Photodynamic therapy methods

Abstract

A method for performing photodynamic therapy is provided. The method includes applying a topical composition to the skin of a patient. The topical composition includes 5-aminolevulinic acid (ALA) hydrochloride and a vehicle including at least one chelating agent for enhancing accumulation of protoporphyrin IX (PpIX) in the skin. The method further includes incubating the topical composition and, after incubation, applying heat from a heat source to the skin for at least a first period of time.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 422,877, filed November 4, 2022, the entire contents of which are incorporated herein by reference.

[0002] BACKGROUND 1. Field of the Disclosure This disclosure relates generally to devices and methods for photodynamic therapy.

[0003] Photodynamic therapy (PDT), photodynamic diagnosis (PD), and / or photochemotherapy generally involve treating and / or diagnosing several types of diseases or disorders associated with the skin or other tissues, such as those within body cavities. PDT may involve administering a photoactivatable drug and exposing the patient to photoactivating light to activate the drug, converting it to a cytotoxic form, and destroying cells associated with the skin disease or disorder. For example, photodynamic therapy or photodynamic diagnosis may be used to treat or diagnose actinic keratosis (AK) on the upper extremities (e.g., the back of the hands or forearms), scalp, or facial areas of a patient, among other locations. AK is typically caused by excessive exposure to ultraviolet (UV) light and may be present, for example, on the face, head, scalp, ears, shoulders, neck, arms, forearms, and hands.

[0004] Additionally, PDT or PD may be used to treat and diagnose other patient indications (e.g., acne, warts, psoriasis, photodermatological damage, cancer) and other areas (e.g., the forearm, back, abdomen, chest, or parts of the leg or arm other than another part of the body). PDT using UV or blue light is indicated for the treatment of mild to moderate acne due to its anti-inflammatory effect on skin cells. The combination of photoactivatable agents with high-intensity red light has been found to be effective but may have significant side effects.

[0005] During this form of photodynamic therapy, the patient is first administered a photoactivatable agent or a precursor of the photoactivatable agent that accumulates in the tissue to be treated. The area to which the photoactivatable agent is administered is then exposed to light, which triggers chemical and / or biological changes in the agent. These changes allow the agent to selectively localize, destroy, or alter the target tissue while causing at most mild and reversible damage to other tissues within the treatment area. One example of a photoactivatable agent precursor is 5-aminolevulinic acid ("ALA" or "5-ALA"), which is commonly used in the photodynamic therapy of actinic keratoses. As used herein, the terms ALA or 5-aminolevulinic acid refer to ALA itself, its precursors, its esters, and its pharmaceutically acceptable salts, such as aminolevulinic acid hydrochloride (HCl). Photosensitization following application of a topical composition containing ALA (e.g., topical solution, emulsion, nanoemulsion, gel) occurs via metabolic conversion of aminolevulinic acid to protoporphyrin IX (PpIX). PpIX is a photosensitizer that accumulates in the skin.

[0006] Illuminators are typically used to provide appropriate light uniformity for therapeutic purposes. These devices generally include a light source (e.g., a fluorescent tube or light-emitting diode (LED)), coupling elements that direct, filter, or otherwise conduct the emitted light so that it reaches its intended target in a usable form, and a control system that starts and stops light production as needed.

[0007] Photodynamic therapy can be performed using certain compositions, such as ALA, in conjunction with an illuminator. Such compositions and / or illuminators (as well as treatment methods, dressings, and other details) have been disclosed, for example, in U.S. Pat. No. 5,954,703 to Golub, entitled "Method and Apparatus for Applying 5-Aminolevulinic Acid," issued September 21, 1999; U.S. Pat. No. 6,223,071 to Lundahl et al., entitled "Illuminator for Photodynamic Therapy and Diagnosis Which Produces Substantially Uniform Intensity Visible Light," issued April 24, 2001; U.S. Pat. No. 10,814,114 to Boyajian et al., entitled "Method and Apparatus for Applying a Topical Solution," issued October 27, 2020; and U.S. Pat. No. 10,814,114 to Boyajian et al., entitled "Adjustable Illuminator for Photodynamic Therapy and Diagnosis Which Produces Substantially Uniform Intensity Visible Light," issued March 17, 2020. (5) U.S. Patent Application Publication No. 2020 / 0246630 to Boyajian et al., entitled “Adjustable illuminator for photodynamic therapy and diagnosis,” issued on August 6, 2020; (6) U.S. Patent No. 11,179,574 to Boyajian et al., entitled “Method of administering 5-aminolevulinic acid (ALA) to a patient,” issued on November 23, 2021; (7) U.S. Patent No. 10,603 to Boyajian et al., entitled “Adjustable illuminators and methods for photodynamic therapy and diagnosis,” issued on March 31, 2020;508, and its progeny, U.S. Patent Application Publication No. 2020 / 0269063, published August 27, 2020; (8) U.S. Patent No. 10,357,567, entitled "Methods for photodynamic therapy," to Lundahl et al., issued July 23, 2019, and its progeny, U.S. Patent No. 11,077,192, issued August 3, 2021, and U.S. Patent No. 11,135,293, issued October 5, 2021; and (9) U.S. Patent Application No. 2020 / 0261580, entitled "Photodynamic therapy method for skin disorders," to Willey, published August 20, 2020. The entire contents of the aforementioned patents and / or patent applications are incorporated herein by reference for background information and the compositions, illuminators, devices, dressings, therapeutic methods, processes and techniques related to photodynamic therapy and diagnosis disclosed therein. Summary of the Invention

[0008] This disclosure describes an illuminator for photodynamic therapy, as well as related techniques and methods of treatment. The illuminator allows for improved maneuverability and control for treatment.

[0009] According to one embodiment, a method for performing photodynamic therapy is provided. The method includes applying a topical composition to the skin of a patient. The topical composition includes 5-aminolevulinic acid (ALA) hydrochloride and a vehicle including at least one chelating agent for enhancing accumulation of protoporphyrin IX (PpIX) in the skin. The method further includes incubating the topical composition and, after incubation, applying heat from a heat source to the skin for at least a first period of time.

[0010] In at least one embodiment, the at least one chelating agent is selected from ethylenediaminetetraacetic acid (EDTA) or a pharmaceutically acceptable salt thereof. In at least one embodiment, the method includes exposing the skin to light from a light source for a second period after incubation, and heat is also applied during the second period. In at least one embodiment, the incubation occurs for about 2 hours to about 3 hours, and the total of the first and second periods is about 13 minutes. In at least one embodiment, light is not applied to the skin before applying heat. In at least one embodiment, applying heat to the skin for 13 minutes increases the amount of PpIX present in the skin by more than 50%. In at least one embodiment, applying heat to the skin for 13 minutes increases the amount of PpIX present in the skin by more than 80%. In at least one embodiment, aminolevulinic acid hydrochloride is present in an amount of 20% w / w of the topical composition, and the at least one chelating agent is ethylenediaminetetraacetic acid (EDTA) present in an amount of about 0.1% to about 0.15% of the topical composition.

[0011] According to one embodiment, the illuminator is provided with at least one articulating joint configured to allow the illuminator panel to move approximately 360 degrees in azimuth and then lock into place. In at least one embodiment, two joints are provided to allow 360 degrees of rotation. According to one embodiment, the illuminator is provided with a control panel or control interface that can be moved relative to the rest of the illuminator. These features allow the illuminator to be positioned in a desired location relative to the patient, while a healthcare provider can access the control panel or interface to administer, control, and monitor therapy.

[0012] The panels may be arranged in various configurations to provide illumination to the area of ​​the body being treated. Uniform illumination is desirable to provide uniform therapeutic benefit to the area being treated. The embodiments described below provide greater than approximately 70% uniformity from approximately 2 to approximately 4 inches from the treatment surface (so that the measured output across the emission area is within about 70% of the maximum measured output across a distance of approximately 2 to approximately 4 inches). In at least one embodiment, the uniformity may be between approximately 70% and approximately 80%, e.g., 72.5% to 77.5%, over a distance of approximately 2 inches to approximately 4 inches.

[0013] In at least one embodiment, the panels may be opened and positioned in a flat or substantially flat arrangement to treat areas such as the patient's back or chest and abdomen. The panels may also be positioned in a U-shape (corresponding to or substantially similar to a "U") with the outer panels parallel or substantially parallel to one another. The panels are configured to be positioned in a U-shaped orientation during treatment, for example, on the head, face, scalp, neck, arms, forearms, hands, feet, and / or legs. The panels may be positioned parallel to the floor, perpendicular to the floor, or in any other position relative to the floor, including treating other parts of the patient (e.g., the torso or back). The panels may have different orientations, such that one panel may be parallel to the floor and another panel may be oriented at an angle relative to the floor. In at least one embodiment, the panels may be placed in a pre-treatment configuration, which is a configuration immediately prior to treatment, for example, for redundancy purposes, and to provide demonstrations, instructions, or education to the patient about the treatment to be performed, after which the panels may be placed in a "patient-ready" position corresponding to the orientation leading to the treatment.

[0014] According to one embodiment, a storage arrangement for a photodynamic therapy illuminator is provided that allows the illuminator to be folded into a compact space when not in use. In this embodiment, the illuminator, including the arm and its panel, does not extend substantially beyond the illuminator base when in the storage (stowed) position. For example, the illuminator, including the arm and panel, does not extend more than 40%, 30%, 20%, 10%, or 0% beyond the illuminator base when in the storage position. In at least one embodiment, the illuminator panel folds around the illuminator pillar in the storage position, thus facilitating a compact storage arrangement. This compact storage arrangement is a significant advantage for healthcare providers due to limited examination and treatment rooms in many clinics, and it also provides additional space for patient examinations and other types of treatment when the illuminator is not in use. Furthermore, this compact arrangement, in conjunction with wheels on the base, allows the illuminator to easily fit through a doorway and be moved to other examination and treatment rooms or other facilities.

[0015] The illuminator may be configured to accommodate a patient standing, sitting, lying down, or in another position. In at least one embodiment, the panel may be rapidly adjusted from a first configuration to a second configuration. For example, the panel may be adjusted from a first configuration useful for treating the patient's scalp or face to a second configuration useful for treating the patient's back, or vice versa, within a period of approximately 20 to 40 seconds or approximately 30 seconds. Various adjustments of the panel and arm can be achieved quickly (within 30 to 60 seconds) without tools.

[0016] The panel may support an array of light sources, such as, for example, light emitting diodes (LEDs). Alternatively, other types of light sources may be used, such as fluorescent or halogen lamps, non-laser light sources, lasers, or other types of light sources. The light source provides illumination to activate the photoactivatable agent, as described above.

[0017] The details of one or more embodiments are set forth in the accompanying drawings and the description below. The drawings are provided for the purpose of illustrating one or more embodiments, with the express understanding that they are not used to limit the scope or meaning of the claims. It should be noted that the specific embodiments are not intended as exhaustive descriptions or as limitations on the broader aspects discussed herein. An aspect described in connection with a particular embodiment is not limited to that embodiment and can be practiced in other embodiments.

[0018] The following terms are used throughout this patent application and are defined below.

[0019] As used herein and in the appended claims, in the context of describing elements (particularly in the context of the claims that follow), singular articles such as "a" and "an," as well as "the," and similar references, should be construed to cover both the singular and the plural unless otherwise indicated herein or clearly contradicted by context. The recitation of ranges of values ​​herein is merely intended to serve as a shorthand method of individually referring to each separate value falling within that range, unless otherwise indicated herein, and each separate 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 clearly contradicted by context. The use of any and all examples or exemplary language (e.g., "etc.") provided herein is intended to better describe embodiments and does not pose a limitation on the scope of the claims unless otherwise stated. No language herein should be construed as indicating any non-claimed element as required.

[0020] The terms "incubation time," "incubation period," or "incubation" can refer to the period from when a drug (such as ALA) is applied to when a treatment period begins, e.g., when illumination occurs. Generally, the incubation time or incubation period can occur before a treatment period. For example, the incubation time can be the interval from when a drug is applied (e.g., topically) to the start of intentional exposure to targeted illumination by an illuminator (e.g., as opposed to ambient illumination) or the start of a treatment process, such as the application of heat (or both heat and light). As will be understood by those skilled in the art, incubation can occur in the dark, which is most common. However, incubation can also occur in the presence of light, including sunlight (e.g., so-called painless PDT). Whether under dark exposure or light exposure, incubation can occur with or without heat.

[0021] Any embodiment illustratively described herein may be suitably practiced in the absence of any element. Thus, for example, terms such as "comprising," "including," and "containing" are intended to be read expansively and not limiting. Furthermore, the terms and expressions employed herein are used as terms of description rather than limitation, and the use of such terms and expressions is not intended to exclude any equivalents of the features shown and described or portions thereof, but recognizes that various modifications are possible within the scope of the claimed technology. Furthermore, the phrase "consisting essentially of" will be understood to include those elements specifically recited and those additional elements that do not materially affect the basic and novel characteristics of the claimed technology. The term "comprising" means "including, but not limited to." Thus, other unrecited materials, additives, devices, or steps may be present.

[0022] Unless otherwise indicated, all numbers expressing quantities of properties, parameters, conditions, and the like used in the specification and claims should be understood as being modified in all instances by the term "approximately" or "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and appended claims are approximations. Any numerical parameter should be construed in light of, at the very least, the number of significant digits and by applying ordinary rounding techniques. When used before numerical designations, e.g., temperature, time, amounts, and concentrations including ranges, the term "approximately" indicates an approximation that may vary by (+) or (-) 10%, 5%, or 1%.

[0023] As will be understood by those skilled in the art, for all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass any possible subranges and combinations of those subranges. Any recited range can be readily recognized as fully delineating and allowing for the same range to be divided into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, a middle third, an upper third, etc. Also, as will be understood by those skilled in the art, all language such as "up to," "at least," "greater than," "less than," etc., refers to a range that is inclusive of the recited numbers and can then be broken down into subranges as described above. Finally, as will be understood by those skilled in the art, a range includes each individual member. [Brief explanation of the drawings]

[0024] The features, aspects, and advantages of the present invention will become apparent from the following description and accompanying exemplary embodiments illustrated in the drawings, which are briefly described below.

