Light-guiding adhesive patch

Abstract

The present invention relates to a light-guiding adhesive patch which can be stably adhered to the surface of an organic material and can effectively transmit light to an adhesion site.

Description

Technical Field

[0001] The present invention relates to a light-conducting adhesive patch. Background Art

[0002] In recent years, photomedicine has gained attention as a medical field that uses light for health and disease. It is used to image or treat diseases and is used in surgery, cardiology, radiology, oncology, diagnosis, drug delivery, dermatology, ophthalmology, etc.

[0003] With the development of diagnosis and treatment technology, the number of curable cancer diseases is increasing, but cancer is still the leading cause of death. About 9% to 17% of cancer patients will develop brain metastasis, and the average survival period of patients with metastatic brain tumors is 3 to 25 months, and the 5-year survival rate is 1.8%. Melanoma, breast cancer, and lung cancer have been found to be common cancers that cause brain metastasis, and various anticancer-radiation therapies are being tried. However, metastatic brain tumors, which account for about 50% of patients with malignant brain tumors, are still difficult to treat.

[0004] In recent years, photodynamic therapy (PDT) has attracted attention as a new alternative treatment method for intractable cancers and malignant brain tumors. Photodynamic therapy uses photosensitizers that react to light in a specific wavelength range. It has the advantages of physical treatment selectivity based on spatial and wavelength selectivity, as well as the lesion selectivity of the drug itself, and is being actively studied as an effective next-generation cancer treatment technology.

[0005] On the other hand, in order to improve the efficiency of photodynamic therapy, technology that can stably deliver light to biological tissues including cancer is actually needed. Summary of the invention

[0006] Technical issues

[0007] The invention provides a light-guiding adhesive patch, which can be stably adhered to the surface of an organic substance and can effectively transmit light to the attachment site.

[0008] However, the problems to be solved by the present invention are not limited to the problems mentioned above, and unmentioned or other problems can be clearly understood by those skilled in the art based on the following description.

[0009] Solution to the problem

[0010] One embodiment of the present invention provides a light-guiding adhesive patch, which includes an adhesive patch portion and a light transmission portion; the above-mentioned adhesive patch portion includes an adhesive portion and a light-guiding layer, the above-mentioned adhesive portion includes an adhesive layer and a core layer, the above-mentioned light-guiding layer is arranged on the above-mentioned adhesive portion and guides light to the above-mentioned adhesive portion; the above-mentioned light transmission portion is connected to the above-mentioned adhesive patch portion, and guides light flowing in from the outside to the above-mentioned adhesive patch portion.

[0011] Effects of the Invention

[0012] The light-guiding adhesive patch according to one embodiment of the present invention has a strong adhesive force to the surface of organic matter such as external tissue of a living body, internal tissue of a living body, cut tissue, etc., and thus has the advantage of being able to be stably attached.

[0013] In addition, the light guide adhesive patch according to one embodiment of the present invention can effectively transmit light to the attachment site.

[0014] However, the effects of the present invention are not limited to the above-mentioned effects, and can be expanded in various forms without departing from the spirit and scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1a and Figure 1b FIG. 1 is a diagram schematically showing a light guide adhesive patch according to an embodiment of the present invention.

[0016] Figure 2 This is a diagram showing the results of measuring the mechanical properties of the core of the light transmission part manufactured in Example 1 of the present invention.

[0017] Figure 3 The results of measuring the adhesive force of the adhesive layer produced in Example 1 of the present invention are shown. Specifically, the adhesive force (kPa) of the adhesive layer produced in Example 1 is shown.

[0018] Figure 4 This is a photograph of the light transmitting unit manufactured in Example 1 of the present invention transmitting light.

[0019] Figure 5 This is a photograph of the light transmitting unit manufactured in Example 2 of the present invention transmitting light.

[0020] Figure 6 This is a photograph of the light guide adhesive sheet manufactured in Example 1 of the present invention.

[0021] Figure 7 This is a photograph of light transmitted by the light-guiding adhesive patch manufactured in Example 1 of the present invention.

[0022] Figure 8 This is a photograph of the light guide adhesive sheet manufactured in Example 2 of the present invention.

[0023] Fig. 9 This is a photograph of light transmitted by the light-guiding adhesive patch manufactured in Example 2 of the present invention.

[0024] Fig.10These are the results of confirming the change in light transmittance depending on whether or not an antioxidant is added to the adhesive layer of Examples 1 and 2 of the present invention.

[0025] Fig.11 Results confirming the photodynamic therapy effect of the light-guiding adhesive patch of the present invention are shown. Fig.11 a and 11c confirmed the apoptotic ability of cells by the combined use of photosensitizer and light irradiation. Fig.11 b The apoptotic ability of cells was confirmed depending on whether antioxidants were added to the adhesive layer.

[0026] Fig.12 The results of confirming the photodynamic therapy effect of the light-guiding adhesive patch of the present invention using a 3D spheroid are shown.

[0027] Explanation of symbols

[0028] 1: Light guide adhesive patch

[0029] 100: Adhesive patch department

[0030] 110: Adhesive layer

[0031] 120: Core layer

[0032] 130: Bonding part

[0033] 140: Light guide layer

[0034] 200: Light transmission unit

[0035] 210: Core

[0036] 220: Coating layer DETAILED DESCRIPTION

[0037] Throughout the specification of this application, when it is indicated that a certain part “includes / comprises” a certain constituent element, unless there is a particular description to the contrary, it means that other constituent elements may be further included, rather than excluding other constituent elements.

[0038] Throughout the present specification, when it is stated that a certain component is “connected” to another component, it includes not only a case where the certain component is directly connected to the other component, but also a case where the two components are connected with other components in between.

[0039] Throughout the present specification, when it is stated that a certain component is “on” another component, it not only includes the case where the certain component is in contact with the other component, but also includes the case where other components exist between the two components.

[0040] Throughout the present specification, “(meth)acrylate” is used to collectively refer to acrylate and methacrylate.

