Dye phototherapy agent, dye phototherapy filter, dye phototherapy needle, and dye phototherapy device

Abstract

To provide a pigment phototherapy agent and a pigment therapy device that are concentrated and taken up by the target tissue, and that allow for targeted treatment of the target tissue through light irradiation. [Solution] A pigment phototherapy agent according to one embodiment of the present invention is a pigment phototherapy agent comprising at least indocyanine green and a local anesthetic containing lidocaine, characterized in that when added to a target tissue, the pigment phototherapy agent is taken up by the tissue, and when the tissue is irradiated with excitation light from the outside, the pigment phototherapy agent thermally denatures the tissue with the excitation light.

Description

[Technical Field]

[0001] The present invention relates to a pigment phototherapy agent, a pigment phototherapy filter, a pigment phototherapy needle, and a pigment phototherapy apparatus. [Background technology]

[0002] Traditionally, a method of treating cancers such as lung cancer, stomach cancer, uterine cancer, and skin cancer by irradiating the affected area with visible light using organic dyes such as porphyrins and phthalocyanines as photoreceptors has been proposed, known as photodynamic therapy (PDT). In addition, photodynamic hyperthermia therapy (PHT) using indocyanine green (ICG) has also been proposed for cancer treatment.

[0003] As an example of PDT, Patent Document 1 discloses a photodynamic therapy using an aqueous liquid composition in which ultrafine particles of an inorganic oxide semiconductor, on which a monolayer of an organic dye is supported on the surface, are dispersed in water.

[0004] Patent Document 1 describes a mechanism for providing a cell-killing effect by utilizing an organic color that allows electron injection from the photoexcited state of the organic color into an oxide semiconductor on which the organic color is surface-supported, thereby generating reactive oxygen species through photosensitized electron transfer of the color. For example, electrons are injected from the photoexcited color into the conduction band of the semiconductor, generating electrons in the conduction band with chemical reducing power from the semiconductor particles. These then transfer to chemical species such as oxygen molecules present in the external solution, generating active radical species. Furthermore, the oxidized form of the color oxidizes chemical species in the external solution. For example, it reacts with hydroxide ions in water to generate OH radicals. Thus, it is disclosed that a cell-killing effect is provided by the generation of chemically active species through the photochemical electron transfer reaction of the color.

[0005] In photodynamic therapy using an aqueous liquid composition in which ultrafine particles of an inorganic oxide semiconductor supporting a monolayer of an organic dye are dispersed in water, examples of organic dyes include cyanine-based, merocyanine-based, oxonol-based, xanthene-based, squalylium-based, polymethine-based, coumarin-based, riboflavin-based, and perylene-based organic dyes, as well as complex dyes such as Ru complexes, metal phthalocyanine derivatives, metal porphyrin derivatives, and chlorophyll derivatives, and organic dyes centered on coumarin.

[0006] Furthermore, Patent Document 1 cites artificial diffuse light sources, lasers, halogen lamps, xenon lamps, metal halide lamps, LEDs, and organic EL elements as examples of light irradiation used in photodynamic therapy, and lists metal halide lamps as particularly preferred light sources because they have a strong radiant intensity spectrum in the visible light. In the photodynamic therapy described in Patent Document 1, an aqueous liquid composition of the drug is administered to the affected area by subcutaneous injection, intravenous injection, surgical means, etc., and after a period in which the subject is kept in an environment where they are not exposed to light, the affected area is irradiated with light.

[0007] The photodynamic therapy described in Patent Document 1 is applicable to cancer cells, atherosclerotic lesions, rheumatoid arthritis lesions, intractable warts, acne vulgaris, papillomavirus, and other skin cancers, with basal cell carcinoma, Bowen's disease, and actinic keratosis being preferred.

[0008] As an example of PHT, Patent Document 2 discloses a technique using copolymers as photosensitizers in photothermal therapy. Patent Document 2 discloses that when cells incorporating a copolymer of quaternary ammonium cation and indocyanine green are irradiated with a near-infrared laser, the ambient temperature rises, apoptosis is induced immediately after irradiation, and a cancer cell killing effect is observed. Patent Document 2 exemplifies the near-infrared laser used under conditions of a wavelength of 808 nm, an intensity of 1.0 W / cm, and irradiation for 5 minutes. [Prior art documents] [Patent Documents]

[0009] [Patent Document 1] Japanese Patent Publication No. 2006-034375 [Patent Document 2] Japanese Patent Publication No. 2024-165437 [Overview of the project] [Problems that the invention aims to solve]

[0010] Patent Document 1 discloses an example of photodynamic therapy in which a photodynamic agent was prepared by adding sodium phosphate and potassium phosphate to an aqueous solution containing pigment-adsorbing nanoparticles, which have brookite-type crystalline titanium dioxide nanoparticles on their surface and anthocyanins extracted from purple sweet potato adsorbed onto them. This agent was then added to mouse thymic lymphoid tumor cells, and the cells were irradiated with light having an emission spectrum of 550-750 nm using a metal halide lamp for one hour, resulting in a cell-killing effect. However, it is difficult to effectively target only mouse thymic lymphoid tumor cells with the photodynamic agent.

[0011] Furthermore, Patent Document 1 discloses another example in which Fast Green FCF, a food additive, is used instead of anthocyanin. However, similar to the former example, it was difficult to add the photodynamic therapy agent only to the treatment site, and it was difficult to enhance the cell-killing effect.

[0012] Patent Document 2 discloses that in photothermal therapy, using a copolymer of quaternary ammonium cation and indocyanine green as a photosensitizer increases the ambient temperature and induces apoptosis immediately after irradiation, resulting in a cancer cell killing effect. Although photosensitizers tend to accumulate in tumors, it has been difficult to add them to any target tissue. Furthermore, while a cell-killing effect against mouse mammary cancer cells (4T-1 cells) has been confirmed through apoptosis induction in cancer cells, therapeutic effects on tissues other than mouse mammary cancer cells have not been confirmed.

[0013] The present invention has been made in view of the above circumstances, and aims to provide a pigment phototherapy agent, a pigment phototherapy filter, a pigment phototherapy needle, and a pigment phototherapy device that allow the pigment therapy agent to be concentrated and taken up at the target treatment site, and that enable targeted thermotherapy to the target cells by light irradiation. [Means for solving the problem]

[0014] A first embodiment of the present invention is a pigment phototherapy agent comprising at least indocyanine green (hereinafter referred to as), characterized in that when added to a target tissue, the pigment phototherapy agent is taken up by the tissue, and when photon energy is irradiated to the tissue from the outside as excitation light, the pigment phototherapy agent thermally denatures the tissue with the excitation light.

[0015] A second embodiment of the present invention is a dye phototherapy agent characterized in that, in the first embodiment of the dye phototherapy agent, the photon energy as excitation light includes at least one of laser, visible light, infrared light, near-infrared light, ultraviolet light, and microwave.

[0016] A third embodiment of the present invention is a pigment phototherapy agent characterized in that, in the first embodiment of the pigment phototherapy agent, the components including indocyanine green and the local anesthetic are prepared to have the pH of physiological saline.