[0025] [Figure 1] FIG. 1 illustrates a front view of an illuminator system in accordance with an exemplary embodiment. [Figure 2]FIG. 2 shows a top perspective view of the illuminator system of FIG. [Figure 3] FIG. 3 shows a front perspective view of the illuminator system of FIG. [Figure 4] FIG. 4 shows a rear view of the illuminator system of FIG. [Figure 5] FIG. 5 shows a front perspective view of the illuminator system of FIG. [Figure 6] FIG. 6 shows a top perspective view of the mounting mechanism of the illuminator system of FIG. [Figure 7] FIG. 7 shows a side perspective view of a panel of the illuminator system of FIG. [Figure 8A] FIG. 8A shows a side view of the illuminator of the illuminator system of FIG. [Figure 8B] FIG. 8B shows a side view of the illuminator of the illuminator system of FIG. [Figure 9] FIG. 9 shows a rear view of the illuminator of the illuminator system of FIG. [Figure 10] FIG. 10 shows a rear view of the illuminator of the illuminator system of FIG. [Figure 11] FIG. 11 shows a front view of the illuminator system of FIG. 1 in the retracted position. [Figure 12] FIG. 12 shows a perspective view of the illuminator system of FIG. 1 in a retracted position. [Figure 13] FIG. 13 shows a top view of a panel of the illuminator system of FIG. [Figure 14] FIG. 14 shows a front view of the interface panel of the illuminator system of FIG. [Figure 15] FIG. 15 shows a front view of the main power switch of the illuminator system of FIG. [Figure 16] FIG. 16 shows a front view of the vertical column lock of the illuminator system of FIG. [Figure 17] FIG. 17 shows a front view of the arm lock of the illuminator system of FIG. [Figure 18] FIG. 18 shows a cross-sectional side view of a panel of the illuminator system of FIG. [Figure 19]FIG. 19 shows a perspective view of a fan plenum of a panel of the illuminator system of FIG. [Figure 20] FIG. 20 shows a detailed cross-sectional view of the fan plenum of the illuminator system of FIG. [Figure 21] FIG. 21 shows a detailed cross-sectional view of the fan plenum of the illuminator system of FIG. [Figure 22] FIG. 22 shows a detailed cross-sectional view of the fan plenum of the illuminator system of FIG. [Figure 23] FIG. 23 shows the touch screen of the illuminator system of FIG. [Figure 24] FIG. 24 shows a schematic diagram of the controller of the illuminator system of FIG. [Figure 25] FIG. 25 shows a block diagram of a method for photodynamic diagnosis or treatment of a patient, according to an exemplary embodiment. [Figure 26] FIG. 26 shows the graphical results relating to the amount of accumulated PpiX. [Figure 27] FIG. 27 shows the graphical results relating to the amount of accumulated PpiX. DETAILED DESCRIPTION OF THE INVENTION

[0026] Various embodiments are described below. It should be noted that a particular embodiment is not intended as an exhaustive description or as a limitation on the broader aspects discussed herein. An aspect described in conjunction with a particular embodiment is not limited to that embodiment and can be implemented in any other embodiment.

[0027] Photodynamic therapy treatment with a light source 1-4 illustrate at least one embodiment of a configurable illuminator system 105. The illuminator system 105 includes an illuminator 100. The illuminator 100 comprises a plurality of panels 10. The panels 10 are provided with LEDs 60 used to emit light for photodynamic therapy for the treatment of skin diseases and disorders (defined as the multi-layered organ including the epidermis, dermis, and subcutaneous tissue, and further including the mucous membranes adjacent to the outer skin). The skin to be treated may be, for example, the surface of the head, face, scalp, neck, arms, legs, torso, genitals, hands or feet, or elsewhere.

[0028] In particular, according to at least one embodiment, the head, face, or neck may be treated using the illuminator 100. Such treatment of the head, face, or neck may occur in a single session or over multiple sessions over a period of time. The face includes, for example, the midsection, eyelids, eyebrows, periorbital area, nose, lips, chin, mandible, preauricular skin, postauricular skin, and sulci. These areas of the face, along with the genitals, hands, and feet, may be at relatively high risk for developing non-melanoma skin cancer ("NMSC," which includes all types of skin cancer that are not melanoma, including keratinocyte carcinoma). Moderate-risk areas include the cheeks, forehead, scalp, and neck. To assess the effectiveness of treatment, lesion counts in a given area may be performed in designated areas of the body, such as the forehead, both cheeks, nose, or chin.

[0029] Photodynamic therapy may cause certain individuals to experience discomfort and / or pain. In at least one embodiment, the illuminator provides a gentle airflow tangential to the skin surface to reduce or minimize pain. The airflow may be provided substantially tangential (i.e., substantially parallel) to the skin surface (at an angle of approximately 0 degrees relative to the skin surface), thus providing a gentle flow across the surface being treated. In another embodiment, the air is provided at an angle of 45° or less relative to the skin surface. In at least one embodiment, the angle may be between approximately 25° and approximately 45°, e.g., approximately 29°, approximately 33°, approximately 37°, or approximately 41°. The airflow may be provided in connection with any of the treatment methods described herein.

[0030] This arrangement avoids direct air impact on the skin surface, which has been found to cause pain or stinging due to sensations (e.g., touch or pressure) on the skin. In at least one embodiment, the gentle air flow is provided to reduce pain and / or discomfort that may be experienced by patients undergoing PDT involving occlusion through a barrier, such as a low-density polyethylene (LDPE) or foil barrier. In particular, the cooled air flow can reduce pain following administration of ALA to a patient during a treatment cycle.

[0031] The following description provides exemplary, but not limiting, discussion of how particular areas may be treated using PDT. In the discussion below, the distance between the treatment surface and the surface of the illuminator is approximately 2 inches to approximately 4 inches, although it should be understood that other distances (e.g., approximately 5 cm to approximately 8 cm) may be utilized. To treat facial lesions, the illuminator described above may be positioned so that the area to be treated is approximately 2 to approximately 4 inches from the surface of the illuminator, with the patient's nose approximately 2 inches or more from the surface of the illuminator and the forehead and cheeks approximately 4 inches or less from the surface. The patient's face and the sides of the patient's ears may be positioned as close as approximately 2 inches from the surface of the illuminator, for example.

[0032] In at least one embodiment, to treat scalp lesions, the illuminator described above may be positioned so that the area to be treated is between about 2 and about 4 inches from the surface of the illuminator, and the patient's scalp is about 2 inches or more from the surface of the illuminator and about 4 inches or less from the surface. The patient's face and the sides of the patient's ears may be positioned as close as about 2 inches from the surface of the illuminator, for example.

[0033] In at least one embodiment, to treat lesions on the upper extremity, such as the dorsum of the hand or forearm, the illuminator described above can be positioned so that the area to be treated is approximately 2 to approximately 4 inches from the surface of the illuminator. A device (e.g., a table) may be used to support the upper extremity during light treatment to increase patient comfort and stabilize the area to be treated. The aforementioned distances may be used in connection with administering treatment according to any of the embodiments of the present disclosure.

[0034] In at least one embodiment, blue light (e.g., light having a wavelength of about 380 nm to about 500 nm) is applied. In at least one embodiment, blue light having a wavelength of about 417 nm (±5 nm) is applied at about 10 mW / cm. 2 is applied for 1000 seconds at an intensity of approximately 10J / cm 2 However, the intensity may be increased (e.g., about 20 mW / cm) to shorten the treatment time. 2 For example, the intensity may be increased to shorten the treatment time by about half. In other embodiments, red light (e.g., red light generated by a light-emitting diode (LED) at 635 nm) may be used. Red light can provide, for example, about 10 to about 75 J / cm2 (e.g., 37 J / cm2) within 10 minutes, or within about 9 to about 11 minutes. 2 The red light may be from about 620 nm to about 750 nm.

[0035] In at least one embodiment, the illuminator may illuminate the lesion with red light of uniform intensity for a predetermined period of time. In certain embodiments, the illuminator illuminates the lesion with blue light of uniform intensity for a first prescribed period of time, and then illuminates the lesion with red light of uniform intensity for a second prescribed period of time. The wavelength of the illuminating light may be selected to match the wavelength that excites the photoactivatable agent and preferably has low absorption by non-target tissue. For example, in at least one embodiment, the illuminator uses low intensity (e.g., about 0.1 J / cm) light. 2 ~about 2 J / cm 2 The illuminator is configured to illuminate the lesion with blue light (e.g., about 417 nm) at a uniform intensity at a wavelength of 1000 nm to photobleach, for example, protoporphyrin IX (PpIX) present on the surface of the patient's skin. In at least one embodiment, the illuminator is configured to illuminate the lesion with blue light (e.g., about 30 J / cm) at a uniform intensity at a wavelength of 1000 nm to photobleach, for example, protoporphyrin IX (PpIX) present on the surface of the patient's skin. 2 ~Approx. 158 J / cm 2 ) to irradiate the lesion with uniform intensity red light (e.g., 635 nm) to activate PpIX present in the deeper layers of the patient's skin, configured to avoid potential damage to the upper layers of the patient's skin.

[0036] Furthermore, the total light intensity (J / cm 2 ) is the irradiance (mW / cm 2 An additional parameter to control for delivery of the correct therapeutic light dose is exposure time (among other parameters that can be controlled to affect treatment), since it is equal to 10 mW / cm multiplied by time (seconds). This may be achieved by a timer that can appropriately control the power delivered to the LED array and can be set by the healthcare provider. Data are based on 10 mW / cm 2 or approximately 9.3 to approximately 10.7 mW / cm 2 Approximately 10 J / cm delivered from a source with an irradiation density of 2 has been shown to produce clinically acceptable results for desired treatment areas (e.g., face, scalp, and extremities).

[0037] In at least one embodiment, the adjustable illuminator provides approximately 20 mW / cm for an exposure time of approximately 580 seconds (approximately 8 minutes, 20 seconds). 2 delivering an irradiation density of 10 J / cm 2 In certain embodiments, lower intensities may be achieved with longer exposure times (e.g., approximately 10 J / cm). 2 Alternatively, an adjustable illuminator may be used with a light dose of approximately 30 mW / cm over the exposure time. 2 may include higher power ranges such as approximately 10 J / cm 2 The selected light dose may also, additionally or alternatively, be administered by varying the irradiance density over the treatment time.

[0038] Exemplary Compositions for Photodynamic Therapy In at least one embodiment, the pharmaceutical composition comprising the photoactivatable agent may be applied using an applicator or by other means, such as a gloved finger, a gauze pad, a swab, a bandage, or a spatula. The pharmaceutical composition may be applied in a topical form (e.g., a compound suitable for administration by application to the surface of a patient's skin), such as, for example, a gel or solution, and may be applied beyond the lesion to be treated. In at least one embodiment, the photoactivatable agent comprises a porphyrin or a porphyrin precursor.

[0039] The amount of photoactivatable agent in a pharmaceutical composition (e.g., a dosage form suitable for topical delivery) can vary. In at least one embodiment, the photoactivatable agent is ALA present in an amount of about 0.1% to about 75% by weight. In at least one embodiment, the amount of photoactivatable agent in the pharmaceutical composition is greater than about 10% by weight. In at least one embodiment, the amount of photoactivatable agent in the pharmaceutical composition is about 20% by weight. In another embodiment, the amount of photoactivatable agent in the pharmaceutical composition is greater than zero.

[0040] For example, in at least one embodiment, ALA may be in the form of a liquid solution containing about 20% ALA, or a 10% ALA gel, or a 20% ALA gel. By way of further example, in at least one embodiment, the photoactivatable agent is provided in a gel containing 20% ​​aminolevulinic acid hydrochloride. In at least one embodiment, the composition in gel form further comprises a local anesthetic. The pH of the gel formulation may be within the range of about 4.5 to about 7.5.

[0041] For example, in at least one embodiment, the composition containing the photoactivatable agent is LEVULAN® (DUSA Pharmaceuticals, Billerica, Massachusetts), a topical formulation of 20% 5-aminolevulinic acid hydrochloride, which may be administered via a KERASTICK® applicator. In at least one embodiment, the composition is AMELUZ® (Biofrontera AG, Leverkusen, Germany), a non-sterile topical formulation of 10% 5-aminolevulinic acid hydrochloride (equivalent to 7.8% of the free acid) in a gel matrix with a nanoemulsion. In at least one embodiment, the photoactivatable agent may be a non-porphyrin agent. In at least one embodiment, approximately 1 gram (78 mg) of 5-aminolevulinic acid hydrochloride gel (ALA) is administered.

[0042] In at least one embodiment, the composition comprising a photoactivatable agent is a composition disclosed in PCT Application No. PCT / IB2022 / 060058, filed October 19, 2022, and U.S. Patent Application No. 17 / 968,931, filed October 19, 2022, which are incorporated by reference in their entireties for the compositions, compounds, and formulas disclosed therein. For example, according to at least one embodiment, the composition comprising a photoactivatable agent comprises: a) a 5-carbon aminoketone compound of formula I, [ka] or a pharmaceutically acceptable salt thereof b) at least one penetration enhancer; c) at least one chelating agent, and d) Optionally, an antifoaming agent.

[0043] Preferably, the at least one penetration enhancer is selected from the group consisting of dialkyl derivatives of acetamide and formamide, pyrrolidone derivatives, fatty acids, fatty acid esters, glycol derivatives, glycerides, azones, polysorbates, macrogolglycerides, polyethylene glycol derivatives, ethoxylated ether derivatives, bile salts, and glycosaminoglycans. More preferably, the topical composition according to the present disclosure comprises dialkyl derivatives of acetamide and formamide (such as dimethylacetamide, dimethylformamide), pyrrolidone derivatives (such as N-methyl-2-pyrrolidone), fatty acids (such as oleic acid), glycol derivatives (such as propylene glycol) and their fatty acid esters (such as propylene glycol monocaprylate, propylene glycol monolaurate), azones (such as laurocapram or 1-n-dodecyl-azacycloheptan-2-one), polysorbates (such as Tween® (Polysorbate) 80), Permeation enhancers include macrogolglycerides (such as stearoyl macrogolglycerides, oleoyl macrogolglycerides, lauroyl macrogolglycerides, capryl-caproyl macrogolglycerides), polyethylene glycol derivatives (such as polyethylene glycol 400), ethoxylated ether derivatives (such as diethylene glycol monoethyl, diethylene glycol monomethyl ether, dipropylene glycol monomethyl ether), glycosaminoglycans (such as chondroitin sulfate), keratan sulfate, dermatan sulfate, heparin sulfate, and heparin sulfate.

