Methods of using therapeutic fiber optic probes and therapeutic systems, as well as photoactivated compounds for use in therapeutic systems.

Abstract

The present invention provides a therapeutic fiber optic probe, which is configured to be inserted into an endoscope or catheter and has a front end that can irradiate light to the side. The therapeutic fiber optic probe includes: a light transmission structure 3, which can output light in a predetermined direction; and a mirror structure 4, which is positioned to receive light output from the light transmission structure; and the mirror structure causes a portion of the received light required for treatment to be reflected with a reflectivity of more than 90% in a direction different from the predetermined direction, thereby generating a light spot that distributes light energy evenly throughout its entirety.

Description

Technical Field

[0001] The present invention relates to a therapeutic optical fiber probe. Prior Art

[0002] Currently, there is a two-step treatment method: administering a drug containing a complex composed of a photosensitive dye and a component that selectively accumulates in specific cells, and then irradiating the patient with light of a specific wavelength that reacts with the photosensitive dye. A photosensitive dye is a substance that reacts to light within a specific wavelength range. After the drug (complex) selectively targets specific cells, these cells are then irradiated with light of a specific wavelength for a specified period of time. This activates the photosensitive dye, which then kills or eliminates the specific cells through biochemical and physical processes. When irradiating specific tissues with light, a fiber optic probe is used for treatment. For example, light therapy can be performed by irradiating an affected area externally or internally with light (including laser light). [Prior Art Literature] (Patent Document)

[0003] Patent Document 1: US Pat. No. 8,425,500 B2 Patent Document 2: US9,323,005B1 Patent Document 3: US2018 / 0214211A1 Summary of the Invention

[0004] [Problems to be solved by the invention]

[0005] However, as the optical fiber probe used in the above-mentioned phototherapy, a front-irradiation type optical fiber probe (ie, a conventional front diffuser) is generally used in which light is irradiated from the front end thereof toward the front (front).

[0006] In this case, the front diffuser only irradiates light from its front end toward the front (front). Therefore, during phototherapy, the front diffuser must be oriented or bent so that its front end faces the affected area.

[0007] However, the front diffuser is designed with a certain allowable curvature radius, limiting the direction and amount of curvature. Furthermore, the irradiation distance from the front diffuser tip to the irradiated surface must be maintained at a certain distance or greater. Therefore, for example, within a narrow lumen, there are areas where light is difficult to irradiate. If an affected area is located in this area, it may be difficult to perform phototherapy or photoimmunotherapy on that affected area.

[0008] As a solution, a tip can be designed to irradiate light in a direction other than the front (front), such as to the side (side). However, using a conventional mirror for reflection has a low reflectivity. For example, the JIS standard for mirror materials (JIS R 3220:2011) stipulates a mirror reflectivity of 83% or higher. Furthermore, in order for a photosensitizing dye to be activated by light of a specific wavelength, a certain level of light energy is required, requiring uniform light energy across the irradiated surface. Furthermore, consider the case where a fiber optic probe is used with an endoscope or catheter. Therefore, the size (diameter) of the fiber optic probe, including the tip, must be set to a size that allows insertion into an endoscope or catheter.

[0009] Therefore, an object of the present invention is to provide a therapeutic optical fiber probe having a size that can be inserted into an endoscope or a catheter and having a front end portion that can efficiently irradiate uniform light to the side (lateral direction). [Technical means to solve the problem]

[0010] To achieve this objective, the present invention includes: a light transmission structure 3 that can output light in a predetermined direction; and a mirror structure 4 that is positioned to receive the light output from the light transmission structure; and the mirror structure reflects a portion of the received light required for treatment in a direction different from the predetermined direction with a reflectivity of more than 90%, thereby generating a light spot with a uniform light energy distribution throughout the entire structure. (Effects of the Invention)

[0011] According to the present invention, a therapeutic optical fiber probe can be realized, which is set to a size that can be inserted into an endoscope or a catheter and has a front end portion that can efficiently irradiate uniform light to the side (side). Simple diagram description