[0041] Hereinafter, the present invention will be described in more detail.

[0042] One embodiment of the present invention provides a light-guiding adhesive patch, which includes an adhesive patch portion and a light transmission portion; the above-mentioned adhesive patch portion includes an adhesive portion and a light-guiding layer, the above-mentioned adhesive portion includes an adhesive layer and a core layer, the above-mentioned light-guiding layer is arranged on the above-mentioned adhesive portion and guides light to the above-mentioned adhesive portion; the above-mentioned light transmission portion is connected to the above-mentioned adhesive patch portion, and guides light flowing in from the outside to the above-mentioned adhesive patch portion.

[0043] The light-guiding adhesive patch according to one embodiment of the present invention has strong adhesion to the surface of organic matter such as external tissue of a living body, internal tissue of a living body, cut tissue, etc., and thus has the advantage of being able to be stably attached. In addition, the light-guiding adhesive patch can effectively transmit light to the attachment site.

[0044] Figure 1a and Figure 1b Schematically shows a light guide adhesive patch according to one embodiment of the present invention. Specifically, Figure 1a The light-guiding adhesive patch 1 having a square cross section of the adhesive patch portion 100 is shown. Figure 1b The light guide adhesive patch 1 is shown in which the cross section of the adhesive patch portion 100 is provided in a circular shape.

[0045] refer to Figure 1a and Figure 1b The light-guiding adhesive patch 1 includes an adhesive patch portion 100 that is bonded to the attachment portion and transmits light. In addition, the light-guiding adhesive patch 1 includes one end connected to an external light source and the other end connected to the adhesive patch portion 100, thereby transmitting the light flowing in from the light source to the light transmitting portion 200 of the adhesive patch portion 100. At this time, the adhesive patch portion 100 may include an adhesive portion 130 and a light guiding layer 140, wherein the adhesive portion 130 is connected to the attachment portion, and the light guiding layer 140 is provided on the adhesive portion 130 to guide the light flowing in from the light transmitting portion 200 to the adhesive portion 130.

[0046] According to one embodiment of the present invention, the bonding part may include a bonding layer and a core layer disposed on one surface of the bonding layer. Specifically, one surface of the bonding layer may be a layer directly in contact with the attachment site, and the core layer may be disposed on the other surface of the bonding layer.

[0047] According to one embodiment of the present invention, the adhesive layer may be a hydrogel adhesive layer comprising a reaction product of a biocompatible polymer and a pyrogallol-based compound. Specifically, the reaction product of the biocompatible polymer and the pyrogallol-based compound may be a hydrogel precursor. Even if there is moisture on the surface of the bonding target, the adhesive layer comprising the hydrogel precursor may effectively maintain bonding ability.

[0048] According to one embodiment of the present invention, the above-mentioned biocompatible polymer may include at least one of polyethylene glycol, gelatin, alginate, hyaluronic acid, hyaluronic acid-adipic acid dihydrazide, polyethylene glycol amine, four-arm polyethylene glycol amine, six-arm polyethylene glycol amine, eight-arm polyethylene glycol amine, chitosan and collagen. At this time, four-arm polyethylene glycol amine may refer to a compound having four polyethylene glycol branches with an amine group at the end combined with the main chain of the structure containing multiple hydroxyls. In addition, six-arm polyethylene glycol amine may refer to a compound having six polyethylene glycol branches with an amine group at the end combined with the main chain of the structure containing multiple hydroxyls. In addition, eight-arm polyethylene glycol amine may refer to a compound having eight polyethylene glycol branches with an amine group at the end combined with the main chain of the structure containing multiple hydroxyls. By using the above-mentioned types of biocompatible polymers, the above-mentioned adhesive layer can effectively reduce the biohazard when attached to the target body.

[0049] According to one embodiment of the present invention, the biocompatible polymer may include an amine-containing biocompatible polymer and an amine-free biocompatible polymer. For example, the amine-containing biocompatible polymer may include at least one of polyethylene glycol amine, four-arm polyethylene glycol amine, six-arm polyethylene glycol amine, eight-arm polyethylene glycol amine, chitosan and collagen. In addition, the amine-free biocompatible polymer may include at least one of polyethylene glycol and gelatin. The amine-containing biocompatible polymer reacts with the pyrogallol-based compound to form a compound with excellent adhesion. Through this compound, even if there is moisture on the surface of the bonding target, the adhesive layer can effectively maintain the bonding ability.

[0050] According to one embodiment of the present invention, the pyrogallol compound may be extracted from plants. By using the pyrogallol compound extracted from plants, the light guide adhesive sheet may be effectively provided with adhesive properties.

[0051] According to one embodiment of the present invention, the pyrogallol-based compound may be a compound represented by the following Chemical Formula 1.

[0052] [Chemical formula 1]

[0053]

[0054] In the above chemical formula 1, R1 is -COOH, -CHO, -NH2, -SH, a linear or branched alkyl group having 1 to 10 carbon atoms, or a linear or branched alkenyl group having 2 to 10 carbon atoms, 3 of R2 to R6 are -OH, and the remaining 2 are hydrogen. Specifically, in the above chemical formula 1, R1 may be -COOH, -CHO, -NH2 or -SH. More specifically, in the above chemical formula 1, R1 may be -CHO. The pyrogallol-based compound represented by the above chemical formula 1 reacts with the above biocompatible polymer to form a hydrogel adhesive layer having excellent adhesion and light conductivity. Specifically, the pyrogallol-based compound represented by the above chemical formula 1 reacts with the above amine-containing biocompatible polymer to form a hydrogel adhesive layer having excellent adhesion and light conductivity. At this time, R1 in the above chemical formula 1 may be a functional group that reacts with the amine group of the amine-containing biocompatible polymer described below.

