Microneedle patch capable of photodynamic therapy and local drug delivery

Abstract

This microneedle patch comprises: a sheet; a biodegradable needle, which is detachably connected to the sheet, extends in one direction from the sheet, and has a drug accommodation part formed therein; and a photosensitizer disposed to encompass the outer surface of the biodegradable needle. The photosensitizer is disposed to be coated on the outer surface of the biodegradable needle, and the biodegradable needle is elongated beyond the thickness of the sheet.

Description

Microneedle patches capable of photodynamic therapy and local drug delivery

[0001] The present invention relates to a microneedle patch capable of photodynamic therapy and local drug delivery.

[0002] This study was supported by the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, and the Ministry of Health and Welfare (government) through the Inter-ministerial Full-cycle Medical Device Research and Development Project, conducted by SNG Biotech, as part of the Inter-ministerial Low-cycle Medical Device Research and Development Project, titled “Development of a High-Functional Stent with Controlled Multiple Releases of Active Oxygen for the Treatment of Obesity and Metabolic Diseases” (Project Identification Number: 2710037293, Subproject Identification Number: RS-2020-KD000036, Research Period: 2024.01.01 ~ 2024.12.31). In addition, the National Research Foundation of Korea funded by the Ministry of Science and ICT (government) supported by the National Research Foundation of Korea conducted by the University of Ulsan through the Individual Basic Research Project, titled “Photodynamic Therapy Study of a Photosenst-Coated Stent-Based Catheter for the Local Treatment of Malignant Esophageal Strictures” (Project Identification Number: 2710061216, Subproject Identification Number: 2022R1A2C2002775, Research period: 2023.03.01~2024.02.29).

[0003] Typically, surgical resection is the primary treatment for cancers of the digestive system, including the esophagus, stomach, colon, and small intestine. Chemotherapy and radiation therapy are also commonly used. These common cancer treatments carry various side effects.

[0004] Side effects of surgical resection can be categorized as acute or chronic, depending on the time of onset. Acute side effects occur immediately after surgery and include bleeding, intestinal obstruction, vascular damage, ureteral damage, rectal rupture, pneumonia, and pulmonary embolism. Chronic side effects include organ dysfunction. Furthermore, the digestive tract is surrounded by vital organs such as the bronchial tubes, lungs, aorta, heart, and liver. Therefore, surgical resection carries a high risk of morbidity and mortality, and requires a long period of time to restore quality of life after surgery.

[0005] Chemotherapy and radiotherapy cause various side effects depending on the type of anticancer drug, type of anticancer treatment, dosage, treatment period, and the patient's constitution and condition.

[0006] To address these issues, endoscopic ultrasound-guided microneedle injections have recently been used to precisely deliver anticancer drugs to target lesions. Photodynamic therapy (PDT) is also being studied. PDT selectively destroys cancer cells where photosensitizing agents have accumulated, sparing adjacent normal tissue and allowing for repeated applications. This approach is emerging as a novel cancer treatment method.

[0007] However, endoscopic ultrasound-guided microneedle injection (USP) poses the challenge of requiring an invasive procedure for cancer cells. Photodynamic therapy (PDT) suffers from the low solubility of photosensitizers and their rapid diffusion into the bloodstream after intravenous injection. Furthermore, intravenous administration of photosensitizers poses significant limitations in daily life, such as the need to block exposure to ultraviolet light for a certain period of time.

[0008] The embodiments of the present invention, devised against the background described above, provide a microneedle patch and a treatment method utilizing the same, which minimize the side effects of anticancer treatment by attaching the microneedle patch to a target lesion site and performing photodynamic therapy and drug delivery only to the target lesion site. Furthermore, the microneedle patch is intended to address the problem of limiting daily life activities, such as UV exposure, by remaining in the digestive tract for a certain period of time.

[0009] A microneedle patch according to a first embodiment of the present invention comprises: a sheet; a biodegradable needle detachably connected to the sheet, extending in one direction from a side of the sheet, and having a drug-receiving portion formed therein; and a photoresponsive agent arranged to surround an outer surface of the biodegradable needle, wherein the photoresponsive agent is arranged by coating on the outer surface of the biodegradable needle.

[0010] The biodegradable needles may extend longer than the thickness of the sheet.

[0011] The biodegradable needle may be formed such that the volume of the drug-receiving portion gradually decreases in the direction from the sheet.

