Topical composition for photodynamic therapy, occlusive dressing, kit using same, photodynamic therapy material, and method for photodynamic therapy

Abstract

Topical composition for photodynamic therapy, occlusive dressing, and kit using same , photodynamic therapy materials, and methods for photodynamic therapy. The present invention provides 5-aminolevulinic acid (ALA) that is applied to the treatment area for photodynamic therapy. To enhance the penetration of the topical composition containing the compound, the topical composition is applied to the treatment area using a light source. By covering the treatment area with a low-density polyethylene barrier before radiation therapy, the area is protected from radiation by Minimizes skin moisture loss.

Description

[Technical Field]

[0001] [Related Applications] This application is based on U.S. Patent Application No. 15 / 869,164, filed January 12, 2018. The benefit of priority is claimed and the entire contents are incorporated by reference.

[0002] The present disclosure generally relates to a 5-aminoleucine compound that is applied to tissue as a treatment site for photodynamic therapy. A topical composition containing hydroxybenzoates (ALA), a low density polyethylene coating for coating the topical composition, Lenbarrier, kit using same, photodynamic therapy material, and low-density polyethylene therefor Use of a barrier, topical compositions and use of a low density polyethylene barrier therefor, and The present invention relates to a method for photodynamic therapy. [Background technology]

[0003] Photodynamic therapy (PDT), photodynamic diagnostics (PD), or photochemotherapy is generally used to treat skin or in or near other tissues, such as within a body cavity, to treat and For example, photodynamic therapy or photodynamic diagnosis is used to treat a patient's Actinic keratosis (actinitis) on the upper extremities (e.g., dorsum of the hands or forearms), scalp, or facial area of ​​a person Furthermore, such techniques can be used to treat or diagnose keratosis. Other indications (e.g., acne, warts, psoriasis, photodamaged skin, cancer) and other areas of the patient (e.g., For example, it can be used for the treatment and diagnosis of the leg or parts of the arm other than the forearm.

[0004] In one form of photodynamic therapy, a patient is first exposed to a photoactive agent that accumulates in the tissue to be treated. A photoactivatable agent or precursor to the photoactivatable agent is then administered to the area where the photoactivatable agent has been administered. Exposure to visible light, which causes chemical and / or biological changes in the photoactivatable agent These changes allow the drug to selectively locate, destroy, or alter target tissue. At the same time, it may cause at most mild and reversible damage to other tissues within the treatment area. An example of a precursor to a photoactivatable agent is 5-aminolevulinic acid ("ALA"); It is commonly used in the photodynamic therapy of actinic keratosis. When referring to ALA or 5-aminolevulinic acid, the terms ALA and 5-aminolevulinic acid are used to refer to ALA itself, its precursors, and their 5-ALA-containing topical compositions Photosensitization after application of a substance (e.g., a topical solution or emulsion) is discussed in more detail below. As shown in Fig. 1, the metabolic conversion of aminolevulinic acid to protoporphyrin IX (PpIX) PpIX is a photosensitizer that accumulates in the skin.

[0005] For photodynamic therapy to be effective, it depends on the intensity and duration, among other factors. It is desirable to have a power output that can be controlled with respect to They are used to provide uniform light suitable for therapeutic purposes. These devices are generally , a light source (e.g., fluorescent tube or LED) and a method for delivering the light to the intended target in a usable form. A coupling element that directs, filters, or otherwise conducts light emitted into and a control system that starts and stops the generation of light when needed.

[0006] Photodynamic therapy uses specific compounds such as ALA in conjunction with an illuminator such as those described above. Such compositions and / or devices can be implemented, for example, by (1) 19 Golub's U.S. Patent No. 5,954,703, issued September 21, 1999, entitled "Invention of a 3D Printer." Title: "Method and Apparatus for Applying 5-Aminolevulinic Acid," (2) April 2, 2001 U.S. Patent No. 6,223,071 to Lundahl et al., issued on the 4th, Titled "Photodynamic Therapy and Diagnostic Illumination Device Producing Visible Light of Substantially Uniform Intensity" (3) Published on June 8, 2017, under U.S. Publication No. 2017 / 0157379, Boy U.S. Patent Application No. 15 / 371,363 to Ajian et al., entitled "Applying a Topical Solution" (4) Boyajian et al., published on April 20, 2017. International Application No. PCT / US2016 / 056572, entitled "Photodynamic Therapy and Diagnostics" "Adjustable Illuminator for the Indoor Use of a Medical Device," (5) U.S. Publication No. 2017 / 01 on April 20, 2017 Boyajian et al., U.S. Patent Application Serial No. 15 / 292,731, issued as 06205 No., Title of invention: "Adjustable illuminator for photodynamic therapy and diagnosis", (6)2017 Boyajia, published August 3, 2017, under U.S. Publication No. 2017 / 0216616 No. 15 / 487,991 to N. et al., entitled "Adjustable Lighting and Light Power Control" The foregoing patents and / or patent applications (1) to (5) are disclosed in the above patents and / or patent applications. The entire contents of (6) are for background information and the photodynamic therapy and diagnostics disclosed therein. and US Pat. No. 6,229,133, which are incorporated herein by reference for their related compositions, devices, processes and techniques. do. Summary of the Invention [Problem to be solved by the invention]

[0007] Through research and experimentation in photodynamic therapy techniques, the inventors have found that Cover the treatment area with polyethylene (e.g., low-density polyethylene (LDPE)) for a period of time. This is particularly effective in minimizing transepidermal water loss (water loss) from the treatment area. Surprisingly, we found that polyolefins with a blocking rate of 65% or more (such as LDPE) RimerBarrier is more durable than other materials such as polyurethane and polyvinylidene chloride (PVdC). Low-density polyethylene is excellent for the arms, legs, chest, back, and head. It can be applied to a wide variety of treatment areas and can be used with drugs other than 5-ALA. do. [Means for solving the problem]

[0008] According to one aspect of the present disclosure, topical 5-aminolevulinic acid (ALA) for photodynamic therapy is A method for enhancing the penetration of therapeutic compositions into tissues is disclosed. This method involves topically applying ALA to the treatment area to be treated. Once applied to the site, the treatment area is covered with a polymer barrier that has an occlusion rate of greater than 65%. It further includes:

[0009] According to another aspect of the present disclosure, topical 5-aminolevulinic acid (ALA) for photodynamic therapy is A method for enhancing the penetration of therapeutic compositions into tissues is disclosed. This method involves topically applying ALA to the treatment area to be treated. After application to the site, the method further includes covering the treatment site with a low density polyethylene barrier. To minimize transepidermal water loss from the treatment area, the treatment area should be kept in a low-density It is then covered with a polyethylene barrier.

[0010] According to yet another aspect of the present disclosure, a method for photodynamic treatment of the stratum corneum is disclosed. The method involves applying 5-aminolevulinic acid (ALA) to the lesions on the stratum corneum and and reducing evaporation from a portion of the stratum corneum that includes the area where the stratum corneum is to be exposed. Heating the area where the lesion is located before or during illumination of the area where the lesion is located include.

[0011] According to a further aspect of the present disclosure, a composition comprising 5-aminolevulinic acid (ALA) and low density polyethylene glycol (LPGE) is provided. A method of using a polyethylene barrier is disclosed, which method applies a composition containing 5-ALA to the treatment site. and after wetting the treatment area, the wet treatment area is sparsely packed. This involves covering the container with a polyethylene barrier.