[0044] The penetration enhancer is present in the composition in an amount ranging from about 10% w / w to about 50% w / w of the composition, such as about 10%, 20%, 30%, 40%, or 50% w / w of the composition, and all ranges and subranges therein. More preferably, the penetration enhancer is present in the composition in an amount ranging from about 20% w / w to about 40% w / w of the composition, such as about 20%, about 30%, or about 40% w / w of the composition, and all ranges and subranges therein.

[0045] In at least one other embodiment, the at least one penetration enhancer is selected from the group consisting of glycol derivatives, polyethylene glycol derivatives, and ethoxylated ether derivatives. In another preferred embodiment, the at least one penetration enhancer is selected from the group consisting of propylene glycol, polyethylene glycol, and 2-(2-ethoxyethoxy)ethanol (Transcutol®). The propylene glycol is present in the composition in an amount ranging from about 10% w / w to about 50% w / w of the composition, e.g., about 10%, 20%, 30%, 40%, or 50% w / w of the composition, including all ranges and subranges therein. Preferably, the propylene glycol is present in the composition in an amount ranging from about 20% w / w to about 40% w / w of the composition, e.g., about 20%, about 30%, or about 40% w / w of the composition, including all ranges and subranges therein. When used as a penetration enhancer, 2-(2-ethoxyethoxy)ethanol (Transcutol®) is present in the composition in an amount ranging from about 2% w / w to about 50% w / w of the composition, such as about 2%, 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, or 40% w / w of the composition, including all ranges and subranges therein. Preferably, 2-(2-ethoxyethoxy)ethanol is present in the composition in an amount ranging from about 4% w / w to about 10% w / w of the composition, such as about 4%, 5%, 6%, 7%, 8%, 9%, or 10% w / w of the composition, including all ranges and subranges therein.

[0046] In at least one other embodiment, the at least one chelating agent is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA) and its pharmaceutically acceptable salts (such as edetate disodium, edetate disodium dehydrate, edetate trisodium, edetate dipotassium, edetate dipotassium dehydrate, edetate calcium disodium, diethylenetriaminepentaacetic acid, etc.) and organic acids (such as citric acid, fumaric acid, malic acid, lactic acid, and glycolic acid). Preferably, the at least one chelating agent is edetate disodium.

[0047] The at least one chelating agent may be present in the composition in an amount ranging from about 0.01% w / w to about 2% w / w of the composition, including, for example, about 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.4%, 0.5%, 0.75%, 0.80%, 0.90%, 1.0%, 1.1%, 1.2%, 1.25%, 1.4%, 1.5%, 1.75%, 1.80%, 1.90%, or 2.0% w / w of the composition, and all ranges and subranges therein. Preferably, the at least one chelating agent is present in an amount ranging from about 0.05% w / w to about 1% w / w, for example, about 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.4%, 0.5%, 0.75%, 0.80%, 0.90%, or 1.0% w / w of the composition, including all ranges and subranges therein.

[0048] For example, EDTA or a pharmaceutically acceptable salt thereof, when used as a chelating agent, may be present in the composition in an amount ranging from about 0.01% w / w to about 2% w / w of the composition, such as about 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.4%, 0.5%, 0.75%, 0.80%, 0.90%, 1.0%, 1.1%, 1.2%, 1.25%, 1.4%, 1.5%, 1.75%, 1.80%, 1.90%, or 2.0% w / w of the composition, and all ranges and subranges therein. Preferably, the amount is in the range of about 0.05% w / w to 1% w / w of the composition, such as about 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.4%, 0.5%, 0.75%, 0.80%, 0.90%, or 1.0% w / w of the composition, including all ranges and subranges therein. In a most preferred embodiment, EDTA or a pharmaceutically acceptable salt thereof is present in the composition in an amount of about 0.1% w / w to about 0.15% w / w of the composition, or in an amount of about 0.1% w / w to about 0.25% w / w of the composition.

[0049] In at least one embodiment, the 5-carbon aminoketone compound is 5-aminolevulinic acid (ALA) or a pharmaceutically acceptable salt thereof. Preferably, the 5-carbon aminoketone compound is the hydrochloride salt of aminolevulinic acid.

[0050] Compounds of Formula I [ka] or a pharmaceutically acceptable salt thereof is present in a composition containing a photoactivatable agent in an amount ranging from about 10% w / w to 70% w / w of the composition, for example, about 10%, 20%, 30%, 40%, 50%, 60%, or 70% w / w of the composition. Preferably, the compound or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 20% w / w to 50% w / w of the composition, for example, about 20%, 25%, 30%, 35%, 40%, 45%, or 50% w / w of the composition. In a most preferred embodiment, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 20% w / w.

[0051] The 5-ALA compound or a pharmaceutically acceptable salt thereof is present in the composition containing the photoactivatable agent in an amount ranging from about 10% w / w to about 70% w / w of the composition, for example, about 10%, 20%, 30%, 40%, 50%, 60%, or 70% w / w of the composition, including all ranges and subranges therein. Preferably, the compound or a pharmaceutically acceptable salt thereof is present in an amount ranging from about 20% w / w to about 50% w / w of the composition, for example, about 20%, 25%, 30%, 35%, 40%, 45%, or 50% w / w of the composition, including all ranges and subranges therein. In a most preferred embodiment, the 5-ALA or a pharmaceutically acceptable salt thereof is present in the composition in an amount of about 20% w / w.

[0052] In at least one embodiment, the composition containing the photoactivatable agent may contain various other inactive ingredients conventionally used in a given product type. The inactive ingredients may be selected from alcohol, isopropyl alcohol, polyethylene glycol, propylene glycol, glycerin, diethylene glycol monoethyl ether, or purified water, or a combination thereof. The composition may further contain a surfactant or humectant and / or moisturizer. The surfactant or moisturizer may be selected from the group consisting of Laureth-4, sodium lauryl sulfate, sodium dodecyl sulfate, ammonium lauryl sulfate, or sodium octech-1 / deceth-1 sulfate. The moisturizer may be selected from the group consisting of polyethylene glycol, propylene glycol, hyaluronic acid, or glycerin.

[0053] In at least one embodiment, compositions containing photoactivatable agents that can be used in accordance with the present disclosure optionally contain an antifoaming agent. Suitable antifoaming agents include, but are not limited to, polydimethylsiloxane and other silicones, certain alcohols, stearates, and glycols. Preferably, the antifoaming agent is a cyclic polydimethylsiloxane. More preferably, the antifoaming agent is cyclomethicone. The antifoaming agent is present in the composition in an amount ranging from about 0.2% w / w to about 1.0% w / w of the composition, such as about 0.2%, 0.25%, 0.4%, 0.5%, 0.75%, 0.80%, 0.90%, or 1.0% w / w of the composition, including all ranges and subranges therein. Preferably, the antifoaming agent is present in the composition in an amount ranging from about 0.2% w / w to about 0.5% w / w of the composition. More preferably, the antifoaming agent is present in the composition in an amount of about 0.5% w / w of the composition.

[0054] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) a 5-carbon aminoketone compound of formula I, [ka] or a pharmaceutically acceptable salt thereof, and b) a vehicle, (i) at least one penetration enhancer, and (ii) A vehicle containing at least one chelating agent.

[0055] In at least one embodiment, the vehicle includes an optional antifoaming agent.

[0056] In another embodiment, a composition comprising a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) a 5-carbon aminoketone compound of formula I, [ka] or a pharmaceutically acceptable salt thereof in dry solid form, and b) a vehicle, (i) at least one penetration enhancer; (ii) at least one chelating agent, and (iii) optionally comprising a vehicle, including an antifoaming agent.

[0057] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) a 5-carbon aminoketone compound of formula I, [ka] or a pharmaceutically acceptable salt thereof in dry solid form, and b) a vehicle, (i) at least one penetration enhancer selected from the group consisting of glycol derivatives, polyethylene glycol derivatives, and ethoxylated ether derivatives; (ii) ethylenediaminetetraacetic acid (EDTA) or a pharmaceutically acceptable salt thereof, and (iii) optionally comprising a vehicle, including an antifoaming agent.

[0058] In at least one other embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) 5-ALA or a pharmaceutically acceptable salt thereof; b) propylene glycol, c) EDTA or a pharmaceutically acceptable salt thereof, and d) Optionally, an antifoaming agent.

[0059] In yet at least one other embodiment, a photoactivatable agent-containing composition that may be used in accordance with the present disclosure comprises: a) 5-ALA or a pharmaceutically acceptable salt thereof in dry solid form, and b) a vehicle, (i) propylene glycol, (ii) EDTA and pharmaceutically acceptable salts, and (iii) optionally comprising a vehicle, including an antifoaming agent.

[0060] In yet another embodiment, a composition comprising a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) a 5-carbon aminoketone compound of formula I, [ka] or a pharmaceutically acceptable salt thereof in dry solid form, and b) a vehicle, (i) propylene glycol, (ii) 2-(2-ethoxyethoxy)ethanol, and (iii) edetate disodium, and (iv) Optionally, a vehicle including an antifoaming agent.

[0061] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) 5-ALA or a pharmaceutically acceptable salt thereof in dry solid form, and b) a vehicle, (i) propylene glycol, (ii) 2-(2-ethoxyethoxy)ethanol, and (iii) edetate disodium, and (iv) Optionally, a vehicle including an antifoaming agent.

[0062] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) a 5-carbon aminoketone compound of formula I, [ka] or a pharmaceutically acceptable salt thereof in dry solid form, and b) a vehicle, (i) propylene glycol in an amount ranging from about 10% w / w to about 50% w / w; (ii) 2-(2-ethoxyethoxy)ethanol in an amount ranging from about 2% w / w to about 50% w / w, and (iii) edetate disodium, and (iv) Optionally, a vehicle including an antifoaming agent.

[0063] In at least one other embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) 5-ALA or a pharmaceutically acceptable salt thereof in dry solid form, and b) a vehicle, (i) propylene glycol in an amount ranging from about 10% w / w to about 50% w / w; (ii) 2-(2-ethoxyethoxy)ethanol in an amount ranging from about 2% w / w to about 50% w / w, and (iii) edetate disodium, and (iv) Optionally, a vehicle including an antifoaming agent.

[0064] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) a 5-carbon aminoketone compound of formula I or a pharmaceutically acceptable salt thereof; [ka] b) propylene glycol, c) 2-(2-ethoxyethoxy)ethanol, and d) Contains edetate disodium.

[0065] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) 5-aminolevulinic acid in an amount of 20% w / w of the composition; b) propylene glycol in an amount of 20% to 40% w / w of the composition; c) Contains EDTA in an amount of 0.1% to 0.5% w / w of the composition.

[0066] In at least one embodiment, the composition containing a photoactivatable agent further comprises 2-(2-ethoxyethoxy)ethanol in an amount of 4% to 10% w / w of the composition.

[0067] In at least one other embodiment, the composition containing a photoactivatable agent further comprises cyclomethicone in an amount of 0.2-0.5% w / w of the composition.

[0068] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) a 5-carbon aminoketone compound of formula I, [ka] or a pharmaceutically acceptable salt thereof (in an amount of 1 to 30% w / w), b) propylene glycol in an amount ranging from about 10% w / w to about 50% w / w; c) 2-(2-ethoxyethoxy)ethanol in an amount ranging from about 2% w / w to about 50% w / w, and d) Contains edetate disodium.

[0069] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) a 5-carbon aminoketone compound of formula I, [ka] or a pharmaceutically acceptable salt thereof, b) ethanol, c) Laureth-4 d) polyethylene glycol, e) isopropyl alcohol, f) propylene glycol, g) 2-(2-ethoxyethoxy)ethanol, h) edetate disodium, i) cyclomethicone, and j) Vehicles include purified water.

[0070] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) a 5-carbon aminoketone compound of formula I, [ka] or a pharmaceutically acceptable salt thereof in dry solid form, and b) a vehicle, (i) ethanol, (ii) Laureth-4, (iii) polyethylene glycol, (iv) isopropyl alcohol, (v) propylene glycol, (vi) 2-(2-ethoxyethoxy)ethanol, (vii) edetate disodium, (viii) cyclomethicone, and (ix) Vehicles include purified water.

[0071] In at least one other embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) 5-ALA or a pharmaceutically acceptable salt thereof; b) ethanol, c) Laureth-4, d) polyethylene glycol, e) isopropyl alcohol, f) propylene glycol, g) 2-(2-ethoxyethoxy)ethanol, h) edetate disodium, i) cyclomethicone, and j) Vehicles include purified water.

[0072] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) 5-ALA or a pharmaceutically acceptable salt thereof in dry solid form, and b) a vehicle, (i) ethanol, (ii) Laureth-4, (iii) polyethylene glycol, (iv) isopropyl alcohol, (v) propylene glycol, (vi) 2-(2-ethoxyethoxy)ethanol, (vii) edetate disodium, (viii) cyclomethicone, and (ix) Vehicles include purified water.

[0073] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) a 5-carbon aminoketone (compound of formula I) or a pharmaceutically acceptable salt thereof in an amount of 20% w / w; [ka] b) ethanol in an amount of 10-15% w / w of the composition; c) Laureth-4 in an amount of 5-10% w / w of the composition; d) polyethylene glycol in an amount of 1-5% w / w of the composition; e) isopropyl alcohol in an amount of 2-4% w / w of the composition; f) propylene glycol in an amount of 20-40% w / w of the composition; g) 2-(2-ethoxyethoxy)ethanol in an amount of 2-4% w / w of the composition; h) edetate disodium in an amount of 0.1 to 0.25% w / w of the composition; i) cyclomethicone in an amount of 0.2 to 0.5% w / w of the composition; j) Contains purified water.

[0074] In at least one other preferred embodiment, a photoactivatable agent-containing composition that may be used in accordance with the present disclosure comprises: a) 5-ALA or a pharmaceutically acceptable salt thereof in an amount of 20% w / w; b) ethanol in an amount of 10-15% w / w of the composition; c) Laureth-4 in an amount of 5-10% w / w of the composition; d) polyethylene glycol in an amount of 1-5% w / w of the composition; e) isopropyl alcohol in an amount of 2-4% w / w of the composition; f) propylene glycol in an amount of 20-40% w / w of the composition; g) 2-(2-ethoxyethoxy)ethanol in an amount of 2-4% w / w of the composition; h) edetate disodium in an amount of 0.1 to 0.25% w / w of the composition; i) cyclomethicone in an amount of 0.2 to 0.5% w / w of the composition; j) Contains purified water.