[0012] The biodegradable needles are provided in a plurality and arranged to be spaced apart from each other, and the thickness of the photoresponsive agent coated on the biodegradable needles arranged on the central side of the sheet among the plurality of biodegradable needles may be thicker than the thickness of the photoresponsive agent coated on the biodegradable needles arranged on the outer side of the sheet.

[0013] The above sheet can be formed of a light-transmitting material.

[0014] The sheet may include one side facing the biodegradable needle and another side opposite the one side, and may be configured to transmit light in a direction radiating from the other side toward the one side when light is irradiated on the other side.

[0015] A photodynamic therapy device according to a second embodiment of the present invention comprises a microneedle patch, and a light irradiator for irradiating light to the microneedle patch, wherein the microneedle patch comprises: a sheet; a biodegradable needle detachably connected to the sheet, extending in one direction from a side of the sheet, and having a drug-receiving portion formed therein; and a photoresponsive agent arranged to surround an outer surface of the biodegradable needle, wherein the photoresponsive agent is arranged by coating on the outer surface of the biodegradable needle.

[0016] The above photoirradiator may be configured to irradiate a laser having a wavelength that activates the photoresponder so that the photoresponder generates active oxygen.

[0017] The biodegradable needles are provided in a plurality and arranged to be spaced apart from each other, and the end of the light irradiator includes an irradiation surface that irradiates light to the sheet, and the irradiation surface can be formed to have an area that includes a plurality of the biodegradable needles when projected toward the biodegradable needles by passing through the sheet.

[0018] According to embodiments of the present invention, by attaching to a target lesion site and performing photodynamic therapy and drug delivery only to the target lesion site, there is an effect of minimizing side effects of anticancer treatment.

[0019] FIG. 1 is a drawing showing a microneedle patch according to one embodiment of the present invention.

[0020] Figure 2 is a drawing showing the needle of Figure 1 inserted into the lesion site.

[0021] Fig. 3 is a drawing showing a state in which a laser is irradiated to the microneedle patch of Fig. 1.

[0022] Figure 4 is a drawing showing a state in which the photoresponse agent of Figure 1 reacts with a laser to generate active oxygen.

[0023] Figure 5 is a drawing showing a state in which the photoresponse agent of Figure 1 reacts with the laser and the photoresponse agent is removed.

[0024] Figure 6 is a drawing showing a state in which the needle of Figure 1 is dissolved and the drug is eluted.

[0025] Figure 7 is a drawing showing the microneedle patch of Figure 1 mounted on an endoscope and approaching the lesion site.

[0026] Figure 8 is a drawing showing a catheter moving inside the endoscope of Figure 7.

[0027] Figure 9 is an enlarged view of part A of Figure 8.

[0028] Hereinafter, specific embodiments for implementing the technical idea of ​​the present invention will be described in detail with reference to the drawings.

[0029] In addition, when explaining the present invention, if it is determined that a detailed description of a related known configuration or function may obscure the gist of the present invention, the detailed description is omitted.

[0030] Additionally, when it is said that a component is 'connected to', 'supported by', or 'in contact with' another component, it should be understood that it may be directly connected to, supported by, or in contact with that other component, but there may also be other components present in between.

[0031] The terminology used herein is intended solely to describe specific embodiments and is not intended to limit the invention. Singular expressions include plural expressions unless the context clearly dictates otherwise.

[0032] Additionally, please note that the terms "top," "bottom," and "side" in this specification are based on the illustrations in the drawings and may be expressed differently if the orientation of the subject changes. For the same reason, some components in the attached drawings are exaggerated, omitted, or schematically depicted, and the sizes of each component do not fully reflect the actual size.

[0033] Additionally, terms that include ordinal numbers, such as "first," "second," etc., may be used to describe various components, but these components are not limited by such terms. These terms are used solely to distinguish one component from another.

[0034] The term "comprising" as used in the specification means specifying a particular characteristic, region, integer, step, operation, element and / or component, but does not exclude the presence or addition of other particular characteristics, regions, integers, steps, operations, elements, components and / or groups.

[0035] Hereinafter, a specific configuration of a microneedle patch according to one embodiment of the present invention will be described with reference to the drawings.

[0036] Referring to FIG. 1, a photodynamic therapy device according to one embodiment of the present invention can be attached to a lesion site (1) and used for photodynamic therapy and anticancer therapy on the lesion site (1). This photodynamic therapy device can be configured to provide focused photodynamic therapy on the lesion site (1). This photodynamic therapy device can include a microneedle patch (10), a light irradiator (20), an endoscope (30), and a catheter (40).

