JP2022552355A - internal UV therapy - Google Patents

Abstract

A UV light delivery device is provided for performing internal UV therapy. The device includes an elongated body separated by proximal and distal ends. The device also includes a UV light source configured to be housed in the housing space. In some embodiments, the UV light source is configured to emit light at wavelengths of significant intensity between 320 nm and 410 nm and is utilized in combination with an endotracheal tube or nasopharyngeal airway. [Selection drawing] Fig. 1D

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is filed March 20, 2020, U.S. Provisional Application No. 62/915,448, filed October 15, 2019, all entitled Internal Ultraviolet Therapy Provisional Application No. 62/992,861, U.S. Provisional Application No. 62/993,595 filed March 23, 2020, U.S. Provisional Application No. 63/000,788 filed March 27, 2020 and U.S. Provisional Application No. 63/012,727, filed April 20, 2020, the contents of which are incorporated herein by reference.

FIELD OF THE DISCLOSURE The present invention is directed to systems and methods for internal ultraviolet therapy.

BACKGROUND OF THE DISCLOSURE The following description includes information that may be useful in understanding the present invention. Any publication to which any of the information provided herein is either prior art or relevant to the presently claimed invention or to which it is specifically or implicitly referenced is not an admission that is prior art.

Infectious, immune-mediated and inflammatory diseases continue to pose a global challenge. Despite significant advances in the last few decades, treatment of these diseases is still suboptimal. For example, many patients develop upper respiratory tract infections and pneumonia while on ventilators, which can lead to death. For example, a patient on ventilator therapy is intubated with an endotracheal tube (“ETT”) and can acquire an infection (eg, pneumonia) through the ventilator system. Therefore, there is a need to reduce the rate of infections, such as viral and bacterial infections, in somatic systems such as the respiratory system of patients.

SUMMARY OF THE DISCLOSURE A UV light delivery system is provided for performing internal UV therapy. The system includes a delivery tube adapted to be placed inside an endotracheal (ET) tube, nasopharyngeal airway (NPA), or other similar device, and a UV light delivery tube adapted to deliver UV light out of the delivery tube. and at least one UV light source within the delivery tube disposed in the at least one UV light source, the at least one UV light source configured to emit a wavelength between 335 nm and 350 nm. The delivery tube can be transparent or partially transparent.

At least one UV light source may be a series of LED light sources. In some examples, the series of LED light sources can be configured to emit UV light with peak wavelengths between 335-350 nm, or between 338-342 nm. A UV light source may be configured to emit light between 335 nm and 350 nm at a threshold intensity sufficient to treat infections.

A UV light source may be configured to deliver UV light along a substantial length of the delivery tube. The delivery tube can be a catheter. A UV light source may be configured to emit only light with an intensity greater than 10% of its maximum intensity between 335 nm and 350 nm.

The system also includes a delivery tube adapted to be positioned inside an endotracheal delivery (ET) tube, and at least one UV wavelength within the ET delivery tube positioned to emit UV wavelengths out of the ET delivery tube. and at least one UV light source configured to emit a wavelength between 335 nm and 350 nm. UV light sources may be configured for intermittent emission. The UV light source may be configured to emit wavelengths including at least one of UV-A and UV-B, or only UV-A.

The system may further comprise a power supply connected to the UV light source.

The UV light source can be configured to treat infectious agents within the ET tube and within the larynx.

Also disclosed is a method of treating a patient for an infectious condition within the patient's body, the method comprising inserting a delivery tube inside a patient's cavity for breathing; Emitting UV-A light in the region of 335-350 nm from the light source and emitting UV wavelengths out of the delivery tube at a threshold intensity for a threshold duration.

The method may include a delivery tube that is a catheter with a series of LED light sources with peak wavelengths between 339-346 nm. The respiratory cavity can be the trachea or nasopharynx.

Infectious conditions may be selected from the group consisting of bacterial infections, viral infections, fungal infections, pneumonia, and combinations thereof.

A threshold duration may include at least 20 minutes. The threshold intensity can include at least 13, 15, or 18 W/m2. The threshold intensity is at least 1,100 microwatts/ ^cm2 , 1,100 microwatts/ ^cm2 , 2,000 microwatts/ ^cm2 , or 2,100 microwatts/ ^cm2 , 2,200 microwatts/ ^cm2 , or an intensity of 2,300 microwatts/cm ² .

The delivery tube can be inserted inside the endotracheal tube. Alternatively, the delivery tube can be inserted inside the endotracheal tube while suctioning the endotracheal tube.

Additional features and advantages disclosed herein will be set forth in, and in part will be apparent from, the description that follows, or may be learned by practice of the principles disclosed herein. . The features and advantages disclosed herein may be realized and obtained by means of the instrumentalities and combinations particularly pointed out in the appended claims. These and other features disclosed herein will become more apparent from the ensuing description and appended claims, or may be learned by practice of the principles presented herein.

For purposes of describing the manner in which the above disclosure and the advantages and features thereof may be obtained, a more specific description of the principles set forth above will be made by reference to the specific examples illustrated in the accompanying drawings. These drawings represent only exemplary aspects disclosed herein, and are therefore not to be considered limiting of its scope. These principles are described and explained with additional specificity and detail through the use of the following figures.

FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's colon, according to the principles disclosed herein. FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's vagina, according to the principles disclosed herein; FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's trachea, according to the principles disclosed herein. FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's nasopharynx, according to the principles disclosed herein; 1 shows a schematic diagram of an exemplary UV light emitting device incorporating LEDs, according to the principles disclosed herein; FIG. 1 shows a schematic diagram of an exemplary UV light emitting device incorporating a cold cathode, according to the principles disclosed herein; FIG. 1 shows an exemplary schematic diagram of a UV spectrum, according to the principles disclosed herein; FIG. FIG. 2 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's rectum and sigmoid colon, according to the principles disclosed herein. FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's colon, according to the principles disclosed herein. FIG. 10 shows a cross-sectional view of a UV light emitting device inserted into a patient's esophagus and stomach, according to the principles disclosed herein. FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device passing through a patient's digestive system, according to the principles disclosed herein. 1 illustrates a side view of an exemplary light source attachment, according to principles disclosed herein; FIG. 1 illustrates a side view of an exemplary light source attachment, according to principles disclosed herein; FIG. 1 illustrates an exemplary Foley catheter incorporating an exemplary UV light emitting device according to the principles disclosed herein; FIG. 2 shows growth curves for E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. FIG. 4 shows growth curves for E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. 1 shows an exemplary UV light emitting device implemented in the colon of a mouse according to the principles disclosed herein. 14A and 14B show an exemplary UV light emitting device disclosed herein inserted into the vaginal canal of a rat according to the principles disclosed herein. FIG. 15A shows growth curves for liquid cultures containing E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. 15B shows an exemplary UV light emitting device disclosed herein implemented in a liquid culture containing E. coli. FIG. 2 shows a growth curve of a liquid culture containing E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. 17A and 17B show growth curves of liquid cultures containing E. coli when implementing exemplary UV light emitting devices disclosed herein. FIG. 2 shows a growth curve of a liquid culture containing E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. FIG. 2 shows a growth curve of a liquid culture containing E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. FIG. 2 shows a growth curve of a liquid culture containing E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. A and B show growth curves of liquid cultures containing E. coli when implementing an exemplary UV light emitting device disclosed herein. 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 23 shows the exemplary UV light emitting device of FIG. 22 attached to a grasping element 200, according to embodiments disclosed herein. 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary process for providing internal ultraviolet therapy, according to embodiments disclosed herein. 1 illustrates an exemplary process for providing internal UV therapy in connection with ETT, according to embodiments disclosed herein. 1 shows a table showing the intensity and duration of exposure of UVA light applied to bacterial cultures in one example. FIG. 4 shows a table showing bacterial counts over time during UV light exposure in one example. 4 shows a growth curve showing bacterial counts over time during UV light exposure using an exemplary system according to the present disclosure; Time lapse images of Petri dishes containing bacteria exposed to UV light are shown compared to controls. FIG. 4 shows growth curves showing E. coli bacterial counts over time exposed to various intensities of UV light using an exemplary system according to the present disclosure; FIG. FIG. 4 shows growth curves showing E. coli bacterial counts over time exposed to various intensities of UV light using an exemplary system according to the present disclosure; FIG. FIG. 4 shows growth curves showing E. coli bacterial counts over time exposed to various intensities of UV light using an exemplary system according to the present disclosure; FIG. FIG. 4 shows growth curves showing E. coli bacterial counts over time exposed to various intensities of UV light using an exemplary system according to the present disclosure; FIG. (Intentionally omitted.) FIG. 4 shows growth curves showing P. aeruginosa bacterial counts over time exposed to varying intensities of UV light using an exemplary system according to the present disclosure. FIG. 4 shows growth curves showing Pseudomonas aeruginosa bacterial counts over time exposed to varying intensities of UV light using an exemplary system according to the present disclosure. FIG. 4 shows growth curves showing Pseudomonas aeruginosa bacterial counts over time exposed to varying intensities of UV light using an exemplary system according to the present disclosure. FIG. 4 shows growth curves showing Pseudomonas aeruginosa bacterial counts over time exposed to varying intensities of UV light using an exemplary system according to the present disclosure. FIG. 4 shows growth curves comparing logarithmic reduction at various intensities at 20 and 40 minutes, respectively, using an exemplary system according to the present disclosure. FIG. 4 shows growth curves comparing logarithmic reduction at various intensities at 20 and 40 minutes, respectively, using an exemplary system according to the present disclosure. FIG. 4 shows growth curves showing reduction in E. coli colony size at various intensities and treatment times using an exemplary system according to the present disclosure. FIG. 4 shows growth curves showing reduction in Pseudomonas aeruginosa colony size at various intensities and treatment times using an exemplary system according to the present disclosure. 4 shows a bar graph showing cell proliferation during exposure to UV-A light using an exemplary system according to the present disclosure; 4 shows a bar graph showing cell proliferation during exposure to UV-A light using an exemplary system according to the present disclosure; 4 shows a bar graph showing cell proliferation during exposure to UV-A light using an exemplary system according to the present disclosure; FIG. 4 shows a bar graph showing no DNA damage to cells during exposure to UV-A light using an exemplary system according to the present disclosure; 4 shows a bar graph showing lack of DNA damage to cells during exposure to UV-A light using an exemplary system according to the present disclosure; 4 shows a bar graph showing lack of DNA damage to cells during exposure to UV-A light using an exemplary system according to the present disclosure; FIG. 4 shows a bar graph showing proliferation of virus-infected cells during exposure to UV light using an exemplary system according to the present disclosure; FIG. FIG. 10 shows a bar graph showing the cell count of infected cells compared to controls after 72 hours of UV light application using an exemplary system according to the present disclosure.

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

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

As used herein, "ETT" refers to an endotracheal tube, which is a flexible tube that is placed through a patient's mouth into the trachea and connected to a ventilator to assist the patient's breathing.

As used herein, "NPA" refers to a nasopharyngeal airway, which is a flexible tube that is placed through the nasal cavity and over the base of the tongue to help open the airway.

As used herein, the term "LED" refers to a light emitting diode, which is a semiconductor light source that emits light across various visible and non-visible light spectrums. LEDs typically have emission spectra that include a range of wavelengths with varying intensities over their emission spectral region, and typically follow a bell-shaped or similarly shaped intensity curve over the wavelength region. A particular LED is typically characterized using the wavelength of its peak emission intensity, or the wavelength at which the LED emits its highest intensity radiation.

Thus, an LED typically emits light over a range of wavelengths, and a particular LED also uses the range of wavelengths for which it emits above a threshold intensity (in some embodiments, a percentage of the LED's maximum intensity). can be characterized. For example, a given LED may emit light 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 emission intensity of the LED is less than 10% of the peak intensity emission wavelength (herein "peak wavelength") of the LED, and in some cases too low to be therapeutically relevant. there is a possibility. Therefore, for many therapeutic applications, only wavelengths between 335 nm and 345 nm will affect the therapy of that particular LED.

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

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

Various embodiments of the invention will now be described. The following description provides specific details for a thorough understanding and enabling description of these embodiments. One skilled in the art will understand, however, that the invention may be practiced without many of these details. Likewise, those skilled in the art will also appreciate that the invention may include many other obvious features not described in detail herein. Additionally, some well-known structures or functions may not be shown or described in detail below to avoid unnecessarily obscuring the related description.

The terms used below are to be interpreted in their broadest reasonable, even when used in conjunction with the detailed description of certain specific embodiments of the invention. In fact, certain terms may even be emphasized below. However, terms that are intended to be interpreted in a restrictive manner are clearly and specifically defined as such in the Detailed Description section.

Although this specification provides details of many specific embodiments, these should not be construed as limitations on the scope of any invention or what may be claimed; It should be construed as a description of features that are characteristic of particular embodiments of particular inventions. Certain features that are described in this specification in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Further, while features are described above as functioning in particular combinations, and may even be originally claimed as such, one or more features from a claimed combination may in some cases be The claimed combination may be separated from the combination and may cover any subcombination or variations of the subcombination.