[0012] According to a further aspect of the present disclosure, there is provided a method for treating rheumatoid arthritis with 5-aminolevulinic acid (ALA) for photodynamic therapy. A method for enhancing tissue penetration of a topical composition of HCl is disclosed. The method comprises: The method includes topically applying the composition to the treatment area to be treated with chemotherapy. After the product has been applied to the treatment area, to minimize transepidermal water loss from the treatment area, The composition further comprises covering the treatment area with a low density polyethylene barrier prior to phototherapy. , when ALA HCl was applied in an amount of 354 mg, the AL concentration was less than about 110 ng / mL. The mean plasma concentration of A (C max ) value. [Brief explanation of the drawings]

[0013] The details of one or more embodiments are set forth in the accompanying drawings and the description below. Other features, aspects, and advantages will become apparent from the description, the drawings, and the claims. In the drawings, like reference numerals are used throughout the various views to denote like elements. The drawings will now be briefly described. [Figure 1A] FIG. 1A illustrates a top view of the body of an illuminator according to an example embodiment. [Figure 1B] FIG. 1B illustrates a top view of the body of an illuminator according to an exemplary embodiment. [Figure 2A] FIG. 2A shows a perspective view of the main body of the illuminator of FIGS. 1A and 1B. [Figure 2B] FIG. 2B shows a perspective view of the main body of the illuminator of FIGS. 1A and 1B. [Figure 3] FIG. 3 shows a perspective view of an illuminator having the body of FIGS. 1A and 1B mounted on a stand. [Figure 4] FIG. 4 shows a representative area that may be treated according to an exemplary embodiment. [Figure 5] FIG. 5 illustrates the evaporative water loss rate for several materials, according to at least one embodiment. [Figure 6] FIG. 6 illustrates occlusion levels for several materials, according to at least one embodiment. [Figure 7] FIG. 7 illustrates the evaporative water loss rate for several materials, according to at least one embodiment. [Figure 8] FIG. 8 illustrates the degree of occlusion for several materials, according to at least one embodiment. [Figure 9] FIG. 9 is a table containing baseline water loss data for the materials referenced in FIGS. [Figure 10] FIG. 10 is a table containing moisture loss data after 3 hours of wear time for the materials referred to in FIGS. [Figure 11] FIG. 11 is a table containing occlusive data for the materials referenced in FIGS. [Figure 12]FIG. 12 is a table containing baseline water loss data for the materials referenced in FIGS. [Figure 13] FIG. 13 is a table containing moisture loss data after 3 hours of wear time for the materials referenced in FIGS. [Figure 14] FIG. 14 is a table containing occlusive data for the materials referenced in FIGS. DETAILED DESCRIPTION OF THE INVENTION

[0014] It will be appreciated that some or all of the figures are schematic for illustrative purposes. These figures are expressly not intended to limit the scope or meaning of the claims. It will be understood that the present disclosure is provided for illustrative purposes only and is not intended to be limiting.

[0015] Various embodiments are described below. Certain embodiments are provided as an exhaustive description, and Note that these are not intended as limitations on the broader aspects discussed herein. An aspect described in connection with a particular embodiment does not necessarily apply to that embodiment. It is not limited to this and can be implemented with any other embodiment.

[0016] The following terms are used throughout and are defined below.

[0017] As used in this specification and the appended claims, singular articles, e.g., "a" and "an" and "the," as well as in the context of describing elements (particularly in the claims below). Similar references (in the context of the claims) should be construed as exhaustive. Unless otherwise indicated or clearly contradicted by context, the singular and plural Both. The recitation of ranges of values ​​herein simply refers to the ranges, unless otherwise specified herein. It is intended to serve as a shorthand method of referring individually to each separate value that falls within a range. All methods described herein are intended to be illustrative unless otherwise indicated herein or apparent by context. The steps may be performed in any suitable order as long as they are not inconsistent with the principles provided herein. Any examples or use of exemplary language (e.g., "such as") are merely illustrative of embodiments. The present disclosure is intended to better illustrate and not to limit the scope of the claims unless otherwise specified. No language in this specification indicates any non-claimed element as essential. should not be construed as such.

[0018] The embodiments illustratively described herein may be used in conjunction with any of the following methods not specifically disclosed herein: It may be suitably practiced without any element(s). Thus, for example: The terms "comprising," "including," "containing," etc. Furthermore, the terms used herein should be read expansively and not restrictively. The terms and expressions are used as terms of description and not of limitation, to show and describe the The use of the claimed technology is not intended to exclude any equivalents of the claimed technology or portions thereof. We recognize that various modifications are possible within the scope of the art. The phrase "consisting essentially of" refers to the elements specifically recited and the elements claimed in the patent application. Those additional elements that do not materially affect the basic and novel characteristics of the technology sought. The wording "comprising" is understood to mean "including, but not limited to" " (including, but not limited to) any other product or service mentioned. Unless otherwise stated, "a" or "an" means one or more.

[0019] Unless otherwise specified, the characteristics, parameters, conditions, etc. used in the specification and claims All numbers expressing quantities are modified in all instances by the term "about." Accordingly, unless otherwise indicated, the following specification and The numerical parameters set forth in the appended claims are approximations. , given the number of significant digits reported, applying normal rounding techniques will yield at least The term "about" should be interpreted as referring to numerical designations, e.g., temperature, time, amount, including ranges. , and when used before the concentration, vary by (+) or (-) 10%, 5%, or 1% The approximate values ​​obtained are shown below.

[0020] As will be appreciated by those skilled in the art, there are many possibilities, particularly with regard to providing written descriptions. For all purposes, all ranges disclosed herein also include any and all possible Any recited ranges include all possible subranges and combinations of those subranges. The same range is divided into at least half, third, quarter, fifth, tenth, etc. As a non-limiting example, the present specification Each range discussed in the book can be easily subdivided into lower third, middle third, and upper third, etc. As will be understood by those skilled in the art, "up to," "at least," and " All terms such as "greater than," "less than," etc., are inclusive of the enumerated figures and are not intended to be limiting unless otherwise specified. Finally, a range that can be later divided into subranges as understood by those skilled in the art is also a range that can be later divided into subranges as follows: Thus, the range includes each individual member. [Example]

[0021] According to one embodiment, a topical composition is provided. The topical composition is for photodynamic therapy. It contains 5-aminolevulinic acid (ALA) and is applied to the tissue at the treatment site. The treatment area is covered with a low-density polyethylene barrier within a specified time after applying the topical composition before After the covering and the low density polyethylene barrier are removed, light therapy is administered to the treatment area.

[0022] According to at least one embodiment, a topical composition is provided and the predetermined time period is 3 hours or less. be.

[0023] According to at least one embodiment, a topical composition is provided having an ALA concentration of 20% by weight. Something that is.

[0024] In accordance with at least one embodiment, an occlusive dressing is provided. The 5-aminolevulinic acid (5ALA) coating is applied to the tissue at the treatment site for photodynamic therapy. (5-ALA), and the topical composition is applied before phototherapy and then an occlusive drain is formed within a specified time. The occlusive dressing covers the treatment area and is applied before phototherapy is administered to the treatment area. is removed.

[0025] According to at least one embodiment, the predetermined time is 3 hours or less.

[0026] According to at least one embodiment, a gap is formed between the low density polyethylene barrier and the treatment area. There is no.

[0027] According to at least one embodiment, a kit is provided. The kit comprises a low density polyethylene and a topical composition containing 5-aminolevulinic acid (ALA).

[0028] According to at least one embodiment, the kit is configured to emit light of uniform intensity. The device further includes an illuminator.

[0029] According to at least one embodiment, the kit includes a low density polyethylene barrier in place. Further comprising a net configured for securing.

[0030] According to at least one embodiment, the kit includes a heater configured to direct heat to the treatment site. It further includes a rotor.

[0031] According to at least one embodiment, the kit includes a step for determining the size of the treatment area or the location of the illuminator. The device further comprises at least one sensor configured to determine

[0032] According to at least one embodiment, the kit includes pre-programmed dosing parameters. The device further comprises a controller configured to store the

[0033] According to at least one embodiment, a photodynamic therapy material is provided. The present study involves the use of a topical composition of 5-aminolevulinic acid (ALA) and a topical formulation of 5-aminolevulinic acid (ALA) applied to tissues at the treatment site. and a low density polyethylene barrier for covering the topical composition to be applied thereto. The barrier covers the treatment area for a predetermined time after applying the topical composition prior to phototherapy, and The high density polyethylene barrier is removed before light therapy is administered to the treatment area.

[0034] According to at least one embodiment, the predetermined time is 3 hours or less.

[0035] At least one embodiment provides topical administration of 5-aminolevulinic acid (ALA) for photodynamic therapy. The present invention relates to the use of a low density polyethylene barrier to promote penetration of therapeutic compositions into tissues. The low density polyethylene barrier minimizes transepidermal water loss from treatment. The low-density polyethylene barrier facilitates the penetration of ALA, and the low-density polyethylene barrier prevents healing after topical application of ALA. It is used to cover the treatment area and is positioned 3 inches from the treatment area to allow light to reach the treatment area. will be removed within a time.

[0036] At least one embodiment provides a method for the treatment of tissue with 5-aminolevulinic acid (ALA) for photodynamic therapy. The present invention relates to the use of a topical composition containing LA and a low-density polyethylene barrier. The polyethylene barrier provides optimal access to tissue by minimizing transepidermal water loss from the treatment area. The low-density polyethylene barrier facilitates the penetration of ALA into the skin after application of a topical ALA composition. It is used to cover the treatment area and is removed from the treatment area to allow light to reach the treatment area. Remove the low-density polyethylene barrier within 3 hours of application.

[0037] In at least one embodiment, while a low density polyethylene barrier is covering the treatment area, It involves the use of a low density polyethylene barrier through which heat is applied to the treatment site.