[0012] FIG1 is a cross-sectional view of a distal end portion of a medical optical fiber probe according to one embodiment of the present invention. FIG2 is a cross-sectional view of the distal end portion of the optical fiber probe for treatment as viewed from the opening side. FIG3 is a diagram showing the results of a test for evaluating the uniformity of reflected light, reflectivity, and temperature rise of a mirror structure. FIG. 4 is a graph showing the reflectivity evaluation test results at specific wavelengths (690 nm band and 530 nm band). Implementation Method

[0013] "Contents of one embodiment" Figures 1 and 2 illustrate the internal structure of the distal end portion 2 of the therapeutic fiber optic probe 1. In the therapeutic fiber optic probe 1, various phototherapy methods (including laser therapy) and / or photoimmunotherapy are applied to the affected area by irradiating light of a specific wavelength required for treatment from the distal end portion 2 toward the side (lateral) of the affected area. Non-limiting examples of such treatments include phototherapy for cancer treatment and cell and tissue ablation, and photoimmunotherapy for killing tumors or tumor cells, treating precancerous lesions, and treating cancer.

[0014] The optical fiber probe 1 for treatment is configured to be applicable to both a modification in which it is used with an endoscope or a catheter (not shown) and a modification in which it is used without an endoscope or a catheter (ie, a modification in which the optical fiber probe 1 for treatment is used alone).

[0015] Therefore, the size (diameter) of the therapeutic fiber optic probe 1, including the distal end portion 2, can be designed to be insertable into an endoscope or catheter. For example, according to the specifications of a typical upper gastrointestinal endoscope, it is designed to fit within the jaws (working channel) of a 2.8 mm diameter.

[0016] As shown in Figures 1 and 2, the therapeutic fiber optic probe 1 comprises a light transmission structure 3, a mirror structure 4, a tubular structure 5, a cover structure 6, and a light-shielding structure 7. The light transmission structure 3 utilizes an existing front diffuser (i.e., an optical fiber) as is, allowing it to transmit various types of light, including laser light. A lens structure 8 (objective lens) is mounted at the distal end of the light transmission structure 3. Light transmitted through the light transmission structure 3 is output from the lens structure 8 in a predetermined direction (e.g., forward).

[0017] The mirror structure 4 is positioned to receive the light output from the light transmission structure 3 (hereinafter referred to as output light L1). In this case, the mirror structure 4 is positioned opposite the distal end (lens structure 8) of the light transmission structure 3. The mirror structure 4 reflects a portion of the received output light L1, which is necessary for treatment, in a direction different from the predetermined direction. Hereinafter, the light reflected from the mirror structure 4 is referred to as reflected light L2. The structure of the mirror structure 4 will be described below.

[0018] The light transmission structure 3 and the mirror structure 4 are housed within the tubular structure 5. The tubular structure 5 extends to cover the entire length of the light transmission structure 3 and covers the mirror structure 4 so that the positional relationship between the front end (lens structure 8) of the light transmission structure 3 and the mirror structure 4 remains fixed.

[0019] The tubular structure 5 comprises a metal mesh structure in the shape of a hollow cylinder. The metal mesh structure is formed by, for example, winding thin, long metal wires (not shown) made of stainless steel in one direction and then in the opposite direction. In this case, the metal mesh structure is a flexible structure formed by winding the stainless steel wires in different directions. This allows the distal end portion 5a of the tubular structure 5 to rotate with good tracking performance. Consequently, the distal end portion 2 of the therapeutic optical fiber probe 1 can also rotate with similar good tracking performance.

[0020] Furthermore, the distal end 5a of the tubular structure 5 houses the distal end (lens structure 8) of the aforementioned light transmission structure 3 and the mirror structure 4. This allows the direction of the reflected light L2 from the mirror structure 4, which receives the output light L1 from the light transmission structure 3, to be freely adjusted by rotating the distal end 5a of the tubular structure 5. As a result, for example, when used in phototherapy, the degree of freedom in the irradiation direction and range of the reflected light L2 from the mirror structure 4 can be increased.