[0075] In at least one embodiment, a composition containing a photoactivatable agent that may be used in accordance with the present disclosure comprises: a) a 5-carbon aminoketone compound of formula I, [ka] or a pharmaceutically acceptable salt thereof in dry solid form, and b) a vehicle, (i) ethanol in an amount of 10-15% w / w of the composition; (ii) Laureth-4 in an amount of 5-10% w / w of the composition; (iii) polyethylene glycol in an amount of 1-5% w / w of the composition; and (iv) isopropyl alcohol in an amount of 2-4% w / w of the composition; (v) propylene glycol in an amount of 20-40% w / w of the composition; (vi) 2-(2-ethoxyethoxy)ethanol in an amount of 2-4% w / w of the composition; (vii) edetate disodium in an amount of 0.1 to 0.25% w / w of the composition; (viii) cyclomethicone in an amount of 0.2 to 0.5% w / w of the composition, and a vehicle comprising the same.

[0076] Exemplary Treatment Methods In at least one embodiment, heating the skin is performed to enhance the effectiveness of photodynamic therapy. Enhanced efficacy correlates with reduced photoactivatable agent incubation time and increased photoactivatable agent absorption. Furthermore, enhanced efficacy is reflected by increased complete incision rates when used for skin cancer. Generally, in at least one embodiment, such results are achieved by administering heat to the affected area, administering a therapeutically effective dose of a pharmaceutical composition, and administering a light dose to the affected area to treat a disease or disorder or skin. Treatment can be further enhanced by pain relief.

[0077] In at least one embodiment, the time between the application of heat to the affected area and the application of ALA can vary. This is known as the "heat-drug interval" and can be seconds, minutes, hours, or days. In at least one embodiment, the heat-drug interval is from about 1 second to about 60 seconds. In at least one embodiment, the heat-drug interval is from about 1 hour to about 24 hours. In at least one embodiment, the "drug-light" interval reflects the period between the administration of the photoactivatable agent and the administration of light (e.g., from illuminator 100). The "duration of exposure" or "exposure time" is the time the skin is continuously exposed (e.g., to a pharmaceutical composition, lighting, etc.).

[0078] ALA can be applied to the surface to be treated (e.g., directly to the lesion to be treated) and to a margin beyond the lesion (e.g., approximately 5 mm or less, e.g., approximately 2-4 mm). ALA can be administered to the affected area without applying ALA to healthy tissue not containing the lesion and / or areas away from the lesion. In certain applications, ALA can be covered with a barrier, such as low-density polyethylene or a foil barrier. The barrier can be provided in a kit with an adhesive, net, or mesh to help secure the barrier in place. In at least one embodiment, ALA can be covered with a material having an occlusion rate of 65% or more, a material having an occlusion rate of 75% or more, or a material having an occlusion rate of 85% or more, or another material after its application to the surface to be treated. Such a material can be provided to retain moisture within the tissue and therefore improve the penetration of ALA. Low-density polyethylene has a density of approximately 0.917 g / cm. 3 ~approximately 0.930g / cm 3 It can be characterized by a density of

[0079] As discussed further below, in at least one embodiment, treatment may be administered to thermally treated skin. A heating element (e.g., a heat source) separate from or integrated with the illuminator 100 may be provided to heat the skin. The heat source may be used to heat the area to be treated. According to one embodiment, a method of treatment includes heating the illuminator to cause heat to radiate from the illuminator and exposing the treatment area to the illuminator. Heating is believed to increase the rate of porphyrin production in the skin. In particular, heat accelerates the conversion of ALA to porphyrins (e.g., photoactivatable porphyrins or protoporphyrins). The relationship between temperature exposure and ALA conversion is nonlinear, and the enzymatic pathway involved in the conversion is highly sensitive to temperature.

[0080] In at least one embodiment, increasing the temperature by about 2°C can, for example, approximately double the rate of protoporphyrin IX (PpIX) production. In at least one embodiment, by heating the skin as described herein, the rate of porphyrin production in the skin increases by about 10%, about 20%, about 30%, about 40%, about 50% or more, about 60% or more, about 70% or more, about 80% or more, or about 85% or more. In at least one embodiment, the rate of porphyrin production in the skin increases by about 50% or more, about 60% or more, about 70% or more, about 80% or more, or about 85% or more by heating the skin for 5 minutes followed by about 8 minutes or about 8 minutes and a 20 second light dose. For example, as described in more detail below, the amount of PpIX in the skin can approximately double with application of heat to a treatment area compared to when heat is not applied to the treatment area.

[0081] In at least one embodiment, heat may be applied before or during illumination with the illuminator 100. For example, ALA may be applied first. Next, the heating element may be activated to apply heat to the patient's skin for a first treatment period for heat soak, which may be, for example, approximately 20 to approximately 30 minutes, or another interval. During heating, the treatment site may be occluded or unoccluded. The treatment site may be heated while occluded. In at least one embodiment, the heat soak may be approximately 18 minutes to approximately 32 minutes, and may or may not be aligned with the first treatment period. After the first treatment period, light may be applied for a second treatment period, for example, approximately 8 minutes to approximately 15 minutes. In at least one embodiment, light may be applied for 8 minutes and 20 seconds. The total heat soak corresponding to the exposure to heat may be approximately 1 minute to approximately 90 minutes.

[0082] In at least one embodiment, the skin is heated to a surface temperature greater than about 37° C. In at least one embodiment, the skin is heated to a surface temperature greater than about 40° C.

[0083] Thus, the present disclosure provides a method of photodynamically treating the surface of a patient (and optionally occluding the patient's skin as part of the treatment). The patient may be irradiated to treat actinic keratosis (AK), disseminated superficial actinic porokeratosis (DSAP) or refractory disseminated porokeratosis, acne (e.g., cystic acne, inflammatory acne, non-inflammatory acne), photodamage, skin cancer (e.g., non-melanoma skin cancer (NMSC), nodular basal cell carcinoma, recurrent nodular basal cell carcinoma, invasive basal cell carcinoma, multifocal basal cell carcinoma), warts, psoriasis, or other skin disorders.

[0084] For example, in at least one embodiment, the LEDs of the illuminator 100 emit light for photodynamic treatment of cystic acne. In particular, the LEDs may emit red light to perform PDT for acne, NMSC, AK, or DSAP on thermally treated skin (e.g., previously or simultaneously heated skin). In at least one embodiment, cystic acne is treated with 10% ALA gel applied at 37 J / cm@630 nm for approximately 1 hour. 2 Treatment may be achieved by delivering a light dose of light while the patient's surface to be treated (treatment surface, skin surface, etc.) is heated or otherwise maintained at a temperature of about 40°C.

[0085] In at least one embodiment, by heating the skin as described herein, a reduction in the incubation time required for ALA can be achieved. Conventional PDT of AK requires 14 (fourteen) hours of incubation with ALA before exposure to blue light. In at least one embodiment, the incubation period can be dramatically reduced. For example, the incubation period can be reduced to less than about 30 minutes, about 30 minutes, about 45 minutes, or about 1 hour. Significant amounts of porphyrins are produced after 20 minutes of incubation of a 20% ALA gel on skin heated to about 40°C, with even greater amounts produced after about 30 minutes. The amount of porphyrins produced after 60 minutes of incubation of a 20% ALA gel without heat is less than that produced after either 20 or 30 minutes with heat.

[0086] Thus, the response to photodynamic therapy is significantly greater on a patient's heated skin than on unheated skin. In at least one embodiment, a heat source may be used for heating for about 15 to about 60 minutes. In at least one embodiment, the incubation period (e.g., incubation time, as further discussed herein) may be about 17 minutes for a 20% ALA gel, where the heat source achieves a skin temperature of about 38°C to about 42°C. In at least one embodiment, a 1-hour incubation period may be used for 10% ALA, where the heat source is a sodium acetate thermal mask used to heat the skin to about 40°C, followed by 37 J / cm at 635 nm. 2 Light dose (e.g., to treat moderate inflammatory or pustular acne). Reductions in lesion counts have been observed as recently as 9 months after a single photodynamic therapy treatment session. In at least one embodiment, a 1-hour incubation period of 20% ALA is performed, and the heat source is a heating pad or sodium acetate heating pouch.

[0087] A method for treating skin diseases or disorders using photodynamic therapy (e.g., red light) on preheated skin may be performed using an illuminator according to the present disclosure. In at least one embodiment, the pharmaceutical composition is a nanoemulsion containing 10% 5-aminolevulinic acid HCl. In at least one embodiment, the light has a wavelength of about 620 to about 640 nm, more specifically about 630 nm. In one embodiment, a suitable light dose is about 37 J / cm. 2 is.

[0088] For example, a method of treating facial acne in a subject in need thereof may be performed, comprising: (i) applying heat to an affected area of ​​the subject's skin using a heat source to achieve a skin temperature of about 38°C to about 42°C for a suitable period of time; (ii) incubating a pharmaceutical composition containing a photoactive agent for a period of less than about 14 hours; (iii) applying a therapeutically effective amount of the incubated pharmaceutical composition to the affected area; and (iv) administering light (e.g., red light) to the affected area to treat the facial acne. In at least one embodiment, the acne is mild acne, moderate acne, or severe acne. In at least one embodiment, the heat source is a heat mask, such as an acetate mask that heats as it crystallizes. In at least one embodiment, the affected area is heated for about 60 minutes.

[0089] In at least one embodiment, the affected area is heated to about 40° C. In at least one embodiment, the incubation period is less than about 3 hours, yet achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 3 hours without the application of heat (i.e., without heating) to achieve a skin temperature of about 38° C. to about 42° C. In at least one embodiment, the incubation period is less than about 1 hour, yet achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 1 hour in the absence of heat to achieve a skin temperature of about 38° C. to about 42° C. In exemplary embodiments, the incubation period is less than about 15 minutes, less than about 10 minutes, or less than about 5 minutes.

[0090] In at least one embodiment, the treatment results in a reduction in the number of acne lesions in a patient suffering from acne. In at least one embodiment, the reduction is sustained for at least three months. In an exemplary embodiment, the treatment results in a reduction in the severity of acne lesions. In at least one embodiment, the reduction is sustained for at least three months. In at least one embodiment, the side effects of the treatment are reduced compared to methods that do not involve heating the skin.

[0091] In at least one embodiment, a method for treating facial non-melanoma skin cancer (NMSC) is provided. The method includes applying heat to achieve a skin temperature of about 38°C to about 42°C, incubating a pharmaceutical composition for less than about 14 hours, applying a therapeutically effective amount of the composition to the affected area, and administering a suitable dose of light (e.g., red light) to the area. In at least one embodiment, the non-melanoma skin cancer is basal cell carcinoma. In at least one embodiment, the non-melanoma skin cancer is squamous cell carcinoma (SCC). In at least one embodiment, the non-melanoma skin cancer is basal cell carcinoma and heat is applied for about 30 minutes or about 20 minutes. In at least one embodiment, the incubation period is (i) less than about 14 hours but achieves efficacy equivalent to that of the pharmaceutical composition incubated for about 14 hours in the absence of heat, (ii) less than about 3 hours but achieves efficacy equivalent to that of the pharmaceutical composition incubated for about 3 hours in the absence of heat, or (iii) less than about 10 minutes.

[0092] In at least one embodiment, a method for treating facial AK is provided. The method includes applying heat to achieve a skin temperature of about 38°C to about 42°C, incubating a pharmaceutical composition for less than about 14 hours, applying a therapeutically effective amount of the composition to the affected area, and administering a suitable dose of light (e.g., red light) to the area. In at least one embodiment, the affected area is heated for about 30 minutes. In at least one embodiment, the affected area is heated to about 40°C. In at least one embodiment, the incubation period is (i) less than about 14 hours but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 14 hours in the absence of heat, (ii) less than about 3 hours but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 3 hours in the absence of heat, (iii) less than about 1 hour but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 1 hour in the absence of heat, or (iv) less than about 10 minutes.

[0093] In at least one embodiment, a method of treating disseminated superficial actinic porokeratosis (DSAP) of the face in a subject in need thereof is provided. The method includes applying heat to achieve a skin temperature of about 38°C to about 42°C, incubating a pharmaceutical composition for less than about 14 hours, applying a therapeutically effective amount of the composition to the affected area, and administering a suitable dose of light (e.g., red light) to the area. In at least one embodiment, the incubation period is (i) less than about 14 hours but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 14 hours in the absence of heat, (ii) less than about 3 hours but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 3 hours in the absence of heat, (iii) less than about 1 hour but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 1 hour in the absence of heat, or (iv) less than about 10 minutes.

[0094] In at least one embodiment, the ALA is incubated simultaneously with the application of heat to the skin, or prior to, or within seconds or minutes after, heating of the skin is initiated. The following discussion describes exemplary examples of how exemplary illuminators may be used to treat skin diseases or disorders, e.g., to perform photodynamic therapy in combination with heat.

[0095] Example - Effect of heat on skin PpIX levels A study was conducted to evaluate the effect of heat application on skin PpIX levels after a photoactivatable agent was applied to the skin. More specifically, the study was conducted on porcine test subjects to investigate the pharmacokinetic profiles of 5-ALA and PpIX for an enhanced topical formulation using Levulan® (i.e., enhanced Levulan®, e.g., with a chelating agent as discussed herein). Three compositions were tested: (i) Levulan® (DUSA Pharmaceuticals, Inc., Billerica, Massachusetts); (ii) Levulan® containing 0.1% ethylenediaminetetraacetic acid (EDTA) present in an amount of about 0.1% w / w of the topical composition; and (iii) Levulan® containing EDTA present in an amount of about 0.15% w / w of the topical composition.

[0096] Each formulation was prepared for application via a Levulan® Kerastick® applicator. The same batch of each formulation (e.g., same batch number, manufacturing date, and expiration date) was used for each porcine test subject. Formulations were stored at a temperature of 20°C to 25°C (68°F to 77°F). The study was conducted on 36 test subjects (sus scrofa domesticus), with 3 test subjects per time point (2 or 3 hours) per formulation, with and without heat. PpIX was assessed after each time point (i.e., 2 and 3 hours of incubation).

[0097] Test subjects were maintained in an environment with 30% to 70% humidity and a temperature of 18°C ​​to 28°C. On the day treatment was administered, test subjects were exposed to approximately 12 hours of darkness and approximately 12 hours of light. Test subjects were protected from light during the test incubation period (either 2 or 3 hours).