[0038] At least one embodiment further comprises applying a compressive pressure to the low density polyethylene barrier. A topical composition of 5-aminolevulinic acid (ALA) containing a low-density polyethylene barrier Regarding use.

[0039] At least one embodiment provides a method for producing 5-aminolevulinic acid (ALA)-derived phospholipids for photodynamic therapy. Low-density polyethylene barrier to facilitate conversion to portoporphyrin IX (PpIX) The use of A, The low-density polyethylene barrier allows the topical 5-ALA composition to penetrate the tissue for photodynamic therapy. Facilitates conversion by promoting penetration, The low-density polyethylene barrier protects the skin by minimizing transepidermal water loss from the treatment area. This promotes the penetration of 5-ALA into tissues, A low-density polyethylene barrier is used to cover the treatment area after application of the topical 5-ALA composition. It must be removed from the treatment area within 3 hours to allow light to reach the treatment area. The present invention relates to the use of a low density polyethylene barrier, characterized in that it is

[0040] At least one embodiment provides a method for producing 5-aminolevulinic acid (ALA)-derived phospholipids for photodynamic therapy. Topical compositions of ALA to facilitate its conversion to portoporphyrin IX (PpIX) Use of a low density polyethylene barrier, which prevents the By minimizing transepidermal water loss and promoting the penetration of ALA into tissues Facilitates conversion, A low-density polyethylene barrier is used to cover the treatment area after application of the topical 5-ALA composition. It must be removed from the treatment area within 3 hours to allow light to reach the treatment area. The present invention relates to a topical composition of 5-ALA characterized by the use of a low-density polyethylene barrier. .

[0041] At least one embodiment provides a 5-aminobenzoate (ABD) for photodynamic therapy in a subject in need thereof. Use of a topical composition comprising minolevulinic acid (ALA), wherein the subject is The lens barrier is designed to cover the treatment area for a predetermined time from application of the topical composition prior to phototherapy. The low-density polyethylene barrier is removed and phototherapy is administered to the treatment area. The present invention relates to the use of a topical composition comprising:

[0042] In at least one embodiment, the low density polyethylene barrier is removed from the treatment site within three hours. The present invention relates to the use of topical compositions that are applied to the skin.

[0043] At least one embodiment provides a low-density photodynamic therapy for photodynamic therapy of a subject in need thereof. The use of an occlusive dressing comprising a polyethylene barrier, wherein photodynamic therapy is applying a topical composition containing 5-aminolevulinic acid (ALA) to the area; The low-density polyethylene barrier prevents the topical composition from being applied for a predetermined period of time prior to phototherapy. The patient is instructed to cover the treatment area internally, and the low-density polyethylene barrier is removed before phototherapy. The present invention relates to the use of an occlusive dressing, characterized in that it is applied to a treatment site.

[0044] In at least one embodiment, the low density polyethylene barrier is removed from the treatment site within three hours. This relates to the use of removable occlusive dressings.

[0045] According to at least one embodiment, a photodynamic therapy agent is applied to a tissue as a treatment site for photodynamic therapy. A low density polyethylene coating is used to coat a topical composition containing 5-aminolevulinic acid (ALA). A method of using a lent barrier, comprising: applying a topical composition to a tissue at a treatment site; and covering the surface of the photosensitive material with a low-density polyethylene barrier to prevent application of the topical composition prior to phototherapy. The low-density polyethylene barrier covers the treatment area for a set period of time, preventing light therapy from being applied to the treatment area. and removing the surface of the substrate prior to the application of the ion beam.

[0046] According to at least one embodiment, a low density polyethylene film is used to coat the topical composition. In the barrier method, the predetermined time is 3 hours or less.

[0047] According to at least one embodiment, 5-aminolevulinic acid (ALA) for photodynamic therapy A method for enhancing tissue penetration of a topical composition of claim 1, wherein the composition comprises a compound selected from the group consisting of hydroxybenzoates, ... ALA is applied topically to the treatment area, and after ALA is applied to the treatment area, it is removed from the treatment area. To minimize transepidermal water loss, the treatment area was covered with low-density polyethylene prior to phototherapy. The treatment area should be covered with a polyethylene barrier and the low-density polyethylene barrier should be removed within 3 hours. and irradiating the area with light.

[0048] According to at least one embodiment, 5-aminolevulinic acid (ALA) for photodynamic therapy The method for enhancing tissue penetration of the topical composition of the present invention is to prevent excessive irritation while maintaining therapeutic efficacy. To avoid this, the low-density polyethylene barrier is removed from the treatment area within 3 hours.

[0049] According to at least one embodiment, 5-aminolevulinic acid (ALA) for photodynamic therapy A method for enhancing tissue penetration of a topical composition of claim 1, wherein the composition comprises a therapeutic agent to be treated with photodynamic therapy. ALA is applied topically to the treatment area, and after ALA is applied to the treatment area, it is removed from the treatment area. To minimize transepidermal water loss, the treatment area was covered with low-density polyethylene prior to phototherapy. and covering the treatment area with a barrier, wherein the treatment area is on the hand or forearm. provide.

[0050] According to at least one embodiment, 5-aminolevulinic acid (ALA) for photodynamic therapy In a method for enhancing tissue penetration of a topical composition of the present invention, a low-density polyethylene barrier is formed over a 3-hour period. Remove from the treatment area within 10 J / cm 2 The treatment area is irradiated with blue light at a light intensity of do.

[0051] According to at least one embodiment, 5-aminolevulinic acid (ALA) for photodynamic therapy In a method for enhancing tissue penetration of a topical composition of the present invention, a low density polyethylene barrier is provided at the treatment area. Remove from the area and then apply 10 to 75 J / cm 2 Red light is irradiated onto the treatment area at a light intensity of .

[0052] According to at least one embodiment, 5-aminolevulinic acid (ALA) for photodynamic therapy The method for enhancing the tissue penetration of the topical composition of the present invention is to increase the maximum plasma concentration of ALA after application of ALA. The blood level is less than about 110 ng / mL.

[0053] According to at least one embodiment, 5-aminolevulinic acid (ALA) and low density polyethylene A method of using a lenbarrier, comprising using a composition containing ALA to moisten the treatment area. and after wetting the treatment area, contacting the wetted treatment area with a low density polyethylene Cover with a len barrier and remove the low-density polyethylene barrier to expose the treatment area and 10J / cm 2 Illuminate the exposed treatment area with a dose of blue light. and illuminating with a light source.

[0054] According to at least one embodiment, 5-aminolevulinic acid (ALA) and low density polyethylene For LenBarrier treatments, low-density polyethylene (LDPE) should be applied within 3 hours of the treatment area being covered. Remove the barrier.

[0055] According to at least one embodiment, 5-aminolevulinic acid (ALA) and low density polyethylene The Len Barrier method involves positioning the treatment area between 2 and 4 inches from the surface of the illuminator. The method further includes positioning the

[0056] According to at least one embodiment, 5-aminolevulinic acid (ALA) for photodynamic therapy In the method for enhancing tissue penetration of a topical composition of claim 1, the treatment site is the dorsal surface of the hand.

[0057] According to at least one embodiment, 5-aminolevulinic acid (ALA) for photodynamic therapy is In a method for enhancing tissue penetration of a topical composition, the treatment site is the dorsal surface of the forearm.

[0058] According to at least one embodiment, 5-aminolevulinic acid (ALA) is used for photodynamic therapy. To facilitate the conversion of PpIX to protoporphyrin IX, low-density polyethylene was used. A method of using a barrier to promote the penetration of a topical 5-ALA composition into tissues. This involves covering the treatment area with a low density polyethylene barrier to facilitate conversion. High-density polyethylene barrier minimizes transepidermal water loss from the treatment area The low-density polyethylene barrier facilitates the penetration of ALA into the skin after application of a topical ALA composition. It is used to cover the area and is positioned 3 inches from the treatment area to allow light to reach the treatment area. The method is characterized in that the ion exchange reaction is removed within a short time.

[0059] According to at least one embodiment, 5-aminolevulinic acid (ALA) is used for photodynamic therapy. To facilitate the conversion of PpIX to protoporphyrin IX, low-density polyethylene was used. The method of using the barrier may further include applying heat to the treatment area to promote the transformation. nothing.

[0060] According to at least one embodiment, 5-aminolevulinic acid (ALA) is used for photodynamic therapy of tissue. Topical 5-ALA to facilitate the conversion of 5-ALA to protoporphyrin IX (PpIX) A method of using the composition and a low density polyethylene barrier, The treatment area is covered with a low-density polyethylene barrier to minimize transepidermal water loss from the treatment area. This includes facilitating conversion by promoting the penetration of ALA through the reduction of A polyethylene barrier is used to cover the treatment area after application of a topical 5-ALA composition. The low density polyethylene barrier prevents light from reaching the treatment area. The method is characterized in that the scavenger virus is removed within 3 hours.

