Light irradiation device for photodynamic therapy

Abstract

A light irradiation device (100) for photodynamic therapy is provided with: a flexible substrate (101); and a light source unit that is disposed on the flexible substrate (101) and includes a first LED element (103a) having a peak wavelength in a range of 400-420 nm, a second LED element (103b) having a peak wavelength in a range of 500-520 nm, and a third LED element (103c) having a peak wavelength in a range of 625-645 nm.

Description

Photodynamic therapy light irradiation device

[0001] The present invention relates to a light irradiation device for photodynamic therapy.

[0002] Photodynamic therapy (PDT) is known as one of the conventional light-based therapies. PDT is a treatment that utilizes the properties of photosensitizers that have affinity for lesions (affected abnormal tissues) in vivo. Specifically, by utilizing the property of photosensitizers that specifically accumulate at lesion sites, a precursor photosensitizer is administered to the living body, and the photosensitizer (including photosensitizers synthesized in vivo from the precursor of the photosensitizer) is irradiated with light (visible light), and reactive oxygen species generated within the tissue are utilized to selectively destroy only the abnormal tissue within the lesion. As such, PDT is expected to be a minimally invasive treatment. In recent years, PDT has been widely used in the treatment of neoplastic lesions in the field of dermatology, and numerous studies have been conducted to attempt clinical applications of PDT for lung cancer, esophageal cancer, gastric cancer, colon cancer, malignant brain tumors, and other cancers. In particular, PDT has attracted attention as a new treatment option for glioblastoma, a malignant brain tumor, because the average survival time is less than two years even with standard treatments (surgery, chemotherapy, and radiation therapy). One of the factors contributing to the intractability of glioblastoma is the presence of refractory tumor stem cells. This intractability includes poor differentiation potential, the possibility of multiple drug efflux, and tolerance to hypoxic environments.

[0003] PDT exerts tumor-selective cell killing effects by utilizing the direct action of excitation light of a specific wavelength on tumor-affinity photosensitizers (PS), which specifically accumulate in tumor cells. When tumor-affinity PS is irradiated with excitation light of a specific wavelength, it transitions from its ground state. The reactive oxygen species (free radicals) and singlet oxygen species generated by the energy conversion during the return to the ground state exert tumor-killing effects. Therefore, it was thought that the therapeutic effect of PDT would be weakened against tumor stem cells surviving under hypoxic conditions. However, it has been reported that the therapeutic effect of PDT is not significantly weakened in tumor stem cells cultured under hypoxic conditions compared to tumor stem cells cultured under normoxic conditions.

[0004] Photodynamic therapy light irradiation devices for performing PDT have traditionally used laser light sources or lamp light sources such as xenon lamps and metal halide lamps. However, in recent years, PDT light irradiation devices that use light-emitting diode (LED) elements as light sources instead of lasers or lamp light sources have been proposed. For example, Patent Document 1 discloses a PDT light irradiation device that includes a light source unit in which LED elements with peak wavelengths of 400 to 420 nm and 500 to 520 nm are arranged in a grid pattern. Patent Document 2 also discloses a PDT light irradiation device that includes LED elements with peak wavelengths of 400 to 420 nm and a fluorescent plate that transmits some of the light emitted from the LED elements and converts the other part to light with a wavelength of 500 to 520 nm.

[0005] JP 2017-6454 A Patent No. 6735995 A

[0006] The light source unit of the PDT light irradiation device described in Patent Document 1 includes an LED element unit consisting of multiple LED elements arranged on a rectangular substrate, and light generated by the LED elements is irradiated through an opening in the light source unit. Typically, in configurations with multiple LED elements, LED elements with a large divergence angle (e.g., a total divergence angle of 135°) are used to achieve a uniform illuminance distribution on the irradiated surface. Therefore, with LED elements with a large divergence angle, illuminance is highly dependent on irradiation distance. Therefore, when the irradiated area has irregularities, such as the nose or cheek, the illuminance on the concave surface is significantly lower than the illuminance on the convex surface, resulting in so-called treatment unevenness. Furthermore, when LED elements with a small divergence angle (e.g., a total divergence angle of 30°) are used, the dependence of illuminance on irradiation distance is reduced, but the illuminance distribution on the irradiated surface is less uniform, ultimately resulting in treatment unevenness.