[0098] As shown in Table 1, the test subjects were divided into 12 groups. [Table 1]

[0099] A portion of the dorsolateral trunk skin of each test subject was divided into 10 blocks for dose application, each block being approximately 2 cm x 2 cm with a 4 cm space between blocks. The test sites were cleaned with ethanol prior to dose application.

[0100] Each dose (of the three formulations) was applied topically to a different block according to the Levulan® administration instructions. A single administration included two applications using the Kerastick® applicator for approximately 15 seconds each, with an interval of approximately 2 minutes between applications. Treatment duration was limited to a single administration.

[0101] After application of the dose, heat was applied to the skin of the test subjects in Groups 7-12. Heat was applied at approximately 39°C to approximately 41°C for approximately 13 minutes after dosing for each group of test subjects. More specifically, test subjects in Groups 7-12 received heat application for approximately 13 minutes after formulation application and the designated incubation time. Heat was provided using an infrared (IR) lamp.

[0102] After 2 hours of incubation, dermal and epidermal samples were collected from designated test subjects (e.g., groups 1, 3, 5, 7, 9, and 11) at the 2-hour time point and tested for the amount of PpIX. After 3 hours of incubation, dermal and epidermal samples were collected from designated test subjects (e.g., groups 2, 4, 6, 8, 10, and 12) at the 3-hour time point and tested for the amount of PpIX.

[0103] The epidermal and dermal layers were separated approximately 10-20 minutes after harvesting the subject's stratum corneum. To separate the epidermis and dermis, the skin samples were then placed in a closed aluminum foil container in a hot air oven at 60-62°C for 5-10 minutes. The epidermal layer was then manually separated from the dermal layer. The dermal and epidermal layers were collected in separate centrifuge containers. The containers were weighed before and after adding the skin layer. The weight difference was calculated to determine the weight of the skin layer. The skin samples were quickly frozen using liquid nitrogen immediately after skin layer separation to stop the continuous production of PpIX in the samples. The samples remained frozen for at least 24 hours before processing for analysis. The aforementioned process was carried out under monochromatic light (i.e., sodium lamp). A homogenization solution was added to the container containing the skin tissue to prepare a 4% w / v tissue homogenate, which was then prepared using a homogenizer under constant cooling using an ice bath. After each run, the homogenizer probe was washed and dried. Tissue homogenate samples were analyzed for 5-ALA and PpIX.

[0104] As shown in Figures 26-27, exposing the formulations to heat resulted in higher PpIX levels after 3 hours of incubation. For example, application of the reference Levulan® without heat application produced approximately 0.628 mcg / g of PpIX after 3 hours of incubation. Application of Levulan® with approximately 13 minutes of heat application produced approximately 0.966 mcg / g of PpIX after 3 hours of incubation. Thus, treatment with heat resulted in a greater than 50% increase in the amount of PpIX produced over treatment without heat.

[0105] In another example, application of Levulan® enhanced with 0.1% EDTA without heat produced approximately 0.771 mcg / g of PpIX after 3 hours of incubation. Application of Levulan® enhanced with 0.1% EDTA with 13 minutes of heat produced approximately 1.776 mcg / g of PpIX after 3 hours of incubation. Thus, treatment with heat produced more than twice the amount of PpIX as treatment without heat.

[0106] Application of Levulan®, enhanced with 0.15% EDTA and no heat applied, produced approximately 1.186 mcg / g of PpIX after 3 hours of incubation. Application of Levulan®, enhanced with 0.15% EDTA and 13 minutes of heat applied, produced approximately 2.146 mcg / g of PpIX after 3 hours of incubation. Thus, treatment with heat resulted in an 80% increase in the amount of PpIX produced over treatment without heat.

[0107] This surprising increase in PpIX over such a short heating period has not been achieved before and was not previously expected. The short heating durations of the disclosed techniques overcome a major drawback of PDT in general: the need for patient exposure to the illuminator for extended periods of time.

[0108] The above-described embodiments are believed to enable a dramatic reduction in total treatment time to be achieved with a concomitant reduction in pain.

[0109] In particular, the compositions described above may be utilized to treat patients in accelerated PDT protocols. For example, in at least one embodiment, a method of performing PDT (e.g., for the treatment of skin disorders) can be performed in which a topical composition is applied to the skin and incubated for a predetermined incubation period.

[0110] In at least one embodiment, a topical composition enhanced with at least one chelating agent is applied to the skin, for example, with an applicator. The topical composition can include ALA (e.g., ALA HCl) enhanced with at least one chelating agent according to any of the embodiments of the present disclosure, such as EDTA, in an amount of about 0.1% w / w to about 0.15% w / w of the composition.

[0111] After topical application, the incubation period may be from about 30 minutes to about 3 hours, and in some embodiments, from about 2 hours to about 3 hours. Optionally, the skin may be occluded during all or part of the incubation period. In some embodiments, the skin is occluded with a barrier, such as a low-density polyethylene (LDPE) barrier or a foil barrier, after application of the ALA enhanced with at least one chelating agent.

[0112] After a predetermined incubation period, the skin is exposed to heat from a heat source, and in some embodiments, light (e.g., from a light source). For example, heat may be applied during the initial portion of treatment, and then both light and heat may be applied during the final portion of treatment. Optionally, airflow may be directed toward the skin during the initial and / or final portions of treatment, which may reduce associated pain. For example, a gentle airflow may be provided during at least the initial portion of treatment (e.g., the first period).

[0113] In some embodiments, the patient may be exposed to heat for about 5 minutes, followed by about 8 minutes of both light and heat. In some embodiments, 8 minutes and 20 seconds of light and heat may be administered. Thus, the initial and final portions of treatment may total about 13 minutes. Light may be applied at a frequency of, for example, 20 mW / cm 2 or about 30 mW / cm 2 In some embodiments, the blue light may be blue light applied at an intensity of 10 mW / cm 2 Blue light may be applied at an intensity of about 10 J / cm 2 In some embodiments, the red light may be delivered for a period sufficient to provide a dose of about 10 J / cm within, for example, less than 10 minutes. 2 ~about 75J / cm 2 In some embodiments, the patient may be exposed to both blue and red light. Any combination of light dosage, duration, and / or intensity described in this disclosure may be utilized.

[0114] In some embodiments, the patient may be exposed to heat for a duration of about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, or about 20 minutes during the initial portion of treatment. After the initial treatment, the patient may be exposed to both heat and light during the final portion of treatment, which may be about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, or about 20 minutes in duration. In some embodiments, the total heating time may be from about 10 minutes to about 30 minutes.

[0115] In some embodiments, illumination can be performed using an illuminator according to the disclosed embodiments described herein. In some embodiments, a kit is provided that includes an illuminator, a heat source, and at least one applicator having a topical composition according to the aforementioned embodiments.

[0116] Illuminator panel configuration 1-4, in at least one embodiment, illuminator 100 preferably has five panels 10 (i.e., panels 10a-10e). The panels 10 may vary in size. For example, first panel 10a may be a first size, second panel 10b may be a second size, third panel 10c may be a third size, fourth panel 10d may be a second size, and fifth panel 10e may be a first size. In at least one alternative embodiment, the panels may be of equal size.

[0117] In conventional adjustable illuminators, the panels are equally sized by width and length and are typically driven at the same power level. The panels are further joined at their edges. Due to this structure, light does not radiate from the "gaps" between the light sources. The lack of light emitting from these areas, along with the uniform power supply to the panels, can result in optical "dead space" in certain portions of the target treatment area. These areas then receive less overall light, resulting in a lower therapeutic dose in these areas. In some instances, the therapeutic dose can be reduced by as much as five times compared to those areas receiving the desired amount of light.

[0118] At least one embodiment of the present disclosure includes multiple panels 10, with at least one panel 10 being a different width than the others. This panel is positioned between two other panels and acts in some way as a "light hinge" to provide sufficient "fill-in" light to reduce or eliminate optical dead space when the panel is bent into a particular configuration. Preferably, a total of five panels can provide a desirable increase in the total size of the potential treatment area. Two of the panels (e.g., panels 10b and 10d in FIG. 2) are preferably narrower than the other three larger panels (e.g., panels 10a, 10c, and 10e in FIG. 2). The panels are positioned alternately, with each narrower panel positioned between two of the three larger panels, allowing for both adjustability and improved uniformity.

[0119] In at least one embodiment, each panel 10 includes an array of light-emitting diodes (LEDs) 60, which may be arranged in an evenly or unevenly spaced pattern across the face of the panel 10. In at least one embodiment, three adjacent panels may be illuminated (e.g., the three inner panels) and two panels may not be illuminated during a given period, such that illumination may be performed with fewer panels than the total number of panels present in the illuminator 100. The number of individual LEDs arranged in a given array is not particularly limited. The panel 10 is configured to uniformly illuminate the treatment surface of the patient via the LEDs. Therefore, a substantially uniform distribution of light may be imparted to the treatment surface.

[0120] Preferably, the LEDs may be distributed across multiple arrays, with each array of LEDs 60 extending as far as possible to the edge of the panel 10. Furthermore, the array of LEDs 60 is preferably sized to provide an overall illumination area for a given treatment area based on a range from the 5th percentile for female subjects of the corresponding size to the 95th percentile for male subjects of the corresponding size for that particular treatment area. The LEDs 60 emit light at an appropriate wavelength according to the intended treatment or to activate a specific photoactivatable drug used in treatment or diagnosis. For example, when ALA is used as a precursor of a photoactivatable drug for the treatment of AK, the LEDs 60 preferably emit blue light having a wavelength of 400 nanometers (nm) or greater, such as about 430 nm, about 420 nm, or about 417 nm. However, the LEDs 60 may also emit visible light in other ranges of the spectrum, such as the 400-700 nm green and / or red range, such as about 625 nm-640 nm, or about 635 nm. For example, the LEDs 60 may emit light having wavelengths of 510 nm, 540 nm, 575 nm, 630 nm, or 635 nm. Furthermore, the LEDs 60 may be configured to emit light continuously or may be configured to blink the diodes based on predetermined intervals. Furthermore, the LEDs 60 may be configured to emit only one wavelength of light (e.g., blue). Alternatively, the LEDs 60 may be configured to emit light of two or more wavelengths from the array. For example, the LEDs 60 may be configured to alternately emit blue and red light.

[0121] In at least one embodiment, each LED 60 in the panel 10 is individually configurable to provide a specific power output to a particular region on the panel 10 to compensate for reduced uniformity. For example, the power output to each individual diode in the array of LEDs 60 may be individually adjusted. More specifically, the LED array may be divided into three general regions, which may be described as "addressable strings." The current to each region is adjusted to adjust the intensity of light emitted from each region. For example, a higher current may be supplied to a particular string or a given region associated with a string to produce a higher light intensity than another string or another region associated with another string. Alternatively, or additionally, the LEDs 60 may be operated at a higher power level.

[0122] Additionally, individually adjusting the power to the LEDs 60 can help reduce or eliminate optical dead space that might otherwise occur where typical illuminator panels are connected. Specifically, the power output and / or emitted light intensity can be increased near the edges of the array of LEDs 60 to compensate for the lack of light emitted from adjacent areas where adjacent panels intersect. Narrow panels 10b, 10d preferably operate at higher power levels and / or higher emitted light intensities compared to wider panels 10a, 10c, 10e to provide additional “fill-in” light. In this way, the LEDs 60 can be controlled so that a higher light intensity is generally emitted from the edges of the panel 10, which can reduce any fall-off effects. Such a configuration therefore provides a more uniform lighting output than one where power and / or intensity are equal across all panels. In at least one embodiment, the illuminator can be configured to adjust each individual diode present in a given LED array, allowing for further calibration.

[0123] In at least one alternative embodiment, other types of light sources, such as fluorescent or halogen lamps, may be used instead of or in addition to LEDs.

[0124] Illuminator Structure and Operation The illuminators may be arranged with a folding device designed to allow for maneuverability and reconfigurability of the illuminator panel. In at least one embodiment, the illuminators are adjustable via a main post. The main post is supported by a hydraulic cylinder according to at least one embodiment. The hydraulic cylinder allows for raising and lowering with manual force applied by a user's fingers and / or hands. The cylinder optionally includes a valve to lock the cylinder in place. Other structures can be utilized, for example, a spring could be used instead of a hydraulic cylinder.

[0125] For example, in at least one embodiment, the illuminator is provided with a vertical post that is optionally provided with one or more support arms. The one or more support arms are configured to support an illuminator panel whose height is adjustable. The post may be pushed down into the body of the illuminator or retracted from the illuminator. The illuminator may be provided with one or more air cylinders (having at least one check valve and / or at least one spring) to allow the post to move with minimal force (e.g., finger pressure). These aspects allow the illuminator to be easily operable and usable under a variety of conditions.

[0126] In at least one embodiment, the illuminator uses a duct arrangement to draw air through an air distributor (e.g., a fan) at the back of the illuminator panel and output the air through a J-shaped duct arrangement so that the air flows gently (e.g., laminar or similar uniform flow) substantially parallel to the front (light-emitting surface) of the panel and substantially tangential to the skin surface. A controller allows a healthcare provider or patient to control the fan speed at different speeds (e.g., low and high) according to the healthcare provider's observations and / or the patient's expressed desires. The air may be room temperature air (e.g., approximately 68°F to approximately 75°F, or approximately 65°F to approximately 72°F).

[0127] Notably, regardless of whether the skin is preheated as described above, the flowing air is cooler than the treatment surface. The temperature is significantly lower than body temperature, and therefore feels cool to the patient. The air may also, in at least one embodiment, be cooled to a temperature lower than room temperature. The airflow may provide evaporative cooling, which reduces the perception or sensation of pain. The air velocity may be, for example, about 3 to about 6 knots, e.g., about 3 knots, about 4 knots, about 5 knots, or about 6 knots. Such air distributors may have an airflow rate of about 7.5 CFM to about 12 CFM, about 14 CFM, about 5 CFM to about 15 CFM, or about 5 CFM to about 20 CFM. Increasing patient comfort in this manner may affect the patient's willingness to complete a treatment course, among other benefits.

[0128] The illuminator may include a thermal management system having additional components other than those described above, for example, an additional air distributor may direct waste heat from the electronic components to the external environment.

[0129] Additionally, in at least one embodiment, the illuminator may include a sensor that detects the size of the treatment area located in front of the illuminator. In at least one embodiment, information from the sensor can be used (e.g., by a controller) to determine correct light delivery parameters based on the sensed treatment area. In at least one embodiment, the sensor is configured to detect an adjusted position of the illuminator manually set by a user. The detected position of the illuminator may then be used to indicate the intended treatment area. Appropriate light delivery parameters for a particular treatment area may be provided based on the detected position set by the user.