[0055] According to one embodiment of the present invention, the pyrogallol compound may include at least one of 2,3,4-trihydroxybenzaldehyde, 2,4,5-trihydroxybenzaldehyde, 3,4,5-trihydroxybenzaldehyde and 2,4,6-trihydroxybenzaldehyde. The pyrogallol compound reacts with the biocompatible polymer to form an adhesive layer with excellent adhesion and light conductivity. Specifically, the pyrogallol compound reacts with the amino-containing biocompatible polymer to form a hydrogel adhesive layer with excellent adhesion and light conductivity.

[0056] According to one embodiment of the present invention, the adhesive layer can be manufactured using a composition for manufacturing an adhesive layer. That is, the adhesive layer can include a reaction product of the composition for manufacturing an adhesive layer. The composition for manufacturing an adhesive layer can include the biocompatible polymer and the pyrogallol-based compound. Specifically, the composition for manufacturing an adhesive layer can include the biocompatible polymer containing an amine group, the biocompatible polymer not containing an amine group, and the pyrogallol-based compound.

[0057] According to one embodiment of the present invention, the content of the biocompatible polymer can be 1 to 30 parts by weight based on 100 parts by weight of the adhesive layer manufacturing composition. When the content of the biocompatible polymer is within the above range, the biohazard can be effectively reduced when the adhesive layer is attached to the target body, and the adhesive layer can effectively maintain the bonding ability even if there is moisture on the surface of the bonding target.

[0058] According to one embodiment of the present invention, based on 100 parts by weight of the composition for manufacturing the adhesive layer, the content of the amine-containing biocompatible polymer is 0.5 parts by weight to 15 parts by weight, and the content of the amine-free biocompatible polymer may be greater than 0 parts by weight and less than or equal to 15 parts by weight. When the content of the amine-containing biocompatible polymer and the amine-free biocompatible polymer is within the above range, the adhesive layer can effectively reduce the biohazard when attached to the target, and even if there is moisture on the surface of the bonding target, the adhesive layer can effectively maintain the bonding ability.

[0059] According to one embodiment of the present invention, the content ratio of the biocompatible polymer not containing amine groups to the biocompatible polymer containing amine groups may be 1:0.5 to 1:5. Specifically, the content of the biocompatible polymer containing amine groups may be greater than the content of the biocompatible polymer not containing amine groups. When the content ratio of the biocompatible polymer containing amine groups to the biocompatible polymer not containing amine groups is within the above range, the adhesive layer can effectively reduce the biohazard when attached to the target body, and even if there is moisture on the surface of the bonding target, the adhesive layer can effectively maintain the bonding ability.

[0060] According to one embodiment of the present invention, the reaction product may contain 0.3 to 30 parts by weight of the pyrogallol compound relative to 100 parts by weight of the biocompatible polymer. That is, the content of the pyrogallol compound may be 0.3 to 30 parts by weight relative to 100 parts by weight of the total content of the biocompatible polymer containing an amino group and the biocompatible polymer containing no amino group contained in the adhesive layer manufacturing composition. On the other hand, the content of the pyrogallol compound may be a content that can react with all the amino groups contained in the biocompatible polymer containing an amino group. Specifically, the content of the pyrogallol compound represented by the chemical formula 1 may be set in such a way that R1 of the pyrogallol compound represented by the chemical formula 1 reacts with the amino group contained in the biocompatible polymer containing an amino group in a 1:1 ratio. When the content of the biocompatible polymer and the pyrogallol compound used to form the reaction product is within the above range, the adhesive layer has a strong adhesive force to the surface of the organic matter, so that it can be stably attached. Furthermore, by adjusting the content of the biocompatible polymer and the pyrogallol compound to the above range, the light-guiding property of the adhesive layer can be effectively improved. That is, the adhesive layer can be stably bonded to the surface of the organic material and can effectively transmit light to the surface of the organic material.

[0061] According to one embodiment of the present invention, the adhesive layer may further include an antioxidant. By including an antioxidant in the adhesive layer, the light guide efficiency of the adhesive layer may be effectively prevented from being reduced. The antioxidant may be an antioxidant used in the art, for example, vitamin B, vitamin C, etc.

[0062] According to one embodiment of the present invention, the core layer may be a hydrogel comprising a cured product of a composition comprising a photoreactive group-containing compound and a photoinitiator. The core layer protects the adhesive layer and can effectively transmit light to the adhesive layer. That is, by providing the core layer on one surface of the adhesive layer, the light transmission efficiency to the attachment portion of the adhesive layer can be improved, and the durability of the adhesive patch portion can be improved.

[0063] According to one embodiment of the present invention, the above-mentioned photoreactive group-containing compound may include at least one of polyethylene glycol di(meth)acrylate, (meth)acrylated hyaluronic acid, (meth)acrylated alginate and (meth)acrylated gelatin. Specifically, the above-mentioned photoreactive group-containing compound may include at least one of polyethylene glycol diacrylate and polyethylene glycol dimethacrylate. In addition, the molecular weight of the above-mentioned photoreactive group-containing compound may be 500g / mol to 3000g / mol. By using the above-mentioned photoreactive group-containing compound of the above-mentioned type, the light transmission efficiency of the above-mentioned core layer can be improved, and a core layer with excellent mechanical properties can be manufactured.

[0064] According to one embodiment of the present invention, the photoinitiator can be any photoinitiator used in the art without limitation. For example, the photoinitiator can be a phenylacetone photoinitiator, a benzoin and its alkyl ether photoinitiator, an acetophenone photoinitiator, an anthraquinone photoinitiator, a thioxanthone photoinitiator, or a thioxanthone photoinitiator. Photoinitiators, ketal photoinitiators, benzophenone photoinitiators, α-aminoacetophenone photoinitiators, acylphosphine oxide photoinitiators, ketone photoinitiators, phenylphosphine oxide photoinitiators, thioxanthone The photoinitiators include, but are not limited to, oxime ester photoinitiators, etc.

[0065] According to one embodiment of the present invention, the core layer may be manufactured using a core layer manufacturing composition. That is, the core layer may include a photocured product of the core layer manufacturing composition. The core layer manufacturing composition may include the photoreactive group-containing compound and a photoinitiator.