[0061] According to at least one embodiment, 5-aminolevulinic acid (ALA) is used for photodynamic therapy of tissue. Topical 5-ALA to facilitate the conversion of 5-ALA to protoporphyrin IX (PpIX) A method for using a composition and a low density polyethylene barrier to promote transformation of a treatment site further comprising applying heat to the

[0062] [Typical lighting fixture] 1A-1B and 2A-2B illustrate configurable 1 illustrates an embodiment of an illuminator. The illuminator includes a body 100, which includes: A plurality of individual panels (e.g., panels 10a-10e, each connected via a telescoping hinge 50) As shown in FIGS. 2A and 2B, it is preferable to have a rotatable connection. At least one side of the panel may have tabs 23 extending from both the top and bottom of the panel. The tabs 23 are positioned such that the sides of the adjacent panels are received between the tabs 23, as shown in FIG. Each panel includes an array of light emitting diodes (LEDs) 60. The number of individual LEDs arranged in a given array is not particularly limited. Other types of light sources, such as halogen lamps, may also be used. to activate specific photoactivatable agents used in therapy or diagnosis, according to the treatment The device emits light at an appropriate wavelength to

[0063] In at least one embodiment, ALA is a photoactivatable agent for the treatment of actinic keratosis. When used as a precursor, the LED array 60 preferably has a wavelength of 400 nanometers (n m) or greater, for example, about 430 nm, about 420 nm, or about 417 nm. However, the LED array 60 emits blue light between 400 and 700 nm. Green and / or red range, for example, about 625 nm to 640 nm, or for example, 635 nm For example, the LED array 60 may also emit visible light in other spectral ranges. and wavelengths of 510 nm, 540 nm, 575 nm, 630 nm, or 635 nm. Furthermore, the LED array 60 may be configured to emit light continuously. Alternatively, the LED array 60 may be configured to blink the diodes based on a predetermined interval. Furthermore, the LED array 60 may be configured to emit only one wavelength of light (e.g., blue). Alternatively, the LED array 60 may be configured to emit two or more The LED array 60 may be configured to emit light of wavelengths of The device may be configured to emit alternating blue and red light for therapeutic purposes. In this configuration, the LED array also emits red light with a wavelength of 570 to 670 nm. Good too.

[0064] In one embodiment of the present disclosure, blue light having a wavelength of about 417 nm is used at 10 mW / cm 2 of Irradiated for 1000 seconds at an intensity of 10 J / cm 2 However, the intensity is It may be increased (e.g., doubled) to shorten the treatment time. For example, the intensity may be increased to shorten the treatment time. In other embodiments, red light (e.g., red light generated by a 635 nm light-emitting diode (LED) Red light can be used for example at 10 to 75 J / cm 2 (For example, 37 J / cm 2 ) dose , for example, can be provided within 10 minutes.

[0065] ALA can be administered in the following applications, for example using a 20% solution of ALA: It can be applied using a gloved finger or spatula. ALA can also be applied by other means, such as in liquid or gel form. It can be applied beyond the area of ​​the lesion to be treated. Therefore, materials other than low density polyethylene may be used as long as they have a closure rate of more than 65%. In some applications, certain materials may be used together as long as they have a degree of occlusion greater than 75%. It can be used.

[0066] Referring again to the exemplary illuminator shown in FIGS. 1A-1B, the main body 100 of the lighting device is attached to a mounting head. The mounting head 40 can be attached to the main body 100 by a movable stand as shown in FIG. 80. This allows the user to properly install the main body 100. The stand 80 is made up of a base 81 and a vertical support 82. 2. The base 81 allows the user to move the illuminator horizontally to the appropriate position. The base may further include a plurality of wheels 87 to allow for easy movement. prevents further horizontal movement of the stand 80 once it is positioned. Additionally, the vertical support 82 can be attached to the base 8 at a pivot point 83. It may be attached to 1.

[0067] The vertical support 82 can function as a mounting structure for the main body 100 at its upper end. The connecting arm 85 is configured to allow the main body 100 to be mounted perpendicularly to the main body 100. It includes a hinge point 86 to allow movement. The stand 80 also includes a stabilizing arm 84. Once the stand 80 and the main body 100 are positioned, the stabilizing arm 84 can be attached to the main body 100. It can be attached to the body 100 to prevent unwanted movement of the body 100 during treatment. Furthermore, as shown in FIG. 3, power is supplied to the main body 100, and the user controls the main body 100 for treatment purposes. A control unit and power supply 90 is mounted on the stand 80 to allow for control of the Alternatively, the control device and power supply 90 may be mounted directly to the main body 100. To provide a cooling system for the ED array 60, one or more Alternatively, multiple fans 70 may be attached to each panel.

[0068] A controller and power supply 90 is also connected to the panels to provide the desired therapeutic effect. The control unit may adjust the power to the light source to achieve uniformity and intensity. A memory device for storing a computer program and a processor for executing the program. may be implemented as hardware, software, or a combination of both. Alternatively, each panel may have individual L on a given panel to allow fine tuning of the illuminator. It may have a dedicated control unit for adjusting the power to the ED array, which may further The LED array 60 can achieve a specific lighting effect by improving uniformity and efficiency. Each diode is individually configured to increase the intensity of light emitted from that diode in order to That's fine.

[0069] The illuminator may further include a timer included in the controller and power supply 90, which The illuminator can indicate to the user the appropriate length of exposure time for a particular treatment. , pre-stored light projections to allow the user to select the desired treatment type. The pre-stored parameters may be programmed with given parameters, e.g. The selected treatment may include pre-stored settings for duration, light intensity, and output wavelength. Based on this, the illuminator is provided with an appropriate power output to achieve the uniformity required for treatment. The lighting is automatically configured to provide the correct amount of illumination.

[0070] Alternatively, the illumination device may include a sensor that detects the size of the treatment area placed in front of the illumination device. The sensor can then determine the correct light illumination based on the sensed treatment area. The sensor determines the illuminator's adjusted position, which is manually set by the user. The detected position of the illuminator can then be used to indicate the intended treatment site. Then, based on the detected position set by the user, a specific treatment area can be selected. The appropriate dose parameters for the location can be provided.

[0071] Such adjustable illuminators allow for infinite configurations that can be tailored to the target treatment area. The configurations range from planar emitters (as shown in Figures 1B and 2B) to 1A and 2A) to a substantially U-shaped configuration. Possible lighting devices can effectively deliver uniform light intensity to a surface such as the face or scalp. In addition to the above, the adjustable illuminator also provides illumination for other parts of the patient's body, particularly the arms and legs, especially the upper extremities. The present invention provides a device that can be easily adapted to treat areas with smaller curvatures. Additionally, adjustable illuminators can also be used on larger areas such as the back or chest. It may be easily positioned to deliver a uniform light intensity to the treatment area.

[0072] The illuminator may illuminate the lesion with uniform intensity red light for a predetermined period of time. In this mode, the illuminator illuminates the lesion with uniform intensity blue light for a first predetermined period of time, and then Second, the lesion is illuminated with uniform intensity red light for a specified period of time. In this form, the illuminator targets protoporphyrin IX (P) present on the surface of the patient's skin, for example. Use low intensity (e.g., approximately 0.1 J / cm) to photobleach pIX. 2 ~About 2J / cm 2 ) The lesion is illuminated with uniform intensity blue light (e.g., 417 nm) at 1000 nm, detecting the presence of erythrocytes in the deeper layers of the patient's skin. High intensity (e.g., approximately 30 J / cm) was used to activate the PpIX present in the 2 ~About 150J / cm 2 ) to irradiate the lesion with uniform intensity red light (e.g., 635 nm), thereby irradiating the patient's skin. to avoid potential damage to the upper layers of the

[0073] Furthermore, the total light dose (J / cm 2 ) is the irradiance (mW / cm 2 ) × time (seconds) Therefore, an additional parameter that must be controlled to deliver the correct therapeutic light dose is exposure time. This can be achieved by the timer mentioned above. The timer is connected to the LED array 60 The power delivered to the device can be appropriately controlled, and the timer can be set by the physician. The data is based on 10mW / cm 2 irradiance density of, or about 9.3 to about 10. 7mW / cm 2 10 J / cm delivered from a source with an irradiance density of 2 However, the desired treatment demonstrated to produce clinically acceptable results for the area (e.g., face, scalp, extremities) The adjustable illuminator provides a clinically acceptable 10J / cm 2 Administer a light dose of For this purpose, an exposure time of 500 seconds (8 minutes 20 seconds) was used at 20 mW / cm 2 The irradiance density of In certain embodiments, lower intensity can be achieved by a longer exposure time (e.g., 10J / cm 2 Alternatively, a 1000 second exposure time for a given light level may be used. The adjustable illuminator provides 30mW / cm over the exposure time. 2 Higher power ranges such as and 10 J / cm 2 The selected light dose also provides a The dose may additionally or alternatively be administered by varying the irradiation density according to the dose.