[0007] On the other hand, the light source unit of the PDT light irradiation device disclosed in Patent Document 2 has multiple LED elements arranged on a flexible substrate. The flexible substrate deforms to conform to the surface of the affected area, which is the irradiated surface. This allows the distance between the irradiated surface and the LED elements to be maintained constant, even if the surface of the affected area is uneven. This allows light to be irradiated with uniform illuminance, preventing uneven treatment. However, the PDT light irradiation device disclosed in Patent Document 2 includes LED elements with a peak wavelength of 400 to 420 nm and a fluorescent plate that transmits a portion of the light emitted from the LED elements and converts the other portion to light with a wavelength of 500 to 520 nm. Therefore, the device irradiates only light with a relatively short peak wavelength. Because short-wavelength light has a limited tissue penetration depth, such a PDT light irradiation device is not necessarily effective for treating tumors located deep within a patient's tissue.

[0008] The present invention has been made in view of the above problems, and its object is to provide an improved PDT light irradiation device that can solve the above problems and achieve a higher therapeutic effect.

[0009] In order to achieve the above object, the PDT light irradiation device is configured to include a flexible substrate and LED elements arranged on the substrate, which emit blue light, green light, and red light, respectively.

[0010] Specifically, the first PDT light irradiation device according to the present invention comprises a flexible substrate and a light source unit including a first LED element having a peak wavelength in the range of 400 nm to 420 nm, a second LED element having a peak wavelength in the range of 500 nm to 520 nm, and a third LED element having a peak wavelength in the range of 625 nm to 645 nm, which are arranged on the flexible substrate.

[0011] According to the first PDT light irradiation device of the present invention, the light source unit is mounted on a flexible substrate, which can deform to conform to the surface of the affected area, thereby maintaining a constant distance between the affected area and the LED elements, even if the affected area has an uneven surface. Therefore, the light source unit can irradiate the affected area with uniform illuminance, preventing uneven treatment. Furthermore, according to the first PDT light irradiation device of the present invention, the light source unit includes not only a first LED element having a peak wavelength in the range of 400 nm to 420 nm and a second LED element having a peak wavelength in the range of 500 nm to 520 nm, but also a third LED element having a peak wavelength in the range of 625 nm to 645 nm. The light emitted by the third LED element having a peak wavelength in the range of 625 nm to 645 nm can reach deeper into the tissue of the affected area compared to the light emitted by the other two LED elements. Therefore, excellent PDT therapeutic effects can be achieved regardless of the location of the affected area.

[0012] The second PDT light irradiation device according to the present invention comprises a flexible substrate, and a light source unit including a white phosphor arranged on the flexible substrate, the white phosphor emitting white light having peak wavelengths within the ranges of 400 nm to 420 nm, 500 nm to 520 nm, and 625 nm to 645 nm, and an LED element having a peak wavelength within the range of 400 nm to 420 nm for exciting the white phosphor.

[0013] According to the second PDT light irradiation device of the present invention, as with the first PDT light irradiation device, the light source unit is mounted on a flexible substrate. This flexible substrate can deform to conform to the surface of the affected area, thereby maintaining a constant distance between the affected area and the LED element, even if the affected area has an uneven surface. Therefore, the light source unit can irradiate the affected area with uniform illuminance, preventing uneven treatment. Furthermore, according to the second PDT light irradiation device of the present invention, the light source unit includes a white phosphor that emits white light with peak wavelengths in the ranges of 400 nm to 420 nm, 500 nm to 520 nm, and 625 nm to 645 nm, and an LED element with a peak wavelength in the range of 400 nm to 420 nm for exciting the white phosphor. Therefore, like the first PDT light irradiation device, light with a peak wavelength in the range of 625 nm to 645 nm can reach deeper into the tissue of the affected area. Therefore, excellent PDT therapeutic effects can be achieved regardless of the location of the affected area.

