Light guiding adhesive patch

Abstract

To provide a light guiding adhesive patch capable of stably adhering to a surface of an organic material and capable of effectively transmitting light to an attachment site.SOLUTION: A light guiding adhesive patch according to one embodiment of the present invention includes: an adhesive patch part that includes an adhesive part including an adhesive layer and a core layer, and a light guiding layer provided on the adhesive part so as to guide light to the adhesive part; and a light transmission part that is connected to the adhesive patch part so as to guide the light traveling in from the outside to the adhesive patch part.SELECTED DRAWING: Figure 1A

Description

Technical Field

[0001] The present invention relates to a light guide adhesive patch.

Background Art

[0002] Recently, photomedicine, which deals with the application of light to health and disease, has attracted attention. It is used for visualizing and treating diseases and is utilized in surgery, cardiology, radiology, oncology, diagnosis, drug delivery, dermatology, ophthalmology, and the like.

[0003] With the development of diagnostic and treatment technologies, the number of cancer disease groups that achieve complete cure is increasing. However, at present, cancer corresponds to the disease with the first leading cause of death. Approximately 9% to 17% of cancer patients show brain metastasis. The average survival period of patients with metastatic brain tumors is 3 to 25 months, and the 5-year survival rate corresponds to 1.8%. Cancers prone to brain metastasis include melanoma, breast cancer, lung cancer, etc. Although various anti-cancer and radiotherapy methods have been attempted, metastatic brain tumors, which account for approximately 50% of patients with malignant brain tumors, are regarded as intractable diseases.

[0004] Recently, photodynamic therapy (PDT) has attracted attention as a new alternative treatment method for overcoming intractable cancers and malignant brain tumors. Photodynamic therapy has the advantage of having physical treatment selectivity based on spatial and wavelength selectivity, along with lesion selectivity using the drug itself by using a photosensitizer that reacts to light in a specific wavelength band, and active research is continuing as an effective next-generation cancer treatment technology.

[0005] On the other hand, at present, a technology capable of stably transmitting light to living tissues including cancer is required to improve the efficiency of photodynamic therapy.

Summary of the Invention

Problems to be Solved by the Invention

[0006] The present invention provides a light guide adhesive patch capable of stably adhering to the surface of an organic substance and effectively transmitting light to the adhesion site.

[0007] However, the problems to be solved by the present invention are not limited to the above-described problems, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

Means for Solving the Problems

[0008] One embodiment of the present invention provides a light-guiding adhesive patch including an adhesive part including an adhesive layer and a core layer, a light-guiding layer provided on the adhesive part for guiding light to the adhesive part, and a light transmission part connected to the light-guiding adhesive patch for guiding light flowing in from the outside to the light-guiding adhesive patch.

Effects of the Invention

[0009] The light-guiding adhesive patch according to one embodiment of the present invention has an advantage that it can stably adhere to the surface of organic substances such as external living tissues, internal living tissues, and cut tissues with strong adhesive force.

[0010] Further, the light-guiding adhesive patch according to one embodiment of the present invention can effectively transmit light to the adhesion site.

[0011] However, the effects of the present invention are not limited to the above-described effects, and can be variously extended without departing from the spirit and scope of the present invention.

Brief Description of the Drawings

[0012]

Figure 1A

Figure 1B

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Mode for Carrying Out the Invention

[0013] Throughout the present specification, when a part includes a certain component, this means that, unless otherwise stated to the contrary, it does not exclude other components but can further include other components.

[0014] Throughout the present specification, when a member is "connected" to another member, this includes not only the case where a member is directly connected to another member but also the case where there is another member present between the two members and they are connected.

[0015] Throughout the present specification, when a member is positioned "above" another member, this includes not only the case where a member is in contact with another member, but also the case where there is still another member between the two members.

[0016] Throughout the present specification, "(meth)acrylate" is used in the sense of a general term for acrylate and methacrylate.

[0017] Hereinafter, the present invention will be described in more detail.

[0018] One embodiment of the present invention provides a light-guiding adhesive patch including an adhesive part including an adhesive layer and a core layer, a light-guiding layer provided on the adhesive part for guiding light to the adhesive part, and a light-transmitting part connected to the light-guiding adhesive patch for guiding light flowing in from the outside to the light-guiding adhesive patch.

[0019] The light-guiding adhesive patch according to one embodiment of the present invention has an advantage that it can stably adhere to the surface of an organic substance such as an external biological tissue, an internal biological tissue, or a cut tissue with a strong adhesive force. Further, the light-guiding adhesive patch can effectively transmit light to the attachment site.