[0021] Furthermore, the tubular structure 5 includes an opening 5b for allowing the reflected light L2 from the mirror structure 4 to pass through. The cover structure 6 is provided to cover the front end 5a of the tubular structure 5, sealing the opening 5b from the outside. This allows the front end of the light transmission structure 3 (the lens structure 8) and the mirror structure 4 to be housed within the cover structure 6.

[0022] In this case, the cover structure 6 is made of a hollow transparent member (eg, glass). Thus, the reflected light L2 from the mirror structure 4 passes through the opening 5b of the tubular structure 5, and then a suitable amount of light is transmitted through the cover structure 6 and directly emitted to the outside.

[0023] Optionally, multiple markers 9 are further provided along the outer circumference of the tubular structure 5 at regular intervals (e.g., at 2.5 mm intervals). For example, the multiple markers 9 are each in the form of a continuous ring extending along the outer circumference of the tubular structure 5 and are affixed by printing or other means. In this case, the thickness and spacing of each marker 9 can be arbitrarily set according to the intended use or application of the therapeutic fiber optic probe 1. These multiple markers 9 can serve as a positioning "ruler" during treatment. For example, when used in an endoscope, these markers can be used to visually determine the size and position of the object of observation (tissue, affected area).

[0024] Next, the mirror structure 4 will be described in detail. As shown in Figures 1 and 2, the mirror structure 4 includes a flat, non-concave reflective portion 4p. The reflective portion 4p is positioned opposite the distal end (lens structure 8) of the light transmission structure 3. The reflective portion 4p is tilted at a predetermined angle θ, with a slope that increases as it moves away from the distal end (lens structure 8) of the light transmission structure 3.

[0025] Here, the tilt angle θ can be defined as the angle θ formed by the reflector 4p relative to the imaginary axis Ax extending parallel to the output light L1 from the light transmission structure 3 (i.e., the angle θ formed by Ax and the reflector 4p).

[0026] In this case, the tilt angle θ can be set according to the intended use or application of the therapeutic optical fiber probe 1. For example, when the reflected light L2 from the mirror structure 4 is tilted 90° relative to the output light L1 from the light transmission structure 3, the tilt angle θ of the reflecting portion 4p can be set to 45°.

[0027] Thus, by setting the inclination angle θ of the reflecting portion 4 p , the reflected light L2 from the mirror structure 4 can be emitted in a direction different from the direction in which the output light L1 from the light transmission structure 3 travels (ie, a predetermined direction).

[0028] Furthermore, if a fixed direction is defined as the output direction of the output light L1 from the light transmission structure 3, i.e., "forward," then different directions can be defined as directions other than the fixed direction, such as "lateral," including directions intersecting or perpendicular to the fixed direction. This allows all light emitted to the outside through the opening 5b of the tubular structure 5 described below to become therapeutic light output "laterally" from the distal end portion 2 of the therapeutic optical fiber probe 1.

[0029] In the embodiment, the reflective portion 4p of the mirror structure 4 has a structure formed by laminating a dielectric multilayer film (not shown). A dielectric multilayer film refers to a reflective mirror having a reflective film formed by alternating layers of high-refractive-index and low-refractive-index dielectric thin films. The reflective portion 4p of the mirror structure 4 constitutes this reflective mirror.

[0030] Furthermore, in some embodiments, the reflective portion 4p (also referred to as the light-transmitting portion) of the mirror structure 4 is configured to transmit light other than the reflected light L2, which is reflected in a different direction. In this case, a light-blocking structure 7 (e.g., a structure coated with black paint or using other means to block emitted light) is provided on the opposite side of the mirror structure 4 from the reflective portion 4p to block the transmitted light. This prevents light that has passed through the reflective portion 4p from escaping to the outside or from reaching the reflective portion 4p as return light.