Similarly, although operations may appear in the figures in a particular order, it is understood that such operations may be performed in the specific order shown or in a sequential order to achieve desirable results. It should not be understood as requiring that all illustrated operations be performed or that all illustrated operations be performed. Multitasking and parallel processing may be advantageous in certain situations. Furthermore, the separation of various system components in the above embodiments should not be understood to require such separation in all embodiments, and the described program components and system generally: It should be understood that they may be integrated together in a single software product or packaged in multiple software products.

Overview UV light in the UV-A region and UV-B region has been used for the treatment of skin diseases, but has not been developed for the treatment of wider infections or inflammations inside the human body. The present disclosure describes a system for emitting therapeutic doses of UV light through a catheter, capsule, endoscope, tube, or port that can be used to manage internal infectious and inflammatory conditions within a patient. do. The UV light source disclosed herein provides a safe and effective alternative to antibiotics and anti-inflammatory/immunosuppressive agents to various internal tracts of patients (e.g., colon, vagina, trachea). It is an object.

In some examples, only UV-A light or only UV-B light may be emitted for certain indications and treatments. For example, the UV light source may have wavelengths centered at or in the region 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 a peak intensity of emission within that region. It should be appreciated that various wavelengths can be provided using the present systems and methods. In some examples, the wavelength region provided can be the longest possible wavelength that is therapeutically effective at a particular intensity and duration of application.

FIG. 1A shows an example of a UV light management system that includes a delivery tube 100 and several UV light sources 150 and a power supply 120 for powering the system. Thus, as shown, a caregiver (eg, a physician) can guide delivery tube 100 into the patient's colon. Once navigated to the patient's intended treatment target, power supply 120 may be energized to emit UV light from light source 150 to the treatment target (eg, colon).

FIG. 1B shows an example of a UV light management system that includes a delivery tube 100, several UV light sources 150, and a power supply 120 for powering the system. Thus, a caregiver (eg, a doctor) can guide delivery tube 100 into the patient's vagina. Once guided into the patient's vagina, delivery tube 100 can be energized by power source 120 to emit therapeutic light (eg, UV light) into the vaginal canal. The UV light source disclosed herein is intended to provide a safe and effective alternative to antibiotics and anti-inflammatory/immunosuppressive agents to the colonic and/or vaginal area.

FIG. 1C shows an embodiment of a UV light management system including delivery tube 100, UV light source 150, power supply 120, and control system. A control system supplies power and controls the duration and/or intensity of therapy. Thus, as shown, a caregiver (eg, a physician) can guide the delivery tube 100 into the patient's trachea during mechanical ventilation. When navigated to the patient's trachea, power source 120 is energized, thereby powering power source 150 via delivery tube 100 (eg, a wired connection) to the trachea and/or other respiratory trachea. It is possible to emit therapeutic light (eg UV light).

For example, as disclosed herein, systems and methods have been developed for providing internal ultraviolet therapy in combination with an endotracheal tube (ETT). Therefore, the delivery tube 100 can be guided within the ETT during patient ventilation. In other examples, the delivery tube 100 can be connected to or incorporated into the ETT, or the ETT can have the light source 150 incorporated into the ETT. Accordingly, the light source 150 may be positioned within the tube 150 and/or the ETT such that the UV light source 150 illuminates respiratory tissue within the tracheal airway surrounding the ETT.

FIG. 1D shows an embodiment of a UV light management system including delivery tube 100, UV light source 150, power supply 120, and control system. A control system supplies power and controls the duration and/or intensity of therapy. Thus, as shown, a caregiver (eg, a physician) can guide the delivery tube 100 to the patient's nasopharynx. When directed to the patient's nasopharynx, power source 120 is energized, thereby powering power source 150 via delivery tube 100 (e.g., a wired connection) to power the nasopharyngeal and/or other respiratory tract. It is possible to emit therapeutic light (eg, UV light) into the trachea.

For example, as disclosed herein, systems and methods have been developed for providing internal ultraviolet therapy in combination with a nasopharyngeal airway (NPA). Thus, the delivery tube 100 can be guided within the patient's NPA. In some embodiments, delivery tube 100 can be sized and configured to fit a nasopharyngeal airway. In some embodiments, delivery tube 100 may be flexible to accommodate the curvature of the nasopharyngeal airway. In other examples, the delivery tube 100 can be connected to or integrated into the NPS, or the NPA can have the light source 150 integrated into the NPA. Thus, light source 150 may be positioned within tube 150 and/or NPA such that UV light source 150 illuminates respiratory tissue within the nasopharynx surrounding the NPA.

Delivery System A delivery tube/rod 100 is provided for delivering therapeutic UV light to various parts of the body. The delivery tube/rod can contain at least one UV light source 150 . Delivery tube/rod 100 can be a catheter, endoscope, capsule (for swallowing or suppositories), or any other medical device configured to house UV light source 150 .

In some examples, the UV delivery tube 100 may be configured as a catheter and may be guided inside the ETT or NPA during respiratory therapy or other therapy of the patient. In some embodiments, the UV delivery tube/rod 100 is configured as an endoscope, which is inserted rectally or orally and directed to the appropriate area to deliver an anti-inflammatory or other therapeutic dose. Deliver UV light. In another embodiment, UV delivery tube/rod 100 can be configured as a catheter that is inserted into an artery, urethra, vagina and urinary tract, ear canal, airway, and the like. In yet another embodiment, UV delivery tube/rod 100 is configured as an indwelling urethral catheter that is inserted into the patient's bladder. In some embodiments, for an inflatable balloon catheter to emit UV light inside a visceral passageway, such as the vagina, rectum, gastroesophageal junction, stomach, biliary tract, or other suitable passageway, A UV light source 150 may be included. In some embodiments, the UV light source 150 can be configured as a caregiver's glove. This configuration can help deliver UV light to a patient's orifice (eg, mouth, rectal, vaginal, or other orifice) for shorter duration treatments.

In some embodiments, UV light source 150 is permanently attached to delivery tube/rod 100 . In other embodiments, delivery tube/rod 100 is configured such that UV light source 150 is configurable to the physician's preference and is attachable and detachable. Delivery tube/rod 100 can include a hollow interior to allow electrical connection to UV light source 150 . In alternative embodiments, UV light source 150 may be wireless and capable of being coupled to delivery tube/rod 100 .

Light Sources Depending on the delivery tube 100 or other delivery device, various light sources 150 capable of emitting UV light are available. For example, FIG. 2 shows an embodiment of a flexible delivery tube 100 (eg, catheter, endoscope, etc.) that includes a series of LED light sources 150 distributed along the tube 100 . In other embodiments, other suitable light sources 150 capable of emitting UV light can be utilized. Each of the light sources 150 is mounted with electrical connections and connected to the power source 120 . LED light sources 150 may be advantageous because their small size and low power requirements allow them to be placed along delivery tube 100 .

Light source 150 may include a control system including circuitry, memory, and one or more processors for controlling the intensity and duration of the output of light source 150 . The control system may include instructions executable by one or more processors for controlling the output of light source 150 . In some examples, the control system may be connected to light source 150 via a wired connection and/or a wireless connection.

Thus, when 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. Therefore, the treatment target area is relatively large and inflammatory diseases that can affect large portions of the colon can be treated.

FIG. 3 shows an embodiment of delivery tube 100 utilizing a cold cathode-based light source 150 connected to power supply 120 . In this embodiment, cold cathode light source 150 delivers light through transparent, flexible delivery tube 100 . This embodiment may include an inert gas filling the delivery tube (or vacuum tube) 100 . Delivery tube 100 may include, for example, a cold cathode tube. Delivery tube 100 may include any cathode emitter that is not electrically heated by a filament. Cold cathode fluorescent lamps, for example, can emit ultraviolet light using discharges of mercury vapor.

However, in most embodiments the gas used in the tube should be inert for safety. For example, a neon gas vapor can be energized with a 12 volt power supply 120 to generate sufficient UV light. In other embodiments, other power supplies with different voltages and/or currents are used to generate sufficiently intense light at the present wavelengths.

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

Power supply 120 may include an on/off switch or other control to turn light source 150 on and off. In some embodiments, the power supply will include the ability to turn on the UV light source at different intensities or adjust the intensity over time depending on where the treatment is being applied. The power supply may vary depending on the type of UV light source 150. For example, the power requirements of LED implementations may be less than the power requirements of cold cathode implementations.

UV Region FIG. 4 shows the UV region that can be implemented by the disclosed device and method. For example, the light source may emit light only in the UV-A and UV-B ranges and not in the UV-C range. In other embodiments, the system and method can emit light in all three UV regions, or can emit light in the visible spectrum. In some embodiments, only UV-A or only UV-B light may be emitted for specific indications and treatments. As previously mentioned, the light source may have a wavelength of maximum intensity centered at 335 nm, 340 nm, or 345 nm, or a region of wavelengths therearound. In other embodiments, light source 150 may emit light in wavelengths between 320 nm and 410 nm, between 250 nm and 400 nm, or other suitable ranges discussed herein.

In some examples, the applied wavelength range may be the longest wavelength range that is therapeutically effective (given the intensity and duration of therapeutic application) for a particular application. For example, the shorter the wavelength, the more likely the treatment will damage the patient's body cells or tissues. Therefore, it is safest to apply the longest wavelength available.

In some embodiments, light sources centered around 345 nm or 340 nm (or ambient wavelengths) may be best, as smaller/shorter wavelengths become more harmful as we approach the UV-C region. For example, the shorter the wavelength, the more energy it has and the more likely it is to damage the patient's tissue and DNA. In some embodiments, the longest wavelengths that still provide sufficient antimicrobial efficacy and are still the safest wavelengths to be effective include: , 344, 345, 346, 347, 348, 349, or 350 nm. Accordingly, the light source 150 disclosed herein can emit light having one or more of the aforementioned wavelengths at therapeutically significant intensity.

In some embodiments, the light source is at It may be an LED with a peak wavelength. In some embodiments, the peak wavelength of the LED may have an error of +/−3 nm, 2 nm, or 1 nm. In some examples, the LED can emit light of significant intensity in the range of +/−4, 5, or 6 nm around its peak intensity emission wavelength. Thus, in some examples, the wavelength range of the LED or other light source can be 340-350 nm (eg, a wavelength range that includes wavelengths with significant emission intensity).

Treatment Regimens The procedures herein can be utilized to treat a number of different inflammatory and infectious diseases. Thus, 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. , different amounts or durations of doses of UV radiation can be administered. For example, in some embodiments, administration time is determined by capsule digestion rate, and other factors (eg, light source power, UV range, etc.) can be manipulated to vary dosage.

In other examples, the phototherapy is administered for 10 minutes, 15 minutes, 18 minutes, 19 minutes, 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, 26 minutes, 27 minutes, 28 minutes, 29 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, or 160 minutes, any range of minutes between 10 minutes and 160 minutes, or other suitable time may be provided by the caregiver. Additionally, the method of the present invention comprises at least 10 minutes, 15 minutes, 18 minutes, 19 minutes, 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, 26 minutes, 27 minutes, 28 minutes, 29 minutes. administering therapy for a threshold duration of , 30 minutes, or 60 minutes. The light source intensity is at least 1,000 microwatts/ ^cm2 , 1,100 microwatts/ ^cm2 , 2,000 microwatts/ ^cm2 , 2,100 microwatts/ ^cm2 , 2,200 microwatts/ ^cm2 , 2,300 microwatts/ ^cm2 , 2,400 microwatts/ ^cm2 , 2,500 microwatts/ ^cm2 , 2,600 microwatts/ ^cm2 , 2,700 microwatts/ ^cm2 , 2,800 microwatts /cm ² , 2,900 microwatts/cm ² , 3,100 microwatts/cm ² , 3100 microwatts/cm ² , 3,200 microwatts/cm ² , 1,000-5,000 microwatts/cm ² , or other suitable strength, depending on factors associated with therapeutic efficacy such as its application. The inventors have determined that UV-A light can be safely applied up to an intensity of 5,000 microwatts/cm ² . In some embodiments, the light will be emitted continuously, and in other embodiments the light will be incorporated into pulse therapy.

The light source 150 can be at various distances from the target based on intensity and target organism. For example, in some embodiments, light source 150 is positioned within 0-2 cm from E. coli (instead of 2.8 cm or 3.5 cm) to kill E. coli using an intensity of 2000 microwatts/cm ² . It may be necessary to have In some examples, the intensity may be 1000-5000 microwatts/cm ² and the distance to the target tissue is 0-1 cm, 0-1.5 cm, 0-2 cm, 0-2.5 cm, It may be 0-3.0 cm, 0-3.5 cm, 0-4.0 cm, or other similar suitable ranges based on light intensity and target pathogen. In other examples, the required timing, distance, wavelength, and intensity may vary depending on the target, such as virus.

Control System In some embodiments, a control system is utilized to control the intensity and duration of the wavelengths emitted from the UV light source. Examples of LED control systems are described, for example, in US Pat. No. 8,350,497, entitled "Method and apparatus for outputting light in a LED-based lighting system," the contents of which are incorporated by reference. is incorporated herein in its entirety.