[0074] In at least one embodiment, a heating element (heat source) may be provided. According to one embodiment, the treatment method comprises: Warm up the illuminator to release heat and place the treatment area over the illuminator. Heat induces the formation of porphyrins (e.g., photosensitive porphyrins or porphyrins) in ALA. The relationship between temperature exposure and ALA conversion is nonlinear. and the enzymatic pathway involved in the conversion is highly temperature sensitive. In this embodiment, increasing the temperature by about 2°C can increase the activity of, for example, protoporphyrin IX ( The production rate of PpIX can be approximately doubled.

[0075] Heat can be applied before or during illumination by the illuminator. For example, first, A can then be applied. The heating element can then be turned on and left for, for example, 20 to 30 minutes. Heat may also be applied to the patient's skin during the first treatment period for a heat soak. During the treatment, the treatment area may or may not be occluded. It can be heated while still in use.

[0076] Following the first treatment period, the light is applied for a second treatment period, for example, approximately 8 to 15 minutes. In at least one embodiment, the heat source can be an infrared quartz heater. In at least one embodiment, the heat source may be an infrared LED, a resistor cartridge, or the like, as described above. a small heater selected from the group including a heater, a positive temperature coefficient heater, or an infrared quartz heater; Contains at least one frame-mounted resistive tape heater or multiple heaters By-products from one or more operating mechanisms of ambient heat or lighting devices in clinical settings Apart from heat, heat may also be intentionally generated and directed to the area to be treated.

[0077] [Administration of 5-ALA] As mentioned above, during photodynamic therapy, the patient receives a total dose of light over the course of treatment. The total light dose is J / cm 2 irradiance (mW / cm) over time (seconds) 2 ) Next, the above-mentioned adjustable lighting device can be used with ALA. This application describes an example method for treating precancerous lesions, such as actinic keratosis, with photodynamic therapy.

[0078] Essentially anhydrous ALA is mixed with a liquid diluent immediately prior to use. Aminolevulinic acid (ALA) hydrochloride, an endogenous 5-carbon aminoketone The chemical name for ALA HCl used in the embodiments disclosed herein is: 5-amino-4-oxopentanoic acid hydrochloride (molecular weight = 167.59). ALA H Cl is highly soluble in water. The structural formula of ALA HCl is as follows: [ka]

[0079] In at least one embodiment, ALA is contained inside the first ampoule in powder form. In the first ampoule, the amount of ALA as a dry solid is 300-400 mg. In at least one embodiment, the amount of ALA HCl is 354 mg. The second ampoule contains the solution vehicle. The second ampoule contains 1.5 mL of the solution vehicle. The solution vehicle may be an alcohol (i.e., an alcohol as defined by the United States Pharmacopeial Convention). Cole) (ethanol content = 48% v / v), water, laureth-4, isopropyl alcohol and polyethylene glycol.

[0080] The first and second ampoules are housed inside a plastic applicator. and the second ampoule is inserted, for example by applying finger pressure or by applying pressure to the ampoule. The ampoule can be crushed inside a device configured to add The ALA contained in the first ampoule was then mixed with the solution contained in the second ampoule. The ampoule is then brought into contact with the applicator and dissolved in the solution vehicle. You may shake the mixture to disperse and dissolve the powdered ALA in the water. The solution should be applied to the patient within 2 hours of preparation.

[0081] In some embodiments, ALA is provided as a ready-to-use solution or as a solution, gel, or cream. The composition may also be provided in a form such as a reconstitution powder for a cream or lotion formulation. In this form, the composition contains 5-aminolevulinic acid hydrochloride in an amount of from about 10% to about 10% by total weight of the composition. In an amount of about 70% w / w, preferably about 20% to about 50% w / w of the total weight of the composition, more preferably Preferably, it is present in an amount of about 30% to about 40% w / w of the total weight of the composition.

[0082] In one embodiment, ALA can be applied as a topical composition at a concentration of 20%. In at least one embodiment, a point applicator is used to apply the ALA mixture topically. Apply ALA to the lesion and allow it to come into contact with the injured surface, so that the injured surface is moistened almost uniformly with ALA. As used herein, the terms "substantial" and "substantial" are used interchangeably. The term (ly) refers to any value within a range defined by a maximum variation of ±15 from the mean value. However, in other embodiments, ALA may be measured by hand (i.e. The ALA is first placed on the practitioner's gloved fingertips, and then applied to the area to be treated. It may be applied by gently tapping it in or with a tool such as a spatula.

[0083] [Barrier obstruction] Following application of ALA to the area to be treated (i.e., the lesion), the area to be treated is covered with polysorbate 80. For example, as shown in FIG. The exemplary embodiment shown in FIG. Although the barrier 200 is depicted surrounding the barrier 300, in certain embodiments, the barrier It should be understood that the catheter 200 may occlude only a portion of the region 300. , the barrier 200 is substantially circular (e.g., forming a sleeve around the portion 300). Although depicted as cylindrical, the barrier 200 can have a variety of shapes.

[0084] Barrier 200 is shown in FIGS. 3 and 4 as part 30 for purely ease of illustration. 0. However, in at least one embodiment , the barrier 200 is attached to the portion 300 so that there is substantially no gap between the barrier 200 and the portion 300. 00. The polyethylene barrier has electrostatic properties that provide a sticky adhesion effect. , which allows the barrier to remain close to the surface of the skin for an extended period of time. Such effects are most pronounced when the skin is moistened with the topical solution, i.e., is first wetted with a topical solution, and then the barrier 200 is placed directly over the wet treatment area. This can be particularly enhanced when applied indirectly.

[0085] In at least one embodiment, a medical professional may provide instructions regarding the application or use of the barrier 200. In some embodiments, one or more medical professionals may provide instructions to the patient (subject of treatment). A practitioner may provide and / or receive instructions. In the present specification, the medical professional may be, for example, but is not limited to, a pharmacist. The healthcare provider may monitor the condition before, during, and after application of the barrier 200, e.g., Patients may be instructed regarding prohibited and permitted activities after the procedure. In embodiments, the health care professional may recommend that the patient undergo treatment within a predetermined period of time from application of the topical composition prior to phototherapy. The subject may be instructed to place the barrier 200 over the treatment area. In this embodiment, the medical professional instructs the subject to cover and maintain the treatment area with the barrier 200. In some embodiments, the subject may be instructed to cover the treatment area. Alternatively or additionally, in at least one embodiment, after a period of time, such as 3 hours. The healthcare professional may be instructed to remove the barrier 200. In some embodiments, the healthcare professional The person can receive instructions, for example, from the kit. may be provided to the professional and / or the patient. Furthermore, in some embodiments The healthcare professional may apply and administer the barrier 200 at the direction and / or with the patient's consent. may be added and / or removed.

[0086] Experimental results show that using low density polyethylene (LDPE) for Barrier 200 It was confirmed that this resulted in a lower water loss rate and better occlusion. The embodiment with the polyethylene barrier 200 was particularly effective for photodynamic therapy.

[0087] FIG. 5 shows the evaporative water loss rate for several materials A through E, as summarized in Table 1 below. The LDPE barrier retains water, allowing ALA to penetrate more easily into the area to be treated. It has been found to be particularly conducive to this. [Table 1]

[0088] The measured water loss rates shown in FIG. 5 (and FIG. 7 below) were measured using the barrier 200 on the dorsal forearm. The transepidermal water loss rate was measured before and after wearing the device for 3 hours. ) moisture loss is at least 2% in a controlled environment with a relative humidity of less than 50% and a temperature of 19-22°C. After a 5-minute adaptation period, measurements were taken on approximately 30 subjects. Such measurements are shown in Figure This corresponds to the bar labeled "Front" in Figures 5 and 7. The measurements were performed using DermaLab® Transepidermal Water. Loss probe (Cortex Technology of Hadsund, Denmark) A calibrated RG1 evaporometer system (Cyc., Broomall, PA) was used. The test was performed using a meter (manufactured by berDERM).