[0014] The third PDT light irradiation device according to the present invention includes a flexible substrate and a light source unit including an LED element arranged on the flexible substrate, which emits pulses of infrared light having peak wavelengths in the ranges of 800 nm to 840 nm, 1000 nm to 1040 nm, and 1250 nm to 1290 nm. Two-photon excitation is a phenomenon in which two photons are simultaneously absorbed by a molecule, causing excitation.

[0015] According to the third PDT light irradiation device of the present invention, as with the first and second PDT light irradiation devices, the light source unit is mounted on a flexible substrate. This flexible substrate can deform to conform to the surface of the affected area, thereby maintaining a constant distance between the affected area and the LED element, even if the affected area has an uneven surface. Therefore, the irradiated area can be irradiated with light at a uniform illuminance, preventing uneven treatment. Furthermore, according to the third PDT light irradiation device of the present invention, the light source unit includes LED elements that emit pulsed infrared light with peak wavelengths in the ranges of 800 nm to 840 nm, 1000 nm to 1040 nm, and 1250 nm to 1290 nm. That is, these LED elements have peak wavelengths twice as long as those of the LED elements in the first and second PDT light irradiation devices. This allows, for example, two-photon excitation of a photosensitizer administered to the affected area. Two-photon excitation is a phenomenon in which two photons are simultaneously absorbed by a molecule, causing excitation.

[0016] The first to third PDT light irradiation devices according to the present invention may be used by being implanted in the human body.

[0017] In this case, metronomic PDT (mPDT), which involves long-term irradiation with low-intensity excitation light, can be performed, and superior therapeutic effects can be obtained compared to conventional PDT, for example, in the treatment of malignant brain tumors.

[0018] The first to third PDT light irradiation devices according to the present invention may be used in combination with a tumor-affinity photosensitizer. The photosensitizer is preferably 5-aminolevulinic acid (ALA). ALA is a substance naturally present in the human body, does not cause serious side effects such as photosensitivity, and is widely used worldwide in photodynamic diagnosis, including intraoperative fluorescence-assisted diagnosis.

[0019] The first PDT light irradiation device according to the present invention may further include a control unit capable of individually controlling the intensities of the light emitted from the first LED element, the second LED element, and the third LED element.

[0020] In this case, the intensity of each color of light can be controlled to be more suitable for treatment depending on the type of disease of the patient and the type of affected organ, thereby achieving a better therapeutic effect.

[0021] The first to third PDT light irradiation devices according to the present invention may be devices for treating skin cancer, lung cancer, esophageal cancer, stomach cancer, pancreatic cancer, bile duct cancer, colon cancer, prostate cancer, cervical cancer, or malignant brain tumors.

[0022] The first to third light irradiation devices for PDT according to the present invention may further include a wall portion provided on the flexible substrate so as to surround the light source unit, and a protective resin portion provided so as to cover the area surrounded by the wall portion.

[0023] In the first to third PDT light irradiation devices according to the present invention, the light source unit may be waterproofed with a biocompatible synthetic material.

[0024] It is preferable that the first to third PDT light irradiation devices according to the present invention further include a power receiving unit for wireless power supply.

[0025] In this case, even if the PDT light irradiation device is implanted in the human body, it can receive power from an external wireless power supply device, making it possible to perform PDT permanently or semi-permanently.

[0026] In this case, the power receiving unit is preferably a power receiving unit for wireless power supply using alternating current electromagnetic waves that do not affect the human body.

[0027] The PDT light irradiation device according to the present invention can irradiate the irradiated surface with light at a uniform illuminance, thereby preventing uneven treatment. Furthermore, since the light can reach deeper within the affected tissue, excellent PDT therapeutic effects can be obtained regardless of the location of the affected area.