Accordingly, in some cases, light source 150 may be connected to a control system that controls the power supplied to light source 150 and the output of light source 150 . The control system can include various electronic circuits for controlling the output of light sources 150, including LEDs, based on individual light source 150 requirements. In some embodiments, if the light source 150 includes multiple LEDs of different wavelength ranges, the control system can determine which LEDs to supply current to and thus determine the wavelength emitted from the light source 150. can.

The following examples are provided to better illustrate the claimed invention and are not intended to be construed as limiting the scope of the invention. To the extent specific materials or steps are mentioned, it is for illustrative purposes only and is not intended to limit the invention. Those skilled in the art may develop equivalent means or reactants without exercising the power of the invention and without departing from the scope of the invention.

Gastrointestinal Tract FIGS. 5-6 illustrate applications for treating colon and/or rectal disorders. For example, FIG. 5 shows that delivery tube 100 containing light source 150 can be inserted into the colon through the anus by a caregiver. In that case, the delivery tube 100 can be directed to a treatment site, e.g., the colon, part or most of the intestine (see, e.g., FIG. 6), or through the mouth into the stomach (see, e.g., FIG. 7). obtain. A power supply (or light source) 120 can then be turned on to illuminate the treatment site with UV light.

In some embodiments, this is used to treat various inflammatory diseases, including diseases such as ulcerative colitis and Crohn's disease, IBD, infectious diseases, as more fully described herein. can be used for As shown, depending on the size, location, and type of disease, delivery tube 100 may include varying amounts of light sources 150 that may be embedded or included in particular portions or lengths of delivery tube 100. .

FIG. 7 shows an embodiment in which an endoscope or other delivery tube 100 is inserted through the oral cavity, through the esophagus, and into the stomach. In this embodiment, stomach infections or inflammatory diseases can be treated with UV light source 150 .

Colonoscopy FIG. 13 shows an example in which a UV emitting device is used for mouse colonoscopy. Colonoscopies and UV applications were safely performed. Parameters included 10 and 30 minutes of UV irradiation at an intensity of 1,100 microwatts/cm ² followed by a routine colonoscopy 72 hours later.

GI therapy may include the following exemplary applications.
1. Treatment of chronic inflammatory bowel disease (IBD) such as ulcerative colitis and Crohn's disease and acute/chronic pouchitis2. Treatment of non-IBD-related proctitis3. 4. Treatment of IBD-related or non-IBD-related fistulae. 5. Treatment of inflammatory strictures; Treatment of microscopic colitis6. 7. Treatment of infectious diarrhea using UV light emitting capsules. 7. Treatment of refractory Helicobacter pylori and MALT lymphoma; 8. Treatment of lichen planus esophagus and pemphigus vulgaris. 10. Treatment of refractory Clostridium difficile. 10. Treatment of colon asthenia, tropical sprue, celiac disease, small intestinal bacterial overgrowth, post-bone marrow transplant infection appendicitis, pseudopolyps (similar to nasal polyps) and radiation enteritis. Treatment of Barrett's esophagus with or without dysplasia12. Treatment of hepatic encephalopathy with daily UV light capsules 13 . Treatment of blind loop syndrome in Roux-en-Y patients by placing an ILT (internal phototherapy) catheter through the remnant stomach PEG14. 15. Treatment of perianal fistulas with clear drains that can emit UV light. 16. Reduced infection rates associated with percutaneous feeding or suction tubes. 16. Treatment of gastrointestinal cancer confined to the mucosa and submucosa. Treatment of hepatobiliary infections, inflammations, and cancers confined to the mucosa and submucosa

Capsules In some embodiments, the delivery device is shaped as a capsule instead of delivery tube/rod 100 . In such embodiments, the capsule is inserted into the patient orally or anally. Capsules can glow for a period of time. For example, the capsule can include a lubricious transparent or translucent polymer or other biocompatible coating to allow passage through the capsule. In some examples, the capsule may include light source 150 and power source 120 . Power source 120 may include, for example, a small battery. In some embodiments, the capsule can be placed and secured in the viscera to provide extended light exposure.

In some embodiments, the capsule is configured such that the UV light 150 is arranged to emit light in all directions from the capsule. Therefore, as the capsule passes through the digestive system, it emits UV light in all directions until the capsule is excreted.

FIG. 8 shows an embodiment of a system utilizing a capsule 800 as a delivery device that can be swallowed by the patient. Capsule 800 may include light source 150 and power source 120 for powering light source 150 . In some embodiments, the capsule or portions thereof are made of a transparent material to allow light to be emitted through the capsule. The capsule may contain a tracking device to assess the position of the capsule within the gastrointestinal tract. The capsule delivery system can be clipped to the hollow organ for continuous or intermittent controlled delivery.

In some examples, the capsule can be no larger than the size of a tablet and can be orally ingestible. The capsule may include a timer to turn the UV light source on and off when the capsule reaches, or is most likely to reach, a particular portion of the digestive tract. For example, a capsule may include a simple timer that turns the capsule on after 30 minutes, 1 hour, or 2 hours. For example, the capsule cannot turn on the light source 150 until the capsule reaches the digestive tract to treat IBS or other infectious or inflammatory conditions.

Photoconductive Delivery Tube In some embodiments, the light source 150 can be positioned inside the delivery tube 100 (e.g., an LED), while in other embodiments the light source 150 is positioned outside the proximal end of the delivery tube 100. , or may be arranged in conjunction with this proximal end. Accordingly, in some embodiments, delivery tube 100 includes an optical fiber or other light-conducting light source to propagate light from light source 150 beyond delivery tube 100 so that the light can be emitted to the treatment site. made from flexible materials.

For example, as shown in FIGS. 9 and 10, a UV light management system can include a delivery rod 940, a UV light source 950, and a light source attachment 900, with the light source attachment 900 between the UV light source 950 and the delivery rod 940. configured to be installed. The delivery rod 940 has a borosilicate segment 930 that excludes UV-C from the light spectrum, followed by a segment made of pure silica (quartz) 900 to extend the UVA/B transmission distance with minimal loss. and

For example, using only pure quartz segments has been shown to produce significant UV-C light emission (eg, 4,300 microwatts/cm ² UV-C), whereas UV light source 950 and delivery rod 940 Using a pure quartz rod with a short segment of borosilicate (e.g., a borosilicate filter) in between results in UV-A and UV-B being detected at the same level without the borosilicate segment, and the delivery rod 940 The UV-C light emitted at the tip will be only 10 microwatts/cm ² , thus UV light is reflected back to the body of delivery rod 940 in order to be delivered across delivery rod 940 . means. UV light source 950 may be configured to be connected to a power supply (not shown) that powers UV light source 950 .

Delivery rod 940 can be a fiber optic rod/catheter. In some exemplary embodiments, the delivery rod 940 is scored using an industrial diamond so that glass cutter oil is used and double-sided pressure is applied to give a clear (rather than opaque) break. It is made by The tip of the delivery rod 940 can be rounded by a drill (eg, a 500 RPM drill) that is ground with a premium diamond polishing pad (eg, 120-200 grit premium diamond polishing pad) and sandpaper (eg, 400 grit sand). paper). The body of the delivery rod 940 is then polished with a 120-200 grit premium diamond polishing pad so that non-UV-C light (eg, UV-A and UV-B) can be emitted across the body of the delivery rod 940. can do. Alternative chemical opacification can be used for custom opacification of the rods.

The light source attachment 900 can include a body 920 and a fastening mechanism 910 (eg, screws, setscrews, fasteners, nails, etc.) that attaches the body 920 to a housing (eg, rod, catheter, handle, etc.). Body 920 may include a front end opening 970 configured to connect to a light source (or power source) and a back end opening 980 configured to connect to a rod (or catheter).

The light source attachment 900 can be made of aluminum for heat conduction and to reduce light intensity degradation. The diameters of both front end opening 970 and rear end opening 980 may vary, for example, to fit a particular catheter, tube, rod, or the like. The light source attachment 900 may also include a convex lens 930 between the front end aperture 970 and the rear end aperture 980 configured to reduce light loss. The convex lens may include a semi-convex heat resistant lens that reduces light loss and focuses light.

Catheter In some examples, the delivery device can be a catheter tube 100 that can be insertable into an artery, urethra, or other portion of the patient's body. For example, catheter tube 100 may include a hollow portion that allows a guidewire to pass therethrough. Thus, the caregiver can guide the guidewire to the treatment site, then thread the catheter over the guidewire and guide the catheter to and beyond the treatment site.

Next, similar to the endoscopic embodiment, the catheter tube 100 can include any of a variety of light sources 150 suitable for applying UV therapy to the interior of arteries. In some examples, this implementation can use smaller light sources 150, such as LEDs.

In another example disclosed herein, the delivery device can be inserted into the bladder as an indwelling urethral catheter (e.g., as shown in FIG. 11) so that UV light can kill urinary tract infections. It may be catheter tube 100 . In another example, the delivery device can be part of a balloon that is inserted into the rectum to treat the rectum with UV light.

Vagina In yet another example, the delivery device may be incorporated into a vaginal rod to treat an infection within the patient's vagina.

FIG. 22 illustrates an exemplary UV light emitting device according to embodiments disclosed herein that can be utilized for intravaginal delivery of UV light in some examples. The present UV light emitting device can include delivery tube/rod 100 . In some embodiments, delivery tube/rod 100 includes a four-sided elongated body 101 . This four-sided elongated body 101 can include a UV light source 150 on each of the four sides. The UV light sources 150 can be staggered on each side of the delivery tube/rod 100 . Delivery tube/rod 100 can include proximal end 102 and distal end 103 . The four sides of elongated body 101 converge on rounded surface 105 toward distal end 103 . Distal end 103 of delivery tube/rod 100 is configured for insertion into a patient, as described above. In contrast, the opposing proximal end 102 is configured for steerability of delivery tube/rod 100 .

FIG. 23 shows the embodiment of the UV light emitting device of FIG. 22 with gripping element 200. FIG. Grasping element 200 can be configured as a handle. Grasping element 200 can be attached to delivery tube/rod 100 at proximal end 102 . Grasping element 200 can be designed to be ergonomically sufficient for a physician or healthcare provider. Grip element 200 can also include an input component 201 configured to receive user input. Input component 201 can be connected to an internal processor that alters the functionality of delivery tube/rod 100 and UV light source 150 . In some embodiments, delivery tube/rod 100 includes 2-20 UV light sources. The delivery tube/rod 100 shown here contains three UV light sources 150 on each of four sides, for a total of twelve UV light sources 150 . It should be appreciated that other configurations are possible that incorporate the features disclosed herein.

FIG. 24 shows an exemplary UV light emitting device 300 according to embodiments disclosed herein. UV light emitting device 300 can include gripping element 350 . Grasping element 350 can be designed to be ergonomically sufficient for a physician or healthcare provider. Grip element 350 can also include an input component 351 configured to receive user input. Input component 351 can be connected to an internal processor that alters the functionality of delivery tube/rod 300 and UV light source 330 . The delivery tube/rod 300 shown here contains two UV light sources 330 on each side of four sides for a total of eight UV light sources 330 . It should be appreciated that other configurations are possible that incorporate the features disclosed herein.

In some embodiments, delivery tube/rod 100 can include a rotating base at its distal end 103 . This rotating base can allow rotation of the delivery tube/rod 100 so that the light emitted from the UV light source 150 is uniform. When treating a patient with a rotating delivery tube/rod 100, uniform UV emissivity is likely to help treat microbial growth. In some embodiments, delivery tube/rod 100 also includes a stepper motor. A stepper motor can allow rotation of the rotating base.

In some embodiments, UV light source 150 is distributed along the entire length of delivery tube/rod 100 and distributed at distal end 103 to achieve wider coverage of UV light source 150 .

In some embodiments, the delivery tube/rod 100 is configured such that the entire delivery tube/rod 100 is illuminated and delivers UV light uniformly. In some embodiments, the delivery tube/rod 100 is configured to emit light waves only in the UV-A and/or UV-B ranges and not light waves in the UV-C range. For example, the peak wavelength of UV light source 150 can include 340 nm. In other broader embodiments, delivery tube/rod 100 (and light source 150) can deliver wavelengths between 320 nm and 410 nm. It should be appreciated that the disclosed delivery tube/rod 100 can be used to provide different wavelengths and different combinations of wavelengths. Other regions of wavelengths can include, for example, 250 nm to 400 nm. In some embodiments, the vertical irradiation length extends between 8-10 cm around delivery tube/rod 100 .

Delivery tube/rod 100 may be made of any suitable construction (eg, rigid or flexible construction), including various polymers that are biocompatible or have biocompatible coatings. FIG. 25 shows an exemplary UV light emitting device 400 according to embodiments disclosed herein. In some embodiments, the delivery tube/rod 100 can include an outer layer of transparent material to allow UV light from the light source 430 to radiate out of the delivery tube/rod 100. In some embodiments, delivery tube/rod 100 may include an outer surface made from, for example, silicone, silica, polyurethane, polyethylene, Teflon/PTFE, borosilicate, or other suitable material. In some embodiments, delivery tube/rod 100 is constructed using copper with a borosilicate outer layer. For optimal cooling, exposed area, and uniformity, delivery tube/rod 100 may include multiple light emitting diodes (LEDs) staggered on a copper rod. In some embodiments, 8 LEDs can be provided on the delivery tube/rod. The spacing of the light sources 430 is the spacing that allows for optimum vertical illumination length. In some embodiments, the vertical irradiation length extends between 8-10 cm around delivery tube/rod 100 .