[0031] Here, the light received by the mirror structure 4 (reflecting portion 4p) includes multiple different wavelengths. The mirror structure 4 (reflecting portion 4p) is designed to reflect light of all wavelengths, but to reflect the target wavelength most strongly. For example, among the target wavelengths, light that can be used for phototherapy or photoimmunotherapy includes light in the wavelength range of 650 to 800 nm, but this is not limited to these. Examples include light with wavelengths of 690 nm, 680 nm, 675 nm, and 670 nm. Furthermore, light with a wavelength around 530 nm is used as guide light.

[0032] When light of a specific wavelength is required, the reflectivity of the mirror structure 4 (reflecting portion 4p) is preferably set to a reflectivity of 90% or more, including at least one wavelength of the required specific wavelength relative to the multiple wavelengths contained in the received light.

[0033] Furthermore, as the amount of reflected light of the mirror structure 4 (reflecting portion 4p), if the amount of light received by the mirror structure 4 (reflecting portion 4p) is set to 100%, the mirror structure 4 (reflecting portion 4p) is preferably set to include the amount of light of a specific wavelength so that the amount of light reflected from the mirror structure 4 (reflecting portion 4p) is at least 90%.

[0034] Features and advantages of one embodiment According to this embodiment, the size (diameter) of the therapeutic fiber optic probe 1, including the distal end 2, can be set to a size suitable for insertion into an endoscope or catheter, and therapeutic light can be output laterally from the distal end 2 of the therapeutic fiber optic probe 1. Furthermore, the distal end 2 of the therapeutic fiber optic probe 1 can be rotated with good tracking performance by means of a tubular structure 5 having a metal mesh structure. This allows for the use of conventional forward irradiation diffusers within a narrow lumen (e.g., for therapeutic purposes) where light is difficult to irradiate. If an affected area is present in this area, phototherapy (e.g., photoimmunotherapy) cannot be successfully performed on the affected area. However, the therapeutic fiber optic probe 1 of this embodiment allows the entire affected area within the narrow lumen to be effectively irradiated with therapeutic light. Consequently, the selectivity and effectiveness of treatment of the affected area are improved.

[0035] According to this embodiment, the tilt angle θ of the mirror structure 4p can be set according to the purpose or application of the therapeutic optical fiber probe 1. For example, the direction of the therapeutic light output "laterally" from the distal end 2 of the therapeutic optical fiber probe 1 can be freely set.

[0036] According to this embodiment, a plurality of markings 9 are provided along the outer circumference of the tubular structure 5 at regular intervals (e.g., 2.5 mm intervals). This eliminates the need for separate measuring tools such as rulers. For example, when used in conjunction with an endoscope, the size and position of the object (tissue, affected area) can be visually determined. Consequently, the selectivity and effectiveness of phototherapy for affected areas can be significantly improved.

[0037] According to this embodiment, the reflective portion 4p of the mirror structure 4 reflects only light of a specific wavelength required for treatment (for example, light in the 650-800 nm wavelength range, such as 690 nm, used for phototherapy or photoimmunotherapy, or green light in the 530 nm wavelength range used as guide light) and outputs it "sideways" from the distal end 2 of the therapeutic optical fiber probe 1. In this case, the reflectivity of the mirror structure 4 (reflective portion 4p) is set to 90% or higher, with respect to the multiple wavelengths contained in the received light, including at least one wavelength of the required specific wavelength. Furthermore, the mirror structure 4 (reflective portion 4p) is set so that the amount of light reflected from the mirror structure, including the light of the specific wavelength, is at least 90%, assuming the amount of light received by the mirror structure 4 (reflective portion 4p) is 100%. In this way, the reflection intensity of the guide light is monitored, thereby enabling light therapy using therapeutic light safely and with high precision.