[0028] Fig. 1 is a plan view showing the outline of the configuration of a PDT light irradiation device according to one embodiment of the present invention. Fig. 2 is a cross-sectional view showing the outline of the cross section taken along line II-II in Fig. 1. Fig. 3 is a diagram showing the wavelength distribution of white light. Fig. 4 is a graph showing the results of an example, with the vertical axis representing the cell viability (%) and the horizontal axis representing the time after PDT, showing the lethal effects of mPDT and aPDT at 0, 3, 6, 12, and 24 hours after treatment. Fig. 4(a) shows the lethal effects of mPDT and aPDT at a constant energy density of 5 J / cm. ２ Figure 4(b) shows a comparison of the cytotoxicity of mPDT and aPDT at a constant energy density of 2.5 J / cm ２ Fig. 4(c) shows a comparison of the cytotoxicity of mPDT and aPDT at different photosensitizer concentrations, and Fig. 4(d) shows a comparison of the cytotoxicity of mPDT at a constant energy density of 5 J / cm ２ Figure 4(e) shows the cytotoxicity of mPDT at different light intensities at 1000 Hz, and Figure 4(e) shows the cytotoxicity of mPDT at a constant light intensity (0.2 mW / cm ２ ) at different energy densities (2.5 and 5 J / cm ２ ), and Fig. 4(f) shows the cytotoxicity of mPDT at a constant light intensity (power density) (0.4 mW / cm ２ ) at different energy densities (2.5 and 5 J / cm ２ ) is a comparison of the cytotoxicity of mPDT.

[0029] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The following description of preferred embodiments is merely exemplary in nature and is not intended to limit the present invention, its application, or uses.

[0030] A PDT light irradiation device according to one embodiment of the present invention will be described with reference to Figures 1 and 2. As shown in Figures 1 and 2, in a PDT light irradiation device 100 according to this embodiment, a plurality of LED elements 103 are arranged on a flexible substrate 101. In this embodiment, the plurality of LED elements 103 are arranged in a 3x3 array to form a light source unit, but the number and arrangement of the LED elements are not particularly limited.

[0031] In this embodiment, the LED elements 103 constituting the light source unit include a first LED element 103a that emits light having a peak wavelength in the range of 400 nm to 420 nm (blue light), a second LED element 103b that emits light having a peak wavelength in the range of 500 nm to 520 nm (green light), and a third LED element 103c that emits light having a peak wavelength in the range of 625 nm to 645 nm (red light).

[0032] The PDT light irradiation device 100 according to this embodiment may include a wireless power supply receiving coil 102 formed on or embedded in a flexible substrate 101. The PDT light irradiation device 100 may further include a power receiving unit 104 for supplying power to LED elements 103 electrically connected to the power receiving coil 102, and a controller 106 as a control unit electrically connected to the LED elements 103 for individually controlling the wavelength and intensity of light emitted by the LED elements 103.

[0033] The PDT light irradiation device 100 according to this embodiment may also include a wall material 107 formed to surround the area on the flexible substrate 101 where the LED elements 103 are arranged, a protective resin layer 108 formed to fill the area surrounded by the wall material 107 and cover the LED elements 103, and a fluorescent screen 109 arranged to cover the protective resin layer 108 and the upper surface of the wall material 107. The fluorescent screen 109 is provided to ensure that the light generated by the LED elements 103 is uniformly irradiated onto the irradiation target. The protective resin layer 108 is preferably made of a biocompatible material, which can waterproof the light source unit. A transparent contact member 110 that contacts the irradiation surface may also be provided to cover at least the fluorescent screen 109. The contact member may be made of a lightweight, tissue-compatible material and may be an adhesive used between the flexible substrate 101 and the light source unit, which can irradiate uniform and uneven areas of the body with a uniform amount of light, does not attenuate light, does not burden the body, and does not cause side effects. The flexible substrate 101, the wall material 107, the protective resin layer 108, the fluorescent screen 109, and the contact member 110 are preferably configured to make the light source unit waterproof.