[0017] A fourth embodiment of the present invention is a pigment phototherapy agent characterized in that, in the first embodiment of the pigment phototherapy agent, at least one of an alexandrite laser, a Q-switched laser, a carbon dioxide laser, a diode laser, and a picosecond laser is used as the laser.

[0018] A fifth embodiment of the present invention is a pigment phototherapy agent characterized in that, in the fourth embodiment of the pigment phototherapy agent, an alexandrite laser is used as the laser.

[0019] The dye phototherapeutic agent according to the sixth aspect of the present invention is characterized in that, in the dye phototherapeutic agent of the first aspect, it is added via the blood vessel or lymphatic system.

[0020] In the dye phototherapeutic agent according to the seventh aspect of the present invention, in the dye phototherapeutic agent of the first aspect, the tissue is a) Lymph node b) Hemangioma c) Collagen d) Elastin e) Muscle f) Sweat gland g) Sebaceous gland h) Hair root i) Bacteria and their secretions or production sites, Trichophyton, axillary odor bacteria, Anaerococcus sp. strain, Corynebacterium genitalium strain, Staphylococcus, skin commensal bacteria, and j) Fibroblast at least any one of the above, as a feature.

[0021] The dye phototherapeutic filter according to the eighth aspect of the present invention is a filter that adjusts the degree of transmission of externally irradiated excitation light to a tissue to which the dye phototherapeutic agent according to any one of the first to seventh aspects is added, wherein the transmission degree of the excitation light is set according to the degree of thermal denaturation of the tissue, and the filter has the function of adjusting the target degree of thermal denaturation for the tissue by being attached to the surface of the epidermis at the site where the tissue is present.

[0022] The dye phototherapeutic filter according to the ninth aspect of the present invention is characterized in that, in the dye phototherapeutic filter of the eighth aspect, the thickness of the filter or the number of laminated layers is set to fall within the allowable range of light rectilinearity.

[0023] The dye phototherapeutic needle according to the tenth aspect of the present invention is a dye phototherapeutic needle for injecting the dye phototherapeutic agent according to any one of the first to seventh aspects into the tissue, comprising a base material to be attached to the outer surface of the epidermis corresponding to the tissue, and a plurality of needles arranged on the inner surface side of the base material, The needle is equipped with, (1) An embodiment having at least one pore in which a pigment phototherapy agent is held inside, (2) Embodiments in which a pigment phototherapy agent is retained on the surface, (3) A mode in which the pigment phototherapy agent is injected into the tissue by dissolving it. It is characterized by being at least one of the following embodiments.

[0024] A pigment phototherapy device according to the 11th embodiment of the present invention is a pigment phototherapy agent according to any of the first to seventh embodiments. A dye phototherapy apparatus using the dye phototherapy agent, comprising at least a therapeutic agent injection device for injecting the dye phototherapy agent into the tissue, and a light irradiation device for irradiating the tissue with the excitation light from an external source. [Effects of the Invention]

[0025] According to the dye phototherapy agent, dye phototherapy filter, dye phototherapy needle, and dye phototherapy device of one embodiment of the present invention, the dye phototherapy agent is concentrated and taken up at the target treatment site, and thermotherapy can be performed on the target cells by irradiation with light. [Brief explanation of the drawing]

[0026] [Figure 1] This is a fluorescence image of sweat gland cells when the dye phototherapy agent of Embodiment 1 of the present invention is added and irradiated with light. [Figure 2] Figure 1 shows a toluidine blue stained image of sweat gland cells. [Figure 3] This is a second fluorescence image of sweat gland cells when the dye phototherapy agent of Embodiment 1 of the present invention is added and irradiated with light. [Figure 4] Figure 3 is a schematic diagram of sweat gland cells. [Figure 5] Figure 3 shows a toluidine blue stained image of sweat gland cells. [Figure 6] Figure 3 is a comparison of the second fluorescence image of sweat gland cells, showing the fluorescence image with a dye phototherapy agent and the toluidine blue stained image. [Figure 7]This is a fluorescence image of sweat gland cells when a dye phototherapy agent according to Embodiment 2 of the present invention is added and irradiated with light. [Figure 8] Figure 7 shows a toluidine blue stained image of sweat gland cells. [Figure 9] This is a dye phototherapy needle according to Embodiment 3 of the present invention. [Figure 10] This is a dye phototherapy needle according to Embodiment 4 of the present invention. [Modes for carrying out the invention]

[0027] Hereinafter, embodiments of the present invention, including a pigment phototherapy agent, a pigment phototherapy filter, and a pigment phototherapy apparatus, will be described with reference to the drawings. However, the embodiments shown below are illustrative examples of a pigment phototherapy agent, a pigment phototherapy filter, and a pigment phototherapy apparatus for realizing the technical concept of the present invention, and the present invention is not limited to these, but is equally applicable to other embodiments included in the claims.

[0028] [Embodiment 1] A dye phototherapy agent, dye phototherapy filter, dye phototherapy needle, and dye phototherapy apparatus according to Embodiment 1 of the present invention will be described with reference to Figures 1 to 6.

[0029] Figure 1 is a fluorescence image of sweat gland cells when the dye phototherapy agent of Embodiment 1 of the present invention is added and irradiated with light, and Figure 2 is a toluidine blue stained image of the sweat gland cells of Figure 1. The dye phototherapy agent of this embodiment is a dye phototherapy agent that contains at least indocyanine green, and when added to a target tissue, the dye phototherapy agent is taken up by the tissue, and when photon energy is irradiated to the tissue from the outside as excitation light, the dye phototherapy agent thermally denatures the tissue with the excitation light.

[0030] Any photon energy can be used as excitation light, as long as it is available. For example, ultraviolet light, infrared light, visible light, electromagnetic waves, microwaves, lasers, IPL, X-rays, etc., can be used as long as they can be visualized by imaging devices such as cameras. For example, when a tissue that has absorbed a dye phototherapy agent is irradiated from the outside with excitation light, for example, with a wavelength of 400 nm or more and 1200 nm or less, the dye phototherapy agent causes thermal denaturation of the tissue by the excitation light and also exerts a cell-killing effect by reactive oxygen species.

[0031] [Pigmented phototherapy agents] As the phototherapy agent, a phototherapy agent containing indocyanine green (ICG) is used. Xylocaine can also be added. The method of adding the phototherapy agent is not particularly limited, but for example, it can be injected into the target site using a phototherapy needle in a syringe. While not particularly limited, the injection method can include subcutaneous injection, intravenous injection, or lymphatic injection. When the phototherapy agent is injected subcutaneously, it is concentratedly taken up by the cells of the target tissue through extravascular pathways. When the phototherapy agent is injected intravenously, it is concentratedly taken up by the cells of the target tissue, such as hemangiomas, through the blood vessels. Furthermore, when the phototherapy agent is injected into the lymphatic system, including lymphatic vessels, it is concentratedly taken up by the cells of the target tissue, such as lymph nodes, through the lymphatic system.

[0032] Indocyanine green (ICG) is preferred as the dye. The osmotic pressure of the dye phototherapy agent is adjusted to be equivalent to that of physiological saline. The dye phototherapy agent may also contain a local anesthetic; for example, the components containing ICG and the local anesthetic are prepared to have the pH of physiological saline.