[0037] A microneedle patch (10) can be attached to a lesion site (1). The microneedle patch (10) can perform photodynamic therapy and anticancer therapy only on the lesion site (1). This microneedle patch (10) can include a sheet (100), a biodegradable needle (200), and a photosensitizer (300).

[0038] A sheet (100) can be attached to a lesion site (1) to cover the lesion site (1). This sheet (100) can be formed to have a larger area than the lesion site (1) so as to cover the lesion site (1). The sheet (100) can support a needle (200). The sheet (100) can be formed of a light-transmitting material (a transparent material or a translucent material). In addition, the sheet (100) can have one side facing the biodegradable needle (200) and the other side being the opposite side of the one side, and the sheet (100) can be configured to cause the light to propagate in a direction in which the light diverges from the other side toward the one side when light is irradiated on the other side. In other words, the sheet (100) can transmit light so that the light propagates in a direction in which it diverges, similar to when light passes through a concave lens.

[0039] The biodegradable needle (200) can accommodate a drug (210) therein. A drug-receiving portion for accommodating the drug (210) can be formed inside the biodegradable needle (200). The drug-receiving portion can be formed inside the biodegradable needle (200) in a shape corresponding to the outer shape of the biodegradable needle (200). The drug (210) accommodated in the drug-receiving portion can be an anticancer agent. The biodegradable needle (200) can be detachably connected to the sheet (100) and supported by the sheet (100). The biodegradable needle (200) can extend in one direction from one side of the sheet (100). The extension length of the biodegradable needle (200) extending in one direction from the sheet (100) can be longer than the thickness of the sheet (100). In other words, the biodegradable needle (200) can extend longer than the length from one side of the sheet (100) to the other side. The one side of the sheet (100) can be the lower side of FIG. 1, and the other side can be the upper side of FIG. 1. In addition, the biodegradable needle (200) can be formed so that its volume gradually decreases in one direction from the one side of the sheet (100). In other words, the biodegradable needle (200) can be formed so that its cross-sectional area gradually decreases in one direction from the top to the bottom of FIG. 1. Since the drug-receiving portion formed inside the biodegradable needle (200) is formed in a shape corresponding to the outer shape of the biodegradable needle (200), the volume of the drug-receiving portion can also be formed so that its volume gradually decreases in one direction from the one side of the sheet (100). Such biodegradable needles (200) can be provided in multiple pieces and arranged to be spaced apart from each other on one side of the sheet (100). These biodegradable needles (200) may be needles formed of a biodegradable polymer.

[0040] The photoresponsive agent (300) may be arranged to surround the outer surface of the biodegradable needle (200). This photoresponsive agent (300) may be formed as a coated layer to surround the outer surface of the biodegradable needle (200). The photoresponsive agent (300) may be specifically accumulated in the lesion site (1) and may be activated by a laser (21) of a specific wavelength. The photoresponsive agent (300) may include one or more of porphyrin, chromatin green, etc. When the laser (21) is irradiated to the photoresponsive agent (300), the photoresponsive agent (300) may be activated and interact with surrounding oxygen to generate active oxygen. This active oxygen may destroy cancer cells in the lesion site (1).

[0041] The thickness of the photoresponder (300) may be thinner than the thickness of the biodegradable needle (200). In addition, the thickness of the photoresponder (300) coated on the biodegradable needle (200) disposed at the center of the sheet (100) may be thicker than the thickness of the photoresponder (300) coated on the biodegradable needle (200) disposed at the outer side of the sheet (100). Since the laser (21) is irradiated to the center of the sheet (100) by the light irradiator (20) described below, more lasers (21) can be irradiated to the center of the sheet (100). If the thickness of the photoresponder (300) coated on the biodegradable needle (200) disposed on the outer side of the sheet (100) is the same as or thicker than the thickness of the photoresponder (300) coated on the biodegradable needle (200) disposed on the center side of the sheet (100), not all of the photoresponders (300) coated on the biodegradable needle (200) disposed on the outer side of the sheet (100) may be activated. However, since the biodegradable needle (200) decomposes after a certain period of time, the drug (210) inside the biodegradable needle (200) can be eluted, and anticancer treatment of the lesion site (1) can be continuously performed.

