with a peak wavelength of 340 nm (2000 μWatt / cm²) just before infection. 2 LED UVA treatment for coronavirus 229E for 20 minutes. The third group did not receive either infection or UVA. After infection, daily UVA treatment (4cm distance, 2000 μWatt / cm² on the surface of the plate) was administered. 2 Cells were treated for 20 minutes with a peak wavelength of 340 nm. The plate was imaged at 16, 72, and 96 hours post-infection, and cell counts were obtained at 72 and 96 hours post-infection.

[0406] UVA is used to rescue ciliated tracheal epithelial cells infected with coronavirus 229E.

[0407] In this experiment, ciliated tracheal epithelial cells (HTeC) plates were infected with Cov-229E as described above. At 24 hours, the plates were divided into two groups. Group 1 was reserved for further infection. In Group 2, a peak wavelength of 340 nm (4 cm distance, 2000 μWatt / cm at the plate surface) was used. 2 A UVA treatment plate (at a certain intensity) was applied for 20 minutes. At 48 hours, the plate was imaged, and live cell counts were obtained.

[0408] UVA is used for brachytherapy of ciliated tracheal epithelial cells infected with coronavirus.

[0409] In the anticipated use of endotracheal devices employing UVA technology, low-intensity light (1300 μWatt / cm² at the plate surface from a distance of only 1 cm) is used. 2 (Intensity) Perform another experiment identical to the one described above for 20 minutes daily. This will be the expected distance between the light tube and the tracheal cells of the ventilated patient from inside the endotracheal tube.

[0410] Levels of coronaviruses in cells, whether or not treated with UVA

[0411] The AllPrep DNA / RNA / Protein Mini Kit (Qiagen) was used to extract total protein from cell samples. Protein was loaded into a Bolt 4-12% Bis-Tris gel (NW04122 Thermo Fisher) and transferred to a Biotrace NT nitrocellulose membrane (27376-991, VWR). Total protein was stained with Ponceau S solution (P7170, Sigma-Aldrich). The membrane was then blocked in 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 a blocking solution diluted with anti-coronavirus spike protein antibody (1:1000; PA5-81777, Thermo Fisher) or mouse anti-MAVS (mitochondrial antiviral signaling) antibody (1:200; SC-166583, Santa Cruz Biotechnology). After washing in Tris-buffered saline + 0.1% Tween 20 (TBS-T), the membrane was covered with either horseradish peroxidase (HRP)-labeled goat anti-rabbit IgG antibody (1:300; 95058-734, VWR) or HRP-labeled goat anti-mouse IgG antibody (1:300; 5220-0286, SeraCare). The membrane was then washed in TBS-T and subsequently exposed to an enhanced chemiluminescent solution (RPN2235, GE Healthcare). Imaging of the immunoreactive protein bands was performed using a ChemiDoc imaging system (Bio-Rad Laboratories, Hercules, CA USA).

[0412] LED UVA light protects ciliated tracheal epithelial cells infected with coronavirus 229E.

[0413] The treatment will use coronavirus 229E and 20 minutes of daily LED UVA (2000 μWatt / cm²). 2 Ciliated tracheal epithelial cells pretreated with a peak wavelength of 340 nm were compared with control cells (without UVA and uninfected) and cells infected with coronavirus but without UVA exposure. Direct visualization showed a clear change in cell morphology after infection (without UVA). However, control cells and infected cells treated daily with UVA showed similar morphology. At 96 hours, the supernatant was removed and viable cells (adhering to the plate) were counted. There was no difference in the number of tracheal cells between the UVA-treated control and infected cells. However, as Figure 63 As shown in the bar graph, the number of viable cells in the infected individuals was significantly reduced compared to those treated with UVA (P = 0.005).

[0414] Interestingly, infected cells treated with LED UVA exhibited reduced levels of Cov-229E spike (S) protein (~130 kDa) compared to untreated infected cells. Furthermore, cells infected with Cov-229E and treated with UVA showed increased levels of MAVS compared to cells infected with Cov-229E but not treated with UVA.

[0415] Therefore, experimental data confirm that UVA light kills coronavirus 229E after epithelial lung tissue is infected, and confirms its effectiveness in combination with ETT and other devices to irradiate lung tissue as a treatment for patients with coronavirus infection.

[0416] Microscopic analysis of cell morphology of tracheal cells transfected with coronavirus 229E

[0417] HTEpC (135,000 cells) were plated in three groups. Group 1 was transfected with CoV-229E (n=3, 50 μL per plate). In Group 2, CoV-229E was exposed to NB-UVA (n=3, 2000 μWatt / cm²) prior to transfection. 2 20 minutes. Group 3 was not exposed to NB-UVA or was transfected (n=3). After transfection, cells were exposed to NB-UVA (4 cm distance, plate surface intensity 2000 μWatt / cm) daily. 2 20 minutes. Plates were imaged at 16, 36, 72, and 96 hours post-transfection, and cell viability (live / dead) counts were obtained at 48 and 72 hours post-transfection. Live / dead cells were determined using 0.4% (1:1) Trypan Blue (Gibco), and cell counts were obtained using an automated cell counter (Biorad T20, Hercules, CA). Cells were maintained at 37°C (5% CO2).