[0038] Figure 3 shows exemplary evaluation test results for a therapeutic fiber optic probe 1 exhibiting the aforementioned characteristics and effects. In the evaluation test, ten therapeutic fiber optic probes 1, for example, samples 1 to 10, were randomly selected from a plurality of manufactured therapeutic fiber optic probes 1. The diameter of the irradiated light spot generated at the target (specifically, the reflector 4p) was measured when the distance between the target and the therapeutic fiber optic probe 1 (specifically, the reflector 4p) was set to a constant value (e.g., 50 mm). The diameter was confirmed to be within the range of 30.5 ± 1.5 mm.

[0039] In this case, if the target radiation intensity within the flat irradiation surface is set to 100%, it is confirmed that the radiation intensity in the irradiation circle measured above is within the range of 100% ± 15% (i.e., near 100%, within the range of -15% to +15%).

[0040] The evaluation test results clearly show that each sample has a minimum and maximum radiation intensity, but the individual samples and the overall average all fall within the range of 100% ± 15% of the target radiation intensity. Furthermore, the reflectivity of the reflective portion 4p of the mirror structure 4 has been shown to exhibit the aforementioned characteristics, with a reflectivity of 90% or higher for light of specific wavelengths (e.g., therapeutic light in the 690 nm band and guiding light in the 530 nm band). Furthermore, this value is measured after reflection from the mirror structure 4 and transmission through the cover structure 6. Therefore, it is believed that the reflectivity of the mirror structure 4 is slightly higher than the value shown in Figure 3. Furthermore, the temperature of the distal end portion 2 of the therapeutic optical fiber probe 1 was measured as it actually rose from room temperature of 20°C.

[0041] Figure 4 shows exemplary evaluation test results for ten therapeutic optical fiber probes 1, representing new samples 101 to 110 different from those described above, focusing on light of specific wavelengths (690 nm therapeutic light and 530 nm guide light). The evaluation test results clearly demonstrate that both types of light (therapeutic light and guide light) exhibit nearly identical reflectivity. This means that the spots generated by the therapeutic light and the guide light have the same size and shape on the target surface, as well as the following uniform optical properties.

[0042] To leverage this characteristic, a dielectric multilayer film is formed on the reflective portion 4p of the mirror structure 4 (also called a microlens) (i.e., multiple dielectric films are laminated to cover the reflective portion 4p of the mirror structure 4). This ensures that the spot of light generated by the reflected light L2 on the target surface (e.g., the affected area) is a true circular spot, and that the light energy distribution (i.e., light intensity distribution) is uniform across the entire surface. Consequently, in treatments of target tissues in subjects, such as photodynamic therapy (PDT), photothermal therapy (PTT), photoimmunotherapy (PIT), and other phototherapy methods, photoactivated compounds (e.g., photoactivatable dyes or complexes) are administered to the subject in advance, thereby activating a chemical reaction and effectively and efficiently applying treatment to the affected area.

[0043] In the embodiment, when treating a target tissue in a subject, the distance between the therapeutic optical fiber probe 1 (specifically, the reflecting portion 4p) and the target (affected part) surface is set to be approximately 5 mm to approximately 80 mm. Furthermore, by configuring the reflective portion 4p of the mirror structure 4 to form a dielectric multilayer film formed by laminating two or more dielectric thin films, it is possible to make the wavelength of about 660 nm to about 820 nm, for example, about 660 nm to about 740 nm, or for example, about 660 nm, about 670 nm, about 675 nm, about 677 nm, about 680 nm, about 685 nm, about 690 nm, about 695 nm, about 700 nm, about 705 nm, about 710 nm, about 715 nm, about 720 nm, about 725 nm, about 730 nm, about 735 nm, about 740 nm, about 745 nm, about 750 nm, about 755 nm, about 760 nm, about 765 nm, about 770 nm, about 775 nm, about 780 nm, about 785 nm, about 790 nm, about 795 nm, about 800 nm, 805 nm, about 810 nm, about 825 nm, about 830 nm, about 835 nm, about 840 nm, about 855 nm, about 860 nm, about 875 nm, about 880 nm, about 890 nm, about 905 nm, about 910 nm, about 920 nm, about 930 nm, about 940 nm, about 950 nm, about 960 nm, about 970 nm, about 980 nm, about 990 nm, about 995 nm, about 1000 nm, about 1010 nm, about 1020 nm, about 1030 nm, about 1040 nm, about 1050 nm, about 1060 nm, about 1070 nm Light with a wavelength of approximately 815 nm, 820 nm, or 675 nm is optimal. In one embodiment, light is emitted at two or more wavelengths, including a therapeutic light band (e.g., therapeutic light in the 675 nm, 677 nm, 690 nm, 780 nm, or 800 nm band) and a guiding light band (e.g., guiding light in the 530 nm band). In this case, only two specific wavelengths (e.g., therapeutic light in the 675 nm, 677 nm, 690 nm, 780 nm, or 800 nm band, and guiding light in the 530 nm band) can be reflected with high precision.