[0034] In this embodiment, as described above, the protective resin layer 108 is provided on the flexible substrate 101, and desirably has flexibility similar to that of the flexible substrate 101. Silicon resin, epoxy resin, etc. may be used as a material for forming the protective resin layer 108. The thickness of the protective resin layer 108 is, for example, 0.5 to 1 mm.

[0035] The contact member 110 is used to apply the PDT light irradiation device 100 to a lesion or an organ containing a lesion. The contact member 110 is preferably transparent. However, the contact member 110 is preferably elastically deformable according to the surface shape of the lesion, which is the irradiation surface, and adheres closely to the lesion. Furthermore, the surface of the contact member 110 preferably has adhesive properties for adhering to the lesion. By providing the contact member 110, areas containing metal materials that cause metal allergies can be kept away from the lesion by the contact member 110. Therefore, the PDT light irradiation device 100 can also be used for patients with metal allergies. The contact member 110 preferably has a transmittance of 80% or more for light emitted from the light source. The contact member 110 can be made of various materials, such as flexible epoxy, polyurethane, or silicone-based transparent resin plates, or silicone-based transparent resin plates, or water-absorbent polymers or styrene-based elastomers with a thin film formed into a plate or plastic bag shape containing water or air.

[0036] The PDT light irradiation device 100 can be used by closely adhering the contact member 110 to the surface of the lesion. Specifically, when the contact member 110 is pressed against the surface of the lesion, the light source unit-mounted flexible substrate 101 deforms in accordance with the surface of the lesion. As a result, the contact member 110 closely adheres to the surface of the lesion. The light source unit-mounted flexible substrate 101 can maintain a constant distance between the irradiation surface and the LED elements 103, even if the irradiation surface is uneven, such as the lesion. Therefore, light with a uniform illuminance can be irradiated onto the irradiation surface of the lesion.

[0037] The PDT light irradiation device 100 according to this embodiment can be implanted in a living body, such as a human body, for the treatment of disease. The PDT light irradiation device 100 can also be used with a biologically administered substance containing a photosensitizer or a photosensitizer precursor for the treatment of disease. The substance administered to the living body can be a compound that reacts appropriately in vivo and accumulates as a porphyrin compound in the affected area. An example of a biologically administered substance is ALA, a precursor to a photosensitizer. ALA is synthesized through an enzymatic reaction to form protoporphyrin IX (PpIX), which functions as a photosensitizer. ALA is a substance naturally present in the human body. It is a biomolecule synthesized from glycine and succinyl coenzyme A (succinyl-CoA) and is used as a preparation for porphyrin synthesis. Therefore, ALA is preferred because it does not cause serious side effects, such as photosensitivity, compared to other porphyrins, such as talaporfin.

[0038] When ALA is used as a substance to be administered to a living body, PpIX functions as a photosensitizer. It is known that the absorption spectrum of PpIX has absorption peaks at wavelengths of 410 nm, 510 nm, 545 nm, 580 nm, and 630 nm. Therefore, it is believed that light emitted from a light source is absorbed by PpIX at a first absorption wavelength of 410 nm, a second absorption wavelength of 510 nm, a third absorption wavelength of 545 nm, a fourth absorption wavelength of 580 nm, and a fifth absorption wavelength of 630 nm, or wavelengths close thereto. The absorbance of PpIX increases in the order of wavelengths 410 nm, 510 nm, 545 nm, 580 nm, and 630 nm, while the propagation of light at these wavelengths in a living body decreases in the order of wavelengths 410 nm, 510 nm, 545 nm, 580 nm, and 630 nm.

[0039] The depth of lesions in living organisms is not always the same; that is, lesions may exist only in shallow regions or in both shallow and deep regions. If the lesion is too deep to be seen from the surface, tumor growth may remain, potentially resulting in insufficient photodynamic therapy efficacy. Because the fifth absorption wavelength of PpIX penetrates deeper into tissue than other wavelengths, it is important to incorporate an LED element 103 that emits light of this wavelength. Therefore, as described above, the PDT light irradiation device 100 according to this embodiment includes a third LED element 103c that emits light (red light) with a peak wavelength in the range of 625 nm to 645 nm. This allows for therapeutic effects even on tumors located deep within tissue.