[0033] [Irradiation with light] Excitation light is irradiated from outside the epidermis of the tissue into which the pigment phototherapy agent has been injected. ICG is a green pigment that absorbs light with a wavelength of about 600-800 nm. For the pigment phototherapy agent containing ICG in this embodiment, light with a wavelength of, for example, 740-780 nm is used as the photon energy for excitation light. Preferably, a 755 nm laser light, such as an alexandrite laser, is preferred. The light source for the excitation light can be not only laser light, but also IPL, LED, and organic EL.

[0034] In this embodiment, light of approximately 600-800 nm was given as an example of the excitation light wavelength. However, the excitation light wavelength in this embodiment is not limited to this, and any photon energy can be used as long as it can be used as excitation light. For example, ultraviolet light, infrared light, visible light, electromagnetic waves, microwaves, lasers, IPL, X-rays, etc., can be used as long as they can be visualized by an imaging device such as a camera.

[0035] For example, the wavelength of the excitation light irradiated from the outside to the tissue that has absorbed the pigment phototherapy agent is not limited to wavelengths of 740-780 nm, but may also be a wavelength of 400 nm to 1200 nm. For example, phototherapy using IPL (Intense Pulsed Light) with wavelengths of 400 nm to 1200 nm is also possible. Depending on the treatment target and treatment goal, the wavelength of IPL suitable for pigment phototherapy is adjusted from the wide wavelength range of IPL.

[0036] For example, when excitation light with a wavelength of 400 nm or more and 1200 nm or less is irradiated, the dye phototherapy agent causes thermal denaturation of the tissue by the excitation light and also exerts a cell-killing effect through reactive oxygen species. Electromagnetic waves, such as microwaves with a wavelength of approximately 1 to 10 cm, can also be used as excitation light. While there are no particular limitations on the type of laser, alexandrite lasers, Q-switched lasers, carbon dioxide lasers, diode lasers, or picosecond lasers can be used.

[0037] [Mechanism of Action] When an excitation light is irradiated from the outside onto the epidermis corresponding to the location of the tissue to which the ICG-containing dye phototherapy agent has been injected, the ICG in the tissue that has taken up the ICG generates heat and releases reactive oxygen species such as singlet oxygen. Reactive oxygen species act particularly on the cell membrane (or cell wall) to produce a cell-killing effect. The mechanism of action in this embodiment is the heat generated by ICG and the cell-killing effect of reactive oxygen species.

[0038] [filter] Excitation light irradiated from the outside of the epidermis penetrates the skin and reaches the tissue to which ICG has been injected. The intensity of the excitation light to be irradiated onto the target tissue is adjusted according to the target and purpose of treatment. In this embodiment, the intensity of the excitation light can be adjusted by using different pigment phototherapy filters. Multiple types of pigment phototherapy filters are provided in advance, each with a set degree of excitation light transmission corresponding to the degree of thermal denaturation of the target tissue.

[0039] A dye phototherapy filter is a transmission filter that transmits excitation light at a desired rate. Depending on the treatment target and purpose, the rate at which the dye phototherapy filter transmits excitation light, i.e., the intensity of the excitation light, can be adjusted by adjusting the area of ​​the portion that transmits the excitation light. Furthermore, the straightness of the excitation light can be improved by adjusting the thickness of the transmission filter. For example, the thickness of the transmission filter is set to 80 μm or more so that excitation light from a laser or LED travels in a straight line. On the other hand, there is no particular upper limit to the thickness of the transmission filter, and although it is not a matter of dotting, it is preferable to keep it at 800 μm or less from the viewpoint of yield and ease of handling.

[0040] A type of photochromic dye filter corresponding to the desired degree of thermal denaturation of the target tissue is selected and used, and the selected filter is applied to the surface of the epidermis where the target tissue is located. The intensity of the excitation light irradiated to the tissue is adjusted by using a pre-prepared photochromic dye filter each time the target thermal denaturation of the target tissue is achieved. By using a disposable type of filter, which is replaced with a new one after each treatment, the filter is easy to handle during treatment and also has hygienic advantages.

[0041] In this embodiment, it has been described that multiple types of dye phototherapy filters are prepared in advance, each with a transmission rate of excitation light corresponding to the degree of thermal denaturation of the tissue to be treated. However, the form of the dye phototherapy filter in this embodiment is not limited to this, and is not necessarily limited to the form in which multiple types of dye phototherapy filters are prepared and stocked in advance. For example, if the treatment purpose is specified, only one type of dye phototherapy filter corresponding to that treatment purpose may be used. Also, since the dye phototherapy filter is in the form of a thin sheet, such as 100 μm thick, it is possible to layer and attach multiple sheets. In this case, for example, if three transmission filters that transmit 90% of the light are layered and used, it will result in a dye phototherapy filter with a transmittance of 73%.

[0042] [Injection of pigment phototherapy agents into tissue] To inject the pigment phototherapy agent into the target tissue, a pigment phototherapy needle, including a syringe, can be used. Furthermore, by using a microneedle patch, for example, on the outer surface of the epidermis corresponding to the target tissue, the pigment phototherapy agent can be effectively injected into the target tissue.

[0043] The phototherapy agent is added to the target tissue via at least one of the following: blood vessels, lymphatic system, and extravascular drainage pathways. Subcutaneous injection of the phototherapy agent allows it to spread through the extravascular drainage pathways, and by utilizing, for example, the specific retention properties of ICG, the phototherapy agent can be concentrated and taken up by the target tissue. Alternatively, by injecting the phototherapy agent into the blood vessels or lymphatic system corresponding to the target tissue, the phototherapy agent can be concentrated and taken up by the target tissue.

[0044] [Understanding the scope of treatment] To determine the area to be injected with the pigment phototherapy agent and the treatment area, it is desirable to first understand the distribution of the target tissue, such as sweat glands, using cross-sectional echo images from an ultrasound imaging device. As the ultrasound probe for the ultrasound imaging device, for example, a linear probe type with 128 or more elements and a driving frequency of 20 MHz or higher can be used. Although not particularly limited, for example, the Aplio i-800 (product name) manufactured by Canon Medical Corporation can be used as the ultrasound imaging device, and the high-frequency linear probe PLI-20020BT (product name) can be used as the ultrasound probe. For example, this ultrasound probe has about 200 ultrasound elements and uses 22 MHz ultrasound for measurement. In another example, an ultrasound probe with about 400 to 600 ultrasound elements and using 33 MHz ultrasound can also be used for measurement. Furthermore, ultrasound probes with even higher frequencies and more elements may be used.

[0045] To quantitatively record the treatment area, markings such as a matrix are applied to the treatment target, for example, the armpit, using color markers. In this embodiment, instead of directly marking the epidermis, a sheet with matrix markings can be attached to the corresponding epidermis area of ​​the treatment target. This allows for the accurate quantification and recording of the distribution information of the treatment target tissue, such as sweat glands, obtained by the ultrasound imaging device, as planar coordinates and depth information.