[0044] In some embodiments of a method for treating a target tissue in a subject, a photoactivatable compound (a dye or a dye complex) is administered to the subject prior to irradiation with light. For example, the photoactivatable compound can be a pharmaceutical agent. Exemplary photoactivatable compounds include, but are not limited to, dyes (e.g., phthalocyanine dyes, silicocyanine dyes, any of the dyes described in WO2021 / 207691, or IRDye (registered trademark) 700DX (Rakuten Medical, Inc.)) and such photoactivatable compounds bound to a targeting agent. Optionally, the targeting agent has specificity for binding to a target on the extracellular surface of cells, such as cancer cells, precancerous cells, or immune cells.

[0045] Exemplary targeting agents include antibodies, peptides, or antigen-binding fragments that specifically bind to a target on cancer cells or in the tumor microenvironment. In one embodiment, the targeting molecule is a bispecific antibody, a scFv, a single-domain antibody (sdAb), a nanobody, a VHH, an isolated single variable domain, an affibody, a z-domain structure, a DARPin, a monobody, an anticalin, an affilin (registered trademark), an affimer type 1 molecule, an affimer type 2 molecule, an affitin, an alphabody, an avimer, a fynomer, a Kunitz domain peptide, a nanoclamp, or a combination thereof. A targeting agent specifically binds to a target molecule, such as a target molecule on the surface of a cell. The target molecule on the cell surface can be an extracellular protein or a receptor. Non-limiting examples of target molecules on the cell surface include epidermal growth factor receptor (EGFR), CD25, PD-1, PD-L1, or prostate-specific membrane antigen (PSMA). In one embodiment, the targeting agent is an anti-EGFR antibody such as cetuximab.

[0046] Exemplary conjugates include, but are not limited to, any of the conjugates described in US8,524,239, WO2017031363, and WO2023159182.

[0047] In one example of the use of the therapeutic fiber optic probe described in this specification, the target tissue is a lumen or opening of a subject, such as the esophagus, uterus, vagina, rectum, or colon. The target tissue is cancerous tissue, cancer cells, tumors, lesions, or cancer within the opening of the target (affected area), such as the esophagus, or endometriosis. In one example, a complex of an anti-EGFR antibody (e.g., cetuximab) and a photoactivatable dye (e.g., IRDye (registered trademark) 700DX (Rakuten Pharmaceutical Co., Ltd.)) is administered to the subject before irradiation with light having a wavelength of approximately 690 nm using the therapeutic fiber optic probe described in this specification.