[0418] Figure 51The images show phased comparisons of the effects of UVA treatment on coronavirus 229E infection in HTeC cells at A) 16 hours, B) 36 hours, C) 72 hours, and D) 96 hours post-transfection. Left panel images 5120, 5126, 5132, and 5138 show uninfected, untreated control cells; middle panel images 5122, 5128, 5134, and 5140 show cells transfected with coronavirus 229E; and right panel images 5124, 5130, 5136, and 5142 show cells transfected with coronavirus 229E and then treated with UVA. As shown, over time, cells transfected with coronavirus 229E exhibited increasing vacuolation and cell death, leading to decreased cell density. In contrast, transfected and UVA-treated cells remained viable and exhibited a morphology similar to the control group.

[0419] Figures 52 to 54 This is a bar graph showing the effect of UVA treatment on HTeC cells transfected with coronavirus 229E at 48 and 72 hours after treatment, compared with the untreated control group. Figures 52 to 54 It has been confirmed that UVA treatment improves cell survival in HTeC cells transfected with coronavirus 229E.

[0420] Example of human research: The effect of intratracheal UVA phototherapy on patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Figures 73 to 76 ).

[0421] Ultraviolet-A light is introduced into the endotracheal tube via catheter for 20 minutes daily for 5 days for newly intubated mechanically ventilated adults with SARS-CoV-2 infection and an endotracheal tube size of 7.5 mm or larger. Pregnant women are excluded. Concurrent therapy is permitted.

[0422] Primary results and measurements: The primary prior measure was respiratory SARS-CoV-2 viral load, obtained from tracheal aspiration before each treatment and on day 6. Clinical outcomes were assessed by day 30, including the World Health Organization (WHO) COVID-19 10-point ordinal clinical severity scale.

[0423] Results Summary: Five participants (mean age 56.6 years, including 3 males) were recruited. At baseline, all participants scored 9 / 10 on the WHO Clinical Severity Scale (10 = death), with an expected mortality rate ranging from 21% to 95%. The mean logarithmic changes in intratracheal viral load from baseline to days 5 and 6 were -2.41 (range -1.16 to -4.54; Friedman p = 0.002) and -3.2 (range -1.2 to -6.77; Friedman p < 0.001), respectively. The absolute bacterial load in the trachea remained constant from day 0 to day 6. No treatment-induced adverse events occurred during the 20-minute treatment period, and there were no changes in oxygenation or hemodynamics. One participant died 17 days after enrollment due to intracranial hemorrhage complications arising from anticoagulation therapy during extracorporeal membrane oxygenation (ECMO). The remaining participants survived and scored 2, 4, 5, and 7 on the WHO scale on day 30.

[0424] In this first-in-human study, endotracheal UVA treatment was safe and significantly reduced respiratory SARS-CoV-2 viral load during treatment. Details of the methods and results are provided below.

[0425] Experimental Design

[0426] In this first-ever human study, five participants were recruited and treated. Inclusion criteria included being over 18 years of age, a positive PCR test for SARS-CoV-2 on a nasal swab, and mechanical ventilation with an endotracheal tube (ETT) ≥7.5 mm in diameter. Pregnant women were excluded. Participants received all standard supportive care and were permitted to receive any other COVID-19 treatment concurrently.

[0427] UVA device

[0428] The UVA therapy device consists of a 5.4mm diameter sterile, sealed multi-LED UVA light conduit, an intratracheal adapter, an umbilical cord cable, and a control unit, all housed within a protective sheath. An example of a UVA therapy device is related to... Figures 64 to 69 The UV light therapy component described herein. The UVA catheter adapter uses a dual-rotating multi-channel port to connect to the ETT to maintain a closed-loop system and prevent environmental exposure to exhaled air when the catheter is introduced into the ETT.

[0429] program

[0430] Within 24 hours of recruitment, subjects received 20 minutes of UVA treatment, repeated once daily for a total of 5 consecutive days. All subjects received 30 minutes of 100% FiO2 prior to the procedure. The UVA catheter was inserted distally into the ETT, with the ventilator adjusting flow rate and respiratory volume to maintain optimal oxygenation. Plastic clips secured the catheter base to the access port to ensure stable and consistent insertion depth throughout the 20-minute treatment. Procedural educational videos are available at [link to video]. Dosage was selected based on the optimal response of human primary tracheal cells infected with coronavirus 229E to UVA exposure observed in in vitro experiments. A maximum of 2 mw / cm was delivered at the tracheal mucosal level. 2 Controlled UVA emission (peak wavelength 340 nm to 345 nm). Predetermined criteria for discontinuing treatment and removing the UVA catheter include O2 saturation falling below 88% or hemodynamic instability.