[0046] The aforementioned pigment phototherapy filter can also be used in conjunction with a marking sheet. In this case, a matrix-like marking for identifying the treatment site is attached to the pigment phototherapy filter. Before diagnosing the target tissue with an ultrasound imaging device, the pigment phototherapy filter with the matrix-like marking can be attached to the epidermis corresponding to the target tissue, for example, the epidermis of the armpit, allowing for accurate quantitative identification and recording of the target tissue.

[0047] The scanning surface of the ultrasound probe is rectangular, having a long side and a short side. The scanning range of the ultrasound probe is determined by scanning approximately 50 mm along the long side of the ultrasound probe 11, for example, from the hand towards the armpit, starting from a marked reference point. Then, one or more scans are performed along the long side of the ultrasound probe for approximately 30 mm in a direction perpendicular to the scanned line. By performing one or more of these long-side scans, the initial parameters of the ultrasound probe are set according to the distribution state of the sweat glands. By performing this initial parameter setting in advance, a clearer cross-sectional echo image of the target tissue, such as sweat glands, can be obtained. Subsequently, a clear cross-sectional echo image of the sweat glands is obtained by scanning in two perpendicular directions along the short side of the ultrasound probe, covering the area including the region where the presence of sweat glands was confirmed by the long-side scan information and the surrounding area. By image recognition using this clear cross-sectional echo image of the sweat glands, information regarding the distribution state of sweat glands in the subcutaneous range of 0.5 to 3.5 mm can be accurately quantified as coordinate information and depth information.

[0048] [Confirmation of fluorescence in tissue to which a pigment phototherapy agent has been added] When excitation light is irradiated from the outside of the epidermis corresponding to the tissue to be treated, the tissue that has concentratedly absorbed the pigment phototherapy agent will fluoresce. This fluorescence of the tissue to be treated is recorded as an image using a camera or similar device. This allows confirmation of the state in which the pigment phototherapy agent has been absorbed into the tissue to be treated, and also allows for the determination of the area to be irradiated with excitation light for thermotherapy. The area of ​​the tissue to be treated can be determined by determining the fluorescence of the tissue to which the pigment phototherapy agent has been added, or by determining the area of ​​the tissue to be treated using the aforementioned ultrasound imaging device, or by using at least one of these methods. In either case, the pigment phototherapy filter can also be used as a marking sheet.

[0049] [Example of experiment 1] Thermotherapy for sweat gland cells Test Example 1 is an example of thermotherapy of sweat gland cells using the dye phototherapy agent of Embodiment 1. Figure 1 is a fluorescence image of sweat gland cells when the dye phototherapy agent of Embodiment 1 of the present invention is added and irradiated with light, and Figure 2 is a toluidine blue stained image of the sweat gland cells of Figure 1.

[0050] (Test method) 1) A pigment phototherapy filter, for example, marked with a matrix pattern, is applied to the epidermis corresponding to the tissue to be treated. The pigment phototherapy filter is selected to transmit excitation light at a predetermined rate, depending on the target and purpose of treatment. In this test example, a pigment phototherapy filter that transmits 50% of excitation light was used for the treatment of axillary hyperhidrosis.

[0051] 2) Use an ultrasound diagnostic device to quantitatively determine the distribution of the tissue to be treated.

[0052] 3) The phototherapy agent is added to the epidermis corresponding to the tissue to be treated using a phototherapy needle such as a syringe. In this test example, the target tissue was sweat gland cells, and the phototherapy agent was injected subcutaneously into the epidermis of the armpit corresponding to the target sweat gland cells using a syringe. The phototherapy agent contains ICG and is not particularly limited, but in this experiment, 0.3 ml of a phototherapy agent containing 0.25 mg / ml of ICG was injected subcutaneously.

[0053] 4) Allow a predetermined amount of time, for example 2 hours, to be allowed to be taken up by the tissue to be treated.

[0054] 5) While excitation light is briefly (for example, a few seconds) irradiated from the outside of the epidermis corresponding to the tissue to be treated, the tissue that has concentratedly absorbed the pigment phototherapy agent will fluoresce. This fluorescence of the tissue to be treated is recorded as an image using a camera or similar device. In this test example, an alexandrite laser with a wavelength of 755 nm is used as the excitation light. Figure 1 shows an example of the image recorded at that time. The maximum output of the alexandrite laser used in this test example was 20 J / cm² when using the large-diameter output light mode, for example, with an 18 mm diameter. 2 That is.

[0055] 6) After recording the fluorescence of the tissue to be treated in 5) above, excitation light is irradiated onto the epidermis corresponding to the target area for a time appropriate to the treatment target and purpose. In this test example, for the purpose of treating axillary hyperhidrosis, the output of the alexandrite laser used for excitation light was set to 20 J / cm². 2 Since a dye phototherapy filter that transmits 50% of the excitation light is attached to the epidermis, the intensity of the excitation light applied to the epidermis corresponding to the treatment target is 20 J / cm². 2 ×50% = 10 / cm 2 The excitation light irradiation time was set to 3 minutes.

[0056] 7) The excitation light described in 6) above is adjusted in intensity and duration according to the excitation light transmittance of the dye phototherapy filter described in 1) above, thereby producing the desired thermotherapy effect on the target tissue.

[0057] (Test results) Figure 1 is an image taken from the outside of the epidermis, showing tissue that has concentratedly absorbed the pigment phototherapy agent and is emitting fluorescence. Figure 2 is an image of sweat gland cells stained with toluidine blue as an example of the target tissue, showing the same area as in Figure 1.

[0058] In Figure 2, the areas stained in dark blue represent the distribution range of sweat gland cells, which are the target tissue. However, since Figure 2 is a monochrome image converted from the original color image, the toluidine blue stained areas are shown as a color close to black or dark (the same applies to toluidine blue stained images in the figures below). In Figure 1, the areas where the tissue has been intensively uptaken by the phototherapy dye are shown as white. The white areas in Figure 1 coincide with the distribution range of sweat gland cells in dark blue in Figure 2, indicating that the phototherapy dye is intensively uptaken by the sweat gland cells, which are the target tissue. Thus, it is thought that phototherapy dyes containing ICG penetrate into the sweat gland cells and stain the entire sweat gland cell.

[0059] After recording the fluorescence of the sweat glands, the tissue to be treated, as shown in Figure 1, a pigment phototherapy filter that transmits 50% of the excitation light is applied to the epidermis of the armpit corresponding to the tissue where the pigment phototherapy agent has been concentrated, for the purpose of thermal treatment of axillary hyperhidrosis. Then, an excitation light output of 20 J / cm² is applied from outside the pigment phototherapy filter. 2 When the Alexandrite laser was applied to the target area for 3 minutes, the amount of sweat from the sweat glands in the area was suppressed, and the odor was significantly reduced.

[0060] In this test example, the excitation light applied to the epidermis of the target area was 10 / cm². 2This output lasts for 3 minutes. In contrast, when using an alexandrite laser with a diameter of 18 mm, the excitation light is 20 J / cm². 2 In conventional hair removal treatments, for example, irradiation was performed for about 5 minutes in the underarms and about 20 minutes in the lower legs. In this experiment, it was found that by irradiating tissue that had concentratedly absorbed the pigment phototherapy agent with excitation light, a thermotherapy effect could be achieved with lower power or shorter irradiation time than that required for conventional treatments.