By using copper to manufacture the body of the delivery tube/rod 100, the delivery tube/rod 100 can withstand reaching high temperature levels. The copper acts as a heat sink and prevents the delivery tube/rod 100 from reaching uncomfortable temperatures. Applicants also suggest operating the light source 150 at a specific current to optimize the temperature of the delivery tube/rod 100 . In some embodiments, light source 150 is operated within the range of 60-100 mA. Within the suggested range, the temperature of the delivery tube/rod 100 does not rise above 40°C, thus achieving the goal of implementing an adequate cooling solution.

26-29 illustrate various embodiments of UV light delivery systems with controller 450. FIG. Controller 450 may include one or more processors, memory, and a battery or other power source. The memory may contain instructions associated with various treatment regimens that may be applied using various intensities and/or durations disclosed herein. For example, the memory may contain data structures that, when executed by a processor, power the light source 150 at given intensities or timings. The controller can be utilized with any of the embodiments disclosed herein, including vaginal, GI, and ETT-based UV light delivery devices.

Referring to FIG. 30, a process is provided for administering internal ultraviolet therapy. The process includes providing a UV light delivery device at step 2501 . The UV light delivery device includes an elongated body including proximal and distal ends. The elongated body includes a receiving space. The UV light delivery device can also include a UV light source configured to be connected to the containment space. In some embodiments, the method also includes rotating the elongated body such that the two UV light sources are configured to uniformly emit UV light out at Step 2503 .

The process may also include, at step 2504, emitting wavelengths between 320 nm and 410 nm with peak wavelengths of 340, 341, 342, 343, 344, 345, 346 nm from the two UV light sources. In some embodiments, this process also includes emitting radiation from two UV light sources out of the elongated body. In some embodiments, the elongated body includes four sides. Each of the four sides of the elongated body includes a receiving space such that a corresponding UV light source 150 is staggered on the elongated body.

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

Respiratory In some examples, the systems and methods disclosed herein can be utilized to deliver UV light to the body passageways of a patient's respiratory system. For example, in some embodiments, delivery tube 150 can be guided to an endotracheal tube (ETT) while the patient is being ventilated. Alternatively, the delivery tube 150 can be directed to the patient's nasopharyngeal airway (NPA). These applications can be used to treat or prevent infections, including viral infections, bacterial infections, pneumonia, and other infections.

In some examples, the delivery tube 100 can be inserted into the ETT during aspiration of the ETT. In other examples, the systems and methods herein can be utilized to improve treatment of empyema by equipping a chest tube with a delivery tube to deliver internal phototherapy.

For example, as disclosed herein, systems and methods have been developed for providing internal ultraviolet therapy in combination with an endotracheal tube (ETT). Therefore, the delivery tube 100 can be guided within the ETT during patient ventilation. In other examples, the delivery tube 100 can be connected to or incorporated into the ETT, or the ETT can have the light source 150 incorporated into the ETT. Accordingly, the light source 150 may be positioned within the tube 150 and/or the ETT such that the UV light source 150 illuminates respiratory tissue within the tracheal airway surrounding the ETT.

For example, as disclosed herein, systems and methods have been developed for providing internal ultraviolet therapy in combination 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 may be connected to or incorporated into the NPA, or the NPA may have the light source 150 incorporated into the NPA. Thus, light source 150 may be positioned within tube 150 and/or NPA such that UV light source 150 illuminates respiratory tissue within the nasopharyngeal airway surrounding the NPA.

In some examples, UV light source 150 within delivery tube 100 can be a series of LEDs. For example, the delivery tube 100 can be a flexible catheter that connects to the ETT or NPA and emits UV light out of the delivery tube 100 to treat the patient's respiratory tract and/or the ETT or NPA. can have LEDs positioned on or within the catheter to treat the interior of the catheter. The LED can be connected with a wired connection to the power supply. In other embodiments, light source 150 may be other suitable light sources 150 other than LEDs.

In this example, the LED has a maximum emission intensity wavelength of 335, 336, 337, 338, 339, 340, 341, 342, 342, 344, 345, 346, 347, 348, 349, 350 nm, or can have any wavelength region between In other embodiments, the LED can emit wavelengths in the 320 nm-410 nm, 250 nm-400 nm, or other suitable regions discussed herein.

FIG. 31 shows a flow chart showing an example of a treatment regimen for treating a patient's respiratory tract and surrounding tissue with UV light. For example, a catheter or other delivery tube 150 with a UV light source may be provided (3100) and guided (3102) into the ETT. The UV light source may then be energized 3104 for various treatments.

In some examples, a delivery catheter with an LED having a wavelength of maximum emission intensity centered at 339, 340, 341, 342, 343, 344, 345, or 346 nm is administered once, twice daily. , or 3 times 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 these or any other suitable timeframe outside of the range) may be energized. The intensity applied is 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500 based on the power of the LED and the distance from the LED light source to the tracheal tissue or other respiratory tracheal tissue. , 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300 uW/cm ² or other suitable intensities between or outside these ranges.

Other Therapeutic Applications and Treatment Regimens The procedures herein can be utilized to treat a number of different inflammatory and infectious diseases. Thus, 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. , different amounts or durations of doses of UV radiation can be administered. For example, in some embodiments, administration time is determined by capsule digestion rate, and other factors (eg, light source power, UV range, etc.) can be manipulated to vary dosage. In other examples, the endoscope can be delivered by the doctor/surgeon for 1 hour, 30 minutes, 2 hours, or other suitable time.

The following are examples of treatment regimens and their applications. Accordingly, the devices and methods disclosed herein can be adapted to treat these different conditions.
Urology and nephrology:
1. Sterilizing the blood of patients with known bacteremia, fungemia, or viremia during dialysis to eradicate or reduce the microbial load. Alternatively, a light needle can be placed in the stoma and turned on outside the dialysis window as well. An ex vivo sensitivity analysis is performed for the narrower wavelength but stronger ILT.
2. 2. Sterilization of indwelling urethral catheters in catheter-dependent patients. 4. Treatment of bladder and urethral cancers confined to the mucosa and submucosa. 4. Treatment of refractory cystitis/urinary tract infections; Addition of UV phototherapy to peritoneal dialysis catheters to reduce the risk of peritonitis and even long-term peritoneal sclerosis.
Cardiology 1 . Sterilizing the blood of patients with known bacteremia, fungemia, or viremia who have an LVAD to eradicate or reduce the microbial load. Alternatively, a light needle can be placed in the stoma and turned on outside the dialysis window as well. An ex vivo sensitivity analysis can be performed for narrower wavelength but more intense UV therapy.
2. Refractory bacterial and fungal endocarditis is treated with direct UV light exposure of the valve. In this case, the photosensitizer may be administered intravenously.
Dentistry 1. Treatment of gingivitis.
2. Treatment of leukoplakia and oral lichen planus.
3. Treatment of cancer confined to the mucosa and submucosa Hematology/Oncology 1 . Treatment of intestinal graft-versus-host disease. In this case, X-ray wavelengths are emitted and kill lymphocytes. It can be used in end-stage Crohn's disease patients awaiting small bowel transplantation or palliative care.
ENT
1. Treatment of chronic sinusitis.
2. Treatment of chronic otitis.
3. Treatment of acute otitis media in patients requiring myringotomy.
4. Treatment of nasal polyps (there is evidence that UV light shrinks nasal polyps, see attached paper).
5. Bad breath treatment.
6. Treatment of recurrent tonsillitis/pharyngitis.
7. Treatment of cancer confined to mucosa and submucosa Surgery 1 . To improve treatment of abscesses by equipping drains with UV light technology.
2. Use with surgical drains to avoid mixed infections.
3. Accelerate the anastomosis healing process.
4. Helps prevent adhesions.
Neurosurgery 1. Intrathecal fiber optic delivery of UV light in the treatment of refractory meningitis.
2. Treatment of refractory shunt infections.
3. Treatment of prion diseases with intrathecal or intrathecal UV therapy.
4-Treatment of JC virus associated with progressive multifocal leukoencephalopathy by reducing viral load.
Gynecology 1. Treatment of bacterial vaginosis or fungal vaginosis.
2. Treatment of rectovaginal/colic fistula.
3. Treatment of cancer confined to the mucosa and submucosa Rheumatology 1 . Intra-articular ILT for the treatment of inflammatory and infectious macroarthritis.
Vaginal therapy 1 . Figures 14A, 14B show an example of a UV light emitting device being used for vaginal treatment in mice.

Experimental Data The following set of experimental data are provided to better illustrate the invention claimed by this application and are not intended to be construed as limiting the scope.

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

FIG. 15B shows an example in which the UV light emitting device disclosed herein is used in a liquid culture containing E. coli. The results of this experiment and similar experiments with other bacteria and the fungus Candida albicans are shown, for example, in FIGS. 21A and 21B. All results demonstrate significant growth of E. coli and other infectious agents in liquid samples where UV-A and UV-B light is emitted by the UV light emitting device disclosed herein. showing a decline.

Example 2: Bacteria In another example, two exemplary devices according to this description were used in UVA experiments for treating bacteria. The first device was a borosilicate rod (3 mm outer diameter) repeatedly etched with a mixture of dilute sulfuric acid, sodium hydrogen fluoride, barium sulfate, and ammonium bifluoride, with UVA emitting laterally at the end of the rod. Added reflective coating. During this process, a side emitting rod of UVA (peak wavelength 345 nm) was obtained as confirmed by a spectrometer (Ocean Optics; Extech). A second device incorporated a narrow band LED with peak wavelength (345 nm).

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

大腸菌（Ｅｓｃｈｅｒｉｃｈｉａ ｃｏｌｉ）、大腸菌ＧＦＰ、緑膿菌（Ｐｓｅｕｄｏｍｏｎａｓ ａｅｒｕｇｉｎｏｓａ）、化膿性レンサ球菌（Ｓｔｒｅｐｔｏｃｏｃｃｕｓ ｐｙｏｇｅｎｅｓ）、表皮ブドウ球菌（Ｓｔａｐｈｙｌｏｃｏｃｃｕｓ ｅｐｉｄｅｒｍｉｓ）、肺炎桿菌（Ｋｌｅｂｓｉｅｌｌａ ｐｎｅｕｍｏｎｉａｅ）、エンテロコッカス・フェカーリス（Ｅｎｔｅｒｏｃｏｃｃｕｓ ｆａｅｃａｌｉｓ）、プロテウス• Stock cultures of Proteus mirabilis, Clostridioides difficile, and Candida albicans were cultured in appropriate liquid media and conditions as indicated in the table shown in FIG. American Type Culture Collection (ATCC) strains and one clinical isolate were cultured in appropriate solid and liquid media following ATCC suggested instructions for each organism (Manassas, VA, USA). Using sterile technique, the vial containing the microbial strain was opened and the entire pellet rehydrated with approximately 500 μL of liquid broth.

Aseptically, the resuspended pellet was transferred to a tube containing 56 mL of the same liquid broth used to resuspend the cells. A few drops of primary broth tubes were used to inoculate solid microbial agar to isolate single colony forming units (CFU). Liquid and solid cultures were incubated at specific temperatures, atmospheric conditions and times as described in FIG.

First, liquid cultures were prepared from a single CFU of each organism to ensure the purity of the strain during UVA therapy. Only fresh pure liquid cultures were used during the experiment. One single colony was added to a 10 mL sterile tube containing 5 mL of liquid medium followed by thorough vortexing to homogenize the microbial cells. The liquid cultures shown in Figure 32 were incubated until reaching 0.5 by McFarland turbidimetry. After filling the standard turbidity, the microbial culture was mixed well for 1 minute and 1000 μL of liquid culture was transferred to two 1.7 mL microcentrifuge sterile tubes to be used as treatments and controls. A 100 μL aliquot of each tube was serially diluted and plated on solid microbial media to determine the number of CFU/mL at baseline as shown in FIG.

Prior to UVA phototherapy, several sterile 1.7 mL tube caps were prepared by punching a small hole in the top using a heated glass rod. The hole had the shape and size of the rod used to transmit the UVA light.

Aseptically, the original cap from the liquid culture in the 1.7 mL tube was replaced with a sterile cap with holes. A UV light transmitter rod (sterilized with 70% ethanol) was placed in a hole made in the top of each cap. An identical rod was also placed in the control tube. Light was transmitted through a glass rod inserted into the tube using a MAX-303 xenon light source (Asahi Spectra USA, Inc., Torrance, Calif.). UV bandwidth and irradiance peak were evaluated (Flame UV-VIS fiber optic spectrometer, Ocean Optics). UV intensity was measured with SDL470 and UV510 UV light meters (Extech, NH, USA) Extech. Absence of UVC was confirmed using an SDL470 UV photometer (Extech, NH, USA). FIG. 32 describes the intensity and duration of exposure of UVA light applied to bacterial cultures.