[0048] Thus, the present embodiments provide a light-activatable conjugate, such as any of the conjugates described herein, or a pharmaceutical composition comprising any of the conjugates described herein, including a laser capable of emitting light at a specific wavelength, and a system for treating a subject suffering from a disease or condition. Specific wavelengths are, for example, from about 650 nm to about 820 nm, or from about 660 nm to about 800 nm, or from about 660 nm to about 740 nm, or for example, about 660 nm, about 670 nm, about 675 nm, about 677 nm, about 680 nm, about 685 nm, about 690 nm, about 695 nm, about 700 nm, about 705 nm, about 710 nm, about 715 nm, about 720 nm, about 725 nm, about 730 nm, about 735 nm, about 740 nm, about 745 nm, about 750 nm, about 755 nm, about 760 nm, about 765 nm, about 770 nm, about 775 nm, about 780 nm, about 785 nm, about 790 nm, about 795 nm, about 800 nm, 805 nm, about 810 nm, about 815 nm, or about 820 nm. The therapeutic fiber optic probe described herein is operably connected to a laser to deliver the light to a target area of ​​a subject. In one example, a system for treating a subject suffering from a disease or condition includes a laser capable of emitting light at approximately 675 nm. In one example, a system for treating a subject suffering from a disease or condition includes a laser capable of emitting light at approximately 677 nm. In one example, a system for treating a subject suffering from a disease or condition includes a laser capable of emitting light at approximately 690 nm. In one example, a system for treating a subject suffering from a disease or condition includes a laser capable of emitting light at approximately 780 nm. In one example, a system for treating a subject suffering from a disease or condition includes a laser capable of emitting light at approximately 800 nm.

[0049] The methods and systems provided herein include methods and systems where the disease or condition being treated is cancer. In some aspects, the cancer is selected from the group consisting of colon cancer, colorectal cancer, pancreatic cancer, breast cancer, skin cancer, lung cancer, non-small cell lung cancer, renal cell carcinoma, thyroid cancer, prostate cancer, head and neck cancer, digestive tract cancer, stomach cancer, small intestinal cancer, spindle cell carcinoma, liver cancer, liver cancer, bile duct cancer, peripheral nerve cancer, brain cancer, skeletal muscle cancer, smooth muscle cancer, bone cancer, adipose tissue cancer, cervical cancer, uterine cancer, genital cancer, lymphoma, and multiple myeloma. In some aspects of the treatment methods provided herein, the steps of administering the complex and irradiating are repeated. In some aspects, the methods and systems provided herein further include the administration of an additional therapeutic agent, such as an additional cancer therapeutic agent (e.g., immunotherapy, radiotherapy, chemotherapy, etc.). In some aspects, the additional therapeutic agent is a checkpoint inhibitor, such as an anti-PD-1 antibody or antigen-binding fragment.

[0050] In medical applications such as photodynamic therapy (PDT) and photoimmunotherapy (PIT), it is necessary to generate the aforementioned uniform light spot on the target (affected area) surface. In the therapeutic optical fiber probe 1, the output light L1 emitted from the light transmission structure 3 generally (usually) diverges within an angular range of 30° to 40°. Therefore, the reflective portion 4p of the mirror structure 4, positioned to receive the output light L1, has an inclination angle θ set to 45° and is constructed by laminating the aforementioned dielectric multilayer film.

[0051] The reflector 4p, formed by laminating a dielectric multilayer film, reflects only the desired wavelength of received light (e.g., 690 nm therapeutic light or 530 nm guidance light) within a 45° ± 17° range (i.e., approximately 45° and within a range of -17° to +17°). This creates a uniform light spot on the target (affected area) surface, as described in this specification.

[0052] For example, when the distance between the therapeutic optical fiber probe 1 (specifically, the reflecting portion 4p) and the target (affected part of the esophagus) surface is 18 mm, the irradiation diameter of the light spot generated on the target (affected part of the esophagus) surface can be 11 mm, which is sufficient for the treatment of cancerous tissues such as early esophageal cancer.

[0053] When a photoactivatable dye or complex is present at the target (affected area), irradiation with light of a specific wavelength activates a chemical reaction, thereby killing cells. As a result, the lesion (e.g., tumor or tumor cells) shrinks or disappears, and as a result, the disease or symptoms are cured.