[0061] The output power of the alexandrite laser, when using an 18mm diameter, is 20 J / cm² as the excitation light. 2 Even under certain conditions, it was confirmed that the output of the excitation light irradiated to the target site can be adjusted by attaching a dye phototherapy filter with the desired excitation light transmittance (50% in this test example) to the epidermis corresponding to the tissue to be treated.

[0062] When an excitation light is irradiated from the outside onto the epidermis corresponding to the location of the treatment target tissue to which the ICG-containing dye phototherapy agent has been injected, the ICG in the tissue that has taken up the ICG generates heat and releases reactive oxygen species such as singlet oxygen. Reactive oxygen species act particularly on the cell membrane (or cell wall) to produce a cell-killing effect. In this embodiment, the ICG generates heat due to cold light, and the cell-killing effect of reactive oxygen species such as singlet oxygen generated along with the heat of the ICG produces therapeutic effects such as suppression of sweating by sweat gland cells.

[0063] Dye phototherapy filters are useful for quantitatively understanding the target tissue, and because they can be disposable, they are easy to handle, resulting in high work efficiency and superior hygiene. Furthermore, since multiple types with different excitation light transmission rates can be prepared in advance, the intensity of the excitation light can be adjusted simply by selecting the filter that transmits the excitation light at a predetermined rate according to the target and purpose of treatment.

[0064] [Example Test 2] Thermotherapy involving concentrated absorption of a pigment phototherapy agent into sweat gland cells. Test Example 2 is an example of thermotherapy in which the dye phototherapy agent of Embodiment 1 is concentrated in sweat gland cells. Figure 3 is a second fluorescence image of sweat gland cells when the dye phototherapy agent of Embodiment 1 of the present invention is added and light is irradiated, Figure 4 is a schematic diagram of the sweat gland cells of Figure 3, Figure 5 is a toluidine blue stained image of the sweat gland cells of Figure 3, and Figure 6 is a comparison diagram of the dye phototherapy agent fluorescence image and the toluidine blue stained image for the second fluorescence image of the sweat gland cells of Figure 3.

[0065] (Test method) The test was conducted under the same conditions as in Test Example 1 described above. In this test example, similar to Test Example 1, the purpose was to treat axillary hyperhidrosis, and the treatment involved thermotherapy with a pigment phototherapy agent incorporated into the target tissue. The pigment phototherapy agent used was a pigment phototherapy agent containing ICG of the same specifications as in Test Example 1. The excitation light was also the same specification alexandrite laser as in Test Example 1, with the same power output and irradiation time. The pigment phototherapy filter applied to the epidermis of the armpit corresponding to the target tissue was also of the same specifications as in Test Example 1. The pigment phototherapy agent was also the same specification as in Test Example 1, with 0.3 ml of a pigment phototherapy agent containing 0.25 mg / ml of ICG, administered by subcutaneous injection.

[0066] While Test Example 1 focused on the area of ​​the armpit where sweat gland cells are concentrated, this test example shows how the pigment phototherapy agent was concentrated in the sweat gland cells, which are the target of treatment, over a wider area including not only sweat gland cells but also subcutaneous tissue and skin tissue other than sweat glands.

[0067] By injecting a phototherapy agent subcutaneously through the epidermis corresponding to the target tissue using a phototherapy needle, the injected phototherapy agent is concentratedly taken up by the target tissue, the sweat gland cells, via the lymphatic system and extravascular pathways corresponding to the target sweat gland cells. In this study, although not particularly limited, a phototherapy needle corresponding to Figure 9 described later was used to concentrate the uptake of the phototherapy agent into the target sweat gland cells via both the lymphatic system and extravascular pathways.

[0068] (Test results) Figure 3 is an image taken from the outside of the epidermis with a camera, showing the fluorescence emitted by tissue that has concentratedly absorbed the pigment phototherapy agent. Figure 4 is a schematic diagram illustrating the sweat gland region within the fluorescent area in Figure 3. Figure 5 is an image stained with toluidine blue, showing sweat gland cells as the target tissue for treatment, with the sweat gland region in the same area as in Figure 3 shown in dark blue.

[0069] In Figure 5, the areas stained in dark blue represent the distribution range of sweat gland cells, which are the target tissue. Toluidine blue is also distributed in areas other than sweat gland cells; for example, some parts of the epidermal tissue appear blue. However, here we will focus on the area corresponding to the sweat gland region shown in the schematic diagram in Figure 4. In Figure 4, area A in the center is the sweat gland region, area B is the subcutaneous tissue region, and area C is the skin tissue region. As shown in Figure 4, the images in Figures 3 to 5 include images of subcutaneous tissue and skin tissue in addition to the sweat gland region.

[0070] In Figure 5, the dark blue areas in the sweat gland region represent sweat gland cells. In Figure 3, the tissue that has concentratedly absorbed the photochromic dye emits fluorescence and appears white in the image. Since this white area in Figure 3 coincides with the dark blue area in Figure 5, it can be seen that this area is the sweat gland cells, which are the target tissue for treatment. Furthermore, it can be seen that the photochromic dye injected subcutaneously in the armpit using the photochromic dye needle is concentratedly absorbed by the sweat gland cells, which are the target tissue for treatment.

[0071] FIG. 6A is a fluorescence image of a dye phototherapeutic agent containing ICG. FIG. 6B is a toluidine blue-stained image of the region corresponding to FIG. 6A. FIG. 6 is an enlarged view of the sweat gland region of FIG. 5. The region that appears white in FIG. 6A matches the toluidine blue-stained region (dark blue region, provided that FIG. 6B is a monochrome image converted from the original color image, so the toluidine blue-stained region is shown as a color close to black or a dark color) in FIG. 6B, which indicates that this region is sweat gland cells as the target tissue for treatment. This demonstrates that the dye phototherapeutic agent injected subcutaneously in the axilla by the dye phototherapy needle is intensively taken up by the sweat gland cells, which are the target tissue for treatment.

[0072] The dye phototherapy needle used in this test example is provided with a large number of needles of different lengths. When the dye phototherapy needle is used, the dye phototherapeutic agent can be injected so as to be distributed at different subcutaneous depths over the surface area of the axillary epidermis corresponding to the target tissue for treatment. By distributing and injecting the dye phototherapeutic agent at different subcutaneous depths, a part of the dye phototherapeutic agent injected subcutaneously is injected at a position close to the sweat gland region, so that it is intensively taken up by the target sweat gland cells directly via the extravascular fluid passage. In addition, a part of the dye phototherapeutic agent injected subcutaneously is injected into the lymphatic system corresponding to the target sweat gland cells, and is intensively taken up by the target sweat gland cells via the lymphatic system.

[0073] After the fluorescence of the sweat glands as the target tissue for treatment was recorded as FIG. 3, for the purpose of hyperthermia treatment of axillary osmidrosis and hyperhidrosis, with a dye phototherapy filter that transmits 50% of excitation light attached to the axillary epidermis corresponding to the tissue where the dye phototherapeutic agent was intensively taken up, from the outside of the dye phototherapy filter, excitation light with an output of 20 J / cm 2 When the alexandrite laser was irradiated for 3 minutes, the amount of sweating from the sweat glands at the target site was suppressed, and the effect of significantly reducing odor was obtained.