At the end of the treatment time, the rods were removed from the treatment and control tubes and the liquid cultures were closed using new sterile caps without holes. Both treated and control groups were homogenized by vortexing. A 100 μL aliquot of each tube was then serially diluted and plated on solid microbial media to determine the number of CFU/mL after UVA treatment, as shown in the table shown in FIG. This process was repeated until all time points listed in FIG. 33 were achieved.

After each time point (baseline and post UVA treatment), 100 μL of liquid microbial cultures (treated and control) were serially diluted in sterile 1×PBS (EMD Millipore, Billerica, Mass.). Final serial dilutions were 1:10 (100 μL microbial culture and 900 μL sterile 1×PBS), 1:100, 1:1000, 1:10,000, 1:100,000. 100 μL of each dilution was plated in duplicate on solid agar plates and incubated at the time, temperature, and atmosphere conditions indicated in FIG. After incubation, colonies were counted using a Scan 300 automatic colony counter (Interscience, Woburn, Mass., USA) and corrected for volume and dilution to define the number of CFU/mL.

A second device used in these experiments incorporated a miniature light-emitting diode (LED) array (345 nm peak wavelength, 10 nm bandwidth) attached to an aluminum heat sink (Seoul Viosys, Gyeonggi-Do, Korea). . In a first experiment, the system was placed 1 cm from the surface of a culture plate with a thick lawn of E. coli and placed at approximately 2000 μW/cm ² for 20 minutes. This light source was subsequently applied to liquid cultures of E. coli and Pseudomonas aeruginosa at 10 ² CFU/mL in separate experiments.

For both conditions, UVA was tested at intensities of 500, 1000, 2000, and 3000 μW/cm ² for 20 and 40 minutes at 1 cm in separate series of experiments to generate dose-response curves. After incubation, colonies were counted using a Scan 300 automatic colony counter (Interscience), colony size was determined, and the number of CFU/mL was defined by correcting for volume and dilution factor.

Results UVA exposure was associated with significant reductions in various pathogenic organisms, including Candida albicans (P=0.007) and Clostridium difficile (P=0.01), as shown in the table presented in FIG. Was. UVA light exposure time of 20 minutes (intensity 1300-3500 μW/cm ² ) was effective against Klebsiella pneumoniae (P=0.17), Enterococcus faecalis (P=0.1), and Streptococcus pyogenes (P=0.64). ) were decreased compared to the control group (P<0.05). UVA light exposure times of 40 and 60 minutes were effective against all microorganisms tested when compared to untreated controls (P<0.05, FIG. 33). In particular, the bactericidal and fungicidal effects showed a dose-dependent response to UVA light, with greater microbial reduction associated with longer exposure times, as shown in FIG.

UVA phototherapy was also applied to a clinically isolated E. coli strain obtained from the human urinary tract. UVA light was tested in five consecutive sets of experiments, exposing the bacterial cultures to 1100-1300 μW/cm ² UVA for 20, 40, 60, and 80 minutes. Compared to baseline, the number of CFU/mL observed in bacterial cultures exposed to UVA light increased at 20 min (P=0.03), 40 min (P=0.03), as shown in FIG. 0002), 60 minutes (P<0.0001) and 80 minutes (P<0.0001).

Finally, experiments were conducted to test the effect of LED narrowband UVA (345 nm peak wavelength) on E. coli and Pseudomonas aeruginosa. In these experiments, this particular wavelength of UVA resulted in a significant reduction of bacterial cells, as shown in Figures 35A-35N. For example, Figure 35A shows a photograph of a bacterial colony in a petri dish and the colony disappearance pattern around the application site of LED light at 20 and 40 minutes.

Figures 35B-35F show graphs showing the time course of colony forming units (CFU) of E. coli under various intensities of UV-A light with a peak wavelength of 345 nm. As shown, an intensity of 2000 uW removed most of the bacteria by 40 minutes (Fig. 35D) and an intensity of 3000 uW removed most of the bacteria by 20 minutes (Figs. 35E and 35F). When the same light was irradiated at 500 uW and 1000 uW intensities, a significant decrease in CFU was seen by 40 min, but only by about half (FIGS. 35C and 35B).

Figures 35G-35J show graphs showing the time course of colony forming units (CFU) of Pseudomonas aeruginosa under different intensities of UV-A light with a peak wavelength of 345 nm. As shown, treatment with intensities of 1000 uW, 2000 uW, and 3000 uW showed a significantly greater reduction in CFU compared to controls (FIGS. 35H, 35I and 35J), with intensities of 2000 uW and 3000 uW up to 20 minutes. At 20° C., most of the bacteria were eliminated (FIGS. 35I and 35J).

Figures 35K-35L show growth curves comparing the log reduction of P. aeruginosa at various intensities at 20 and 40 minutes, respectively. Figure 35M shows growth curves showing the reduction in E. coli colony diameter at various intensities and treatment times. Figure 35N shows growth curves showing the reduction in P. aeruginosa colony diameter at various intensities and treatment times.

When examining the effect of light intensity on the reduction of E. coli and Pseudomonas aeruginosa, a dose-response effect was seen on both bacterial load and colony size (FIGS. 35B-35N). The ideal UVA intensity to affect bacteria appears to be 2000-3000 μW/cm using a narrowband LED with a peak wavelength of 345 nm, and in some examples the type and species of bacteria or pathogen, as well as other factors disclosed herein.

Example 3 Safety Data Three experiments were performed to assess the safety of UVA on mammalian cells. In the first experiment, HeLa cells in culture were exposed to UVA. HeLa cells were added to DMEM cell culture medium (Gibco, Waltham, Mass.) plus 10% bovine serum (Omega Scientific, Tarzana, CA) and 1x antibiotic-antimycotic (100x Gibco) in 60x15mm cell culture dishes (Falcon). and cultured at 37° C. (5% CO ₂ ) for 24 hours to obtain 1,000,000 to 1,800,000 cells per plate. At this point, cells were exposed to UVA LED light (1800 μW/cm ² ) for 0 minutes (control), 10 minutes, or 20 minutes. After 24 hours, cells were removed with 0.05% trypsin EDTA (1x) (Gibco), stained with trypan blue (trypan blue 0.4% ready-to-use (1:1) (Gibco)) and automated cell counting. Quantification was performed with an instrument (Biorad T20, Hercules, Calif.). A similar experiment used LED UVA light at a higher intensity (5000 μW/cm ² ) for 20 minutes. Again, HeLa cells were quantified 24 hours after UVA exposure.

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

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

Wild-type 129S6/SvEv mice (n=20, female=10) and BALB/cJ mice (n=10, female=5) were used for UVA photosafety studies. All animals were anesthetized prior to treatment. Prior to UVA phototherapy, animals were placed in an induction chamber containing isoflurane anesthetic gas (1-5%). The carrier gas for isoflurane was compressed oxygen (100% oxygen). Once the respiratory rate slowed (approximately 1 breath per second), the animal was removed from the induction chamber and kept sedated using nose cone anesthesia (1-2% isoflurane). Depth of anesthesia was confirmed by toe pinching and no response.

Under anesthesia, a customized rod (D=4 mm, L=40 mm) was introduced through the anus to the splenic flexure. The control group underwent the same procedure with the same but unlit rods. The light source and measurement device used were the same as those described in the liquid culture experiment.

In the first experiment, 5 BALB/cJ mice were subjected to 30 minutes of colonic UVA exposure (2,000 μW/cm ² ) and compared to 5 mice treated with unlit optical rods in the same manner. .

In a second experiment, 10 129S6/SvEv mice were exposed to colonic UVA exposure (3,000-3,500 μW/cm ² ) for 20 min per day for 2 consecutive days, and 10 mice treated with unlit rods. compared with 5 males (5 males).

Colonoscopy before and after UVA phototherapy A rigid pediatric cystoscope (Olympus A37027A) was used to assess the intestinal mucosa before and after 7 days of UVA exposure. Endoscopy was performed on anesthetized animals. The method of sedation is as described above.

The anus was first lubricated with an aqueous gel (Astroglide®, BioFilm, Inc., Vista, Calif., USA). The endoscope was then inserted into the splenic flexure and the colon was insufflated using room air injected through the endoscope port. All endoscopies were recorded and interpreted blinded by two gastroenterologists familiar with animal model endoscopies. Endoscopic images were analyzed based on perianal examination, intestinal wall transparency, mucosal hemorrhage, and focal lesions.

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

The data for bacterial counts between groups were not normally distributed and were compared using a nonparametric test (Mann Whitney U test). Other quantitative data were compared by t-test using GraphPad Prism 7 (GraphPad, San Diego, Calif.).

Results Overall, based on cell proliferation over time, LED UVA appeared safe in the mammalian cells tested (HeLa, alveolar A549, and primary tracheal cells). All plates continued to grow cells despite UVA exposure, with 1.5-2-fold more cells per plate than controls, indicating continued robust replication. For HeLa cells, UVA did not affect the number of viable cells after 24 hours compared to unexposed controls (approximately 2000 μW/ ^cm2 of UVA for 10 minutes), as shown in Figure 36A. and 20 min, P=0.99 and P=0.55, respectively). Higher intensity UVA (5000 μW/cm ² ) did not affect HeLa cell proliferation as shown in the bar graph depicted in FIG. 36B. Similar findings were also seen with alveolar cells at 2000 μW/cm ² for 20 min, as shown in FIG. 36C (P=0.99). Finally, the growth of ciliated epithelial cells was also unaffected after UVA irradiation at about 1000 μW/cm ² and about 2000 μW/cm ² for 20 minutes.

In addition, exposure to UVA did not cause DNA damage in any of the cell lines analyzed, showing narrow lines as shown in Figure 36D (HeLa cells), Figure 36E (alveolar cells), and Figure 36F (tracheal cells). Levels of 8-oxo-2′-deoxyguanosine (8-OHdG) in cells treated with band-LED UVA were similar to controls not exposed to UVA (P<0.05). Higher intensity LED UVA (5000 μW/cm ² ) appeared to increase levels of 8-OHdG (P=0.07), although the percentage of 8-OHdG was generally 0.01% of total DNA. remained well below the accepted threshold.

UVA light exposure is not associated with endoscopic or histological damage. Exposure to intracolonic broad-spectrum UVA light was performed using an optical rod designed to radiate laterally into the colon. Only the left side of the colon up to the splenic flexure was exposed to UVA light, so the unexposed right side served as an autologous control. In the first experiment, 5 mice under anesthesia were given a 30 min colonic UVA exposure (2,000 μW/cm 2 ) and compared to 5 mice treated with unlit optical rods in the same manner.

In a second experiment, 10 mice (129S6/SvEv, male=5) were exposed to colonic broad-spectrum UVA exposure (3,000-3,500 μW/cm ² ) for 20 min per day for 2 consecutive days, Comparisons were made with 10 mice (male=5) treated with unlit rods. No perforation, bleeding, or death was observed in any experiment. Colonoscopy images of mice show no change before and after UVA exposure.

In both experiments, endoscopic evaluation of mice before and after UVA administration revealed no mucosal erythema, disruption, ulceration or bleeding macroscopically. Full-thickness colon specimens exposed to broad-spectrum UVA showed chronic/acute inflammation, cystitis, crypt abscess, granulation, compared with control and untreated colon segments, as assessed by a blinded pathologist (SS). No tumors, ulcers, or dysplasia were seen.

RNA Virus Experimental Data Further, experimental data was obtained using the disclosed system and method to treat various RNA viruses with UVA light. Consequently, the data show that UV-A light emitted from an LED with a peak wavelength of 340 nm can kill RNA viruses such as coxsackievirus. For example, Coxsackievirus-infected HeLa cells survived when this UV-A treatment was applied, but not when UV-A phototherapy was not applied after infection. Furthermore, experimental data showed only 15% loss of UV-A light after passing through the ET tube.

In late December 2019, an outbreak of novel coronavirus infection (SARS-CoV-2 or COVID-19, formerly known as 2019-nCoV) was reported in Wuhan, China. COVID-19 is a viral infection that replicates efficiently in the upper respiratory tract. As part of its mechanism of action, the virus infects ciliated tracheal epithelial cells, which then slough off and impair alveolar function. Secondary bacterial infections have also been noted, and both of these processes can lead to further inflammation, acute respiratory distress syndrome (ARDS), and ultimately death. It is estimated that 10-15% of those infected will have a severe clinical course and approximately 5% will become critically ill requiring mechanical ventilation due to organ failure such as the respiratory system. The case fatality rate for COVID-19 has been estimated to range from 0.5% to 9.5%, although this estimate reflects prioritization of testing symptomatic patients and the There is a time lag of 14 days and I'm confused. Deaths are believed to be due to secondary infections, including respiratory failure in the ARDS setting and/or ventilator-associated pneumonia (VAP).