[0089] The vapor pressure gradient estimation method was used. Probes measured temperature and relative humidity at fixed points along the skin. and the value equivalent to evaporation water loss (gm / m 2 hr) can be derived. Sampling is The baseline measurements were taken at 4 pulses / second, before applying the barrier 200 to the stratum corneum. The barrier properties of the stratum corneum for each subject are shown. Measurements were taken 3 hours after applying Barrier 200. The values ​​indicate the barrier properties of the materials shown in Tables 1-2. Such measurements are 5 and 7 correspond to the bar graph labeled "After." Each barrier 200 was cut to cover a 5 cm test site area. For testing purposes, the barrier 2 The area of ​​the subject's skin without the barrier 200 was fixed with hypoallergenic medical tape. The measurement was carried out as a control.

[0090] FIG. 6 illustrates the degree of occlusion for several materials according to at least one embodiment. Specifically, Figure 6 shows the degree of occlusion for the materials shown in Figure 5, summarized in Table 1 above. Evaporative water loss when subjects wore Barrier 200 compared to the rate of evaporation of Sline As shown in Figure 6, the barrier material E reduces the rate of water loss from the skin surface. It blocks more than 85% of water vapor from evaporating. In one embodiment, it blocks more than 65% of water vapor. Polymer barriers that provide greater than 75% protection are particularly useful for photodynamic therapy. Polymer barriers with a degree of occlusion that can be achieved are particularly effective in photodynamic therapy. The higher occlusive properties of LDPE materials may help minimize transepidermal water loss from the treatment area. This promotes the penetration of 5-ALA into the tissue. The tissue is the skin of the subject, especially the stratum corneum, or other tissue. It may also be woven.

[0091] Like Material E, Materials B and C prevent approximately 75% of water vapor from evaporating from the skin surface. On the other hand, materials A and D are considered to be semi-occlusive barriers.

[0092] FIG. 7 illustrates the evaporative water loss rates of several materials according to at least one embodiment. Specifically, Figure 7 shows the results for several materials W to Z and E, as summarized in Table 2 below. Barrier Material E is the same material shown in Table 1 and discussed above. Materials W to Z contained LDPE and polyvinylidene chloride. [Table 2]

[0093] FIG. 8 illustrates the degree of occlusion for several materials according to at least one embodiment. Specifically, Figure 8 shows the degree of occlusion for the materials shown in Figure 7, summarized in Table 2 above. In particular, materials E, W, and Y were significantly more occlusive than materials X and Z. and Z only block about 35% of the water vapor from evaporating and are therefore essentially semi-occlusive. Material E, due to its flexible nature, easily wraps around the treatment area, which helps retain moisture. It can be promoted.

[0094] FIG. 9 is a table containing baseline water loss data for the materials referenced in FIGS. 5 and 6. In particular, Figure 9 shows the average and standard deviation values ​​for each of the materials A to E shown in Table 1. FIG. 10 provides baseline measurements for each subject. FIG. 11 is a table containing moisture loss data for materials after 3 hours of wear time. and a table containing occlusion data for the materials referenced in Figures 7 and 6. FIG. 13 is a table containing baseline water loss data for the materials referenced in FIG. 7 and and a table containing moisture loss data after 3 hours of wear time for the materials referenced in FIG. FIG. 14 is a table containing occlusion data for the materials referenced in FIGS.

[0095] As mentioned above, the barrier 200 is positioned over at least a portion of the area to be treated, for example, the back of the hand. In some embodiments, and particularly For larger treatment areas, such as the forearm, additional structure may be provided to secure the barrier 200 in place. The low density polyethylene wrap can be used to cover the dressing 210 shown in FIG. In one embodiment, the dressing 210 is -Surg, manufactured by Derma Sciences Inc., Plainsboro, Jersey Surgical nets such as the ilast® tubular elastic dressing retainer. The dressing 210 is a tubular elastic stretchable material designed to function as a secondary dressing. It can be a net, which can be applied with relatively weak pressure and without adhesive tape to create a barrier 20 0 in place. That is, the secondary dressing 210 adheres to the barrier 200. A slight compressive pressure can be applied. The dressing 210 is placed over the barrier 200 and In some embodiments, the secondary drain may be a sleeve that fits around the A dressing and / or tape may be applied. In this case, treatment may be carried out according to the exemplary implementations described below.

[0096] [Treatment Protocol] Once ALA is applied to the upper limbs, the upper limbs should be occluded for no more than 3 hours before phototherapy. For example, a limb can be occluded for 2 to 3 hours. As mentioned above, ALA , minimal to mid-face, scalp, or upper extremities when used as part of photodynamic therapy It is a porphyrin precursor that can treat a variety of conditions, including actinic keratosis of any thickness. Thus, in at least one embodiment, a portion of the face, a portion of the scalp, or The entire upper limb or part or all of the upper limb can be covered with an occlusive barrier. Cut.

[0097] Treating facial and scalp lesions without applying an occlusive barrier after applying ALA When 5-ALA was used to treat psoriasis, the formation of photosensitive porphyrins and photosensitization of the treated lesions were observed. The lesions were observed by illuminating the area between 14 and 18 hours after administration of ALA. The illuminator illuminates the lesion with, for example, blue light of uniform intensity for a predetermined period of time. According to a preferred treatment, the visible light has a nominal wavelength of 417±5 nm. do.

[0098] When ALA is used to treat lesions on the upper extremities, the illumination time should be adjusted to ensure adequate occlusive barrier protection. When used on the face or scalp, the time can be significantly shorter than that on the face or scalp. (1) The time between application of ALA to the upper limb and occlusion and (2) illumination of the upper limb is approximately 3 hours. If the treatment site is occluded for more than 3 hours, irritation may occur to the skin where ALA is applied. Excessive irritation can cause itching, wheals, and redness, including symptoms that persist after a treatment session has ended. This may be indicated by redness or other symptoms. In particular, excessive irritation may be caused by, for example, Adverse skin events such as scaling, crusting, ulceration, rash, crusting, tenderness, and itching 3 hours is characterized by the reduction of such excessive stimulation while maintaining the therapeutic effect. This represents the nominal maximum time that the upper limbs should be occluded after application of ALA to prevent ulcerative colitis. and clearance of actinic keratosis lesions 12 weeks after PDT. The time between application of ALA to other body parts (other than the face, scalp, and upper limbs) and illumination was 3 It may be time.

[0099] Once the occlusion barrier 200 is removed, light treatment as described above, e.g., 10 J / cm 2 For example, red and / or blue light can be used to illuminate the Once applied, A200 is removed within 3 hours and 10 J / cm 2 to deliver a dose of Light intensity: 10J / cm 2 The exposed area may be irradiated with blue light so that the 2 ~75J / cm 2 In some embodiments, the treatment may be performed with red light at a dose of Light may be applied while the site is still occluded. Light and heat may be applied while the tissue is still occluded.

[0100] To treat facial lesions, the area to be treated should be between 2 and 4 inches from the surface of the illuminator. The patient's nose is more than 2 inches from the surface of the illuminator, and the forehead and cheeks are more than 4 inches from the surface. The illuminator can be positioned as described above so that the patient's face is in the side of the patient's face. The ears must be at least two inches from the surface of the lighting fixture.

[0101] To treat scalp lesions, the area to be treated should be within 2 to 4 inches of the surface of the illuminator. The patient's scalp should be no less than 2 inches from the surface of the illuminator and no more than 4 inches from the surface. The side of the patient's face and the patient's ears can be covered by the illuminator. The device must be at least 2 inches from the surface.

[0102] To treat lesions on the upper extremities, such as the back of the hand or the forearm, the area to be treated must be illuminated with an illumination device. You can position such a lighting device so that it is between 2 and 4 inches from the surface of the Equipment (e.g., tables) can be positioned to increase patient comfort and stabilize the area to be treated. It may also be used to support the upper extremities during phototherapy.

[0103] Optimizing patients with multiple actinic keratosis (AK) lesions on the upper extremities by localized occlusion Systemic effects of topically administered ALA and protoporphyrin IX (PpIX) Two open-label pharmacokinetic studies were conducted to assess potential exposure. According to an embodiment, a topical composition of 20% w / w 5-aminolevulinic acid (ALA) is The drug was applied topically via an applicator directly to the patient's upper extremity, followed by a 3-hour incubation period. After the incubation period, the area was covered with an occlusive polyethylene film. Each subject received 10 mW / cm 2 Sent at 10J / cm 2 of visible blue light Ta.