[0074] In this example, we used a dye phototherapy needle corresponding to Figure 9 described later, but this example is not limited to this, and other types of dye phototherapy needles can be used. In this case as well, by knowing the location of the target tissue and because the dye phototherapy agent utilizes the specific retention properties of ICG, the dye phototherapy agent can be concentrated and taken up by the target tissue. In other words, the dye phototherapy agent in this example has its ICG-containing components, concentration, and pH adjusted so that it is easily taken up by, for example, sweat gland cells, and the injection site into the subcutaneous tissue is quantitatively determined.

[0075] [Embodiment 2] Embodiment 2 of the present invention will be described with reference to Figures 7 and 8, describing a dye phototherapy agent, a dye phototherapy filter, a dye phototherapy needle, and a dye phototherapy apparatus. Embodiment 1 described a thermotherapy in which the dye phototherapy agent is concentrated in the treatment area, but this embodiment describes a thermotherapy in which the dye phototherapy agent is more targeted and delivered to the treatment tissue.

[0076] [Test Example 3] Thermotherapy involving concentrated delivery of a pigment phototherapy agent to target tissue in sweat gland tissue. Test Example 3 is an example of thermotherapy in which the dye phototherapy agent of Embodiment 2 is concentrated in the sweat gland cells. Figure 7 is a fluorescence image of sweat gland cells when the dye phototherapy agent according to Embodiment 2 of the present invention is added and light is irradiated, and Figure 8 is a toluidine blue stained image of the sweat gland cells of Figure 7.

[0077] (Test method) The test was conducted under the same conditions as in Test Example 1 described above. In this test example, similar to Test Example 1, the purpose was to treat axillary hyperhidrosis, and the treatment involved thermotherapy with a pigment phototherapy agent incorporated into the target tissue. However, the target of treatment in this test example was more narrowly defined, focusing on the sweat gland region and specifically the acinar cells of the sweat glands.

[0078] The phototherapy agent used was a phototherapy agent containing ICG of the same specifications as that used in Test Example 1. The excitation light was also the same specification alexandrite laser as in Test Example 1, with the same power output and irradiation time. The phototherapy filter applied to the epidermis of the armpit, corresponding to the treatment target tissue, was also the same specification as in Test Example 1. For the phototherapy agent, 0.3 ml of a phototherapy agent containing 0.25 mg / ml ICG of the same specifications as in Test Example 1 was administered by subcutaneous injection.

[0079] While Test Example 1 focused on the area in the armpit where sweat gland cells are concentrated, this test example targets a more specific tissue for treatment, specifically the acinar cells within the sweat gland region, and concentrates the uptake of the pigment phototherapy agent there.

[0080] By injecting a phototherapy agent subcutaneously through the epidermis corresponding to the target tissue using a phototherapy needle, the injected phototherapy agent is concentratedly taken up by the target tissue, the sweat gland cells, via the lymphatic system and extravascular pathways corresponding to the target sweat gland cells. In this test example, although there is no particular limitation to the phototherapy needle, by using the one corresponding to Figure 10 described later, the phototherapy agent is concentratedly taken up by the target sweat gland acinar cells via both the lymphatic system and the extravascular pathways.

[0081] (Test results) Figure 7 is an image taken from the outside of the epidermis with a camera, showing the fluorescence emitted by tissue that has concentratedly absorbed the pigment phototherapy agent. Figure 8 is an image stained with toluidine blue, which is the target tissue for treatment, and the sweat gland region in the same area as in Figure 7 is shown as dark blue. However, as with Figure 6B, the toluidine blue stained area is a dark blue area in a color image, but since Figure 8 is a monochrome image converted from the original color image, the toluidine blue stained area is shown as a color close to black or a dark color.

[0082] In Figure 8, the area enclosed by the white line (the area stained in dark blue) represents the distribution range of sweat gland cells, which are the target tissue. Toluidine blue is also distributed in tissues other than sweat gland cells, but here we will focus on area A enclosed by the white line and area B enclosed by the black line in Figure 8.

[0083] In Figure 8, within region A enclosed by the white line, the dark blue areas represent sweat gland mammary cells. Region B enclosed by the black line represents the sweat gland ducts. In Figure 7, tissue that has concentratedly absorbed the pigment phototherapy agent fluoresces and appears white in the image. Region A enclosed by the white line in Figure 7 and region A enclosed by the white line in Figure 8 correspond to each other in terms of their arrangement, and region B enclosed by the black line in Figure 7 and region B enclosed by the black line in Figure 8 correspond to each other in terms of their arrangement.

[0084] In Figure 8, the degree of uptake of the phototherapy agent into the tissue can be determined from the fluorescence intensity (intensity of the white glowing areas). Here, the degree of uptake is evaluated on a four-point scale: +2 (very high uptake), +1 (high uptake), -1 (low uptake), and -2 (very low uptake). The degree of uptake of the phototherapy agent into the acinar cells of the sweat glands in region A, enclosed by the white lines in Figure 8, was evaluated as +2 (very high uptake). The degree of uptake of the phototherapy agent into the sweat gland ducts in region B, enclosed by the black lines in Figure 8, was evaluated as -1 (low uptake). In addition, in regions other than region A and region B enclosed by the black lines in Figure 8, some uptake of the phototherapy agent is also taken up by the background cells, but the uptake is very weak compared to the area of ​​acinar cells, the target tissue of the sweat glands in region A enclosed by the white lines.

[0085] The pigment phototherapy needle used in this test example (see Figure 10) has multiple injection holes along its length, allowing the pigment phototherapy agent to be injected over a wide area distributed in depth from the epidermis. Therefore, by using this pigment phototherapy needle, the pigment phototherapy agent is distributed and injected over a wide area to different depths in the subcutaneous tissue, and the pigment phototherapy agent injected subcutaneously is concentratedly taken up directly by the sweat gland acinar cells near the injection holes via extravascular fluid pathways. In addition, a portion of the pigment phototherapy agent injected subcutaneously is injected into the lymphatic system corresponding to the target sweat gland acinar cells and is concentratedly taken up by the target sweat gland acinar cells via the lymphatic system. Because the pigment phototherapy agent of this embodiment utilizes the specific retention properties of ICG, it is hardly taken up by tissues that are not normally targeted for treatment, such as the sweat gland ducts in region B enclosed by the black line in Figure 8.

[0086] After recording the fluorescence of the sweat glands, the tissue to be treated, as shown in Figure 7, a dye phototherapy filter that transmits 50% of the excitation light is attached to the epidermis of the armpit corresponding to the region where the sweat gland acinar cells, the target tissue to be treated, are concentrated with the dye phototherapy agent, for the purpose of thermal treatment of axillary hyperhidrosis. Then, from outside the dye phototherapy filter, an excitation light output of 20 J / cm² is applied. 2 When the Alexandrite laser was applied to the target area for 3 minutes, the amount of sweat from the sweat glands in the area was suppressed, and the odor was significantly reduced.