[0040] In this embodiment, the wireless power supply device that supplies power to the PDT light irradiation device 100 via the power receiving coil 102 is usually installed outside the living body, and therefore, when used to supply power to the light source unit, AC electromagnetic waves of a value that does not affect the living body are used. The temperature of the flexible substrate 101 equipped with the light source unit during operation is preferably controlled to, for example, 41°C or less to minimize the effect on the living body.

[0041] The flexible substrate 101 is advantageous for irradiating both flat and uneven areas of a living body. Specifically, the flexibility of the flexible substrate 101 equipped with a light source unit allows it to provide uniform illuminance and spectral distribution to the irradiated surface, whether the irradiated surface is flat or uneven. The structure and size of the flexible substrate 101 equipped with a light source unit can be changed depending on the type of disease or the type of organ in the living body. For example, the flexible substrate 101 is a flexible insulating substrate made of a resin material such as polyimide, which is an insulating film. However, the material of the flexible substrate 101 is not limited to polyimide, and any insulating material may be used as long as it has the required mechanical strength and flexibility. In addition to polyimide resin film, films such as fluororesin, silicone resin, and polyethylene terephthalate resin can be used as the flexible substrate 101. Furthermore, the flexible substrate 101 can be a highly reflective resin film coated with a resin containing a white pigment (white resin, white resist, etc.), a highly reflective film mixed with a white pigment, a liquid crystal polymer film, etc. The thickness of the flexible substrate 101 is, for example, 25 μm to 200 μm, and more preferably 40 to 100 μm. If the flexible substrate 101 is too thin, it may be difficult to obtain the required mechanical strength. On the other hand, if the flexible substrate 101 is too thick, it may be difficult to obtain the required flexibility. The size of the flexible substrate 101 is not limited. It is preferable that the flexible substrate 101 be large enough to cover the lesion to be irradiated. However, if the flexible substrate 101 is formed to a size that allows the light source unit to irradiate light while covering the lesion and its surroundings, it is possible to reduce the restraint on the patient and minimize the burden on the patient.

[0042] The PDT light irradiation device 100 is suitable for localized lesions with a relatively small area of ​​approximately a few centimeters. In the PDT light irradiation device 100 according to this embodiment, the flexible substrate 101 is preferably formed to a size corresponding to the localized lesion. Furthermore, the flexible substrate 101 is preferably transparent so that light emitted by the LED elements 103 can pass through. Specifically, the flexible substrate 101 preferably has a transmittance of 80% or more for light emitted from the LED elements 103. This configuration reduces the power consumption of the light source unit and the heat generated by the light source unit.

[0043] The PDT light irradiation device 100 according to this embodiment can be used to treat various cancers, such as skin cancer, lung cancer, esophageal cancer, stomach cancer, pancreatic cancer, gallbladder cancer, colon cancer, prostate cancer, cervical cancer, and malignant brain tumors. In the treatment of these diseases, the optimal excitation wavelength of the light source unit varies depending on the target organ of the living body. For example, in the case of malignant brain tumors, the optimal excitation wavelength preferably includes red light, which has a higher tissue penetration ability.

[0044] In this embodiment, the PDT light irradiation device 100 includes a first LED element 103a that emits light having a peak wavelength in the range of 400 nm to 420 nm, a second LED element 103b that emits light having a peak wavelength in the range of 500 nm to 520 nm, and a third LED element 103c that emits light having a peak wavelength in the range of 625 nm to 645 nm. However, instead, a white-emitting phosphor and an LED element 103 that emits blue light to excite the phosphor may be provided. As shown in FIG. 3 , the white light includes peak wavelengths of blue, green, and red light, and therefore can be used in place of the above-mentioned colors of light.