[0104] The first of the two studies enrolled a total of 29 participants. Each eligible subject had at least one upper extremity treatment site. At least six Grade 1 or Grade 2 AK lesions and at least one in the other upper extremity treatment site There were also 12 grade 1 or grade 2 AK lesions. The treatment site designated at baseline was followed up until week 4 after treatment. Extensors of both distal upper limbs (i.e., dorsal hand / forearm) as defined in the protocol A total of 14 participants were enrolled in the second of the two studies. At least six Grade 1 or Grade 2 AK lesions in one upper extremity treatment site and at least 12 Grade 1 or Grade 2 AK lesions in the other upper extremity treatment site Men who had been pregnant and non-pregnant women were eligible for the study.

[0105] Topical application of ALA to the upper extremities resulted in lower ALA and PpIX than intravenous and oral administration The method according to at least one embodiment resulted in a systemic exposure to about 35 This involves applying up to two topical solution compositions containing 4 mg of ALA. The liquid administration was compared with intravenous and oral administration at a dose of approximately 100 mg of ALA. As mentioned above, the strength of 5-ALA was approximately 20% by weight. The mean plasma concentration of ALA (C max ) values. "C" max The term "maximum observed" refers to the actual values ​​measured after application of the test drug. Refers to the observed plasma concentration.

[0106] In particular, after topical application, the geometric mean maximum plasma concentration was approximately 98 ng / mL at a median of 2 hours after application. and the geometric mean area under the curve (AUC t ) was 577ng*h. After baseline correction, the geometric mean maximum plasma concentrations of ALA were 2.0 times higher than the median. The mean mean AUCt was 282 ng*h / mL. In the form of a topical solution, when applied at a strength of about 20% by weight, the The geometric mean area under the curve (AUCτ) values ​​for ALA less than r / mL are shown. AUC t The term "" refers to the plasma concentration- up to the final quantifiable / non-negative plasma concentration It refers to the area under the time curve.

[0107] In another study, after topical application, the geometric mean maximum plasma concentration was approximately 61% at a median of 2 hours after application. ng / mL and geometric mean AUC t The mean blood pressure was 727 ng*h / mL, with a variation of approximately 30%. After baseline correction, the geometric mean maximum plasma concentration of 5-ALA was approximately 152% of the median at 2 h. 39 ng / mL, geometric mean AUC t The mean blood pressure was 182ng*h / mL. The estimated bioavailability of 54 mg of ALA after topical application was approximately 1.0%. In one embodiment, the systemic bioavailability following topical administration of 354 mg of ALA HCl was The bioavailability is less than about 5%. The term AUC refers to the rate and extent of absorption. τ and C max Depending on the value is determined.

[0108] In accordance with at least one embodiment, 4 to 15 patients with mild to moderate actinic keratosis are treated with In a multicenter, randomized, parallel-group, assessor-blinded, and vehicle-controlled study of 269 patients Photodynamic therapy was performed to treat the lesions on the upper extremities. More specifically, it was located on the back of the hand and / or on the forearm between the elbow and the base of the fingers. The age range was 45-90 years (mean age 68 years), and 90% were Fitzpatrick Ski n Type I, II, or III. Subjects were randomized 1:1 to treatment. Each subject was assigned to apply ALA to the back of one hand or the forearm lesion, and then The hands or the back of the back were then occluded with a low-density polyethylene barrier for 3 hours. After removing the ethylene barrier, 10 J / cm 2 A dose of blue light of 10mW / cm 2 Irradiate with If damage remained at the treated site, treatment was repeated after 8 weeks.

[0109] Complete clearance (i.e., resolution of actinic keratosis) occurred in 31% (all) of subjects receiving 5-ALA. This was achieved by 42 of 135 subjects. compared with 13% (i.e., 17 of 134 subjects) of subjects who received the liquid vehicle alone. Complete clearance was achieved 12 weeks after initial treatment compared to the control group. Among the subjects who underwent steroid therapy, the recurrence rate was 58% at 12-month follow-up. The recurrence rate was shown to be %. Complete resolution was achieved 12 weeks after treatment. Subjects with at least one recurrent lesion during the 12-month follow-up period after the 12-week evaluation corresponds to the ratio of

[0110] Thus, the present disclosure provides a method for photodynamically treating a surface of a patient and, as part of the treatment, treating the patient's skin. The present invention provides a method for occluding skin, including the treatment of actinic keratosis, acne, photodamaged skin, and cancer. Patients may be exposed to light to treat rash, warts, psoriasis, or other skin conditions. do.

[0111] Although the specification contains details of certain specific implementations, these are not intended to be limiting unless otherwise specified. should not be construed as limitations on the Certain features described herein in the context of separate implementations should be construed as Conversely, features described in the context of a single embodiment may also be combined in a single implementation. The various features described may be used in multiple embodiments separately or in any suitable subcombination. Furthermore, features may be implemented in any manner not described above as working in particular combinations. Although it may be possible to claim this initially, one or more of the combinations claimed Multiple features can be extracted from the combination, and the claimed combination is a partial combination. The invention can be directed to the alignment or transformation of the structure.

[0112] The configurations and arrangements of the lighting systems shown in the various exemplary embodiments are exemplary only. It is important to note that this is merely a guide and does not limit its nature. All changes and modifications that come within the spirit and / or scope of the disclosed embodiments are protected. Of course, some features may not be necessary, and various features may be Embodiments lacking such features are considered to be within the scope of this disclosure, the scope of which is limited by the claims. When the word "some" is used, the item is The term "item" may include the item and / or the entire item, provided that the item is not part of the "item" and / or the entire item.

[0113] Additional advantages and modifications will readily occur to those skilled in the art. Accordingly, the present invention In broader aspects, the specific details and representative apparatus and methods shown and described herein Therefore, what is claimed is within the scope of the appended claims and their equivalents. Various modifications may be made without departing from the spirit and scope of the general inventive concept as defined herein. Positives can be added. [Explanation of symbols]

[0114] 10a~10e Panels 23 tabs 40 Mounting Head 50 Telescopic hinge 60 LED array 70 fans 80 Movable Stand 81 Base 82 Vertical support 83 Pivot Point 84 Stabilizing Arm 85 connecting arm 86 Hinge Point 87 wheels 90 Control Devices and Power Supplies 100 units 200 Barrier 210 Dressing materials 300 parts

Claims

1. 5-aminolevulinic acid (ALA) applied to tissue as a treatment site for photodynamic therapy A topical composition comprising: The topical composition is applied prior to phototherapy and within a predetermined time the treatment area becomes a low density pigment. and after the low-density polyethylene barrier is removed, the treatment area is covered with a polyethylene barrier. A topical composition characterized in that the phototherapy is administered to the affected area.

2. 10. The topical composition of claim 1, wherein the predetermined time period is 3 hours or less.

3. 2. The topical composition of claim 1, wherein the concentration of ALA is 20% by weight.

4. 5-aminolevulinic acid (ALA) applied to tissue as a treatment site for photodynamic therapy an occlusive dressing comprising a low density polyethylene barrier for covering a topical composition comprising And, Applying the topical composition prior to phototherapy and then applying the occlusive dressing for a predetermined period of time. A material covers the treatment area, and the occlusive dressing is placed over the treatment area before the light therapy is administered to the treatment area. An occlusive dressing characterized in that the occlusive dressing is removed.

5. 5. The occlusive dressing of claim 4, wherein the predetermined time period is 3 hours or less.

6. 5. The method of claim 4, wherein there is no gap between the low density polyethylene barrier and the treatment area. Occlusive dressings.

7. a low density polyethylene barrier; a topical composition containing 5-aminolevulinic acid (ALA); tt.

8. 10. The apparatus of claim 7, further comprising an illuminator configured to emit light of a uniform intensity. tt.

9. and a netting configured to secure the low density polyethylene barrier in place. The kit of claim 7, comprising:

10. 10. The device of claim 7, further comprising a heater configured to direct heat to the treatment site. tt.

11. At least one sensor configured to determine the size of the treatment area or the position of the illuminator. The kit of claim 8 , further comprising a sensor.

12. a controller configured to store preprogrammed dosing parameters; The kit according to claim 8 .

13. a topical composition of 5-aminolevulinic acid (ALA); low-density polyethylene to cover the topical composition that is applied to the tissue at the treatment site; a photodynamic therapy material comprising: The low density polyethylene barrier is applied after the topical composition is applied prior to phototherapy. The treatment area is covered for a predetermined period of time, and the low density polyethylene barrier adheres to the treatment area. A photodynamic therapy material that is removed before phototherapy is administered.

14. 14. The photodynamic therapy material of claim 13, wherein the predetermined time period is 3 hours or less.