[0130] Referring again to FIGS. 1-4 , in at least one embodiment, each panel 10 includes at least one vent 68. The vent 68 may be configured to actively (e.g., push / pull) or passively (e.g., provide a path) exhaust air from the panel 10. In at least one embodiment, the panel 10 may include multiple vents 68. For example, the panel 10 may include a first vent 68 and a second vent 68. The first vent may be located at or proximate to a first edge of the panel 10, and the second vent 68 may be located at or proximate to a second edge of the panel 10. Each panel 10 may also include at least one fan 70. The fan 70 may be configured to draw air into the panel 10 or exhaust air from the interior of the panel 10. The fan 70 may be located on the rear surface of the panel 10. The fan 70 may be located in a central position of the panel 10. In at least one embodiment, panel 10 includes multiple fans 70. For example, panel 10c includes a first fan 70 positioned proximate a first edge of panel 10c and a second fan 70 positioned proximate a second edge of panel 10c.

[0131] Each panel 10 may include a distance sensor 11. The distance sensor 11 may detect the distance between the panel 10 and a treatment surface (affected area) placed in front of the panel 10. The distance sensor 11 may be automatically turned on when the associated panel 10 is turned on. Detecting the distance between the panel 10 and the treatment surface can facilitate individual adjustment of each panel 10 so that each panel 10 is at a desired distance from the treatment surface.

[0132] As shown in FIG. 6 , in at least one embodiment, the panels 10 may be coupled together via hinges 58 or other adjustable connection points to facilitate movement of the panels 10 relative to one another. For example, the panels 10 may be rotatably connected via nested hinges 58. The illuminator 100 may be configured to fold and unfold via the hinges 58 depending on use. For example, the panels 10 may be in an unfolded (e.g., flat) configuration when treating areas such as the patient's back, chest, or abdomen. The panels 10 may be in a folded (e.g., U-shaped) configuration when treating areas such as the face, scalp, arms, or legs. For example, the outermost panels 10 may face each other (at least partially). The panels 10 may also be in a folded configuration when in a storage position. For example, the panels 10 may be wrapped around at least a portion of the illuminator system 105 (e.g., vertical column 82) when the illuminator 100 is not in use. The hinges 58 may include torque inserts to maintain the position of the panel 10 without the use of additional locks. The hinges 58 may also include hard stops that prevent the panel 10 of the illuminator 100 from having an undesired configuration. For example, the hinges 58 may prevent the panel 10 from being fully open (e.g., flat) or from bending beyond the flat configuration (e.g., into an inverted U-shape).

[0133] As shown in FIG. 3 , the illuminator system 105 may include a movable stand 80. The movable stand 80 may simplify moving the illuminator system 105 between various positions and orientations. For example, the movable stand 80 may include a vertical column 82 coupled to a base 81. The vertical column 82 may extend perpendicular to the base 81. The base 81 may provide support for the vertical column 82 and other components of the illuminator system 105 coupled to the vertical column 82. The base 81 may be movable. For example, the base 81 may include multiple wheels, shown as casters 87. For example, the base 81 may include four casters 87. The casters 87 may facilitate rotation of the illuminator system 105 from a first position to a second position or from a first orientation to a second orientation.

[0134] As shown in FIG. 3 , in at least one embodiment, the illuminator system 105 includes one or more hooks 83. For example, the illuminator may include a first hook 83a and a second hook 83b. The first hook 83a and the second hook 83b may be disposed on a first side of the vertical column 82. The first hook 83a may be disposed above the second hook 83b. The hooks 83 may be rotatably coupled to the vertical column 82. The illuminator system 105 may also include a handle 84 (e.g., a stabilizing arm). The handle 84 may be disposed around three sides of the vertical column 82. For example, the handle 84 may extend from the first side of the vertical column 82, wrap around the second side of the vertical column 82, and connect to the vertical column 82 via the third side of the vertical column 82. The handle 84 may be spaced apart from the vertical column 82, except for first and second connection points disposed on the first and third sides of the vertical column 82.

[0135] For example, as shown in FIGS. 1-4, the illuminator system 105 may further include an extension member 86. The extension member 86 may be partially disposed within the vertical column 82. The vertical column 82 and the extension member 86 may be configured as a telescoping structure, such that the extension member 86 extends or slides within the vertical column 82 and extends or slides vertically from the vertical column 82 between different positions. The extension member 86 may be configured to adjust the height of the illuminator 100. For example, as shown in FIGS. 1-2, when the extension member 86 is in a retracted position (low position) and a majority of the extension member 86 is generally disposed within the vertical column 82, the illuminator is in a low position. Conversely, when the extension member 86 is in an extended position (extended or raised position) and a majority of the extension member 86 is generally disposed outside the vertical column 82, the illuminator 100 is in a high (raised or elevated) position, as shown in FIGS. 3-4. The different positions may be based on the use of illuminator 100 and take into account one or more of: (i) patient characteristics (e.g., a relatively short person compared to a relatively tall person), (ii) patient orientation (e.g., standing versus sitting), or (iii) location of the treatment target area (e.g., back compared to forearm). The position of extension member 86 may be adjusted manually or automatically (e.g., via power). Extension member 86 may be configured to maintain any position between a top position (e.g., fully extended) and a bottom position (e.g., fully retracted).

[0136] 2, the top of extension member 86 may be coupled to connecting arm 85 or may be integral with connecting arm 85 (e.g., to a single component). Connecting arm 85 extends horizontally from the top of extension member 86. Connecting arm 85 is configured to move with extension member 86 as extension member 86 moves relative to vertical column 82 (e.g., as extension member 86 moves in and out of vertical column 82). Connecting arm 85 may comprise a material strong enough to support other components of illuminator system 105 (e.g., illuminator 100).

[0137] Connecting arm 85 has a joint shown as pivot point 89. Pivot point 89 divides connecting arm 85 into two portions, a first portion and a second portion. The first portion can be a fixed portion 97, and the second portion can be a movable portion 98. Movable portion 98 can extend from an end of fixed portion 97. Movable portion 98 is rotatably coupled to fixed portion 97. For example, movable portion 98 can pivot about pivot point 89. For example, movable portion 98 can rotate vertically about pivot point 89. In at least one embodiment, movable portion 98 rotates approximately 90 degrees about pivot point 89 (such that it can rotate within a range of 0 to approximately 90 degrees).

[0138] For example, the fixed portion 97 may define a horizontal plane. The movable portion 98 may rotate between a horizontal position (e.g., parallel to the fixed portion 97 and disposed within a horizontal plate) and a vertically downward position (e.g., perpendicular to the fixed portion 97 and extending downward). The horizontal position may be a use position or a treatment position. The vertically downward position may be a storage position. In at least one embodiment, the movable portion 98 may rotate up to approximately 180 degrees (e.g., within a range of approximately 0 to 180 degrees) about the pivot point 89. For example, the movable portion 98 may rotate between a vertically downward position and a vertically upward position (e.g., perpendicular to the fixed portion 97 and extending upward). The vertically upward position may be a use position or a treatment position. The movable portion 98 may also be configured to remain at any other angle relative to the fixed portion 97.

[0139] In at least one embodiment, the illuminator system 105 includes an arm lock 22, as shown in FIGS. 1 and 17 , among others. The movable portion 98 may be folded to a vertical position, for example, when the illuminator system 105 is not in use or is stored. The movable portion 98 may be rotated to a horizontal position, for example, when the illuminator system 105 is used for treatment. The arm lock 22 may be located at a position where the movable portion 98 couples with the fixed portion 97. For example, the arm lock 22 may be located at the pivot point 89. The pivot point 89 may be located proximate the midpoint of the connecting arm 85 such that the arm lock 22 may be located proximate the midpoint of the connecting arm 85. The arm lock 22 may be activated when no force is applied. The arm lock 22 may be depressed to unlock or release the movable portion 98. The arm lock 22 may automatically lock the movable portion 98 in position when the movable portion 98 reaches the use position or the fully stored position.

[0140] The connecting arm 85 is configured to support the illuminator 100 in various positions described herein. The movable portion 98 is coupled to the illuminator 100 via a mounting mechanism 40, as shown in FIGS. 4-6 . The mounting mechanism 40 may include a bracket 42 coupled to the movable portion 98. The bracket 42 defines a first axis of rotation, shown as a bracket axis 44. The bracket 42 may extend from a first side of the movable portion 98. For example, the bracket 42 may extend from a bottom side of the movable portion 98 when the movable portion 98 is in a horizontal position. The mounting mechanism 40 may further include a plate 46. The plate 46 is coupled to at least one of the multiple panels 10 of the illuminator 100. The plate 46 is preferably coupled to a central panel (e.g., panel 10c) of the illuminator 100. The plate 46 is preferably positioned at a central position on the rear side of the panel 10. The plate 46 defines a second axis of rotation, shown as a plate axis 48. The plate axis 48 may be perpendicular or substantially perpendicular to the bracket axis 44 .

[0141] In at least one embodiment, the plate 46 includes at least one protrusion 50. The protrusion 50 extends from the plate 46 and couples with the bracket 42. In at least one embodiment, the plate 46 includes two protrusions 50. Connecting the plate 46 to the bracket 42 via the protrusion 50 facilitates securing the illuminator 100 to the movable stand 80. The protrusion 50 is rotatably coupled to the bracket 42 such that the protrusion 50 and the plate 46 can rotate about the bracket axis 44. With the illuminator 100 coupled to the plate 46, the illuminator 100 can rotate about the bracket axis 44. For example, the illuminator can be tilted approximately ±90 degrees from a stored position (e.g., with the center panel 10 facing the floor). The bracket 42 may utilize one or more torque inserts that can hold the illuminator 100 in any position without additional locking. The movable portion 98 may remain stationary while the illuminator 100 rotates or tilts.

[0142] As shown in FIG. 7 , the illuminator 100 may rotate or tilt about the bracket axis 44. Rotation about the bracket axis may facilitate positioning of the illuminator 100 for treatment. For example, the illuminator 100 may rotate about the bracket axis 44 such that the illuminator 100 is positioned below the connecting arm 85 (e.g., in a retracted or neutral position) with the movable portion 98 in a horizontal position. In such an embodiment, the panel 10 may face toward the floor (or ground) on which the illuminator system 105 is located. The central panel 10 of the illuminator may be oriented horizontally.

[0143] The illuminator 100 may be rotated about the bracket axis 44 so that the illuminator 100 is positioned on the side of the connecting arm 85. For example, the illuminator 100 may be rotated approximately 90 degrees so that the panel 10 faces toward the wall. In such an embodiment, the central panel 10 of the illuminator may be oriented vertically. The illuminator 100 may be rotated approximately 90 degrees (e.g., within a range of approximately 0 degrees to approximately 90 degrees) to either the left or right side of the movable portion 98, as shown by the arrow in FIG. 7 . In this manner, the illuminator 100 may be rotated up to approximately 180 degrees (e.g., within a range of approximately 0 degrees to 180 degrees) about the bracket axis 44. One or more torque inserts may hold the illuminator 100 in any position throughout the allowed 180-degree range of motion.

[0144] The plate 46 may be rotatably coupled to the panel 10 such that the panel 10, and the other panels 10 of the illuminator 100, can rotate about a plate axis 48 relative to the plate 46. For example, as shown in FIGS. 5 and 6 , the illuminator 100 may rotate approximately 90 degrees from a retracted or neutral position (e.g., the center panel 10 is aligned with the fixed portion 97 of the connecting arm 85). In at least one embodiment, the mounting mechanism 40 includes a positioning guide 52 on the plate 46 and a position indicator 54 on the panel 10. The positioning guide 52 indicates the rotation range (e.g., approximately 90 degrees) of the illuminator 100. The position indicator 54 indicates where the illuminator 100 is currently positioned within the rotation range. For example, as shown in FIG. 6 , the positioning guide 52 may indicate that the illuminator 100 can rotate as long as the position indicator 54 is aligned with a portion of the positioning guide 52. As the illuminator 100 rotates, the position indicator 54 may move about the positioning guide 52. When the position indicator 54 reaches the end of the positioning guide 52, the attachment mechanism 40 may prevent the illuminator 100 from rotating further in that direction. For example, the attachment mechanism 40 may have a detent on each end of the positioning guide 52 to lock the illuminator 100 in place. The position of the illuminator 100 may be locked in position for treatment when the position indicator 54 aligns with the end of the positioning guide 52.

[0145] The illuminator 100 can be rotated to move from a first position, in which the position indicator 54 is aligned with the first end of the positioning guide 52, to a second position, in which the position indicator 54 is aligned with the second end of the positioning guide 52. Movement between the first and second positions can involve rotating the illuminator 100 approximately 90 degrees. To move between the first and second positions, the illuminator 100 can be moved approximately 90 degrees to the left (e.g., clockwise) or 90 degrees to the right (e.g., counterclockwise). The illuminator 100 can also be moved to any intermediate position located between the first and second ends of the positioning guide 52. The illuminator 100 is configured to remain at any desired angle during operation. For example, the position indicator 53 can be located between the first and second ends of the positioning guide 52 when the illuminator 100 is in use.

[0146] As shown in FIGS. 8A-13, the illuminator 100 may rotate about both the bracket axis 44 and the plate axis 48 regardless of the position of the movable portion 98 of the connecting arm 85 or the height of the extension member 86. For example, in FIG. 8A, the extension member 86 is in a low (retracted) position, the movable portion 98 of the connecting arm 85 is in a horizontal position, and the illuminator 100 rotates about the bracket axis 44 so that the illuminator 100 is positioned on the left side of the connecting arm 85, and the illuminator 100 rotates so that the panels 10a-10e are positioned in a horizontal orientation. In FIG. 8B, the extension member 86 is in the same low position, the movable portion 98 is in the same horizontal position, and the panels 10a-10e are still in the same horizontal orientation, but the illuminator 100 rotates in the opposite direction about the bracket axis 44 so that the illuminator 100 is positioned on the right side of the connecting arm 85. For example, the illuminator 100 rotates under the connecting arm 85 to switch from the left side to the right side. The same movement can be accomplished when extension member 86 extends from vertical column 82 and is not fully deployed.