[0431] Tracheal (ET) aspirates were collected before each UVA treatment and 24 hours after the last UVA treatment to assess SARS-CoV-2 viral load and total bacterial abundance. Absolute quantification of bacterial load represents culturable and unculturable, viable and non-viable, pathogenic and non-pathogenic bacteria.

[0432] The global challenges associated with the COVID-19 pandemic serve as a painful reminder of the urgent need for safe and effective treatments for drug-resistant and / or novel pathogens. While externally applied UV therapy is commonly used for dermatological conditions, internal UV therapy has never been performed before. In this first-in-human study, intratracheal UVA light was shown to be safe in severely ill COVID-19 patients. Furthermore, a significant reduction in intratracheal SARS-CoV-2 levels was observed 5 days after UVA treatment.

[0433] A significant independent association was found between respiratory SARS-CoV-2 viral load and mortality. Severe COVID-19 cases exhibited a longer duration and later viral peak in respiratory samples compared to mild cases. Of the five participants, four had high viral loads in their baseline ET aspirates, regardless of the timing of symptom onset.

[0434] No treatment-induced adverse events occurred during the 25 UVA treatments, and serious / critical adverse events were not related to our intervention. Oxygenation and hemodynamics remained stable throughout all treatments. Bronchoscopy in two subjects showed normal tracheal appearance, consistent with our preclinical in vivo and in vitro safety studies. Although oxygenation was stable at the time of stroke, patient 2 died due to ECMO-related anticoagulation complications (intracranial hemorrhage). Hemorrhage occurs in approximately 50% of ECMO patients, with an 85% mortality risk associated with intracranial hemorrhage. Despite being in a highly critical condition, four of the five subjects survived with significant clinical improvement. Figure 73 )

[0435] The participants had a diverse distribution of several known risk factors for COVID-19 severity, including age (38–65 years), sex (2 women and 3 men), race (1 non-Hispanic white, 3 Hispanic white, and 1 African American), and BMI (range 25–36). Of the 5 patients, 3 had the minimum permissible ETT size (7.5 mm) without any TEAEs; however, patients with ETT < 7.5 mm were excluded. In this study, a logarithmic reduction of 3.2 after 5 days of UVA treatment exceeded the natural rate of decline in respiratory viral load.

[0436] Baseline, hospitalization, and ICU admission information, including relevant clinical, laboratory, and radiological data, were recorded for all patients up to 30 days after recruitment. The World Health Organization (WHO) COVID-19 10-point ranking severity scale was calculated at recruitment and on days 15 and 30 post-recruitment. 6 The SOFA and SAPS III scores are calculated based on the worst score within 24 hours of ICU admission.

[0437] Results and Statistical Analysis

[0438] The primary endpoint was the change in SARS-CoV-2 viral load from ET inhalation from day 0 to the last day of treatment. Secondary outcomes included changes in absolute bacterial load in the trachea and changes in clinical outcomes, including duration of mechanical ventilation, duration of stay in the ICU, and duration of stay in the ward; changes in laboratory parameters (including inflammatory markers); and changes in the WHO COVID-19 10-point Sequential Improvement Scale from baseline to day 15 and day 30.

[0439] The Freidman test was used to detect daily differences in viral and bacterial load. A one-sample t-test was used to analyze changes in inflammatory markers and bacterial load from day 0 to day 1. The Spearman rank test was used to assess correlation. A significance level of α = 0.05 was used.

[0440] result:

[0441] Five participants were recruited (mean age 56.6 years, 3 males). Figure 73 and Figure 76 The baseline characteristics of the recruited participants were summarized. At intubation, all five patients were critically ill, with a WHO COVID-19 Sequence Count (SQC) score of 9 and a SOFA score predicting a mortality rate of 20-95%. All patients received 20 minutes of treatment daily for five days, starting within the first 36 hours after intubation. Except for study subject #1, who was extubated on day 6, all patients received pre-treatment and ET aspiration on day 6. Therefore, a total of 29 ET aspirations were analyzed.

[0442] Primary and secondary results

[0443] Except for Subject 2, who had undetectable viral load at all time points (indicating viral clearance since the last nasal swab), all subjects had elevated viral load at baseline (range 3.4 x 10⁻⁶). 4 -1.64x10 7 (copies / ml). There was no significant correlation between the date of symptom onset and baseline (Spearman R = -0.70, p = 0.23) or viral load on day 6 (Spearman R = -0.21, p = 0.83).