[0054] The above description describes one embodiment of the present invention. This embodiment is provided as an example and is not intended to limit the scope of the invention. This embodiment may be implemented in various other forms and may be omitted, replaced, or modified without departing from the spirit of the invention. Furthermore, this embodiment is intended to be within the scope and spirit of the invention and encompassed by the inventions described in the claims and their equivalents.

[0055] 1: Identify sensor therapy fiber optic probe 2: Front end 3: Optical transmission structure 4: Mirror Construct 4p: Reflection part 5: Tubular structure 5a: front end 5b: Opening 6: Cover structure 7: Light-shielding structure 8: Lens structure 9: Mark Ax: imaginary axis L1: output light L2: reflected light θ: angle

[0056] Domestic storage information (please note the order of storage institution, date, and number) none Overseas deposit information (please note the order of deposit country, institution, date, and number) none

Claims

1. A therapeutic fiber optic probe, comprising: The light transmission structure can output light in a predetermined direction; and the mirror structure is disposed at a position that can receive light output from the aforementioned light transmission structure and is composed of multiple light reflective surfaces; and the aforementioned mirror structure causes a portion of the received light required for treatment to be reflected with a reflectivity of more than 90% in a direction different from the aforementioned predetermined direction, and generates a light spot that exerts a uniform light energy distribution throughout its entirety.

2. The therapeutic fiber optic probe as described in claim 1, wherein, The aforementioned mirror structure is composed of a dielectric multilayer film formed by alternating layers of high-refractive-index and low-refractive-index dielectric films. The aforementioned dielectric multilayer film causes a portion of the light received by the aforementioned mirror structure to be reflected in the aforementioned different directions with a reflectivity of more than 90%, and generates the aforementioned light spot that exerts a uniform light energy distribution throughout the entire structure.

3. The therapeutic fiber optic probe as described in claim 1, wherein, The aforementioned mirror structure allows light other than light reflected in the aforementioned different directions to be transmitted from the received light.

4. The therapeutic fiber optic probe as described in claim 1, wherein, The light received by the aforementioned mirror structure includes a plurality of wavelengths that are different from each other. The aforementioned mirror structure only reflects the specific wavelength of light required for treatment among the plurality of wavelengths contained in the received light.

5. The therapeutic fiber optic probe as described in claim 4, wherein, The aforementioned mirror structure includes light of at least one wavelength or more of the aforementioned specific wavelength, relative to the plurality of wavelengths contained in the received light, and is set to have a reflectivity of 90% or more.

6. The therapeutic fiber optic probe as described in claim 4, wherein, If the amount of light received by the aforementioned mirror structure is set to 100%, then the aforementioned mirror structure is configured such that the amount of light reflected from the aforementioned mirror structure, including the amount of light of the aforementioned specific wavelength, is at least 90%.

7. The therapeutic fiber optic probe as described in claim 1, wherein, The aforementioned therapeutic fiber optic probe has a tubular structure that houses the aforementioned light transmission structure and the aforementioned mirror structure inside. A plurality of marks are selectively and equally spaced along the outer periphery of the aforementioned tubular structure, and the plurality of aforementioned marks can be used as a ruler during treatment.

8. A treatment system comprising a therapeutic fiber optic probe as described in any one of claims 1 to 7, and a photoactivated compound.

9. The treatment system as described in claim 8, wherein, The aforementioned photoactivated compounds are phthalocyanine dyes or complexes of the aforementioned phthalocyanine dyes.

10. The treatment system as described in claim 9, wherein, The aforementioned phthalocyanine dye or its complex is a silicon phthalocyanine dye.

11. The treatment system as described in claim 8, wherein, The aforementioned photoactivated compounds include IRDye 700DX and the target compound.

12. The therapeutic fiber optic probe as described in any one of claims 1 to 7, for the treatment of esophageal cancer, uterine cancer, vaginal cancer, colorectal cancer, or endometriosis.

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