[0042] The light irradiator (20) can generate a laser that activates a photoresponder. The light irradiator (20) can be configured to irradiate a laser with a wavelength and intensity that activates the photoresponder so that the photoresponder generates active oxygen. Porphyrin, chromatin green, etc. used as the photoresponder (300) can be activated in the wavelength range of 660 nm to 690 nm. The light irradiator (20) can include a light source and an optical cable, and light generated from the light source can be irradiated to the microneedle patch (10) through the optical cable. An irradiation surface is provided at an end of the optical cable for irradiating the light to the sheet (100) of the microneedle patch (10), and when the irradiation surface is projected toward the biodegradable needles (200) by passing through the sheet (100), the irradiation surface can have an area in which a plurality of biodegradable needles (200) can be arranged within the projected irradiation surface. In other words, when the biodegradable needles (200) penetrate the sheet (100) and are projected toward the irradiation surface, all of the projected plurality of biodegradable needles (200) can be placed on the irradiation surface.

[0043] Hereinafter, a treatment method using a microneedle patch according to one embodiment of the present invention will be described with reference to the drawings.

[0044] Referring to FIGS. 2 and 7 to 9, after the holder (44) with the microneedle patch (10) attached is mounted on the endoscope (30), the lesion site (1) can be approached and the biodegradable needle (200) can be inserted into the lesion site (1). The microneedle patch (10) can be approached to the lesion site (1) by the endoscope (30) and catheter (40) described below, and can be inserted into the lesion site (1) by the catheter (40). After the catheter (40) inserts the biodegradable needle (200) of the microneedle patch (10) into the lesion site (1), the holder (44), which is an accessory part excluding the attached microneedle patch (10), can be withdrawn from the endoscope (30). The method by which the microneedle patch (10) approaches the lesion site (1) and is inserted into the lesion site (1) will be described later.

[0045] Referring to FIG. 3, when a catheter (40) is withdrawn from an endoscope (30), a light irradiator (20) is moved to the vicinity of a lesion site (1) through the endoscope (30), and the light irradiator (20) moved to the vicinity of the lesion site (1) can irradiate a laser (21) to the other surface of the sheet (100). The laser (21) is irradiated toward the center of the other surface of the sheet (100), and can be irradiated to the entire area of ​​the sheet (100) along the other surface of the sheet (100). The laser (21) irradiated to the entire area of ​​the sheet (100) can react with a photoresponder (300) to activate the photoresponder (300).

[0046] Referring to FIGS. 4 and 5, the photoresponse agent (300) activated by the laser (21) can be decomposed while generating active oxygen by interacting with surrounding oxygen. The active oxygen generated in this way can be emitted from the photoresponse agent (300) coated on the surface of the biodegradable needle (200) and destroy cancer cells in the lesion site (1). The photoresponse agent (300) can be completely activated by the laser (21) and removed from the biodegradable needle (200). When the photoresponse agent (300) is removed from the biodegradable needle (200), the biodegradable needle (200) can be brought into direct contact with the lesion site (1) and biodegraded by the lesion site (1).

[0047] Referring to Fig. 6, when the biodegradable needles (200) are fully biodegraded, the drug (210) may be released into the lesion site (1) by directly contacting the lesion site (1). The released drug (210) may act on cancer cells in the lesion site (1) to cause an anticancer effect. In addition, the sheet (100) may be detached from the lesion site (1) as the biodegradable needles (200) dissolve. The detached sheet (100) may move along the patient's digestive system and be removed from the patient's body through the patient's defecation.

[0048] Hereinafter, with reference to the drawings, a method for approaching and inserting a microneedle patch (10) into a lesion site (1) will be described.

[0049] Referring to Fig. 7, a holder (44) to which a biodegradable needle (200) is attached is mounted on an endoscope (30) and moved to a lesion site (1), and a microneedle patch (10) can be accessed to the lesion site (1) through the endoscope (30). The microneedle patch (10) can be accessed to the lesion site (1) by a catheter (40) moved inside the endoscope (30).

[0050] Referring to FIGS. 8 and 9, a catheter (40) can be used to attach a microneedle patch (10) to a lesion site (1). This catheter (40) can include a manipulation part (41), a connection part (42), and a push part (43).

[0051] The operating unit (41) is placed on the outside of the endoscope (30) and can be operated by the user. This operating unit (41) is connected to the push unit (43) by the connecting unit (42) and can operate the push unit (43) by the user's operation.

[0052] The connecting portion (42) is formed to extend from the operating portion (41) so that the end can be connected to the push portion (43). This connecting portion (42) can be inserted into the interior of the endoscope (30) and moved along the endoscope (30). The connecting portion (42) can be formed to be a predetermined length longer than the length of the endoscope (30).