[0045] Furthermore, in this embodiment, instead of the first LED element 103a, the second LED element 103b, and the third LED element 103c, or the white-emitting phosphor and the LED element 103 emitting blue light for exciting it, a light source unit including an LED element that irradiates pulsed infrared light having a peak wavelength in the ranges of 800 nm to 840 nm, 1000 nm to 1040 nm, and 1250 nm to 1290 nm may be used. The peak wavelengths of 800 nm to 840 nm, 1000 nm to 1040 nm, and 1250 nm to 1290 nm are peak wavelengths that are twice the peak wavelengths of the light emitted by the first LED element 103a, the second LED element 103b, and the third LED element 103c. This enables two-photon excitation when excitation is performed by the first LED element 103a, the second LED element 103b, and the third LED element 103c. Two-photon excitation is a phenomenon in which two photons are simultaneously absorbed by a molecule, causing excitation.

[0046] The PDT light irradiation device 100 according to this embodiment can be used for metronomic PDT (mPDT), which involves long-term irradiation with low-intensity excitation light. The use of mPDT has the potential to provide a more effective treatment for various diseases, including malignant brain tumors. Furthermore, the use of mPDT can suppress photobleaching, a phenomenon in which PS in tumor cells is destroyed by high-intensity light irradiation used in conventional PDT. Previous studies have suggested that mPDT may be more effective than conventional PDT (see, for example, X. Shi et al., Journal of Photochemistry & Photobiology, B: Biology 198 (2019) 111586).

[0047] An example of a test comparing the mPTD described in the above document with a conventional PTD is described below. Table 1 below shows the types of mPDT and acute photodynamic therapy (aPDT) used in the test, as well as the intensity and duration of irradiation. The columns indicate the test group, PDT type, and joules per square centimeter (J / cm). ２ ) and power density in milliwatts per square centimeter (mW / cm ２), exposure time (hours, minutes, seconds: h, min, s), and ALA concentration (mM). Many current PDT clinical trials use aPDT, which involves short, high-intensity light exposure administered intraoperatively. In mPDT, both the photosensitizer and light are delivered continuously over a long period of time at a slower rate, increasing selective tumor cell death through the induction of apoptosis.

[0048]

[0049] The results of this test are shown in Figure 4. Figure 4 is a graph showing the cell viability (%) on the vertical axis and the time after PDT on the horizontal axis, and shows the lethal effects of mPDT and aPDT at 0, 3, 6, 12, and 24 hours after treatment. Note that Figure 4(a) shows the lethal effects of mPDT and aPDT at a constant energy density of 5 J / cm. ２ Figure 4(b) shows a comparison of the cytotoxicity of mPDT and aPDT at a constant energy density of 2.5 J / cm ２ Fig. 4(c) shows a comparison of the cytotoxicity of mPDT and aPDT at different photosensitizer concentrations, and Fig. 4(d) shows a comparison of the cytotoxicity of mPDT at a constant energy density of 5 J / cm ２ Figure 4(e) shows the cytotoxicity of mPDT at different light intensities at 1000 Hz, and Figure 4(e) shows the cytotoxicity of mPDT at a constant light intensity (0.2 mW / cm ２ ) at different energy densities (2.5 and 5 J / cm ２ ), and Fig. 4(f) shows the cytotoxicity of mPDT at a constant light intensity (power density) (0.4 mW / cm ２ ) at different energy densities (2.5 and 5 J / cm ２ ) is a comparison of the cytotoxicity of mPDT.

[0050] As shown in Figures 4(a) and (b), mPDT has a lower cell survival rate and a higher therapeutic effect than aPDT at the same energy density. Furthermore, as shown in Figure 4(c), the higher the concentration of ALA administered, the higher the therapeutic effect. As shown in Figure 4(d), the higher the light intensity at the same energy density, the higher the therapeutic effect. Furthermore, as shown in Figures 4(e) and (f), the higher the energy density at the same light intensity, the higher the therapeutic effect. As described above, mPDT is thought to provide better therapeutic effects for various diseases, including malignant brain tumors, than conventional PDT.