[0444] From baseline to day 5 and day 6, the mean logarithmic changes in intratracheal viral load were -2.41 (range -1.16 to 4.54; Friedman p = 0.002) and -3.2 (range -1.2 to 6.77; Friedman p < 0.001), respectively. Figure 74 and Figure 75 )

[0445] The quantitative range of absolute intratracheal bacterial load at baseline is 1x10. 3 Up to 1.7x10 6 CFU / ml, and remained statistically significant during UVA treatment. (Not shown)

[0446] Figure 76 The course of illness for each subject is shown. The WHO Clinical Severity Scale score improved by an average of 1.6 points on day 15 and 3.6 points on day 30. Subject 2, whose baseline viral load was undetectable, improved by 4.75 points on day 30. (Not shown) All subjects survived except for subject 2, who received palliative care following intracranial hemorrhage induced by ECMO-related anticoagulation and died on day 17.

[0447] Safety results

[0448] No treatment-emergent adverse events (TEAEs) or early treatment discontinuation were observed in the study. Oxygen saturation and hemodynamics remained stable throughout all treatments. No subjects experienced pneumothorax, subcutaneous emphysema, or ETT displacement. Adverse events were considered unrelated to UVA treatment. Two subjects underwent bronchoscopy to place tracheostomy tubes to prolong intubation time; the trachea appeared normal, without erythema or fragility. The DSMB did not recommend any changes to the treatment protocol for future planned trials.

[0449] The disclosed UV phototherapy system and method offer numerous technical advantages. These advantages include significant improvements in the field of internal UV phototherapy. Furthermore, the disclosed light conduit configuration, including an LED assembly and a cooling tube with an open end within the light conduit, allows for the implementation of the UV light conduit with a small diameter, enabling its deployment within an ETT or NPA while providing adequate cooling. Additionally, the UVA wavelength, intensity, and duration disclosed herein provide effective and safe antiviral UV therapy. Moreover, the UV phototherapy system configuration provides effective internal treatment against viruses while the patient is ventilated by a mechanical ventilator.

[0450] In one embodiment, a UV light transmission device for performing in vivo ultraviolet therapy is provided, the device comprising: an elongated body separated by a proximal end and a distal end, wherein the elongated body includes at least one receiving space; at least one UV light source configured to be received at the at least one receiving space; wherein the at least one UV light source is configured to emit a wavelength having a peak wavelength of 340 nm between 320 nm and 410 nm. In one example of the device, the device may optionally include at least one UV light source positioned to emit radiation outward from the elongated body. A second example of the device may optionally include the first example and may further include a plurality of UV light sources dispersed along the length of the elongated body. A third example of the device may optionally include one or more of the first and second examples, and further includes a power source electrically connected to the at least one UV light source. A fourth example of the device may optionally include one or more of the first to third examples, and further includes wherein the elongated body includes four sides. A fifth example of the device may optionally include one or more of the first to fourth examples, and further includes that each of the four sides of the elongated body includes at least one receiving space, such that the corresponding plurality of UV light sources are staggered on the elongated body. A sixth example of the device may optionally include one or more of the first to fifth examples, and further includes a receiving space and a corresponding UV light source at the proximal end. A seventh example of the device may optionally include one or more of the first to sixth examples, and further includes that the elongated body is at least partially transparent. An eighth example of the device may optionally include one or more of the first to seventh examples, and further includes that the elongated body at least partially comprises borosilicate glass. A ninth example of the device may optionally include one or more of the first to eighth examples, and further includes that the elongated body at least partially comprises copper. A tenth example of the device may optionally include one or more of the first to ninth examples, and further includes that the elongated body comprises a copper body with a borosilicate glass coating. An eleventh example of the device may optionally include one or more of the first to tenth examples, and further includes a rotary motor configured to rotate the elongated body and consequently the at least one UV light source. A twelfth example of the device may optionally include one or more of the first to eleventh examples, and further includes a rotating base connected to the distal end of the elongated body, such that the elongated body is configured to rotate about the rotating base.

[0451] In some embodiments, a method for performing in vivo ultraviolet therapy may include: providing a UV light delivery device comprising: an elongated body separated into proximal and distal ends, wherein the elongated body includes at least two receiving spaces; and at least two UV light sources configured to be received at the at least two receiving spaces; and rotating the elongated body such that the at least two UV light sources are configured to emit UV light outward in a uniform manner. A first example of the method may further include emitting wavelengths with a peak wavelength of 340 nm between 320 nm and 410 nm from the at least two UV light sources. A second example of the method may optionally include the first example and further include emitting radiation outward from the elongated body from the at least two UV light sources. A third example of the method may optionally include one or more of the first and second examples, and further include wherein the elongated body includes four sides. A fourth example of the method may optionally include one or more of the first to third examples, and may further include wherein each of the four sides of the elongated body includes at least one receiving space, such that corresponding plurality of UV light sources are staggered on the elongated body. A fifth example of the method may optionally include one or more of the first to fourth examples, and may further include the elongated body including a receiving space and a corresponding UV light source at a proximal end. A sixth example of the method may optionally include one or more of the first to fifth examples, and may further include the elongated body being at least partially transparent. A seventh example of the method may optionally include one or more of the first to sixth examples, and may further include the elongated body comprising at least partially borosilicate glass. An eighth example of the method may optionally include one or more of the first to seventh examples, and may further include the elongated body comprising at least partially copper.