[0066] According to one embodiment of the present invention, the content of the compound containing photoreactive groups may be 5 g to 90 g based on 100 mL of the core layer manufacturing composition. That is, the content of the compound containing photoreactive groups may be 5 w / v% to 90 w / v%. When the content of the compound containing photoreactive groups is within the above range, a core layer having excellent light transmission efficiency may be formed.

[0067] According to one embodiment of the present invention, the content of the photoinitiator can be 0.01g to 5g based on 100mL of the core layer manufacturing composition. That is, the content of the compound containing the photoreactive group can be 0.01w / v% to 5w / v%. When the content of the photoinitiator is within the above range, the photocuring reaction of the cured product can be carried out stably. In addition, by adjusting the content of the photoinitiator to the above range, the mechanical properties of the core layer can be controlled, and an adhesive patch portion with desired properties can be easily manufactured.

[0068] According to one embodiment of the present invention, the light-guiding layer may be a hydrogel light-guiding layer containing at least one of alginate, hyaluronic acid, chitosan and gelatin, and the hydrogel light-guiding layer is disposed on the bonding portion, and can guide the light flowing in from the light-transmitting portion to the bonding portion. Thus, the bonding portion can more stably transmit light to the surface of the organic matter, and further, by disposing the light-guiding layer containing the above-mentioned substance on the bonding portion, when an uneven or uniform external force is applied to the bonding patch portion, the external force is dispersed, so that the bonding portion can be bonded more stably.

[0069] According to one embodiment of the present invention, the thickness ratio of the adhesive layer to the core layer may be 1:5 to 1:40. When the thickness ratio of the adhesive layer to the core layer is within the above range, the adhesive layer can be stably bonded to the surface of the organic matter and the external force applied to the bonding portion can be effectively dispersed.

[0070] According to one embodiment of the present invention, the thickness ratio of the adhesive layer to the light-guiding layer may be 1:0.1 to 1:2. That is, the thickness ratio of the light-guiding layer may be 1:0.1 to 1:2 relative to the sum of the thicknesses of the adhesive layer and the core layer. When the thickness ratio of the adhesive layer to the light-guiding layer is within the above range, the adhesive patch portion may effectively transmit light to the surface of the organic matter. In addition, by adjusting the thickness ratio of the adhesive portion and the light-guiding layer to the above range, the light-guiding layer disperses the external force, and the bonding stability of the adhesive portion may be further improved.

[0071] According to one embodiment of the present invention, the light transmission part is provided in contact with one surface of the adhesive layer, and may include: a core for guiding light to the adhesive patch part, and a coating layer provided on the surface of the core. Figure 1a and Figure 1b One end of the core 210 is disposed in contact with one surface (e.g., side surface) of the bonding portion 130, and a light source may be disposed at the other end of the core 210. In addition, the coating layer 220 may be disposed in a form of wrapping the entire surface of the core 210 along the outer circumference of the core 210. In addition, one end of the coating layer 220 is disposed in contact with one surface (e.g., side surface) of the bonding portion 130 and one surface (e.g., side surface) of the light guide layer 140, and a light source may be disposed at the other end of the coating layer 220.

[0072] According to one embodiment of the present invention, the core can mainly transmit the light emitted from the light source to the adhesive patch portion. The coating layer protects the core and also plays a role of auxiliary transmission of the light to the adhesive patch portion. That is, by forming the coating layer on the surface of the core, the light transmission efficiency of the light transmission portion can be improved, and the durability of the light transmission portion can be improved.

[0073] According to one embodiment of the present invention, the core may include a cured product of a composition including a photoreactive group-containing compound and a photoinitiator. That is, the core may be a photocured product of a core manufacturing composition including the photoreactive group-containing compound and the photoinitiator.

[0074] According to one embodiment of the present invention, the photoreactive group-containing compound may include at least one of polyethylene glycol di(meth)acrylate, (meth)acrylated hyaluronic acid, (meth)acrylated alginate, and (meth)acrylated gelatin. Specifically, the photoreactive group-containing compound may include at least one of polyethylene glycol diacrylate and polyethylene glycol dimethacrylate. In addition, the molecular weight of the photoreactive group-containing compound may be 500 g / mol to 3000 g / mol. By using the above-mentioned photoreactive group-containing compound of the above-mentioned type, the light transmission efficiency of the core can be improved, and a core with excellent mechanical properties can be manufactured.

[0075] According to one embodiment of the present invention, the photoinitiator can be any photoinitiator used in the art without limitation. For example, the photoinitiator can be acetophenone-based photoinitiators, benzoin and its alkyl ether photoinitiators, acetophenone-based photoinitiators, anthraquinone-based photoinitiators, thioxanthone-based photoinitiators, ketal-based photoinitiators, benzophenone-based photoinitiators, α-aminoacetophenone-based photoinitiators, acylphosphine oxide-based photoinitiators, ketone-based photoinitiators, phenylphosphine oxide-based photoinitiators, thioxanthone-based photoinitiators, oxime ester-based photoinitiators, etc., but the types of the photoinitiators are not limited.

[0076] According to one embodiment of the present invention, the core can be manufactured using a core manufacturing composition. That is, the core can include a photocured product of the core manufacturing composition. The core manufacturing composition can include the photoreactive group-containing compound and a photoinitiator. Based on 100 mL of the core manufacturing composition, the content of the photoreactive group-containing compound can be 5 g to 90 g. That is, the content of the photoreactive group-containing compound can be 5 w / v% to 90 w / v%. When the content of the photoreactive group-containing compound is within the above range, a core with excellent light transmission efficiency can be formed.

[0077] According to one embodiment of the present invention, the content of the photoinitiator can be 0.01 g to 5 g based on 100 mL of the core manufacturing composition. That is, the content of the photoreactive group-containing compound can be 0.01 w / v% to 5 w / v%. When the content of the photoinitiator contained in the core manufacturing composition is within the above range, the photocuring reaction of the cured product can be stably performed. In addition, by adjusting the content of the photoinitiator to the above range, the mechanical properties of the core are controlled, and the light transmission part can be made soft and well bendable.