[0147] In FIG. 9, the illuminator 100 is still positioned to the right of the connecting arm 85 (as viewed from the right side of the figure), but the illuminator 100 has rotated about the plate axis 48 so that the panels 10a-10e are positioned in a vertical orientation. In FIG. 10, the movable portion 98 is oriented vertically, and the illuminator 100 can still rotate about either the plate axis 48 or the bracket axis 44 to a desired orientation. The orientation of the panels 10 relative to each other can also be modified at any position. For example, the panels 10 may move between a flat configuration and a folded configuration, with the movable portion 98 in a vertical position. For example, FIG. 10 shows the movable portion 98 in a vertical position with the panel 10 in a flat configuration. FIGS. 11-12 show the movable portion 98 still in a vertical position, but with the panel 10 in a folded configuration. FIG. 13 shows the movable portion 98 in a horizontal position with the panel 10 in a folded configuration.

[0148] The components of the illuminator system 105 described herein facilitate movement of the illuminator 100 to provide uniform light to the desired treatment area. The illuminator 100 can be moved between a fully retracted position and various operating positions, as well as various intermediate positions therebetween. In the fully retracted position, (i) the extension member 86 is in its lowest position (e.g., with a majority of the extension member 86 disposed within the vertical column 82), (ii) the movable portion 98 of the connecting arm 85 is in a vertically downward position (perpendicular to the fixed portion 97), and (iii) the central panel 10 of the illuminator 100 is aligned with the movable portion 98 (e.g., in a vertical and neutral position relative to both the bracket axis 44 and the plate axis 48). Furthermore, when the illuminator 100 is fully retracted, the panel 10 of the illuminator 100 is maintained in a U-shaped configuration and configured to surround at least a portion of the vertical column 82. The panel 10 of the illuminator 100 is foldable within the contours of the base 81 and the vertical column 82.

[0149] In at least one embodiment, the operating position includes extension member 86 extending at least partially from vertical column 82 (vertical column lock 21 can lock vertical column 82 at any height), movable portion 98 of connecting arm 85 being horizontal and parallel to fixed portion 97, illuminator 100 being positioned at any orientation relative to bracket axis 44 and plate axis 48, and panels 10 of illuminator 100 in any configuration providing light to the desired treatment area. With respect to plate axis 48, illuminator 100 may be substantially parallel to movable portion 98 of connecting arm 85 or may be rotated approximately 90 degrees to be substantially perpendicular to movable portion 98. Illuminator 100 may also be at any angle between 0 and 90 degrees relative to plate axis 48. With respect to the bracket axis 44, the illuminator 100 may be in a neutral position, lying in the same vertical plane as the fixed portion 97 of the connecting arm 85, or may either (i) be rotated by up to approximately 90 degrees (e.g., in a range of approximately 0 to 90 degrees) in a first direction disposed on a first side of the movable portion 98 (outside the plane of the fixed portion 97), or (ii) be rotated by up to approximately 90 degrees (e.g., in a range of approximately 0 to 90 degrees) in a second direction disposed on a second side of the movable portion 98 (also out of the plane of the fixed portion 97).

[0150] 15 , the illuminator system 105 includes a main power switch 96. The main power switch 96 may control when power is supplied to the illuminator system 105. The main power switch 96 may be a two-position rocker switch that can be toggled between two positions. For example, the first position may activate (e.g., turn on) the illuminator system 105, and the second position may deactivate (e.g., disconnect) all electrical components of the illuminator system 105. The first position may place the illuminator system 105 in standby mode. At least one emitter (e.g., LED 60) may be located adjacent to the main power switch 96. The emitter is configured to provide illumination when the illuminator system 105 is in standby mode. The main power switch 96 may be located on the base 81 adjacent to a receptacle for a detachable power cord (e.g., a medical-grade power cord).

[0151] As shown in FIG. 16 , the illuminator system 105 includes a vertical column lock 21. The vertical column lock 21 may be located below the handle 84. The vertical column lock 21 may be movable between a first position and a second position. The first position may be an up position that unlocks the vertical column 82 so that the extension member 86 can move in and out of the vertical column 82, allowing the height of the illuminator 100 to be adjusted. A bezel adjacent to the vertical column lock 21 may be a first predetermined color (e.g., green or another color) when the vertical column lock 21 is in the up position to indicate that the vertical column 82 is unlocked. The second position may be a down position that locks the vertical column 82 so that the extension member 86 is fixed in its current position. The bezel adjacent to the vertical column lock 21 may be a second predetermined color (e.g., red or another color) when the vertical column lock 21 is in the down position to indicate that the vertical column 82 is locked.

[0152] Illuminator Sensor Configuration and Interface As shown in FIGS. 1 and 14 , the illuminator system 105 may include an interface panel 90. The interface panel 90 may be supported by the vertical column 82. The interface panel 90 may be coupled to or detachable from the vertical column 82. The interface panel 90 may include any number of buttons, switches, or other controls to control aspects of the illuminator system 105. For example, the interface panel 90 may include a power button 91 a and a status indicator 91 b. The power button 91 a may control settings for the illuminator system 105. For example, the power button 91 a may load one of two pre-programmed treatment cycles into the illuminator system 105. For example, the last treatment cycle used (e.g., 10 mW or 20 mW) may be loaded and the time displayed (e.g., 16:40 or 8:20).

[0153] The status indicator 91b may indicate the status of the illuminator system 105. For example, different colors or frequencies of the status indicator 91b may have different meanings. For example, a first color (e.g., blue) may indicate a first state (e.g., normal operation), and a second color (e.g., amber) may indicate a second state (e.g., a fault state). A flashing first color may indicate a third state, and a solid first color may indicate a fourth state. Activating the power button 91a (e.g., pressing the button) for a predetermined time may cause a predetermined action. For example, pressing the power button 91a while a treatment cycle is “paused” may cancel the treatment cycle and clear the displayed time. Activating the master power switch 96 (described in more detail below) and pressing the power button 91a may toggle to load or clear a treatment cycle for the illuminator system 105.

[0154] The status indicator 91b may include an array of LEDs arranged around the power button 91a (e.g., in a circular pattern or a different pattern). The status indicator 91b displays the status of the illuminator system 105. In at least one embodiment, the status indicator 91b may be solid blue (or another color) at the start of treatment, indicating that the control electronics of the illuminator system 105 are functioning properly and the associated software is ready for use. The status indicator 91b may change from solid blue to slowly flashing blue (or another color) when the illuminator system 105 is placed in pause mode. In at least one embodiment, other colors or other colors may be used. The status indicator 91b may return to solid blue when the cycle resumes. The status indicator 91b may be solid amber or flashing amber (or another color) if a fault condition is detected (i.e., in response to detecting a fault).

[0155] The interface panel 90 may include a time adjuster 92. For example, the time adjuster 92 may be a button configured to control the treatment time of the panel 10 (e.g., the time the illuminator is activated). The maximum treatment time may be predetermined. For example, the maximum treatment time may be set to 30 minutes. The time adjuster 92 may be used to manually adjust or automatically turn off the LEDs of the panel 10 after the set exposure time has elapsed. The time adjuster 92 may include an up button 92a and a down button 92b to increase or decrease the time, respectively. When initially pressed, the up button 92a and the down button 92b change the displayed reading relatively slowly (e.g., within a first predetermined period, such as 15 seconds). If the up button 92a or the down button 92b remains pressed, the displayed reading changes more quickly (e.g., within a second predetermined period shorter than the first period, e.g., within 5 seconds). Quickly pressing and releasing the up button 92a or the down button 92b allows adjustment of the displayed time. For example, each press may be timed by a given interval (eg, 1 second).

[0156] The interface panel 90 may include a level adjuster 93. For example, the level adjuster 93 may be a button configured to adjust the intensity or power setting (e.g., power level) of the illuminator 100. For example, the level adjuster 93 may toggle the power between two settings (e.g., 10 mW and 20 mW). The power level may be selected after pressing the power button and status indicator 91 to load one of the pre-programmed cycles. The time adjuster 92 may automatically set the correct time for the selected power level. The selected power level may be displayed above the level adjuster 93. For example, a 10 mW setting may be displayed as "10," and a 20 mW setting may be displayed as "20."

[0157] The interface panel 90 may include a comfort adjuster (comfort controller, patient setting controller) 94. For example, the comfort adjuster 94 may be a button or other interface configured to control a patient comfort fan. For example, the comfort adjuster 94 may be a button or other interface configured to toggle the fan setting between off, low, and high. The patient comfort fan may be controllable by a healthcare provider or the patient by pressing the power button and status indicator 91 to load a treatment cycle. The comfort adjuster 94 can be used to cycle through three settings. The patient cooling fan may automatically stop when a cycle timer reaches zero during treatment.

[0158] The interface panel 90 may include a start / stop button 95. For example, the start / stop button may be configured to start a programmed treatment cycle, pause an active treatment cycle, or resume a paused treatment cycle. Pressing the start / stop button 95 while a treatment cycle is active may cause one or more of the following: (i) pausing or stopping the treatment cycle, (ii) turning off the LED, and (iii) ending a countdown implemented by a timer. The power button and status indicator 91 may flash a predetermined color to indicate that the system is paused. The illuminator system 105 may automatically return to standby mode if left paused for a predetermined period of time or longer. For example, the illuminator system 105 may automatically return to standby mode if left paused for five minutes. Pressing the start / stop button 95 while the system is paused may resume the treatment cycle, illuminate the LED, and cause the timer to resume its countdown. The power button and status indicator 91 may display a steady predetermined color to indicate a normal operating state (e.g., a steady blue, or another color).

[0159] 23 , the illuminator system 105 may include a touchscreen 200. The touchscreen 200 may be part of the interface panel 90, the controller 115, or some other separate device (e.g., a user device). The touchscreen 200 may allow a user to control, monitor, and adjust settings of the illuminator system 105. For example, the touchscreen 200 may include at least one of a power button 91 a, a status indicator 91 b, a time adjuster 92, a lever adjuster 93, a comfort adjuster 94, and / or a start / stop button 95. The touchscreen 200 may include additional features (e.g., buttons, displays, notifications, etc.) for the user to monitor and control settings.

[0160] For example, the touchscreen 200 may provide a heat controller 201 for controlling heat directed at a patient for pain management. The touchscreen 200 may provide a notification window 202 to provide notifications or alerts to the user. The touchscreen 200 may provide a time indicator 203. The time indicator 203 may display the time remaining for treatment. The time displayed on the time indicator 203 may change as time progresses or as adjusted via the time adjuster 92. In at least one embodiment, the remaining exposure time is displayed in minutes and seconds. Before pressing the start / stop button 95, the exposure time indicator displays the amount of exposure time set. When the start / stop button 95 is pressed, the exposure time indicator 203 decrements the amount of remaining exposure time. The exposure time indicator 203 may automatically turn off when the display reaches zero. The interface panel 90 may include some or all of these additional features even if the interface panel 90 does not include the touchscreen 200.

[0161] The illuminator system 105 may include one or more sensors 110. In at least one embodiment, the illuminator system 105 may include a sensor 110 configured to detect the size of the treatment area on the patient. In at least one embodiment, the illuminator system 105 may include a sensor 110 configured to detect the position of the illuminator 100. The position of the illuminator 100 may include the height of the extension member 86, the orientation of the illuminator 100 (e.g., vertical, horizontal, right, or left of the connecting arm 85), or the configuration of the panel 10 (e.g., U-shaped, flat, etc.). The position of the illuminator 100 and the size of the treatment area can be used to determine the correct light delivery parameters for treatment. The sensor 110 can be located on any component of the illuminator system 105. For example, the sensor 110 may be located on the vertical column 82, the panel 10, and / or the connecting arm 85, among others. The sensor 110 can be any type of sensor configured to detect data indicative of the position of the illuminator.

[0162] The illuminator system 105 may include a controller 115. As shown in FIG. 24 , the controller 115 may be configured to monitor and control various components of the illuminator system 105. For example, the controller 115 may be configured to control the heat source current to provide different power levels to accommodate different tissue geometries and to vary the current over time to adjust the patient's pain tolerance. The variation in current may be responsive to input from a sensor, such as a distance sensor or a sensor indicating the relative position of the panel.

[0163] In at least one embodiment, the controller 115 may also be configured to transition the illuminator system 105 between curved and flat geometries and maintain uniformity and power throughout the transition. The controller 115 may also include processing circuitry 116. The processing circuitry 116 may include a processor 117 and memory 118. The memory 118 (e.g., storage device) may include one or more devices (e.g., RAM, EPROM, optical disk storage, magnetic disk storage, flash memory, hard disk storage, or any other medium) for storing data and / or computer code for completing or facilitating the various processes and functions described in this disclosure. The memory 118 may be or include temporary or non-transitory memory and may include any type of information structure to support the various activities and information structures described in this disclosure.

[0164] According to at least one embodiment, memory 118 is communicatively coupled to processor 117 and includes computer code for executing (e.g., by processor 117) the processes described herein. Processor 117 may be a general-purpose single-chip or multi-chip processor, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general-purpose processor may be a microprocessor, or any typical processor, controller, microcontroller, or state machine. Processor 117 may also be implemented as a combination of computing devices, such as a combination of a DSP and a microprocessor, multiple microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration. In at least one embodiment, particular processes and methods may be performed by circuitry designed for a given function.

[0165] In at least one embodiment, memory 118 may include a delivery parameter database 119. Delivery parameter database 119 may include relationships between dosage (including exposure time), light intensity, distance between the panel and the treatment surface, and size of the treatment surface, among other data related to treatment via illuminator system 105. For example, a particular exposure duration to light from illuminator 100 may be associated with a particular light intensity, a particular distance between the panel and the treatment surface, and a particular size of the target surface. Processor 117 can use the data stored in delivery parameter database 119 to determine appropriate delivery parameters for a treatment session for a patient.

[0166] In at least one embodiment, controller 115 may include input / output (I / O) circuitry 120. I / O circuitry 120 may be configured to receive signals or data from external devices and to transmit signals or data to external devices.

[0167] In at least one embodiment, the controller 115 may include a user interface 121. The user interface 121 may be a touchscreen. The user interface 121 may be configured to display information received by the controller 115 via the I / O circuitry 120 or to display information retrieved from the memory 118. The user interface 121 may be configured to receive input from a user. For example, the user interface 121 may have an interactive section where the user can interact with and provide information. The interactive section may be a button, switch, or input field, among others. The controller 115 may receive user input via the I / O circuitry 120 and may be configured to store the user input in the memory 118 or generate an output using the user input. For example, the user interface 121 may be configured to provide a display indicating the orientation and position of the illuminator 100 based on information received from the distance sensor 111 and the sensor 110. For example, when the illuminator 100 is in an in-use configuration, the user interface 121 may show the illuminator 100 in its current position. The display may include the current distance of each panel 10 from the treatment area detected by the distance sensor 11.