[0452] In another embodiment, a UV delivery device for performing in vivo ultraviolet therapy may include an elongated body separated into proximal and distal ends, wherein the elongated body includes at least one receiving space, wherein the elongated body and the at least one receiving space comprise a copper body and the elongated body comprises a borosilicate glass coating; and at least one UV light source configured to be received at the at least one receiving space. In a first example, the device may include wherein the at least one UV light source is configured to emit a wavelength having a peak wavelength in the range of 343 nm to 345 nm, between 320 nm and 410 nm. In a second example, which may optionally include the first example, the device may include wherein the at least one UV light source is positioned to emit radiation outward from the elongated body. In a third example, which may optionally include one or more of the first and second examples, the device may further include a plurality of UV light sources dispersed along the length of the elongated body. In a fourth example, which may optionally include one or more of the first to third examples, the device further includes a power source electrically connected to the at least one UV light source. In a fifth example, which may optionally include one or more of the first to fourth examples, the device further includes wherein the elongated body comprises four sides. In a sixth example of the device, which optionally includes one or more of the first to fifth examples, the device further includes the at least one UV light source comprising a light-emitting diode. In a seventh example of the device, which optionally includes one or more of the first to sixth examples, the device further includes the at least one receiving space on each of the four sides of the elongated body, such that corresponding plurality of UV light sources are staggered on the elongated body. In an eighth example of the device, which optionally includes one or more of the first to seventh examples, the device further includes a corresponding UV light source at a proximal end. In a tenth example of the device, which optionally includes one or more of the first to ninth examples, the device further includes a rotary motor configured to rotate the elongated body and consequently rotate the at least one UV light source. In an eleventh example of the device, which optionally includes one or more of the first to tenth examples, the device further includes a rotating base connected to the distal end of the elongated body, such that the elongated body is configured to rotate about the rotating base.

[0453] In another embodiment, a method of treating a patient with antibacterial agents includes irradiating the patient's internal tissues for at least 10 minutes with a light source emitting a set of wavelengths in the UV-A and / or UV-B range. A first example of the method may further include wherein the UV-A and / or UV-B range includes at least 320 nm to 345 nm. A second example of the method may optionally include the first example and further include wherein at least 10 minutes includes 18 minutes to 22 minutes. A third example of the method may optionally include one or more of the first and second examples and may further include wherein an intensity of 2,000 μWatt / cm is applied. 2 And the distance to the patient's internal tissues includes 0 to 1 cm.

[0454] Selected implementation plan

[0455] While the foregoing description and appended claims disclose several embodiments of the invention, other alternative aspects of the invention are disclosed in the following further embodiments.

[0456] Implementation Scheme 1. A system for performing in vivo ultraviolet therapy, the system comprising: an endotracheal tube (ETT); and a light conduit including: a light delivery portion including an LED array positioned to circumferentially emit light outward; a cooling tube including at least one opening; and an ETT connector configured to connect to the ETT.

[0457] Implementation Scheme 2. The system according to Implementation Scheme 1, wherein a portion of each LED in the LED group is in direct contact with the cooling pipe.

[0458] Implementation Scheme 3. The system according to Implementation Scheme 1, wherein, within the cooling tube, cooling gas flows in a first direction toward and out of the at least one opening, and flows back in the light guide tube in a second direction opposite to the first direction.

[0459] Implementation Scheme 4. The system according to Implementation Scheme 1 further includes a heat sink connected to each LED in the LED group.

[0460] Implementation Scheme 5. The system according to Implementation Scheme 1, wherein the LED group emits a peak wavelength in the range of 340nm to 349nm.

[0461] Implementation Scheme 6. The system according to Implementation Scheme 1, wherein the LED group emits wavelengths with peak wavelengths ranging from 343nm to 345nm between 320nm and 410nm.

[0462] Implementation Scheme 7. The system according to Implementation Scheme 1, wherein the LED group emits a peak wavelength in the range of 340nm to 345nm.

[0463] Implementation Scheme 8. The system according to Implementation Scheme 1, wherein the ETT connector includes a valve.

[0464] Implementation Scheme 9. The system according to Implementation Scheme 1 further includes a compressor system, the compressor system comprising: one or more processors; an air compressor; and a dual connector, the dual connector comprising an air connector and an electrical connector.