[0078] According to one embodiment of the present invention, the coating layer may include one or more hydrogel layers containing at least one of alginate, hyaluronic acid, chitosan and gelatin. Specifically, the coating layer may include one or more hydrogel layers containing the above-mentioned substances, and two or more hydrogel layers may be formed of the same substance or different substances. In addition, the thickness of the two or more hydrogel layers included in the coating layer may be the same or different. The coating layer containing the above-mentioned substances is arranged on the core, and through the core, the transmission of light can be assisted and the core layer can be prevented from being damaged.

[0079] According to one embodiment of the present invention, the thickness ratio of the core to the coating layer may be 1:0.2 to 1:4. When the thickness ratio of the core to the coating layer is within the above range, the optical transmission part can effectively transmit light to the adhesive patch part. In addition, the optical transmission part can be prevented from being damaged, and the deformation of the optical transmission part can be easily achieved. That is, the optical transmission part can be bent without being damaged, thereby improving the applicability of the light-guiding adhesive patch.

[0080] According to one embodiment of the present invention, the ratio of the area of ​​the bonding portion to the cross-sectional area of ​​the core may be 1:0.004 to 1:0.04. That is, the ratio of the area of ​​the bonding layer to the cross-sectional area of ​​the core may be 1:0.004 to 1:0.04, and the ratio of the area of ​​the core layer to the cross-sectional area of ​​the core may be 1:0.004 to 1:0.04. Figure 1a , the area of ​​the bonding portion refers to the cross-sectional area of ​​the bonding portion in the xy plane, and the cross-sectional area of ​​the core may refer to the cross-sectional area of ​​the core in the yz plane. At this time, light may be irradiated to the core in the x-axis direction (direction perpendicular to the yz plane). When the ratio of the area of ​​the bonding portion to the cross-sectional area of ​​the core is within the above range, light irradiated from the light source may stably reach the bonding patch portion through the light transmission portion.

[0081] One embodiment of the present invention provides a method for manufacturing a light guide adhesive patch, including: a step of manufacturing an adhesive patch portion, and a step of manufacturing a light transmission portion.

[0082] According to the method for manufacturing a light guide adhesive sheet according to one embodiment of the present invention, a light guide adhesive sheet that can be stably adhered to the surface of an organic substance and can effectively transmit light to the attachment site can be easily manufactured.

[0083] The manufacturing method of the above-mentioned light-guiding adhesive patch may be a method for manufacturing the light-guiding adhesive patch according to the above-mentioned embodiment. In the manufacturing method of the light-guiding adhesive patch according to the present embodiment, the adhesive layer, core layer, adhesive portion, light-guiding layer, adhesive patch portion, core, coating layer and light-transmitting portion may be the same as the adhesive layer, core layer, adhesive portion, light-guiding layer, adhesive patch portion, core, coating layer and light-transmitting portion in the light-guiding adhesive patch according to the above-mentioned embodiment.

[0084] According to an embodiment of the present invention, the step of manufacturing the adhesive patch portion may include a step of manufacturing an adhesive layer, a step of manufacturing a core layer, and a step of manufacturing a light guide layer.

[0085] The step of manufacturing the adhesive layer can be performed using an adhesive layer manufacturing composition comprising the biocompatible polymer and the pyrogallol compound. Specifically, the adhesive layer manufacturing composition can be dried at a temperature of 20° C. to 40° C. to manufacture a film-like adhesive layer and shaped into a desired shape.

[0086] The step of manufacturing the core layer can be performed by using a core layer manufacturing composition containing the photoreactive group-containing compound and the photoinitiator. Specifically, the core layer manufacturing composition can be placed in a mold and irradiated with 1 mW / cm 2 ~100mW / cm 2 The core layer is manufactured by curing the core layer manufacturing composition with ultraviolet rays for 5 to 10 minutes.

[0087] In order to manufacture the above-mentioned bonding part, the bonding part can be manufactured by attaching the bonding layer to the manufactured core layer. In this case, the core layer is attached to one surface of the bonding layer, and a release film can be attached to the other surface of the bonding layer exposed to the outside.

[0088] The step of manufacturing the light-guiding layer can use a hydrogel precursor solution to manufacture the light-guiding layer. In this case, the hydrogel precursor solution can contain at least one of alginate, hyaluronic acid, chitosan and gelatin. Specifically, the hydrogel precursor solution is coated on one surface of the core layer of the bonding portion and immersed in a reactive solution, so that the light-guiding layer can be formed on the core layer. In this case, the reaction solution can include a reactive substance that reacts with the compound contained in the hydrogel precursor solution to form a hydrogel. For example, the reactive substance can be calcium chloride.

[0089] According to an embodiment of the present invention, the step of manufacturing the light transmission portion may include a step of manufacturing the core and a step of manufacturing the coating layer.

[0090] The step of manufacturing the core can be performed by using a core manufacturing composition containing the photoreactive compound and the photoinitiator. Specifically, the core manufacturing composition can be placed in a mold and irradiated with 1 mW / cm 2 ~100mW / cm 2 The core is manufactured by curing the core manufacturing composition with ultraviolet rays for 5 to 10 minutes.

[0091] The step of manufacturing the coating layer can use a hydrogel precursor solution to manufacture the coating layer. In this case, the hydrogel precursor solution can contain at least one of alginate, hyaluronic acid, chitosan and gelatin. Specifically, the manufactured core is immersed in the hydrogel precursor solution and then immersed in a reactive solution to form a coating layer on the core. In this case, the reaction solution can include a reactive substance that reacts with the compound contained in the hydrogel precursor solution to form a hydrogel. For example, the reactive substance can be calcium chloride.