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

There is currently no cure for COVID-19, and conventional means to reduce secondary infections in mechanically ventilated patients have so far proven inadequate. Broad antiviral and antimicrobial approaches that are safe and effective in these patients should potentially reduce viral load, secondary infections and VAP, time on mechanical ventilation, and death from respiratory failure.

As disclosed herein, ultraviolet (UV) light has antibacterial properties. UVC (110-280 nm), widely used for industrial disinfection (16), has been shown to have deleterious effects on human DNA. External UVA (320-400 nm) and UVB (280-320 nm) devices are FDA-approved for indications for human diseases such as psoriasis, eczema, and cutaneous lymphoma. These wavelengths penetrate mucosal and submucosal tissue. Of the three spectra, UVA appears to be the least damaging to mammalian cells. Currently, there are no studies demonstrating the effect of internal application of UVA light on bacterial or viral infections. Advances in light-emitting diodes (LEDs) have made it possible to apply narrow-band UVA to internal organs.

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

Example 4: Coxsackievirus Obtaining Coxsackievirus Samples and Infecting Cells Recombinant Coxsackievirus B (pMKS1) expressing an enhanced green fluorescent protein (EGFP-CVB) plasmid was isolated using ClaI restriction enzyme (ER0142, Thermo Fisher). Linearized and linearized plasmids were purified using standard phenol/chloroform extraction and ethanol precipitation. Viral RNA was then generated using the mMessage mMachine T7 transcription kit (AM1344, Thermo Fisher). Viral RNA was then transfected into HeLa cells (approximately 80% confluency) using Lipofectamine 2000 (11668027, Thermo Fisher). When the cells showed approximately 50% cytopathic effect, the cells were scraped and the cell/media suspension was collected. The mixture was then subjected to 3 rounds of rapid freeze-thaw cycles and centrifuged at 1000×g for 10 minutes to clear the medium of cell debris. The supernatant was used as passage 1 virus stock. The passage 1 viral stock was then layered onto separate HeLa cells (approximately 80% confluency) to expand the stock into a passage 2 viral stock and used for subsequent experiments.

UVA Treatment of HeLa Cells Infected with Group B Coxsackievirus HeLa cells were used in four different experiments using enhanced green fluorescent protein (EGFP)-expressing group B coxsackievirus (EGFP-CVB). In the first experiment, HeLa cells (253,000 per plate) (n=12 plates) were cultured for 24 hours. Half of the EGFP-CVB aliquots were exposed to LED UVA (2000 μW/cm ² , peak wavelength 340 nm) for 20 minutes and the other half was not. HeLa cells were then infected with either UVA-exposed or non-UVA-exposed virus (MOI=0.1). After 6 hours, the supernatant was removed and the cells were washed twice with 1x sterile PBS (pH=7.0). Fresh DMEM medium was added. Virus-infected plates exposed to UVA were exposed to UVA (2000 μW/cm ² ) for an additional 20 minutes. Dead cells in the supernatant were collected and quantified after 24 hours. Viable cells from 6 plates (3 UVA-treated and 3 unUVA-treated) were evaluated. Of the remaining 6 plates, 3 plates that were initially exposed to UVA with a peak wavelength of 340 nm were further exposed to UVA (2000 μW/cm ² ) for 20 minutes. After an additional 24 hours, dead and live cell counts were obtained from the remaining plates.

Pretreatment of HeLa cells with UVA against group B coxsackievirus infection In a second experiment, HeLa cells (235,000 cells) were plated and then incubated with DMEM for 24 hours. Plates were then divided into unexposed controls (n=3) and those exposed to LED UVA (2000 μW/cm ² , peak wavelength 340 nm) for 20 minutes (n=3). After an additional 24 hours, all plates were infected with EGFP-CVB (MOI=0.1). After an additional 24 hours, cells were counted as previously described.

Pretreatment of Group B Coxsackievirus with UVA for HeLa Cell Infection In a third experiment, HeLa cells were cultured for 24 hours prior to infection with EGFP-CVB (MOI=0.1). Immediately prior to infection, half of the EGFP-CVB aliquot was exposed to LED UVA (2000 μW/cm ² , peak wavelength 340 nm) and the other half was left unexposed. After 24 hours, viable cell counts were obtained.

Long-Term UVA Treatment of HeLa Cells During Group B Coxsackievirus Infection In this experiment, 250,000 HeLa cells were plated. After 24 hours, cells were divided into 3 groups. In the first group, cells were infected with EGFP-CVB (MOI=0.1). These cells served as positive infection controls. In group 2, HeLa cells were infected with EGFP-CVB (MOI=0.1) treated with UVA (2000 μW/cm2, 20 minutes, peak wavelength of 340 nm), and after 6 hours, the infected cells were treated with UVA (2000 μW/ ^cm2 ). , peak wavelength 340 nm) for 20 minutes, then on the 2nd day, 2 times for 20 minutes at 8 hour intervals, and on the 3rd day, 2 times for 20 minutes at 8 hour intervals, a total of 4 additional treatments were performed. . Group 3 was not infected with EGFP-CVB but was treated with UVA 5 times at the same time points used in group 2. This was a non-infectious positive control to demonstrate the safety of UVA. Imaging and cell counts were acquired in all conditions.

UVA Treatment of Group B Coxsackievirus-Infected Alveolar (A549) Cells In preliminary experiments with alveolar cells, we determined that the ideal time point for cell death due to infection is 48 hours post-infection. In this study, 200,000 alveolar cells were plated and counted after 48 hours (754,000 cells). Alveolar cells were then infected with EGFP-CVB (MOI=0.1). Twenty-four hours post-infection, alveolar cell plates were exposed to LED UVA (2000 μW/cm ² , peak wavelength 340 nm) for 0 minutes (control) or 20 minutes (treatment), repeating every 24 hours for 3 days. Imaging and cell counts were taken at 96 hours.

Results Pretreatment with UVA only prior to infection of HeLa cells with group B coxsackievirus does not reduce infection. Treated with group B coxsackievirus exposed to LED UVA light of wavelength 340 nm, approximately 2000 μW/cm ² for 20 minutes. The impact on infection rates at 24 hours did not differ between groups.

UVA pretreatment of HeLa cells prior to group B coxsackievirus infection does not reduce viral effects ² LED UVA for 20 minutes and no further UVA treatment. EGFP-CVB was added to both groups. Both groups were equally infected, suggesting that treatment of HeLa cells prior to infection had no effect on infection rate.

UVA treatment after group B coxsackievirus infection reduced viral effects on HeLa cells In this study, UVA was applied after HeLa cells were infected with EGFP-CVB. Treated cells were exposed to LED UVA with a peak wavelength of 340 nm, approximately 2000 μW/cm ² at 6 hours post-infection, followed by cell number determination at 72 hours post-infection and exposure twice daily for an additional 2 days. This was compared to infected but untreated controls. In the treated group, UVA light prevented cell death from EGFP-CVB, increasing the cell number to 339,333±60,781 at 72 hours, as shown in the bar graph depicted in FIG. Untreated controls showed no viable cells remaining on the plates at 48 and 72 hours. Importantly, a third group of HeLa cells that were not infected but were exposed to UVA at the same time interval showed a cell count of 2,413,333±403,773 after 72 hours, indicating normal cell proliferation. It has been seen.

Effect of UVA treatment on group B coxsackievirus-infected alveolar (A549) cells Cell death was much less in EGFP-CVB-infected alveolar cells than that seen in HeLa cells. At 96 hours post-infection, a clear and extensive infection was seen in the cells of the control group. Alveolar cells treated with LED UVA with a peak wavelength of 340 nm also showed infection, but visual assessment indicated a lower infection rate, suggesting much fewer cells emitting a viral EGFP signal. Viable cell counts also appeared to be higher in the UVA-treated group when compared to the untreated group.

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

Ciliated tracheal epithelial cells (Promocell, Heidelberg, Germany) were plated in three groups (135,000 per plate). One group was infected with coronavirus 229E (Cov-229E) (50 uL per plate). In another group, coronavirus 229E was treated with LED UVA with a peak wavelength of 340 nm (2000 μW/cm ² ) for 20 minutes just prior to infection. A third group received neither infection nor UVA. After infection, cells were treated with UVA (4 cm distance, 2000 μW/cm ² at plate surface, peak wavelength 340 nm) for 20 minutes daily. Plates were imaged at 16, 72, and 96 hours and cell counts were obtained at 72 and 96 hours post-infection.

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

UVA for short-range treatment of ciliated tracheal epithelial cells infected with coronavirus
Assuming an intratracheal device using UVA technology, another experiment was compared to the one above using lower intensity light (1300 μW/cm ² at the surface of the plate from a distance of only 1 cm) for 20 minutes per day. performed identically. This is the expected distance between the tracheal cells of a patient being ventilated from inside the endotracheal tube and the optical catheter.

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

LED UVA light preserves ciliated tracheal epithelial cells infected with coronavirus 229E Ciliated tracheal epithelial cells were pretreated with coronavirus 229E and exposed daily to LED UVA (2000 μW/cm ² ; peak wavelength 340 nm) for 20 min. was compared to control cells (no UVA, no infection) and cells infected with coronavirus but no UVA exposure. Direct visualization showed distinct changes in cell morphology (without UVA) with infection. On the other hand, control cells and infected cells treated with daily UVA showed similar morphology. After 96 hours the supernatant was removed and the viable cells (adhering to the plate) were counted. There was no difference in tracheal cell numbers between control and UVA-treated infected cells. However, as shown in the bar graph shown in Figure 38, there was a significant reduction in viable cells among infected cells compared to UVA-treated cells (P = 0.005).

Interestingly, infected cells treated with LED UVA showed a decrease in Cov-229E spike (S) protein (approximately 130 kDa) when compared to untreated infected cells. In addition, Cov-229E infected and UVA treated levels had elevated levels of MAVS when compared to Cov-229E infected but not UVA treated cells.

Therefore, this experimental data confirms that UV-A light kills coronavirus 229E after it infects lung epithelial tissue, and as a treatment for coronavirus-infected patients, it is used in combination with ET tubes to irradiate lung tissue. It is intended to verify that

Computer and Hardware Implementation of the Disclosure It should first be noted that the disclosure herein may be implemented by any type of hardware and/or software, and may be pre-programmed general-purpose computing devices. be understood. For example, the system may be implemented using a server, personal computer, portable computer, thin client, or any suitable device or devices. The present disclosure and/or components thereof may be a single device at a single location, or multiple devices at a single location or multiple locations, wherein the multiple devices include electrical cables, They are connected together via any communication medium such as fiber optic cable, or wirelessly, using any suitable communication protocol.

It should also be noted that the disclosure is illustrated and discussed herein as having multiple modules that perform certain functions. It should be understood that these modules are shown schematically based on their functionality only for purposes of clarity and are not necessarily representative of specific hardware or software. In this regard, these modules may be hardware and/or software implemented to substantially perform the specific functions discussed. Further, these modules may be combined together within this disclosure or split into additional modules based on the specific functionality desired. Therefore, this disclosure should not be construed as limiting the present invention, but merely as depicting exemplary embodiments thereof.

The computing system can include clients and servers. A client and server are generally remote from each other and typically interact through a communication network. The relationship of client and server arises by virtue of computer programs running on the respective computers and by having a client and server relationship to each other. In some implementations, the server sends data (eg, HTML pages) to the client device (eg, for the purpose of displaying the data to and receiving user input from a user interacting with the client device). Data generated at the client device (eg, results of user interactions) can be received from the client device at the server.

Embodiments of the inventive subject matter described in this application can be implemented in a computing system that includes back-end components (e.g., data servers) or middleware components (e.g., application server), or a front-end component (e.g., a client computer with a graphical user interface or web browser that allows users to interact with embodiments of the inventive subject matter described herein), or including any combination of two or more such backend, middleware, or frontend components; The components of the system can be interconnected by any form or medium of digital data communication (eg, a communication network). Examples of communication networks include local area networks (“LAN”) and wide area networks (“WAN”), internetworks (such as the Internet), and peer-to-peer networks (such as ad-hoc peer-to-peer networks).

Embodiments of the subject matter and operations described herein may be computer software, firmware, or hardware comprising digital electronic circuits or structures disclosed herein and equivalents of those structures. , or a combination of one or more thereof. Embodiments of the subject matter described herein may be stored as one or more computer programs, i.e., on a computer storage medium, for execution by or for controlling the operation of a data processing apparatus. It can be implemented as one or more modules of encoded computer program instructions. Alternatively, or in addition, the program instructions are generated to encode information into an artificially generated propagated signal, e.g., for transmission to a receiving device suitable for execution by a data processing device. It can be encoded in the generated electrical, optical, or electromagnetic signal. A computer storage medium can be or be included in a computer readable storage device, a computer readable storage substrate, a random or serial access memory array or device, or a combination of one or more thereof. Moreover, although a computer storage medium is not a propagated signal, a computer storage medium can be a source or destination of computer program instructions encoded in an artificially generated propagated signal. Also, a computer storage medium may be or be contained within one or more separate physical components or media (eg, multiple CDs, disks, or other storage devices).

The operations described herein can be implemented as operations performed by a "control system" on data stored in one or more computer-readable storage devices or received from other sources.