[0465] Implementation Scheme 10. The system according to Implementation Scheme 9 further includes an umbilical cable conduit comprising: an air channel; an electrical conductor; a light guide connector configured to connect to the light guide; and a compressor connector configured to connect to the compressor system.

[0466] Implementation Scheme 11. The system according to Implementation Scheme 10 further includes a light source controller, the light source controller including: one or more processors; a memory; a control system connected to the memory and including one or more processors, the control system being configured to execute machine-executable code to cause the LED group to emit light for a specified duration and intensity.

[0467] Implementation Scheme 12. The system according to Implementation Scheme 11, wherein the specified duration is at least 20 minutes, 40 minutes or 60 minutes per day and lasts for at least 1 day, 2 days, 3 days, 4 days or 5 days.

[0468] Implementation Scheme 13. The system according to Implementation Scheme 11, wherein the intensity comprises at least 1,100 μWatt / cm 2 1,500 μWatt / cm 2 2,000 μWatt / cm 2 2,100 μWatt / cm 2 2,200 μWatt / cm 2 2,300 μWatt / cm 2 2,400 μWatt / cm 2 2,500 μWatt / cm 2 2,600 μWatt / cm 2 2,700 μWatt / cm 2 2,800 μWatt / cm 2 2,900 μWatt / cm 2 3,000 μWatt / cm 2Or 2mw / cm 2 .

[0469] Implementation Scheme 14. A method of deploying the light guide in the system for performing in vivo ultraviolet therapy according to Implementation Scheme 11, the method comprising: connecting the ETT connector to the ETT; deploying the light guide into the ETT by pushing the light guide through the valve; providing an instruction to the controller to energize the LED group; and energizing the air compressor to pump air through the air channel into the cooling pipe and discharge it from the at least one opening.

[0470] Implementation Scheme 15. The method according to Implementation Scheme 14 further includes determining a temperature based on a signal received from a temperature sensor in thermal contact with the light transmission unit, and adjusting the flow rate of the air compressor based on the determined temperature.

[0471] Implementation Scheme 16. The method according to Implementation Scheme 14 further includes determining a temperature based on a signal received from a temperature sensor in thermal contact with the light transmission section, and adjusting the power transmitted to the LED by the light source controller based on the determined temperature.

[0472] Implementation Scheme 17. A method for treating a patient with a respiratory tract infection, the method comprising: intubating the patient with an ETT; connecting a light conduit to the ETT, wherein the light conduit includes an LED array and a cooling channel; and radiating UV-A light from the LED array outward along the basic length of the light conduit to treat the patient's infection while ventilating the patient.

[0473] Implementation Scheme 18. The method according to Implementation Scheme 17, wherein the infection includes at least one of pneumonia, bacteria, virus, RNA virus, coronavirus or SARS-CoV-2.

[0474] Implementation Scheme 19. The method according to Implementation Scheme 17, wherein the radiation is at 2,000 μWatt / cm 2 Perform at that intensity for 20 minutes.

[0475] Implementation Scheme 20. The method according to Implementation Scheme 17, wherein at least 1,000 μWatt / cm 2 The intensity of the radiation is measured.

[0476] Implementation Scheme 21. The method according to Implementation Scheme 17, wherein the infection is SARS-CoV-2 and the radiation is applied for at least 20 minutes per day for at least five days.

[0477] Implementation Scheme 22. The method according to Implementation Scheme 17, wherein the radiation is administered for at least 10 minutes and the intensity is 1,000 μWatt / cm. 2 Up to 5,000 μWatt / cm 2 between.

[0478] Implementation Scheme 23. The method according to Implementation Scheme 17, wherein a UV light source integrated in a conduit is used to perform outward radiation of light from the ETT, the conduit being introduced into the tube of the ETT.

[0479] Implementation Scheme 24. A method for treating a patient with a respiratory tract infection, the method comprising: intubating the patient with an ETT; and radiating UV-A light outward from the ETT to treat the infection.

[0480] Implementation Scheme 25: The method according to Implementation Scheme 24, wherein the infection includes at least one of pneumonia, bacteria, virus, RNA virus or coronavirus.

[0481] Implementation Scheme 26. The method according to Implementation Scheme 24, wherein the treatment lasts for 10 to 30 minutes and the intensity is 1,000 μWatt / cm. 2 Up to 5,000 μWatt / cm 2 The radiation between them.

[0482] Implementation Scheme 27. The method according to Implementation Scheme 24, wherein at least 1,000 μWatt / cm 2 The intensity of the radiation is measured.

[0483] Implementation Scheme 28. The method according to Implementation Scheme 24, wherein the treatment lasts for at least 10 minutes and the intensity is 1,000 μWatt / cm. 2 Up to 5,000 μWatt / cm 2 The radiation between them.