[0092] According to one embodiment of the present invention, a manufactured light transmission part is attached to one side of a manufactured adhesive patch part, thereby a light-guiding adhesive patch can be manufactured. In order to attach the adhesive patch part to the light transmission part, an adhesive or adhesive film used in the art that is harmless to the human body can be used. In addition, a light transmission part is provided on one side of the adhesive patch part, and the adhesive patch part and the light transmission part are combined by using a hydrogel precursor solution and a reactive solution, thereby a light-guiding adhesive patch can be manufactured. In addition, a manufactured core is provided on one side of an adhesive part including an adhesive layer and a core layer, and a light-guiding layer and a coating layer can be formed together by using a hydrogel precursor solution and a reactive solution. Thus, a light-guiding adhesive patch in which the adhesive patch part and the light transmission part are integrally provided can be manufactured.

[0093] Below, in order to specifically illustrate the present invention, embodiments will be cited to illustrate in detail. However, embodiments according to the present invention can be deformed into various forms, and it is not interpreted that the scope of the present invention is limited to the embodiments described in detail below. The embodiments of this specification are provided to more fully illustrate the present invention to those skilled in the art.

[0094] Example

[0095] Example 1

[0096] The following method was used to produce Figure 1a A light guide adhesive patch of the form shown in the figure.

[0097] 1) Manufacturing of adhesive patch parts

[0098] (1) Manufacturing of core layer

[0099] A composition for producing a core layer was prepared by mixing polyethylene glycol diacrylate having a molecular weight of 700 g / mol as a compound containing a photoreactive group, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (Sigma Aldrich) as a photoinitiator, and distilled water.

[0100] At this time, the content of polyethylene glycol diacrylate was 80 g (80 w / v%) based on 100 mL of the core layer composition. In addition, the content of the photoinitiator was 1 g (1 w / v%) based on 100 mL of the core layer composition.

[0101] Then, the core layer composition was placed in the mold and irradiated with 5 mW / cm 2 Finally, a core layer with a width of 15 mm, a length of 15 mm, and a thickness of 2 mm was produced.

[0102] (2) Manufacturing of Adhesive Layer

[0103] Hyaluronic acid-adipic acid dihydrazide was prepared as an amine-containing biocompatible polymer, and 2,3,4-trihydroxybenzaldehyde was prepared as a pyrogallol-based compound.

[0104] Then, hyaluronic acid-adipic acid dihydrazide, 2,3,4-trihydroxybenzaldehyde and distilled water were mixed to prepare a composition for manufacturing an adhesive layer. At this time, the content of hyaluronic acid-adipic acid dihydrazide was 1 part by weight based on 100 parts by weight of the composition for manufacturing an adhesive layer. On the other hand, the amount of 2,3,4-trihydroxybenzaldehyde was adjusted in a manner corresponding to 1:0, 1:1 and 1:5 according to the amino group of the six-arm polyethylene glycol amine and the aldehyde group of 2,3,4-trihydroxybenzaldehyde. At this time, the content of 2,3,4-trihydroxybenzaldehyde was 0, 10 and 50 parts by weight, respectively, relative to the total content of hyaluronic acid-adipic acid dihydrazide 100 parts by weight.

[0105] Then, the adhesive layer manufacturing composition was dried at room temperature to manufacture a film-like adhesive layer, and shaped to manufacture an adhesive layer having a width of 15 mm, a length of 15 mm, and a thickness of 0.1 mm. Then, the manufactured adhesive layer was attached to one surface of the core layer manufactured above, thereby manufacturing an adhesive portion.

[0106] (3) Fabrication of light guide layer

[0107] A 2 w / v% alginate solution and a 100 mM calcium chloride solution were prepared.

[0108] Then, after coating the other surface of the core layer to which the adhesive layer was not attached with an alginate solution, the core layer was immersed in a calcium chloride solution to form an alginate hydrogel. That is, a light-guiding layer containing an alginate hydrogel was formed on the other surface of the core layer. At this time, the light-guiding layer was formed on the core layer in a form of 15 mm in width, 15 mm in length, and 1 mm in thickness. Thus, an adhesive patch portion was finally manufactured.

[0109] 2) Manufacturing of light transmission unit

[0110] (1) Core manufacturing

[0111] Example 1-1 (Photoinitiator 0.2w / v%)

[0112] A core manufacturing composition was prepared by mixing polyethylene glycol diacrylate having a molecular weight of 700 g / mol as a compound containing a photoreactive group and 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (Sigma Aldrich) as a photoinitiator with distilled water. At this time, the content of polyethylene glycol diacrylate was 80 g (80 w / v%) based on 100 mL of the core manufacturing composition. In addition, the content of the photoinitiator was 0.2 g (0.2 w / v%) based on 100 mL of the core manufacturing composition.

[0113] Then, the core manufacturing composition was placed in the mold and irradiated with 5 mW / cm 2 Finally, a core with a diameter of 2 mm and a length of 30 mm was produced.

[0114] Example 1-2 (Photoinitiator 0.6w / v%)

[0115] A core of the light transmission portion was produced by the same method as in Example 1-1, except that the content of the photoinitiator was adjusted to 0.6 w / v%.

[0116] Example 1-3 (Photoinitiator 1w / v%)

[0117] A core of the light transmission portion was produced by the same method as in Example 1-1, except that the content of the photoinitiator was adjusted to 1 w / v%.

[0118] Example 1-4 (photoinitiator 1w / v%, 50mW / cm 2 )

[0119] In the above Example 1-1, the content of the photoinitiator was adjusted to 1 w / v%, and the ultraviolet intensity was adjusted to 50 mW / cm 2 , except for this, the core of the light transmission part was manufactured by the same method as the above-mentioned Example 1-1.

[0120] (2) Manufacturing of coating layer

[0121] A 2 w / v% alginate solution and a 100 mM calcium chloride solution were prepared.

[0122] Then, the manufactured core was immersed in an alginate solution and then immersed in calcium chloride to form an alginate hydrogel. That is, a coating layer containing an alginate hydrogel was formed on the surface of the core. At this time, the coating layer had a thickness of 0.5 mm and a length of 30 mm. Thus, a light transmission part was finally manufactured.