The term "control system" encompasses any type of apparatus, device, and machine for processing data, including, by way of example, programmable processors, computers, systems on a chip, or a plurality thereof or combinations thereof. . The device may include special-purpose logic circuits, such as FPGAs (Field Programmable Gate Arrays) or ASICs (Application Specific Integrated Circuits). In addition to hardware, the apparatus also includes code that creates an execution environment for a computer program of interest, such as processor firmware, protocol stacks, database management systems, operating systems, cross-platform runtime environments, virtual machines, or any of these. can include code that constitutes a combination of one or more of Devices and execution environments can implement a variety of different computing model infrastructures, such as web services, distributed computing and grid computing infrastructures.

A computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, declarative or procedural languages. , and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, object, or other unit suitable for use in a computing environment. Computer programs may, but need not, correspond to files in a file system. A program may be part of a file holding other programs or data (e.g., one or more scripts stored in a markup language document), a single file dedicated to the intended program, or multiple associated files. (eg, a file that stores one or more modules, subprograms, or portions of code). A computer program can be deployed to be executed on one computer or on multiple computers located at one site or distributed across multiple sites and interconnected by a communication network.

One or more programmable processors perform the processes and logic flows described herein to execute one or more computer programs to perform actions by operating on input data and generating output. can be executed. Also, the processor and logic flow can be implemented by and implemented as dedicated logic circuitry, such as FPGAs (Field Programmable Gate Arrays) or ASICs (Application Specific Integrated Circuits).

Processors suitable for the execution of a computer program include, by way of example, both general and special purpose microprocessors, and one or more processors of any kind of digital computer. Generally, a processor receives instructions and data from read-only memory, random-access memory, or both. The basic elements of a computer are a processor for performing actions according to instructions and one or more memory devices for storing instructions and data. Generally, a computer also includes one or more mass storage devices, such as magnetic, magneto-optical or optical disks, for storing data, or for receiving data from or using these mass storage devices. operably coupled to transfer data to a storage device, or both. However, a computer need not include such devices. Additionally, the computer may be connected to another device such as a mobile phone, a personal digital assistant (PDA), a mobile audio or video player, a game console, a global positioning system (GPS) receiver, or a portable storage device, just to name a few. (eg, a universal serial bus (USB) flash drive). Devices suitable for storing computer program instructions and data include, for example, semiconductor memory devices such as EPROM, EEPROM and flash memory devices; magnetic disks such as internal hard disks or removable disks; magneto-optical disks; Includes all forms of non-volatile memory, media and memory devices, including ROM and DVD-ROM discs. The processor and memory may be supplemented by, or incorporated into, dedicated logic circuitry.

CONCLUSION The various methods and techniques described above provide numerous means of implementing the invention. Of course, it is to be understood that not necessarily all objectives or advantages described may be achieved in accordance with any particular embodiment described herein. Thus, for example, one skilled in the art may seek to achieve or optimize one benefit or advantages taught herein without necessarily achieving other objectives or advantages taught or suggested herein. , will recognize that the method can be done. Various alternatives are mentioned herein. Some embodiments specifically include one, another, or some features, while others specifically exclude one, another, or some features, and still others. It is to be understood that one reduces a particular feature by including one, another, or several advantageous features.

Moreover, the skilled artisan will recognize the applicability of various features from different embodiments. Likewise, the various elements, features and steps discussed above, and other known equivalents for each such element, feature or step, may be used in various combinations by those skilled in the art to A method can be performed in accordance with the principles described in the literature. Of the various elements, features, and steps, some are specifically included and others are specifically excluded in various embodiments.

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

In some embodiments, the terms "a" and "an" and "the" are used in the context of describing certain embodiments of this application (especially in the specific context of the claims below). and similar referents can be construed to cover both singular and plural forms. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated herein as if it were individually listed herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples or exemplary language (e.g., "such as") provided herein with respect to particular embodiments is intended only to better illustrate the present application and may is not intended to limit the scope of the application, which is claimed in any manner. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the application.

Certain embodiments of the application are described herein. Variations on those embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. It is contemplated that those skilled in the art may employ such variations as appropriate and may practice the application otherwise than specifically described herein. Accordingly, many embodiments of this application include all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by this application unless otherwise indicated herein or otherwise clearly contradicted by context.

Particular implementations of the subject matter have been described. Other implementations are within the following claims. In some cases, the actions recited in the claims can be performed in a different order and still achieve desirable results. Moreover, the processes illustrated in the accompanying figures do not necessarily require the particular order or sequential order illustrated to achieve desirable results.

All patents, patent applications, patent application publications, and other materials such as articles, books, specifications, publications, documents, articles, and/or the like referenced herein are hereby incorporated by reference. The entirety of which is incorporated herein for all purposes, but any prosecution file history associated therewith, either inconsistent or inconsistent with this document, or in the present or future application to this application. Anything that may have a limiting effect on the broadest scope of the claims associated with the document is excluded. By way of example, if there is any inconsistency or inconsistency between the description, definition and/or use of a term in connection with any of the incorporated materials and that in connection with this document, the description, definition, and/or use shall prevail.

Finally, it is to be understood that the embodiments of the application disclosed herein are illustrative of the principles of the embodiments of the application. Other modifications that can be used may be within the scope of this application. Thus, by way of example and not limitation, alternative configurations of embodiments of the present application may be utilized in accordance with the teachings herein. Accordingly, the embodiments of the application are not limited to those precise ones shown and described.

[Invention 1001]
A system for providing internal ultraviolet therapy, comprising:
a delivery tube;
at least one UV light source within the delivery tube positioned to deliver UV light out of the delivery tube, the at least one UV light source configured to emit a wavelength between 335 nm and 350 nm; UV light source and
The system, comprising:
[Invention 1002]
1002. The system of claim 1001, wherein said delivery tube is adapted to be placed inside an endotracheal (ET) tube.
[Invention 1003]
1002. The system of invention 1001, wherein the light source is a series of LED light sources.
[Invention 1004]
1002. The system of claim 1001, wherein said array of LED light sources is configured to emit UV light with a peak wavelength between 335-350 nm.
[Invention 1005]
1002. The system of claim 1001, wherein said series of LED light sources is configured to emit UV light with a peak wavelength between 338-342 nm.
[Invention 1006]
1002. The system of claim 1001, wherein said UV light source is configured to deliver UV light around said delivery tube.
[Invention 1007]
1002. The system of claim 1001, further comprising a power supply connected to said UV light source.
[Invention 1008]
1002. The system of claim 1001, wherein said UV light source is configured to deliver UV light along a substantial length of said delivery tube.
[Invention 1009]
1003. The system of invention 1002, wherein the ET tube is configured to be connected to a ventilator.
[Invention 1010]
1002. The system of claim 1001, wherein the majority of light intensity in the spectral region of said UV light source is between 335 nm and 350 nm.
[Invention 1011]
1002. The system of claim 1001, wherein said UV light source is configured to only emit light with a threshold intensity between 335nm and 350nm.
[Invention 1012]
1002. The system of claim 1001, wherein said UV light source is configured to only emit light with an intensity greater than 10% of its maximum intensity between 335 nm and 350 nm.
[Invention 1013]
1002. The system of invention 1001, wherein said delivery tube is adapted to be placed in a nasopharyngeal airway.
[Invention 1014]
A system for providing internal ultraviolet therapy, comprising:
a delivery tube;
a UV light source connected to the delivery tube and configured to emit a wavelength between 335 nm and 350 nm;
memory;
a control system coupled to said memory and comprising one or more processors, said control system configured to execute machine executable code to cause said UV light source to emit wavelengths;
The system, comprising:
[Invention 1015]
1015. The system of invention 1014, further comprising a power supply connected to said UV light source.
[Invention 1016]
1015. The system of Claim 1014, wherein said control system is further configured to execute machine executable code to cause said UV light source to emit wavelengths for at least 20 minutes, 40 minutes, or 60 minutes.
[Invention 1017]
1018. The system of the present invention 1017, wherein the UV light source is configured to treat bacteria in the ET tube and in the patient's larynx and trachea.
[Invention 1018]
1018. The system of the present invention 1017, wherein said UV light source comprises a series of LED light sources.
[Invention 1019]
1018. The system of the present invention 1017, wherein said delivery tube is positioned inside an ET tube.
[Invention 1020]
1018. The system of the present invention 1017, wherein said delivery tube is integrated with an ET tube.
[Invention 1021]
The control system further executes the machine executable code to illuminate the UV light source at least 1,100 microwatts/cm ² , 100 microwatts/cm ² , 2,000 microwatts/cm ² , or 2,100 microwatts/cm 2 . microwatts/cm2 ^, 2,200 microwatts/cm2 ^, 2,300 microwatts/cm2 ^, 2,400 microwatts/cm2 ^, 2,500 microwatts/cm2 ^, 2,600 microwatts/ ^cm2 , 2,700 microwatts/cm ² , 2,800 microwatts/cm ² , 2,900 microwatts/cm ² , or 3,000 microwatts/cm ² . system of the present invention 1017.
[Invention 1022]
1017 of the present invention , wherein the control system is further configured to execute the machine-executable code to cause the UV light source to emit a wavelength having a threshold intensity comprising at least 13, 15, or 18 W/ ^m2 . system.
[Invention 1023]
A method of treating a patient for an infectious condition in the patient, comprising:
inserting the delivery tube into a cavity in the patient's body;
emitting UV-A light in the range of 335-350 nm from a UV light source disposed within the delivery tube to emit UV wavelengths out of the delivery tube at a threshold intensity for a threshold duration;
The above method, comprising
[Invention 1024]
1023. The method of invention 1023, wherein said delivery tube is a catheter equipped with a series of LED light sources having peak wavelengths between 339-346 nm.
[Invention 1025]
1023. The method of the present invention 1023, wherein said body cavity is a respiratory cavity.
[Invention 1026]
1026. The method of invention 1025, wherein said respiratory space is the trachea.
[Invention 1027]
1026. The method of invention 1025, wherein said respiratory cavity is the nasopharynx.
[Invention 1028]
1023. The method of invention 1023, wherein said infectious condition is selected from the group consisting of bacterial infection, viral infection, fungal infection, and combinations thereof.
[Invention 1029]
1023. The method of the invention 1023, wherein said infectious condition is pneumonia.
[Invention 1030]
1024. The method of invention 1023, wherein said threshold duration comprises at least 20 minutes.
[Invention 1031]
1023. The method of invention 1023, wherein said threshold intensity comprises at ^least 13, 15, or 18 W/m2 .
[Invention 1032]
the threshold intensity is at least 1,100 microwatts/cm2 ^, 100 microwatts/cm2 ^, 2,000 microwatts/cm2 ^, or 2,100 microwatts/cm2 ^, 2,200 microwatts/ ^cm2 ; 2,300 microwatts/cm2 ^, 2,400 microwatts/cm2 ^, 2,500 microwatts/cm2 ^, 2,600 microwatts/cm2 ^, 2,700 microwatts/cm2 ^, 2,800 microwatts /cm ² , 2,900 microwatts/cm ² , or 3,000 microwatts/cm 2 , or 3,000 microwatts/cm ² .
[Invention 1033]
The method of invention 1026, wherein said delivery tube is inserted inside an endotracheal tube.
[Invention 1034]
1027. The method of invention 1026, wherein the delivery tube is inserted inside the endotracheal tube while suctioning the endotracheal tube.
For purposes of describing the manner in which the above disclosure and the advantages and features thereof may be obtained, a more specific description of the principles set forth above will be made by reference to the specific examples illustrated in the accompanying drawings. These drawings represent only exemplary aspects disclosed herein, and are therefore not to be considered limiting of its scope. These principles are described and explained with additional specificity and detail through the use of the following figures.

FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's colon, according to the principles disclosed herein. FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's vagina, according to the principles disclosed herein; FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's trachea, according to the principles disclosed herein. FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's nasopharynx, according to the principles disclosed herein; 1 shows a schematic diagram of an exemplary UV light emitting device incorporating LEDs, according to the principles disclosed herein; FIG. 1 shows a schematic diagram of an exemplary UV light emitting device incorporating a cold cathode, according to the principles disclosed herein; FIG. 1 shows an exemplary schematic diagram of a UV spectrum, according to the principles disclosed herein; FIG. FIG. 2 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's rectum and sigmoid colon, according to the principles disclosed herein. FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device inserted into a patient's colon, according to the principles disclosed herein. FIG. 10 shows a cross-sectional view of a UV light emitting device inserted into a patient's esophagus and stomach, according to the principles disclosed herein. FIG. 3 shows a cross-sectional view of an exemplary UV light emitting device passing through a patient's digestive system, according to the principles disclosed herein. 1 illustrates a side view of an exemplary light source attachment, according to principles disclosed herein; FIG. 1 illustrates a side view of an exemplary light source attachment, according to principles disclosed herein; FIG. 1 illustrates an exemplary Foley catheter incorporating an exemplary UV light emitting device according to the principles disclosed herein; FIG. 2 shows growth curves for E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. FIG. 4 shows growth curves for E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. 1 shows an exemplary UV light emitting device implemented in the colon of a mouse according to the principles disclosed herein. 14A and 14B show an exemplary UV light emitting device disclosed herein inserted into the vaginal canal of a rat according to the principles disclosed herein. FIG. 15A shows growth curves for liquid cultures containing E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. 15B shows an exemplary UV light emitting device disclosed herein implemented in a liquid culture containing E. coli. FIG. 2 shows a growth curve of a liquid culture containing E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. 17A and 17B show growth curves of liquid cultures containing E. coli when implementing exemplary UV light emitting devices disclosed herein. FIG. 2 shows a growth curve of a liquid culture containing E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. FIG. 2 shows a growth curve of a liquid culture containing E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. FIG. 2 shows a growth curve of a liquid culture containing E. coli when implementing an exemplary UV light emitting device disclosed herein. FIG. A and B show growth curves of liquid cultures containing E. coli when implementing an exemplary UV light emitting device disclosed herein. 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 23 shows the exemplary UV light emitting device of FIG. 22 attached to a grasping element 200, according to embodiments disclosed herein. 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein; 1 illustrates an exemplary process for providing internal ultraviolet therapy, according to embodiments disclosed herein. 1 illustrates an exemplary process for providing internal UV therapy in connection with ETT, according to embodiments disclosed herein. 1 shows a table showing the intensity and duration of exposure of UVA light applied to bacterial cultures in one example. FIG. 4 shows a table showing bacterial counts over time during UV light exposure in one example. 4 shows a growth curve showing bacterial counts over time during UV light exposure using an exemplary system according to the present disclosure; Time lapse images of Petri dishes containing bacteria exposed to UV light are shown compared to controls. FIG. 4 shows growth curves showing E. coli bacterial counts over time exposed to various intensities of UV light using an exemplary system according to the present disclosure; FIG. FIG. 4 shows growth curves showing E. coli bacterial counts over time exposed to various intensities of UV light using an exemplary system according to the present disclosure; FIG. FIG. 4 shows growth curves showing E. coli bacterial counts over time exposed to various intensities of UV light using an exemplary system according to the present disclosure; FIG. FIG. 4 shows growth curves showing E. coli bacterial counts over time exposed to various intensities of UV light using an exemplary system according to the present disclosure; FIG . FIG. 4 shows growth curves showing P. aeruginosa bacterial counts over time exposed to varying intensities of UV light using an exemplary system according to the present disclosure. FIG. 4 shows growth curves showing Pseudomonas aeruginosa bacterial counts over time exposed to varying intensities of UV light using an exemplary system according to the present disclosure. FIG. 4 shows growth curves showing Pseudomonas aeruginosa bacterial counts over time exposed to varying intensities of UV light using an exemplary system according to the present disclosure. FIG. 4 shows growth curves showing Pseudomonas aeruginosa bacterial counts over time exposed to varying intensities of UV light using an exemplary system according to the present disclosure. FIG. 4 shows growth curves comparing logarithmic reduction at various intensities at 20 and 40 minutes, respectively, using an exemplary system according to the present disclosure. FIG. 4 shows growth curves comparing logarithmic reduction at various intensities at 20 and 40 minutes, respectively, using an exemplary system according to the present disclosure. FIG. 4 shows growth curves showing reduction in E. coli colony size at various intensities and treatment times using an exemplary system according to the present disclosure. FIG. 4 shows growth curves showing reduction in Pseudomonas aeruginosa colony size at various intensities and treatment times using an exemplary system according to the present disclosure. 4 shows a bar graph showing cell proliferation during exposure to UV-A light using an exemplary system according to the present disclosure; 4 shows a bar graph showing cell proliferation during exposure to UV-A light using an exemplary system according to the present disclosure; 4 shows a bar graph showing cell proliferation during exposure to UV-A light using an exemplary system according to the present disclosure; FIG. 4 shows a bar graph showing no DNA damage to cells during exposure to UV-A light using an exemplary system according to the present disclosure; 4 shows a bar graph showing lack of DNA damage to cells during exposure to UV-A light using an exemplary system according to the present disclosure; 4 shows a bar graph showing lack of DNA damage to cells during exposure to UV-A light using an exemplary system according to the present disclosure; FIG. 4 shows a bar graph showing proliferation of virus-infected cells during exposure to UV light using an exemplary system according to the present disclosure; FIG. FIG. 10 shows a bar graph showing the cell count of infected cells compared to controls after 72 hours of UV light application using an exemplary system according to the present disclosure.

The following are examples of treatment regimens and their applications. Accordingly, the devices and methods disclosed herein can be adapted to treat these different conditions.
Urology and Nephrology:
1. Sterilizing the blood of patients with known bacteremia, fungemia, or viremia during dialysis to eradicate or reduce the microbial load. Alternatively, a light needle can be placed in the stoma and turned on outside the dialysis window as well. An ex vivo sensitivity analysis is performed for the narrower wavelength but stronger ILT.
2. 2. Sterilization of indwelling urethral catheters in catheter-dependent patients. 4. Treatment of bladder and urethral cancers confined to the mucosa and submucosa. 4. Treatment of refractory cystitis/urinary tract infections; Addition of UV phototherapy to peritoneal dialysis catheters to reduce the risk of peritonitis and even long-term peritoneal sclerosis.
Cardiology 1 . Sterilizing the blood of patients with known bacteremia, fungemia, or viremia who have an LVAD to eradicate or reduce the microbial load. Alternatively, a light needle can be placed in the stoma and turned on outside the dialysis window as well. An ex vivo sensitivity analysis can be performed for narrower wavelength but more intense UV therapy.
2. Refractory bacterial and fungal endocarditis is treated with direct UV light exposure of the valve. In this case, the photosensitizer may be administered intravenously.
Dentistry 1. Treatment of gingivitis.
2. Treatment of leukoplakia and oral lichen planus.
3. Treatment of cancer confined to the mucosa and submucosa Hematology/Oncology 1 . Treatment of intestinal graft-versus-host disease. In this case, X-ray wavelengths are emitted and kill lymphocytes. It can be used in end-stage Crohn's disease patients awaiting small bowel transplantation or palliative care.
ENT
1. Treatment of chronic sinusitis.
2. Treatment of chronic otitis.
3. Treatment of acute otitis media in patients requiring myringotomy.
4. Treatment of nasal polyps ( evidence suggests that UV light shrinks nasal polyps).
5. Bad breath treatment.
6. Treatment of recurrent tonsillitis/pharyngitis.
7. Treatment of cancer confined to mucosa and submucosa Surgery 1 . To improve treatment of abscesses by equipping drains with UV light technology.
2. Use with surgical drains to avoid mixed infections.
3. Accelerate the anastomosis healing process.
4. Helps prevent adhesions.
Neurosurgery 1. Intrathecal fiber optic delivery of UV light in the treatment of refractory meningitis.
2. Treatment of refractory shunt infections.
3. Treatment of prion diseases with intrathecal or intrathecal UV therapy.
4-Treatment of JC virus associated with progressive multifocal leukoencephalopathy by reducing viral load.
Gynecology 1. Treatment of bacterial vaginosis or fungal vaginosis.
2. Treatment of rectovaginal/colic fistula.
3. Treatment of cancer confined to the mucosa and submucosa Rheumatology 1 . Intra-articular ILT for the treatment of inflammatory and infectious macroarthritis.
Vaginal therapy 1 . Figures 14A, 14B show an example of a UV light emitting device being used for vaginal treatment in mice.

Figures 35B-35E show graphs showing the time course of colony forming units (CFU) of E. coli when irradiated with varying intensities of UV-A light with a peak wavelength of 345 nm. As shown, an intensity of 2000 uW removed most of the bacteria by 40 minutes (Fig. 35D) and an intensity of 3000 uW removed most of the bacteria by 20 minutes (Fig. 35E ) . When the same light was irradiated at 500 uW and 1000 uW intensities, a significant decrease in CFU was seen by 40 min, but only by about half (FIGS. 35C and 35B).

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

Claims (34)

A system for providing internal ultraviolet therapy, comprising:
a delivery tube;
at least one UV light source within the delivery tube positioned to deliver UV light out of the delivery tube, the at least one UV light source configured to emit a wavelength between 335 nm and 350 nm; and a UV light source. 3. The system of claim 1, wherein the delivery tube is adapted to be placed inside an endotracheal (ET) tube. 3. The system of Claim 1, wherein the light source is a series of LED light sources. 2. The system of claim 1, wherein the series of LED light sources are configured to emit UV light with peak wavelengths between 335-350 nm. 2. The system of claim 1, wherein the series of LED light sources are configured to emit UV light with peak wavelengths between 338-342 nm. 2. The system of Claim 1, wherein the UV light source is configured to deliver UV light around the delivery tube. 3. The system of claim 1, further comprising a power supply connected to said UV light source. 3. The system of Claim 1, wherein the UV light source is configured to deliver UV light along a substantial length of the delivery tube. 3. The system of claim 2, wherein the ET tube is configured to connect to a ventilator. 2. The system of claim 1, wherein the majority of light intensity in the spectral region of the UV light source is between 335 nm and 350 nm. 2. The system of claim 1, wherein the UV light source is configured to only emit light with a threshold intensity between 335nm and 350nm. 2. The system of claim 1, wherein the UV light source is configured to emit only light with an intensity greater than 10% of its maximum intensity between 335 nm and 350 nm. 3. The system of claim 1, wherein the delivery tube is adapted for placement in a nasopharyngeal airway. A system for providing internal ultraviolet therapy, comprising:
a delivery tube;
a UV light source connected to the delivery tube and configured to emit a wavelength between 335 nm and 350 nm;
memory;
a control system coupled to said memory and comprising one or more processors, said control system configured to execute machine executable code to cause said UV light source to emit wavelengths; said system. 15. The system of Claim 14, further comprising a power supply connected to said UV light source. 15. The system of claim 14, wherein the control system is further configured to execute machine executable code to cause the UV light source to emit wavelengths for at least 20 minutes, 40 minutes, or 60 minutes. 18. The system of claim 17, wherein the UV light source is configured to treat bacteria within an ET tube and within a patient's larynx and trachea. 18. The system of Claim 17, wherein the UV light source comprises a series of LED light sources. 18. The system of claim 17, wherein the delivery tube is positioned inside an ET tube. 18. The system of Claim 17, wherein the delivery tube is integrated with the ET tube. The control system further executes the machine executable code to provide at least 1,100 microwatts/cm ² , 100 microwatts/cm ² , 2,000 microwatts/cm ² , or 2,100 microwatts/cm 2 to the UV light source. microwatts/ ^cm2 , 2,200 microwatts/ ^cm2 , 2,300 microwatts/ ^cm2 , 2,400 microwatts/ ^cm2 , 2,500 microwatts/ ^cm2 , 2,600 microwatts/ ^cm2 , 2,700 microwatts/cm ² , 2,800 microwatts/cm ² , 2,900 microwatts/cm ² , or 3,000 microwatts/cm ² . 18. The system of claim 17, wherein: 18. The control system of claim 17, wherein the control system is further configured to execute the machine executable code to cause the UV light source to emit a wavelength having a threshold intensity comprising at least 13, 15, or 18 W/ ^m2 . System as described. A method of treating a patient for an infectious condition in the patient, comprising:
inserting the delivery tube into a cavity in the patient's body;
Emitting UV-A light in the range of 335-350 nm from a UV light source disposed within the delivery tube to emit UV wavelengths out of the delivery tube at a threshold intensity for a threshold duration. The method above. 24. The method of claim 23, wherein the delivery tube is a catheter with a series of LED light sources with peak wavelengths between 339-346 nm. 24. The method of claim 23, wherein said body cavity is a respiratory cavity. 26. The method of claim 25, wherein said respiratory space is the trachea. 26. The method of claim 25, wherein said respiratory cavity is the nasopharynx. 24. The method of claim 23, wherein said infectious condition is selected from the group consisting of bacterial infection, viral infection, fungal infection, and combinations thereof. 24. The method of claim 23, wherein said infectious condition is pneumonia. 24. The method of claim 23, wherein said threshold duration comprises at least 20 minutes. 24. The method of claim 23, wherein said threshold intensity comprises at least 13, 15, or 18 W/m< ² >. said threshold intensity is at least 1,100 microwatts/cm ² , 100 microwatts/cm ² , 2,000 microwatts/cm ² , or 2,100 microwatts/cm ² , 2,200 microwatts/cm ² ; 2,300 microwatts/ ^cm2 , 2,400 microwatts/ ^cm2 , 2,500 microwatts/ ^cm2 , 2,600 microwatts/ ^cm2 , 2,700 microwatts/ ^cm2 , 2,800 microwatts 24. The method of claim 23, comprising an intensity of 2,900 microwatts/ ^cm2 , 2,900 microwatts/ ^cm2 , or 3,000 microwatts/ ^cm2 . 27. The method of claim 26, wherein the delivery tube is inserted inside an endotracheal tube. 27. The method of claim 26, wherein the delivery tube is inserted inside the endotracheal tube while suctioning the endotracheal tube.

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