[0087] As can be seen in Figure 7, when excitation light is irradiated from the outside of the epidermis corresponding to the target tissue, the thermotherapy effect is enhanced only in the region where the sweat gland acinar cells, which are the target tissue, are concentrated and take up the pigment phototherapy agent. Therefore, by irradiating with excitation light of adjusted intensity for a target time, hyperhidrosis can be treated by reducing the sweating function of only the sweat gland acinar cells, which are the target tissue, to the desired degree. In addition, this also provides a therapeutic effect of reducing the odor caused by body odor.

[0088] In this example, we used a dye phototherapy needle corresponding to Figure 10, which will be described later. However, this example is not limited to this, and other types of dye phototherapy needles can be used. In this case as well, by determining the location of the target tissue and because the dye phototherapy agent utilizes the specific retention properties of ICG, it is possible to concentrate the uptake of the dye phototherapy agent into the target tissue. Specifically, in this example, the dye phototherapy agent has been adjusted in terms of ICG-containing components, concentration, and pH to facilitate uptake by, for example, sweat gland cells, and the injection site into the subcutaneous tissue has been quantitatively determined.

[0089] [Embodiment 3] A dye phototherapy agent, dye phototherapy filter, dye phototherapy needle, and dye phototherapy apparatus according to Embodiment 3 of the present invention will be described with reference to Figure 9. Figure 9 shows a dye phototherapy needle 10 according to Embodiment 3 of the present invention.

[0090] The pigment phototherapy needle 10 in Figure 9 is an example of a microneedle patch configuration. The microneedle patch has a base material and multiple needles 30 arranged on the base material. The base material 20 is, for example, a circular sheet-like member, with multiple needles 30 arranged on the side that comes into contact with the skin. In the example in Figure 9, there are multiple types of needles 30 with different lengths, for example, three types of needles 30, and each needle 30 is provided with a stepped portion 30s at a common height position. The portion of the needle closer to the tip than the stepped portion 30s is used to puncture the skin.

[0091] The needle 30 holds the aforementioned pigment phototherapy agent. For example, since the aforementioned pigment phototherapy agent is coated on the surface of the needle 30, when the needle 30 is inserted into the epidermis corresponding to the tissue to be treated, the pigment phototherapy agent is injected subcutaneously. Alternatively, if a hole is provided along the axis from the tip of the needle 30 toward the base in the longitudinal direction, the pigment phototherapy agent can be held in this hole, and when the needle 30 is inserted into the epidermis, the pigment phototherapy agent can be injected subcutaneously into this hole. Furthermore, the needle 30 itself can contain the pigment phototherapy agent and be designed to dissolve when inserted into the epidermis. In this case, the pigment phototherapy agent contained in the needle 30 itself dissolves when inserted subcutaneously, thereby injecting the pigment phototherapy agent subcutaneously. Alternatively, two or more of these methods of holding the pigment phototherapy agent by the needle 30 can be combined.

[0092] In this embodiment, the pigment phototherapy needle 30 is provided with numerous needles 30 of different lengths, as shown in Figure 9. Using this pigment phototherapy needle 30, the pigment phototherapy agent can be injected to different subcutaneous depths across a surface area of ​​the epidermis of the armpit corresponding to the target tissue. By distributing and injecting the pigment phototherapy agent to different subcutaneous depths, a portion of the pigment phototherapy agent injected subcutaneously is injected close to the sweat gland area and is therefore concentratedly taken up by the target sweat gland cells directly via the extravascular pathway. In addition, a portion of the pigment phototherapy agent injected subcutaneously is injected into the lymphatic system corresponding to the target sweat gland cells and is concentratedly taken up by the target sweat gland cells via the lymphatic system. Since each needle 30 is provided with a stepped portion 30s at a common height position, it is easy to set the length of the puncture portion of the needle 30 and to puncture the subcutaneously to the desired depth.

[0093] Figure 9 shows an example in which many needles 30 of different lengths are provided, but this embodiment is not limited to this. For example, needles 30 of different thicknesses may be provided, needles 30 of the same dimensions may be used, or a combination of these may be used. Also, in Figure 9, a stepped portion is provided at a common height position, but this embodiment is not limited to this. For example, the height positions of the stepped portions of each needle 30 may be partially or entirely different, some or all of the needles 30 may have two or more stepped portions, some or all of the needles 30 may not have stepped portions, or a combination of these may be used.

[0094] [Embodiment 4] A dye phototherapy agent, dye phototherapy filter, dye phototherapy needle, and dye phototherapy apparatus according to Embodiment 4 of the present invention will be described with reference to Figure 10. Figure 10 shows a dye phototherapy needle according to Embodiment 4 of the present invention.

[0095] The pigment phototherapy needle in Figure 10 has one or more needles 30A provided on a base material 20. Each needle 30A has a hollow hole 31 aligned in the axial direction and a plurality of communication holes 32 extending from the hollow hole 31 to the outer circumference and tip of the needle 30A, connecting the hollow hole 31 to the outside of the outer circumference of the needle 30A. Multiple communication holes 32 are provided so as to be distributed in the longitudinal and circumferential directions of the needle 30A. Since the aforementioned pigment phototherapy agent is held in the hollow hole 31 and the communication holes 32, when the pigment phototherapy needle is inserted into the epidermis corresponding to the tissue to be treated, the pigment phototherapy agent is injected subcutaneously through each communication hole.

[0096] In this embodiment, the pigment phototherapy needle is provided with multiple communication holes 32 along the length and circumferential directions of the needle 30A, allowing the pigment phototherapy agent to be injected over a wide area distributed in the depth direction from the epidermis. Therefore, by using this pigment phototherapy needle, the pigment phototherapy agent is distributed and injected over a wide area to different depths in the subcutaneous tissue, and the pigment phototherapy agent injected into the subcutaneous tissue is concentratedly taken up directly into the target tissue near the injection hole via an extravascular fluid pathway. In addition, a portion of the pigment phototherapy agent injected into the subcutaneous tissue is injected into the lymphatic system corresponding to the target tissue and is concentratedly taken up by the target tissue via the lymphatic system.

[0097] Figure 10 shows an example of a dye phototherapy needle in which multiple communication holes are provided at six locations in the longitudinal direction and distributed in the circumferential direction. However, this embodiment is not limited to this, and for example, the distribution of communication holes may differ from that in Figure 10, include communication holes that penetrate the tip of the needle 30A, have only one communication hole, be in the form of a microneedle patch as in Embodiment 3 with multiple needles 30A arranged on the adhesive surface of the substrate, be in the form of an injection needle for the needle 30A, or be a combination of these.

[0098] [Embodiment 5] A dye phototherapy agent, a dye phototherapy filter, a dye phototherapy needle, and a dye phototherapy apparatus according to Embodiment 5 of the present invention will be described. The dye phototherapy apparatus of this embodiment is a dye phototherapy apparatus that uses a dye phototherapy agent according to any of Embodiments 1 to 4, and comprises at least a treatment agent injection device for injecting the dye phototherapy agent into the target tissue and a light irradiation device for irradiating the corresponding epidermis of the target tissue with excitation light from the outside.