[0123] Then, a light guide adhesive patch having a configuration in which a light transmission portion is connected to one side of the adhesive patch portion was manufactured.

[0124] Example 2

[0125] The following method was used to produce Figure 1b A light-guiding adhesive patch of the shape shown in the figure.

[0126] 1) Manufacturing of adhesive patch parts

[0127] (1) Manufacturing of core layer

[0128] A core layer having a diameter of 8 mm and a thickness of 2 mm was manufactured by the same method as in Example 1 above.

[0129] (2) Manufacturing of Adhesive Layer

[0130] An adhesive layer having a diameter of 8 mm and a thickness of 0.1 mm was produced by the same method as in Example 1. Then, the produced adhesive layer was attached to one surface of the core layer produced above, thereby producing an adhesive portion.

[0131] (3) Fabrication of light guide layer

[0132] A light guide layer having a diameter of 8 mm and a thickness of 1 mm was formed on the other surface of the core layer by the same method as in Example 1. Thus, an adhesive patch unit was finally manufactured.

[0133] 2) Manufacturing of light transmission unit

[0134] (1) Core manufacturing

[0135] A light transmission core having a diameter of 2 mm and a length of 30 mm was manufactured by the same method as in Example 1.

[0136] (2) Manufacturing of coating layer

[0137] By the same method as in Example 1, a coating layer having a thickness of 0.5 mm was produced on the surface of the core produced as described above, thereby finally producing a light transmission unit.

[0138] Then, a light guide adhesive patch having a configuration in which a light transmission portion is connected to one side of the adhesive patch portion was manufactured.

[0139] Experimental example

[0140] Determination of mechanical properties of the light-transmitting core

[0141] The mechanical properties of the optical transmission core manufactured in Examples 1-1 to 1-4 were measured using Discovery Hybrid Rheometer 2 (TAInstrument). Specifically, the storage modulus (G') and loss modulus (G"), and the dielectric loss tangent (Tan(δ)) value of the optical transmission core were measured at a frequency of 1 Hz.

[0142] Figure 2 This is a graph showing the results obtained by measuring the mechanical properties of the core of the optical transmission part manufactured in Example 1 of the present invention. Specifically, the measured storage modulus (G') and loss modulus (G"), and dielectric loss tangent (Tan(δ)) values ​​of the optical transmission part core manufactured in Examples 1-1 to 1-4 are shown.

[0143] refer to Figure 2 It is understood that the mechanical properties of the produced core can be controlled by adjusting the content of the photoinitiator contained in the composition for producing the core.

[0144] Ex vivo evaluation of adhesive strength of adhesive layer

[0145] The adhesive strength of the adhesive layer produced by the same method as in Example 1 was measured using a universal testing machine (UTM; 34SC-1, Instron). Specifically, first, a PET film as a backing substrate was attached to a pig skin tissue processed into 1 cm×2 cm. The adhesive layer was shaped into 1 cm×1 cm and attached between two pig skin tissues. After 5 minutes, it was stretched at a speed of 20 mm / min, and the adhesion strength (kPa) was calculated as the maximum load (N) compared to the area where the film was attached.

[0146] Figure 3 The results of measuring the adhesive force of the adhesive layer produced in Example 1 of the present invention are shown. Specifically, the adhesive force (kPa) of the adhesive layer produced in Example 1 is shown.

[0147] refer to Figure 3 It is found that the adhesive force of the adhesive layer can be controlled by adjusting the content of 2,3,4-trihydroxybenzaldehyde which is a pyrogallol-based compound.

[0148] Light transfer evaluation

[0149] It was evaluated whether the light transmission unit manufactured in the above-described examples could smoothly transmit light incident from the outside.

[0150] Specifically, Avalight-LED (Avantes) was prepared as a light irradiation device capable of adjusting the wavelength of light. One end of the light transmission unit manufactured in Example 1 and Example 2 was connected to the light irradiation device, and the light irradiation device was driven to confirm whether the light transmission unit could transmit light.

[0151] Figure 4 This is a photograph of the light transmitting unit manufactured in Example 1 of the present invention transmitting light. Figure 5 This is a photograph of the light transmitting unit manufactured in Example 2 of the present invention transmitting light.

[0152] refer to Figure 4 and Figure 5 , it was confirmed that the light transmission parts manufactured in Examples 1 and 2 transmit light flowing into one end to the other end well. In particular, referring to Figure 5 It was confirmed that the light transmission part can smoothly transmit the light flowing into one end to the other end even when it is bent.

[0153] In addition, it was evaluated whether the light guide adhesive patch manufactured in the above-mentioned Examples could smoothly transmit light incident from the outside.

[0154] Figure 6 is a photograph of the light-guiding adhesive patch manufactured in Example 1 of the present invention. Figure 7 This is a photograph of light transmitted by the light-guiding adhesive patch manufactured in Example 1 of the present invention. Figure 8 is a photograph of the light-guiding adhesive patch manufactured in Example 2 of the present invention. Fig. 9 This is a photograph of light transmitted by the light-guiding adhesive patch manufactured in Example 2 of the present invention.

[0155] refer to Figure 7 and Fig. 9 , it was confirmed that the light-guiding adhesive patch manufactured in Example 1 and Example 2 can smoothly transmit the light flowing in from the end of the light transmission part to the adhesive patch part. In particular, reference Fig. 9 It was confirmed that even when the light transmission part is bent, the light flowing in from the end of the light transmission part can be smoothly transmitted to the adhesive patch part.

[0156] Confirmation of the light transmission improvement effect

[0157] In order to improve the light transmittance of the existing brown-colored bioadhesive patch (without anti-oxidant, w / o AO) as in Examples 1 and 2, an antioxidant (AO) was added to the adhesive layer of Examples 1 and 2, a transparent light-guiding adhesive patch was manufactured, and the degree of improvement in its light transmittance was measured.