15. Tissue penetration of topical 5-aminolevulinic acid (ALA) compositions for photodynamic therapy 1. Use of a low density polyethylene barrier to promote The low density polyethylene barrier minimizes transepidermal water loss from treatment. The low density polyethylene barrier facilitates the penetration of the ALA into the skin. The cloth is used to cover the treatment area afterwards, and the cloth is used beforehand to allow light to be applied to the treatment area. The use of a low-density polyethylene barrier characterized by being removed from the treatment site within 3 hours. For.

16. Topical compositions and low-density 5-aminolevulinic acid (ALA) for photodynamic therapy of tissues - Patent Application 20070122997 Use of a high-strength polyethylene barrier, The low density polyethylene barrier minimizes transepidermal water loss from the treatment area. Thus, the penetration of the ALA into the tissue is facilitated, and the low-density polyethylene barrier It is used to cover the treatment area after application of a topical composition of ALA, and to prevent light from reaching the treatment area. The low density polyethylene barrier is placed within 3 hours of the treatment site to allow irradiation. A topical composition of 5-aminolevulinic acid (ALA) and a low-density polymeric polymer, characterized by removing Use of a polyethylene barrier.

17. While the low density polyethylene barrier covers the treatment area, heat is applied to the treatment area.

16. Use of a low density polyethylene barrier according to claim 15.

18. 17. The method of claim 16, further comprising applying a compressive pressure to the low density polyethylene barrier. Use of the above-described topical 5-aminolevulinic acid (ALA) composition and a low-density polyethylene barrier 。

19. Protoporphyrin IX (Pp) from 5-aminolevulinic acid (ALA) for photodynamic therapy IX) Use of a low density polyethylene barrier to facilitate conversion to The low density polyethylene barrier is adapted to deliver the topical ALA composition to tissue for photodynamic therapy. facilitating the transformation by promoting tissue penetration of the substance; The low density polyethylene barrier minimizes transepidermal water loss from the treatment area. This promotes the penetration of ALA into the tissue, The low-density polyethylene barrier is attached to the treatment area after application of the ALA topical composition. and a light source is used to cover the treatment area to allow light to be irradiated onto the treatment area.

1. Use of a low density polyethylene barrier characterized in that it is removed from a surface of the device within 3 hours.

20. Protoporphyrin IX (Pp) from 5-aminolevulinic acid (ALA) for photodynamic therapy IX) A topical composition of ALA and a low-density polyethylene barrier to facilitate conversion to Use, The low density polyethylene barrier minimizes transepidermal water loss from the treatment area. thereby facilitating the conversion by promoting the penetration of the ALA into tissues, The low-density polyethylene barrier is attached to the treatment area after application of the ALA topical composition. and a light source is used to cover the treatment area to allow light to be irradiated onto the treatment area. A topical composition of ALA and low-density polyethylene characterized by being removed from the skin within 3 hours. Use of barriers.

21. 5-aminolevulinic acid (ALA) for photodynamic therapy in subjects in need thereof 1. Use of a topical composition comprising: The subject is protected from application of the topical composition prior to phototherapy by a low density polyethylene barrier. You will be instructed to cover the treatment area for a specified period of time from The low-density polyethylene barrier is removed and the phototherapy is administered to the treatment area.

20. The use of a topical composition comprising:

22. 3. The method of claim 2, wherein the low density polyethylene barrier is removed from the treatment site within 3 hours.

1. Use of the topical composition according to claim 1.

23. Patent application title: CLOSED PHOTODYNAMIC TREATMENT SYSTEM COMPRISING A LOW-DENSITY POLYETHYLENE BARRIER FOR PHOTODYNAMIC TREATMENT OF A SUBJECT IN NEED OF PHOTODYNAMIC TREATMENT 1. Use of an occlusive dressing, comprising: The photodynamic therapy involves applying a topical composition containing 5-aminolevulinic acid (ALA) to the treatment area. applying a The subject is protected from application of the topical composition prior to phototherapy by a low density polyethylene barrier. and instructing the user to cover the treatment area for a predetermined period of time from The low-density polyethylene barrier is removed and the phototherapy is administered to the treatment area.

1. Use of an occlusive dressing, characterized in that

24. 3. The method of claim 2, wherein the low density polyethylene barrier is removed from the treatment site within 3 hours.

3. Use of the occlusive dressing material according to claim 3.

25. 5-aminolevulinic acid (ALA) applied to tissue as a treatment site for photodynamic therapy 1. A method of using a low density polyethylene barrier to cover a topical composition comprising: 、 covering the topical composition applied to the tissue as the treatment site; The low density polyethylene barrier is maintained at a predetermined time from application of the topical composition prior to phototherapy. the low density polyethylene barrier covers the treatment area and prevents the light therapy from reaching the treatment area. and removing the coating before applying the coating to the substrate.

26. 26. The method of claim 25, wherein the predetermined time is 3 hours or less.

27. Enhanced tissue penetration of topical 5-aminolevulinic acid (ALA) compositions for photodynamic therapy A method of advancing topically applying ALA to the treatment area to be treated with photodynamic therapy; After the ALA is applied to the treatment area, it minimizes transepidermal water loss from the treatment area. To minimize the risk of irritation, the treatment area is covered with a low-density polyethylene barrier prior to phototherapy. 、 Within 3 hours, the low-density polyethylene barrier is removed and the treatment area is then irradiated with light. and

28. The low-density polyethylene barrier prevents excessive irritation while maintaining therapeutic efficacy.

28. The method of claim 27, wherein the treatment is removed from the treatment area within 3 hours.

29. Enhanced tissue penetration of topical 5-aminolevulinic acid (ALA) compositions for photodynamic therapy A method of advancing topically applying ALA to the treatment area to be treated with photodynamic therapy; After the ALA is applied to the treatment area, it minimizes transepidermal water loss from the treatment area. To minimize the risk of irritation, the treatment area is covered with a low-density polyethylene barrier prior to phototherapy. , including The method wherein the treatment area is on the hand or forearm.

30. The low density polyethylene barrier was removed from the treatment area within 3 hours, and then J / cm ２ 28. The method of claim 27, wherein the treatment area is irradiated with blue light at a light intensity of

31. The low density polyethylene barrier is removed from the treatment area, and then 10 to 75 J / cm ２ 30. The method of claim 29, wherein the treatment area is irradiated with red light at a light intensity of

32. 2. The method of claim 1, wherein the maximum plasma concentration of ALA after application of the ALA is less than about 110 ng / mL.

7. The method according to claim 7.

33. A method using 5-aminolevulinic acid (ALA) and a low-density polyethylene barrier. 、 contacting the treatment area with a composition comprising ALA to moisten the treatment area; And, After wetting the treatment area, cover the wet treatment area with the low density polyethylene barrier. And, removing the low density polyethylene barrier to expose the treatment area; 10 J / cm ２ and illuminating the exposed treatment area with an illuminator to irradiate the area with a dose of blue light. and irradiating.

34. and removing the low-density polyethylene barrier within three hours after the treatment area is covered. The method according to claim 33.

35. The treatment area may be positioned between 2 inches and 4 inches from the surface of the illuminator.

34. The method of claim 33, further comprising:

36. 30. The method of claim 29, wherein the treatment area is the dorsal surface of the hand.

37. 30. The method of claim 29, wherein the treatment site is the dorsal surface of the forearm.

38. Protoporphyrin IX (Pp) from 5-aminolevulinic acid (ALA) for photodynamic therapy IX) A method of using a low density polyethylene barrier to facilitate conversion to To facilitate the conversion by promoting penetration of the ALA topical composition into tissues, covering the treatment area with said low density polyethylene barrier; The low density polyethylene barrier minimizes transepidermal water loss from the treatment area. This promotes the penetration of the ALA, The low density polyethylene barrier protects the treatment area after application of the ALA topical composition. and covering the treatment area to allow light to be irradiated onto the treatment area. The method is characterized in that the substance is removed within 3 hours.

39. 39. The method of claim 38, further comprising applying heat to the treatment area to promote the conversion. How to post.

40. Protoporphyrin IX from 5-aminolevulinic acid (ALA) for photodynamic therapy of tissues ALA topical composition and low-density polyethylene barrier to facilitate conversion to (PpIX) A method of using A, The low density polyethylene barrier covers the treatment area, and the low density polyethylene barrier Promoting the penetration of the ALA by minimizing transepidermal water loss from the treatment area. facilitating said conversion by The low density polyethylene barrier protects the treatment area after application of the ALA topical composition. Used to cover, The low density polyethylene barrier is formed on the surface of the treatment area to allow light to reach the treatment area. The method is characterized in that the treatment is removed from the treatment area within 3 hours.

41. 41. The method of claim 40, further comprising applying heat to the treatment area to promote the conversion. How to post.

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