[0168] In at least one embodiment, the controller 115 may be communicatively coupled to one or more components of the illuminator system 105. For example, the controller 115 may be communicatively coupled to the distance sensor 11. The distance sensor 11 may be configured to send a signal to the controller 115 indicative of the distance between the panel 10 and the treatment area. For example, the controller 115 may be communicatively coupled to the sensor 110. The sensor 110 may be configured to send a signal to the controller 115 indicative of the position or orientation of the illuminator 100. The controller 115 may be communicatively coupled to the mounting mechanism 40. The controller 115 may be configured to send commands to the mounting mechanism 40 to orient the illuminator 100 in a desired position. The controller 115 may be communicatively coupled to the panel 10 of the illuminator 100. The controller 115 may be configured to send commands to the panel 10 to orient the panel 10 in a desired configuration (e.g., a U-shape). The controller 115 may be communicatively coupled to the components via a wired or wireless connection.

[0169] Illuminator cooling system and method As shown in FIGS. 18-23 , at least one of the panels 10 of the illuminator system 105 (e.g., panel 10c) may include a patient cooling fan system 66. The patient cooling fan system 66 may be configured to blow air across the surface of the panel 10 such that the air is tangential to the patient's skin and provides a soothing effect to the patient. The patient cooling fan system 66 includes a fan plenum 74. The fan plenum 74 may define a serpentine path for air to flow, shown as air path 75. For example, the fan plenum 74 may include a body 78 and a neck 79. The body 78 defines a cavity for receiving air. The cavity may have a first thickness. The body 78 transitions to a neck 79 having a second thickness. The first thickness is greater than the second thickness. The neck 79 may define a serpentine air path 75 for the airflow 76 until the air reaches a plenum outlet 77.

[0170] In at least one embodiment, a fan plenum 74 may be disposed within the panel 10. The patient cooling fan system 66 may include a fan 70. The fan 70 may be configured to draw air from the environment and force the air into the fan plenum 74. The fan 70 may push the air through an air path 75 in the fan plenum 74 to a plenum outlet 77. The air path 75 and the plenum outlet 77 are configured to generate an airflow 76 that moves parallel or substantially parallel to the face of the panel 10.

[0171] In at least one embodiment, the panel 10 may include multiple fan plenums 74. For example, a first fan plenum 74 may be located at a first edge of the panel 10, and a second fan plenum 74 may be located at a second edge of the panel 10. The first and second fan plenums 74 may generate airflows 76 parallel or substantially parallel to the face of the panel 10, but the first airflow 76 from the first fan plenum 74 may be directed in a first direction and the second airflow 76 from the second fan plenum 74 may be directed in a second direction. The second direction may be opposite to the first direction. For example, the first airflow 76 may travel below the face of the panel 10, and the second airflow 76 may travel above the face of the panel 10.

[0172] In at least one embodiment, the heat source may be provided separately from or integrated into the illuminator 100. In at least one embodiment, the heat source (heat delivery device) may be an infrared (IR) quartz heater. In at least one embodiment, the heat source may comprise a resistive tape heater attached to a frame, as described above, or multiple heaters, including at least one selected from the group including IR LEDs, resistive cartridge heaters, positive temperature coefficient heaters, or IR quartz heaters. The heat may be intentionally generated and directed toward the area to be treated, as opposed to ambient heat in a clinical setting or by-product heat from one or more operating mechanisms of the illuminator. In at least one embodiment, the heat is intentionally generated and directed toward the patient, who is further heated by the ambient and / or by-product heat. In at least one embodiment, the heat is administered in the form of a heat mask, such as a sodium acetate mask configured to heat upon crystallization. In at least one embodiment, the heat source is a heating pad.

[0173] Therefore, components or operating mechanisms of the illuminator can be configured to generate heat that can be intentionally targeted toward the patient. For example, the illuminator may include one or more fans that draw air across such components or mechanisms and deliver heat to the patient. The heat may reduce pain or discomfort experienced by the patient. As described above, heating additionally accelerates the conversion of ALA to porphyrins.

[0174] 25, a method 250 of providing photodynamic therapy is shown, according to an exemplary embodiment. Method 250 may include detecting the position of the illuminator (step 251), identifying a treatment area (step 252), determining delivery parameters (step 253), and initiating treatment (step 254). In particular, the method may include detecting the position of illuminator 100, for example, when the illuminator is in a neutral position or rotated up to 90° relative to an axis.

[0175] In step 251, one or more processors and / or sensors may detect the position of the illuminator 100. For example, the controller 115 may receive a signal from a sensor 110 indicating the position of the panel 10 of the illuminator 100. For example, the sensor 110 may be a distance sensor or a sensor indicating the relative position of the panel 10 of the illuminator 100. The controller 115 may receive signals from multiple sensors 110 indicating the position of corresponding panels 10. The controller 115 may determine the position of the illuminator 100 based on the multiple signals. Step 251 may include at least one of detecting a height of the extension member 86, detecting an orientation of the movable portion 98 of the connecting arm 85 (e.g., vertically downward, vertically upward, horizontal), detecting an orientation of the illuminator 100 (e.g., a rotation angle about at least one of the bracket axis 44 and the plate axis 48), and / or detecting an arrangement of the multiple panels 10 of the illuminator 100 (e.g., U-shaped, flat).

[0176] In step 252, one or more processors or sensors may identify characteristics of the treatment area. For example, the controller 115 may identify or infer the position, shape, or size of the treatment area based on the position of the illuminator 100. For example, signals received by the controller 115 may indicate that the panel 10 of the illuminator 100 is positioned vertically in a U-shape and at a particular height. Based on the signals and / or data from the sensors, the controller 115 may identify the patient's face as the treatment area. Identifying the treatment area may also include determining the shape or size of the treatment area. For example, the controller 115 may determine the size of the treatment area based on signals received from the sensors 11, 110. In some embodiments, a panel position sensor may be used to identify characteristics of the treatment area, for example, based on a look-up table. In some embodiments, active optical or ultrasonic sensors may be used to identify characteristics of the treatment area.

[0177] In at least one embodiment, detecting the location of the illuminator and / or identifying the treatment area, such as its location, shape, or size, may be determined in further ways to enhance the photodynamic therapy provided using illuminator 100. For example, by using a sensor to detect the shape of the surface to be treated, the LED array can be individually configured to emit more intense light only in areas that require it. Additionally, sensors may be used to detect the orientation of one or more panels (e.g., whether the panels are angled or folded flat) and configure the LEDs to emit more or less intense light in areas as desired.

[0178] In particular, in at least one embodiment, at least one sensor detects the orientation of the at least one panel and provides the detection information (detection result) to the controller 115. The sensor may include one or more encoders, such as one or more angle encoders, provided at one or more positions on the panel. In at least one embodiment, the at least one sensor is a microswitch configured to sense the position of the at least one panel. In at least one embodiment, the multiple sensors may include encoders, microswitches, or a combination thereof. The sensor is in communication with the controller 115 and configured to provide the controller 115 with information regarding the panel orientation, such as the angle at which the panel is positioned. The controller then controls the light intensity according to the detection result. In at least one embodiment, the multiple sensors provide information to the controller so that the controller can make a determination regarding whether the illuminator has a configuration that is one of multiple preset configurations. For example, the controller may store information related to one or more preset configurations (e.g., curved illuminator, flat illuminator, etc.) in a memory.

[0179] When the controller receives information transmitted from the sensor, the controller may compare the sensed information with preset configurations to determine a match between the sensed information and one or more preset configurations. The controller may further store protocols for varying intensity that are executed upon determining a match between the sensed information and the preset configurations. For example, if the illuminator is detected to be in a U-shaped configuration, the controller implements a light intensity output that correlates with a preset protocol for a U-shaped illuminator. The controller may further compare the existing intensity with the intensity associated with the particular configuration to determine whether the intensity should be adjusted. This allows for increased uniformity of light exposure in an efficient manner as power output and / or light intensity are increased for only certain diodes, if necessary. In at least one embodiment, multiple preset configurations may be presented to a healthcare provider, for example, on a touchscreen, which may then select a preset configuration that corresponds to the physical placement of the illuminator in the treatment or clinical environment.

[0180] In step 253, the one or more processors may determine delivery parameters. For example, the controller 115 may compare data received from the sensors 11, 110 with data stored in the delivery parameter database 119. Based on the comparison, the controller 115 may determine delivery parameters appropriate for treatment for a given position of the illuminator 251 and a given treatment area. The delivery parameters may be, among other things, duration of exposure or light intensity.

[0181] The one or more processors may detect the adjusted position of the illuminator 100. In such an embodiment, steps 251-253 may be repeated until the final position of the illuminator 100 is established.

[0182] At step 254, the one or more processors may initiate a treatment cycle. For example, the controller 115 may initiate a treatment cycle based on the determined delivery parameters. The controller 115 may activate the LEDs 60 of the panel 10 of the illuminator 100 at a specified intensity based on the delivery parameters. The controller 115 may set a treatment duration based on the delivery parameters. The controller 115 may activate the patient cooling fan system 66.

[0183] Thus, the controller allows a healthcare provider to control one or more of: (i) treatment cycle, (ii) LED activation, (iii) LED intensity, (iv) treatment duration, and (v) patient cooling (i.e., fan cooling) (among other aspects of the treatment). A healthcare provider may use controller 115 to adjust any or all of (i)-(v) throughout the treatment. In particular, controller 115 may be used to operate patient cooling fan system 116 to direct cooled air toward the patient (e.g., operated by the healthcare provider or the patient). Thus, cooled air may be delivered in response to input from controller 115 as it is operated during treatment. For example, providing cooled air to the patient via patient cooling fan system 116 may reduce sensations of pain or discomfort experienced by the patient.

[0184] It should be noted that when used herein to describe various embodiments, the term "example" is intended to indicate that such embodiment is an example, representation, and / or illustration of possible embodiments (and such term does not necessarily imply that such embodiment is an exceptional example or super-example).

[0185] As used herein, the term "substantially" and similar terms are intended to have a broad meaning consistent with common and accepted usage by those skilled in the art to which the subject matter of this disclosure pertains. It should be understood by those skilled in the art upon reviewing this disclosure that these terms are intended to enable the description of the particular features being described and claimed without limiting the scope of these features to the precise numerical ranges provided. Accordingly, these terms should be interpreted as indicating that insubstantial or insignificant modifications or variations of the subject matter described and claimed are considered to be within the scope of the invention as recited in the appended claims.

[0186] As used herein, the terms "coupled," "connected," and the like refer to the direct or indirect joining of two members to one another. Such joining may be static (e.g., permanent) or movable (e.g., removable or releasable). Such joining may be achieved by the two members, or by the two members and any additional intermediate members integrally formed with each other or with the two members as one unitary body, or by the two members and any additional intermediate members attached to each other.

[0187] While the specification includes details of specific implementations, these should not be construed as limitations on the scope of any embodiment or what may be claimed, but rather as descriptions of features specific to particular implementations of particular embodiments. Certain features described herein in the context of separate implementations may also be implemented in combination in a single implementation. Conversely, various features described in the context of a single implementation may also be implemented separately in multiple implementations or in any suitable subcombination. Furthermore, even if features may be described above as acting in a particular combination and are initially claimed as such, one or more features from the claimed combination may, in some cases, be separated from that combination, and the claimed combination may be directed to a subcombination or variation of the subcombination. For example, the implementations described herein can be used in conjunction with (and applied to) the compositions, illuminators, devices, dressings, treatment methods, processes, and techniques described in the above-cited patents and / or patent applications.

[0188] The construction and arrangement of the various exemplary embodiments are illustrative only. Upon recognizing that one or more embodiments have been described in detail in this disclosure, those skilled in the art who consider this disclosure will further appreciate that many modifications (e.g., changes in the size, dimensions, structure, shape and proportions of various elements, parameter values, mounting arrangements, orientations, etc.) are possible without substantially departing from the novel teachings and advantages of the subject matter described herein. Other substitutions, modifications, changes, and omissions may be made in the design, operating modes, and arrangements of the various exemplary embodiments without departing from the scope of the present disclosure.

Claims

1. 1. A method of administering photodynamic therapy, comprising: on the patient's skin, (a) 5-aminolevulinic acid (ALA) hydrochloride, and (b) applying a topical composition comprising a vehicle containing at least one chelating agent to enhance accumulation of protoporphyrin IX (PpIX) in the skin; incubating the topical composition; After incubation, applying heat from a heat source to said skin for at least a first period of time.

2. 10. The method of claim 1, wherein the at least one chelating agent is selected from ethylenediaminetetraacetic acid (EDTA) or a pharmaceutically acceptable salt thereof.

3. 3. The method of claim 1 or claim 2, further comprising, after incubation, exposing the skin to light from a light source for a second period of time, wherein the heat is also applied for a second period of time.

4. 4. The method of claim 3, wherein the second period of time is about 8 minutes.

5. 4. The method of claim 3, wherein the second period of time is approximately 8 minutes and 20 seconds.

6. 6. The method of any one of claims 3 to 5, wherein the incubation occurs for about 2 hours to about 3 hours, the sum of the first period and the second period being about 13 minutes.

7. The method of any one of claims 1 to 6, wherein no light is applied to the skin before applying the heat.

8. 8. The method of any one of claims 1 to 7, wherein applying heat to the skin for 13 minutes increases the amount of PpIX present in the skin by more than about 50%.

9. 9. The method of any one of claims 1 to 8, wherein applying heat to the skin for 13 minutes increases the amount of PpIX present in the skin by more than about 80%.

10. 10. The method of any one of claims 1 to 9, wherein the aminolevulinic acid hydrochloride is present in an amount of 20% w / w of the topical composition and the at least one chelating agent is present in an amount of about 0.1% to about 0.15% of the topical composition.

11. The method of any one of claims 1 to 10, further comprising directing a flow of air towards the skin for at least the first period of time.

12. 12. The method of claim 11, further comprising directing the air flow toward the skin for at least the first period of time and a second period of time after the first period of time.

13. The method of any one of claims 1 to 12, further comprising occluding the skin during incubation.

14. The method of any one of claims 1 to 13, wherein the first period of time is about 5 minutes.

15. A kit comprising a lighting device, a heat source, and an applicator containing the topical composition of claim 1.

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