[0158] In the light wavelength range of 355nm to 590nm used for photodynamic therapy (PDT) using a photosensitizer such as Hypericin, the results of measuring the improvement in light transmission efficiency using LEDs under the patch were as follows: Fig.10 As confirmed in the , there were differences between the light wavelengths, but in the developed "w / AO" patch group, it was confirmed that a statistically significant (Mann-Whitney nonparametric unpaired t-test; *: p value < 0.05) improvement in light transmittance of at least 1.2 times to a maximum of 36.3 times could be obtained compared to the "w / o AO" group.

[0159] Confirming the effectiveness of photodynamic therapy (PDT) treatment

[0160] Using a 530±15 nm LED that can maximize light transmission, and using the malignant brain tumor U87 cell line, the improvement in PDT efficiency using the light-guiding adhesive patch of the present invention was confirmed.

[0161] Specifically, in order to verify the cancer cell killing effect of PDT, the WST-1 cell viability assay was used. When verifying the improvement of PDT efficiency, the verification for setting PDT conditions was first performed. When the toxicity caused by the photosensitizer itself and light irradiation was tested, no specific cell apoptosis was observed within the range of 50μM hypericin photosensitizer concentration (incubated at 37°C for 2 hours) or 30mJ light irradiation at 530nm, but when the photosensitizer and light irradiation were performed simultaneously, statistically significant cell apoptosis (reduced cell survival rate) was confirmed ( Fig.11 a). Subsequently, when the PDT efficiency using the "w / o AO" patch and the "w / AO" patch was compared, it was confirmed that a statistically significant PDT-cell apoptosis efficiency could be obtained ( Fig.11 b). When the corresponding cell signal changes were measured by qRT-PCR, it was confirmed that when the "w / AO" patch was used for PDT, the CDK2 and p21 signals related to cell division (cell cycle) had significant changes, confirming that it also affected the cell apoptosis mechanism ( Fig.11 c).

[0162] At the same time, the apoptotic ability of cells was confirmed using 3D spheroids, which are closer to living organisms than 2D cell culture. Fig.12 As confirmed in the validation, it was confirmed that in the group using the "w / AO" patch, inhibition of cell growth and induction of cell apoptosis-necrosis in the peripheral area were observed compared to the group using the "w / o AO" patch, thereby confirming that the PDT efficiency of the developed "w / AO" light-guiding adhesive patch was improved.

Claims

1. A light-guiding adhesive patch, wherein: include: An adhesive patch portion, the adhesive patch portion comprising an adhesive portion and a light guide layer, the adhesive portion comprising an adhesive layer and a core layer, the light guide layer being disposed on the adhesive portion and guiding light to the adhesive portion; as well as The light transmission part is connected to the adhesive patch part and guides the light flowing in from the outside to the adhesive patch part.

2. The light-guiding adhesive patch according to claim 1, wherein: The adhesive layer is a hydrogel adhesive layer comprising a reaction product of a biocompatible polymer and a pyrogallol compound.

3. The light-guiding adhesive patch according to claim 2, wherein: The biocompatible polymer comprises at least one of polyethylene glycol, gelatin, alginate, hyaluronic acid, hyaluronic acid-adipic acid dihydrazide, polyethylene glycol amine, four-arm polyethylene glycol amine, six-arm polyethylene glycol amine, eight-arm polyethylene glycol amine, chitosan and collagen.

4. The light-guiding adhesive patch according to claim 2, wherein: The pyrogallol-based compound is a compound represented by the following chemical formula 1: [Chemical formula 1] In the chemical formula 1, R1 is -COOH, -CHO, -NH2, -SH, a linear or branched alkyl group having 1 to 10 carbon atoms, or a linear or branched alkenyl group having 2 to 10 carbon atoms, Three of R2 to R6 are -OH, and the remaining two are hydrogen.

5. The light-guiding adhesive patch according to claim 2, wherein: The reaction product contains 0.3 to 30 parts by weight of the pyrogallol compound relative to 100 parts by weight of the biocompatible polymer.

6. The light-guiding adhesive patch according to claim 1, wherein: The core layer is a hydrogel including a cured product of a composition including a compound containing a photoreactive group and a photoinitiator.

7. The light-guiding adhesive patch according to claim 6, wherein: The photoreactive group-containing compound comprises at least one of polyethylene glycol di(meth)acrylate, (meth)acrylated hyaluronic acid, (meth)acrylated alginate, and (meth)acrylated gelatin.

8. The light-guiding adhesive patch according to claim 1, wherein: The light-guiding layer is a hydrogel light-guiding layer comprising at least one of alginate, hyaluronic acid, chitosan and gelatin.

9. The light-guiding adhesive patch according to claim 1, wherein: The thickness ratio of the bonding portion to the light guide layer is 1:0.1 to 1:

2.

10. The light-guiding adhesive patch according to claim 1, wherein: The light transmission unit comprises: a core disposed in contact with one surface of the adhesive layer and guiding light to the adhesive patch portion; and The coating layer is disposed on the surface of the core.

11. The light-guiding adhesive patch according to claim 10, wherein: The core is a hydrogel including a cured product of a composition including a photoreactive group-containing compound and a photoinitiator.

12. The light-guiding adhesive patch according to claim 11, wherein: The photoreactive group-containing compound comprises at least one of polyethylene glycol di(meth)acrylate, (meth)acrylated hyaluronic acid, (meth)acrylated alginate, and (meth)acrylated gelatin.

13. The light-guiding adhesive patch according to claim 10, wherein: The coating layer includes one or more hydrogel layers containing at least one of alginate, hyaluronic acid, chitosan and gelatin.

14. The light-guiding adhesive patch according to claim 10, wherein: A thickness ratio of the core to the coating layer is 1:0.2 to 1:

4.

15. The light-guiding adhesive patch according to claim 1, wherein: A ratio of an area of ​​the bonding portion to a cross-sectional area of ​​the core is 1:0.004 to 1:0.04.

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