[0484] Implementation Scheme 29. The method according to Implementation Scheme 24, wherein at least 2,000 μWatt / cm 2 The intensity of the radiation is measured.

[0485] Implementation Scheme 30. The method according to Implementation Scheme 24, wherein the radiation is performed for 18 to 22 minutes.

[0486] Implementation Scheme 31. The method according to Implementation Scheme 24, wherein a UV light source separate from the ETT is used to perform outward radiation of light from the ETT.

[0487] Implementation Scheme 32. The method according to Implementation Scheme 24, wherein a UV light source integrated with the ETT is used to perform outward radiation of light from the ETT.

[0488] Implementation Scheme 33. A system for performing in vivo ultraviolet therapy, the system comprising: an endotracheal tube (ETT); and a UV light delivery device configured to emit light through a portion of the ETT.

[0489] Implementation Scheme 34. The system according to Implementation Scheme 33, wherein the UV light delivery device is separate from the ETT.

[0490] Implementation Scheme 35. The system according to Implementation Scheme 33, wherein the UV light delivery device is configured to be connected to the ETT.

[0491] Implementation Scheme 36. The system according to Implementation Scheme 33, wherein the UV light delivery device is configured to be mounted within the ETT.

[0492] Implementation Scheme 37. A method for performing in vivo ultraviolet therapy, comprising: providing a UV light delivery device including a UV light source; and inserting the UV light delivery device into a patient's nasal tube to treat an infection.

[0493] Implementation Scheme 38. The method according to Implementation Scheme 37, wherein the UV light source includes at least one LED, the at least one LED being configured to emit a peak wavelength in the range of 340 nm to 349 nm.

[0494] Implementation Scheme 39. The method according to Implementation Scheme 37, wherein the infection is a coronavirus infection or other RNA virus infection.

[0495] Implementation Scheme 40. The method according to Implementation Scheme 37, wherein the UV light source is directed to the respiratory tract.

[0496] Implementation Scheme 41. The method according to Implementation Scheme 37, wherein the UV light source is a UV-A light source.

[0497] Implementation Scheme 42. The method according to Implementation Scheme 37, wherein the UV light source is activated for 10 to 30 minutes.

[0498] in conclusion

[0499] The various methods and techniques described above provide multiple ways to implement the present invention. It should be understood, of course, that not all of the stated objectives or advantages can be achieved according to any particular embodiment described herein. Therefore, for example, those skilled in the art will recognize that the methods can be performed in a manner that achieves or optimizes one or more advantages as taught herein, without necessarily achieving other objectives or advantages as 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 mitigate a particular feature by including one, another, or several advantageous features.

[0500] Furthermore, those skilled in the art will recognize the applicability of the various features from different embodiments. Similarly, those skilled in the art can use the various elements, features, and steps described above, as well as other known equivalents for each such element, feature, or step, in various combinations to perform the method according to the principles described herein. In different embodiments, some of the various elements, features, and steps will be specifically included while others will be specifically excluded.

[0501] Although this application has been disclosed in the context of certain embodiments and examples, those skilled in the art will understand that the embodiments of this application extend beyond the specifically disclosed embodiments, thereby extending to other alternative embodiments and / or uses and variations thereof.

[0502] In some embodiments, the terms “a,” “an,” and “the,” as used in the description within the context of a particular embodiment of this application, and similar references (particularly in the context of certain following claims), may be understood to cover both the singular and the plural. References to numerical ranges herein are intended only as a shorthand method for individual references to each individual value falling within that range. Each individual value is included in the specification as if it were individually referenced herein, unless otherwise stated herein. All methods described herein may be performed in any suitable order unless otherwise stated herein or clearly contradicted by the context. Unless otherwise stated, the use of any and all examples or exemplary language (e.g., “such as”) provided with respect to certain embodiments herein is intended only to better clarify the application and does not constitute a limitation on the scope of the application. No language in the specification should be construed as indicating any unclaimed element essential to the implementation of this application.

[0503] This document describes certain embodiments of this application. Variations of these embodiments will become apparent to those skilled in the art upon reading the foregoing description. It is anticipated that those skilled in the art can appropriately employ such variations and implement this application in ways different from those specifically described herein. Therefore, many embodiments of this application include all variations and equivalents of the protected subject matter recited in the appended claims as permitted by applicable law. Furthermore, unless otherwise stated herein or clearly contradicted by the context, this application includes any combination of the foregoing elements in all their possible variations.

[0504] Specific embodiments of this subject matter have been described. Other embodiments are within the scope of the following claims. In some cases, the actions described in the claims can be performed in a different order and still achieve the desired result. Furthermore, the processes shown in the accompanying drawings do not necessarily require the specific order or sequence shown to obtain the desired result.