[0053] The push unit (43) may be positioned at the extended end of the connection unit (42). This push unit (43) may be positioned inside the holder (44) and may be moved forward in the direction in which the connection unit (42) extends. In other words, the push unit (43) may be moved from the rear side (left side of FIG. 9) of the holder (44) to the front side (right side of FIG. 9) of the holder (44) by the user manipulating the operating unit (41). As the push unit (43) is moved from the rear side of the holder (44) to the front side of the holder (44), the microneedle patch (10) mounted on the front side of the holder (44) may be pushed forward so that the biodegradable needle (200) of the microneedle patch (10) may be inserted into the lesion site (1).

[0054] The holder (44) can hold a microneedle patch (10). The holder (44) can have a space formed therein for a push portion (43) to move. When the holder (44) is mounted on the front of the endoscope (30), the push portion (43) can be positioned at the extended end of the connection portion (42) so that it is positioned inside. The rear side of the holder (44) is connected to the extended end of the connection portion (42), and the microneedle patch (10) can be held at the front side of the holder (44).

[0055] This catheter (40) can be withdrawn from the endoscope (30) after the microneedle patch (10) is brought close to the lesion site (1) and the biodegradable needle (200) of the microneedle patch (10) is inserted into the lesion site (1).

[0056] Hereinafter, the operation and effect of a microneedle patch (10) and a treatment method using the same according to one embodiment of the present invention will be described.

[0057] A microneedle patch (10) according to one embodiment of the present invention is positioned by coating a photosensitizer (300) on the outer surface of a biodegradable needle (200) inserted into a lesion site (1), thereby enabling photodynamic therapy and anticancer therapy to be performed only on the lesion site (1), thereby having the effect of minimizing side effects of anticancer therapy.

[0058] Although the embodiments of the present invention have been described as specific embodiments, these are merely examples, and the present invention is not limited thereto, but should be construed to have the broadest scope in accordance with the technical concepts disclosed in this specification. Those skilled in the art may combine / substitute the disclosed embodiments to implement patterns of shapes not specified, but this also does not depart from the scope of the present invention. In addition, those skilled in the art may easily modify or alter the disclosed embodiments based on this specification, and it is clear that such modifications or alterations also fall within the scope of the present invention.

Claims

1. Sheet; A biodegradable needle detachably connected to the sheet, extending in one direction from the sheet side, and having a drug-receiving portion formed therein; and Including a photoresponsive agent arranged to surround the outer surface of the biodegradable needle, The above photoresponse agent is disposed by coating on the outer surface of the biodegradable needle, Microneedle patches.

2. In paragraph 1, The biodegradable needle extends longer than the thickness of the sheet, Microneedle patches.

3. In paragraph 1, The biodegradable needle is formed so that the volume of the drug-receiving portion gradually decreases as it goes in one direction from the sheet. Microneedle patches.

4. In paragraph 1, The above biodegradable needles are provided in multiples and arranged so as to be spaced apart from each other, The thickness of the photoresponse agent coated on the biodegradable needles arranged on the center side of the sheet among the plurality of biodegradable needles is thicker than the thickness of the photoresponse agent coated on the biodegradable needles arranged on the outer side of the sheet. Microneedle patches.

5. In paragraph 1, The above sheet is formed of a light-transmitting material, Microneedle patches.

6. In paragraph 5, The sheet includes one side facing the biodegradable needle and the other side being the opposite side of the one side, and is configured to transmit light in a direction radiating from the other side toward the one side when light is irradiated on the other side. Microneedle patches.

7. Microneedle patches, and Including a light irradiator that irradiates light to the above microneedle patch, The above microneedle patch, sheet; A biodegradable needle detachably connected to the sheet, extending in one direction from the sheet side, and having a drug-receiving portion formed therein; and Including a photoresponsive agent arranged to surround the outer surface of the biodegradable needle, The above photoresponse agent is disposed by coating on the outer surface of the biodegradable needle, Photodynamic therapy device.

8. In paragraph 7, The above photoirradiator is configured to irradiate a laser having a wavelength that activates the photoresponder so that the photoresponder generates active oxygen. Photodynamic therapy device.

9. In paragraph 7, The above biodegradable needles are provided in multiples and arranged so as to be spaced apart from each other, The end of the above light irradiator includes an irradiation surface that irradiates light to the sheet, The above-mentioned investigation surface is formed to have an area including a plurality of the biodegradable needles when projected toward the biodegradable needles through the sheet. Photodynamic therapy device.

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