[0099] The therapeutic agent injection device for injecting the pigment phototherapy agent into the target tissue uses the aforementioned pigment phototherapy needles, and the light irradiation device for irradiating the corresponding epidermis of the target tissue with excitation light from the outside uses the aforementioned excitation light. With the therapeutic agent injection device of this embodiment, the pigment phototherapy agent is injected into the target tissue, and by irradiating the epidermis corresponding to the target tissue where the pigment phototherapy agent has been concentrated with excitation light from the outside, thermotherapy can be performed on the target tissue according to the treatment purpose.

[0100] In this embodiment, the target tissue to which the pigment phototherapy agent is injected is not limited to the aforementioned sweat gland cells, but for example, a) Lymph nodes b) Hemangioma c) Collagen d) Elastin e) muscle f) sweat glands g) sebaceous glands h) Hair root or hair follicle i) Bacteria and their secretions or production parts, dermatophytes, axillary osmidrosis, Anaerococcus SP. strain, Corynebacterium genitalium strain, Staphylococcus, or commensal skin bacteria, j) Fibroblasts, and k) Pigmentation including melasma, These are some examples.

[0101] a) Regarding lymph nodes, by injecting a pigment phototherapy agent into the lymphatic system, the pigment phototherapy agent can be concentratedly absorbed by utilizing the heterogeneous retention of ICG.

[0102] b) For hemangiomas, by injecting a photochromic dye into the blood vessels, the heterogeneous retention of ICG can be utilized to allow for concentrated uptake of the photochromic dye. Furthermore, because hemoglobin in the blood has the property of absorbing light, it tends to enhance the effect of thermotherapy using photochromic dyes.

[0103] c) Regarding collagen, by utilizing the heterogeneous retention properties of ICG, it is possible to concentrate the uptake of pigment phototherapy agents.

[0104] d) Regarding elastin (elastic fibers within proteins (elastic fibers, collagen fibers)), the different retention properties of ICG allow for concentrated uptake of the pigment phototherapy agent. In particular, by concentrating ICG on the elastic fibers within proteins (elastic fibers, collagen fibers), targeted thermotherapy can be achieved.

[0105] e) For muscles, the pigment phototherapy agent can be injected subcutaneously using a pigment phototherapy needle in a manner such as subcutaneous injection, allowing the pigment phototherapy agent to be concentrated and taken up by the target muscle tissue through extravascular pathways.

[0106] f) For sweat glands, for example, the procedure in Test Examples 1-3 allows for concentrated uptake of the pigment phototherapy agent into the target tissue.

[0107] g) In the case of sebaceous glands, the pigment phototherapy agent can be concentrated in the sebaceous glands by utilizing the heterogeneous retention properties of ICG.

[0108] h) For hair roots or hair follicles, the pigment phototherapy agent can be concentrated in the hair by utilizing the heterogeneous retention properties of ICG.

[0109] i) In the case of bacteria and their secretions or production parts, dermatophytes, axillary osmidrosis, Anaerococcus SP. strain, Corynebacterium genitalium strain, Staphylococcus, or commensal skin bacteria, not only the bacteria themselves but also their secretions or production parts, such as dermatophytes and the secretions or production parts of dermatophytes, can be concentrated in uptake of the pigment phototherapy agent by utilizing the heterogeneous retention properties of ICG.

[0110] j) For fibroblasts, the heterogeneous retention of ICG can be utilized to allow them to take up pigment phototherapy agents intensively.

[0111] k) For hyperpigmentation including melasma, by utilizing the heterogeneous retention properties of ICG, it is possible to concentrate the uptake of the pigment phototherapy agent, thereby achieving effective thermotherapy focused on the target hyperpigmented area.

[0112] The above embodiments exemplify the pigment phototherapy agent, pigment phototherapy filter, pigment phototherapy needle, and pigment phototherapy apparatus for realizing the technical concept of the present invention. The present invention is not limited to these, and can be equally applied to other embodiments, such as modifications to these embodiments or combinations of the technologies described in these embodiments. [Explanation of Symbols]

[0113] 10… Pigment light therapy needle 20...Base material 30, 30A... Needle 30s…Step part 31...Hollow hole 32...Communication hole 32

Claims

1. A pigment phototherapy agent comprising at least indocyanine green, When added to the target tissue, the pigment phototherapy agent is taken up by the tissue. A dye phototherapy agent characterized in that, when photon energy is irradiated to the tissue from the outside as excitation light, the dye phototherapy agent causes thermal denaturation of the tissue by the excitation light.

2. The dye phototherapy agent according to claim 1, characterized in that the photon energy as excitation light includes at least one of laser, IPL, visible light, infrared light, near-infrared light, ultraviolet light, and microwave.

3. The pigment phototherapy agent according to claim 1, characterized in that the component containing indocyanine green is adjusted to have an osmotic pressure equivalent to that of physiological saline.

4. The dye phototherapy agent according to claim 1, characterized in that the light source of the excitation light is at least one of a laser, IPL, LED, and organic EL.

5. The pigment phototherapy agent according to claim 4, characterized in that at least one of the following is used as the laser: an alexandrite laser, a Q-switched laser, a carbon dioxide laser, a diode laser, and a picosecond laser.

6. The pigment phototherapy agent according to claim 1, characterized in that it is added to the aforementioned tissue via at least one of the blood vessels, the lymphatic system, and the extravascular fluid passage.

7. The aforementioned organization, a) Lymph nodes b) Hemangioma c) Collagen d) Elastin e) muscle f) sweat glands g) Sebaceous glands h) Hair root or hair follicle i) Bacteria and their secretions or production parts, dermatophytes, axillary osmidrosis, Anaerococcus SP. strain, Corynebacterium genitalium strain, Staphylococcus, or commensal skin bacteria, j) Fibroblasts, and k) Pigmentation including melasma, The pigment phototherapy agent according to claim 1, characterized in that it is at least one of the following.

8. A filter for adjusting the degree to which an externally irradiated excitation light is transmitted to tissue to which a pigment phototherapy agent according to any one of claims 1 to 7 has been added, The degree of transmission of excitation light is set according to the degree to which the aforementioned tissue is thermally denatured. A pigment phototherapy filter characterized by having the function of adjusting the target degree of thermal denaturation of the tissue by being attached to the surface of the epidermis in the area where the tissue is present.

9. The dye phototherapy filter according to claim 8, characterized in that the thickness or number of layers of the filter is set to be within an acceptable range for light straight-line propagation.

10. A pigment phototherapy needle for injecting a pigment phototherapy agent according to any one of claims 1 to 7 into the tissue, A substrate to be attached to the outer surface of the epidermis corresponding to the aforementioned tissue, Multiple needles arranged on the inner surface of the substrate, Equipped with, The aforementioned needle is (1) An embodiment having at least one pore in which a pigment phototherapy agent is held inside, (2) An embodiment in which a pigment phototherapy agent is held on the surface, (3) A method in which the pigment phototherapy agent is injected into the tissue by dissolving it. A pigment phototherapy needle characterized by being at least one of the following embodiments.

11. A pigment phototherapy device using a pigment phototherapy agent according to any one of claims 1 to 7, A therapeutic agent injection device for injecting the aforementioned pigment phototherapy agent into the tissue, A light irradiation device that irradiates the aforementioned tissue with the excitation light from the outside, A pigment therapy device characterized by comprising at least the following.

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