[0505] All patents, patent applications, published texts of patent applications, and other materials such as articles, books, specifications, publications, documents, and / or things cited herein, except for any history of litigation documents related to them, any content inconsistent with or conflicting with this document, or any content that may have a limiting effect on the broadest scope of the claims relating to the text now or thereafter, are incorporated herein in their entirety for all purposes. For example, if there is any inconsistency or conflict between the description, definition, and / or use of terms relating to any incorporated material and the description, definition, and / or use of terms relating to this document, the description, definition, and / or use of terms in this document shall prevail.

[0506] Finally, it should be understood that the embodiments of this application disclosed herein are illustrative of the principles of the embodiments of this application. Other variations may be adopted within the scope of this application. Therefore, as examples and not limitations, alternative constructions of the embodiments of this application can be used in accordance with the guidance herein. Thus, the embodiments of this application are not limited to the embodiments precisely illustrated and described.

Claims

1. A system for performing in vivo ultraviolet therapy, the system comprising: an endotracheal tube; and a light guide tube, the light guide tube comprising: a light delivery portion at a proximal end of the light guide tube, the light delivery portion comprising a set of LEDs positioned to emit light circumferentially outward, the set of LEDs configured to emit UV-A; a cooling tube comprising at least one opening toward the proximal end; and an endotracheal tube connector at the proximal end and configured to connect to the endotracheal tube, wherein the light guide tube is configured to be deployed into the endotracheal tube by advancing through the endotracheal tube connector such that a desired length of the light guide tube is placed within the endotracheal tube.

2. The system of claim 1, wherein, a portion of each LED in the set of LEDs is in direct contact with the cooling tube.

3. The system of claim 1, wherein, within the cooling tube, a cooling gas flows in a first direction toward the at least one opening and out via the at least one opening, and within the light guide tube, backflows in a second direction opposite the first direction.

4. The system of claim 1, further comprising a heat sink connected to each LED in the set of LEDs.

5. The system of claim 1, wherein, the set of LEDs emit a peak wavelength in the range of 340 nm - 345 nm or in the range of 340 nm to 349 nm.

6. The system of claim 1, wherein, the set of LEDs emit light only in the UV-A and UV-B ranges and not in the UV-C range, or the set of LEDs emits only UV-A light or wavelengths between 320 nm and 410 nm with a peak wavelength in the range of 343 nm to 345 nm.

7. The system of claim 1, wherein, the cooling tube is centrally placed relative to the LEDs.

8. The system of claim 1, wherein, the endotracheal tube connector comprises a flap valve.

9. The system of claim 1, further comprising a compressor system, the compressor system comprising: one or more processors; an air compressor; and a dual connector comprising an air connector and an electrical connector.

10. The system of claim 9, further comprising a umbilical tube, the umbilical tube comprising: an air channel; an electrical conductor; a light guide tube connector configured to connect to the light guide tube; and a compressor connector configured to connect to the compressor system.

11. The system of claim 10, further comprising a light source controller, the light source controller comprising: one or more processors; one or more memories connected to the one or more processors; the light source controller configured to execute machine executable code to cause the set of LEDs to emit light at a specified duration and intensity. the specified duration is at least 20 minutes, 40 minutes, or 60 minutes per day in at least 1 day, 2 days, 3 days, 4 days, or 5 days.

14. A method of deploying the light guide tube in the system for performing in vivo ultraviolet therapy of claim 11, the method comprising:

12. The system of claim 11, wherein, connecting the endotracheal tube connector to the endotracheal tube; 13. The system of claim 11, wherein, said intensity comprises at least 1,100 μWatt / cm 2 , 1,500 μWatt / cm 2 , 2,000 μWatt / cm 2 , 2,100 μWatt / cm 2 , 2,200 μWatt / cm 2 , 2,300 μWatt / cm 2 , 2,400 μWatt / cm 2 , 2,500 μWatt / cm 2 , 2,600 μWatt / cm 2 , 2,700 μWatt / cm 2 , 2,800 μWatt / cm 2 , 2,900 μWatt / cm 2 , 3,000 μWatt / cm 2 or 2 mWatt / cm 2 . deploying the light guide tube into the endotracheal tube by advancing the light guide tube through the endotracheal tube connector; ​ ​ providing instructions to the controller to energize the LED set; and energizing the air compressor to pump air through the air passageway into the cooling tube and out the at least one opening.

15. The method of claim 14, further comprising determining a temperature based on a signal received from a temperature sensor in thermal contact with the light delivery portion, and adjusting a flow rate of the air compressor based on the determined temperature.

16. The method of claim 14, further comprising determining a temperature based on a signal received from a temperature sensor in thermal contact with the light delivery portion, and adjusting power delivered to the LEDs by the light source controller based on the determined temperature.

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