[0051] As described above, the PDT light irradiation device of the present invention has LED elements mounted on a flexible substrate, which can deform to conform to the surface of the affected area. This allows the distance between the irradiated surface and the LED elements to be maintained constant, even if the surface of the affected area is uneven. This allows light to be irradiated with uniform irradiance, preventing uneven treatment. Furthermore, the PDT light irradiation device of the present invention can irradiate light having peak wavelengths in the ranges of 400 nm to 420 nm, 500 nm to 520 nm, and 625 nm to 645 nm, making it applicable to a wide range of affected areas in the depth direction. Light having a peak wavelength in the range of 625 nm to 645 nm is particularly useful because it can reach deeper parts of the irradiated tissue. Therefore, the PDT light irradiation device of the present invention can achieve excellent PDT therapeutic effects regardless of the location of the affected area. In particular, the PDT light irradiation device of the present invention can achieve high therapeutic effects when used for mPDT.

[0052] REFERENCE SIGNS LIST 100 PDT light irradiation device 101 Flexible substrate 102 Power receiving coil 103 LED element 104 Power receiving section 105 Conductor 106 Controller 107 Wall material 108 Protective resin layer 109 Fluorescent screen 110 Contact member

Claims

1. A light irradiation device for photodynamic therapy comprising: a flexible substrate; and a light source unit including: a first LED element having a peak wavelength in the range of 400 nm to 420 nm, a second LED element having a peak wavelength in the range of 500 nm to 520 nm, and a third LED element having a peak wavelength in the range of 625 nm to 645 nm, arranged on the flexible substrate.

2. A light irradiation device for photodynamic therapy comprising: a flexible substrate; and a light source unit including: a white phosphor disposed on the flexible substrate, the white phosphor emitting white light having peak wavelengths within the ranges of 400 nm to 420 nm, 500 nm to 520 nm, and 625 nm to 645 nm; and an LED element having a peak wavelength within the range of 400 nm to 420 nm for exciting the white phosphor.

3. A light irradiation device for photodynamic therapy comprising: a flexible substrate; and a light source unit including an LED element arranged on the flexible substrate that irradiates pulses of infrared light having peak wavelengths within the ranges of 800 nm to 840 nm, 1000 nm to 1040 nm, and 1250 nm to 1290 nm.

4. The light irradiation device for photodynamic therapy according to any one of claims 1 to 3, which is implanted in the human body for use.

5. A photodynamic therapy light irradiation device according to any one of claims 1 to 3, used together with a tumor-affinity photosensitizer.

6. The photodynamic therapy light irradiation device according to claim 5, wherein the tumor-affinity photosensitizer is 5-aminolevulinic acid.

7. A light irradiation device for photodynamic therapy as described in claim 1, further comprising a control unit capable of individually controlling the intensities of light emitted from the first LED element, the second LED element, and the third LED element.

8. A light irradiation device for photodynamic therapy according to any one of claims 1 to 3, for treating skin cancer, lung cancer, esophageal cancer, stomach cancer, pancreatic cancer, bile duct cancer, colon cancer, prostate cancer, cervical cancer, or malignant brain tumor.

9. A photodynamic therapy light irradiation device according to any one of claims 1 to 3, further comprising: a wall portion provided on the flexible substrate so as to surround the light source unit; and a protective resin portion provided so as to cover the area surrounded by the wall portion.

10. A light irradiation device for photodynamic therapy according to any one of claims 1 to 3, wherein the light source unit is waterproofed by a biosynthetic material.

11. A light irradiation device for photodynamic therapy according to any one of claims 1 to 3, further comprising a power receiving unit for wireless power supply.

12. The light irradiation device for photodynamic therapy according to claim 11, wherein the power receiving unit is a power receiving unit for wireless power supply using alternating current electromagnetic waves that do not affect the human body.

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