[0020] FIG. 1A and FIG. 1B are diagrams schematically showing a light-guiding adhesive patch according to one embodiment of the present invention. Specifically, FIG. 1A shows a light-guiding adhesive patch 1 in which the cross-section of the adhesive patch part 100 is provided in a rectangular form, and FIG. 1B shows a light-guiding adhesive patch 1 in which the cross-section of the adhesive patch part 100 is provided in a circular form.

[0021] Referring to FIGS. 1A and 1B, the light guide adhesive patch 1 includes an adhesive patch portion 100 that is adhered to an attachment site and transmits light. Further, the light guide adhesive patch 1 includes a light transmission portion 200 having one end connected to an external light source and the other end connected to the adhesive patch portion 100 to transmit the light flowing in from the light source to the adhesive patch portion 100. At this time, the adhesive patch portion 100 may include an adhesive portion 130 in contact with the attachment site and a light guide layer 140 provided in the adhesive portion 130 to guide the light flowing in from the light transmission portion 200 to the adhesive portion 130.

[0022] According to an embodiment of the present invention, the adhesive portion may include an adhesive layer and a core layer provided on one surface of the adhesive layer. Specifically, one surface of the adhesive layer may be a layer directly in contact with the attachment site, and the core layer may be provided on the other surface of the adhesive layer.

[0023] According to an embodiment of the present invention, the adhesive layer may be a hydrogel adhesive layer including 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. The adhesive layer including the hydrogel precursor can effectively maintain the adhesive ability even when moisture is present on the surface of the object to be adhered.

[0024] According to one embodiment of the present invention, the biocompatible polymer can include at least one of glycol, gelatin, alginate, hyaluronic acid, hyaluronic acid - adipic acid dihydrazide, polyethylene glycol amine, 4 - arm polyethylene glycol amine, 6 - arm polyethylene glycol amine, 8 - arm polyethylene glycol amine, chitosan, and collagen. At this time, 4 - arm polyethylene glycol amine can mean a compound in which four polyethylene glycol branched chains having amino groups at their ends are bonded to a main chain having a structure containing polyhydroxy groups. Also, 6 - arm polyethylene glycol amine can mean a compound in which six polyethylene glycol branched chains having amino groups at their ends are bonded to a main chain having a structure containing polyhydroxy groups. Further, 8 - arm polyethylene glycol amine can mean a compound in which eight polyethylene glycol branched chains having amino groups at their ends are bonded to a main chain having a structure containing polyhydroxy groups. By using the biocompatible polymers of the above - mentioned types, the biological harmfulness can be effectively reduced when the adhesive layer adheres to the object body.

[0025] According to one embodiment of the present invention, the biocompatible polymer may include an amino group-containing biocompatible polymer and an amino group-free biocompatible polymer. For example, the amino group-containing biocompatible polymer may include at least one of polyethylene glycol amine, 4-branched polyethylene glycol amine, 6-branched polyethylene glycol amine, 8-branched polyethylene glycol amine, chitosan, and collagen. Further, the amino group-free biocompatible polymer may include at least one of polyethylene glycol and gelatin. The amino group-containing biocompatible polymer can react with the pyrogallol-based compound to form a compound having excellent adhesiveness. Thereby, the adhesive layer can effectively maintain the adhesive ability even when moisture is present on the surface of the adhesion target.

[0026] According to one embodiment of the present invention, the pyrogallol-based compound may be extracted from a plant. By using a pyrogallol-based compound extracted from a plant, the adhesive performance of the light guide adhesive patch can be effectively imparted.

[0027] According to one embodiment of the present invention, the pyrogallol-based compound may be a compound represented by the following Chemical Formula 1 (Chemical Formula 1).

[0028]

Chemical Formula

[0029] In Chemical Formula 1, R 1 is -COOH, -CHO, -NH 2 , -SH, a linear or branched alkyl having 1 to 10 carbon atoms, or a linear or branched alkenyl having 2 to 10 carbon atoms, and three of R 2 to R 6 are -OH, and the remaining two are hydrogen. Specifically, in Chemical Formula 1, R 1 may be -COOH, -CHO, -NH 2 or -SH. More specifically, in Chemical Formula 1, R 1It may be -CHO. The pyrogallol-based compound represented by the chemical formula 1 can react with the biocompatible polymer to form a hydrogel adhesive layer excellent in adhesiveness and light conductivity. Specifically, the pyrogallol-based compound represented by the chemical formula 1 can react with the amino group-containing biocompatible polymer to form a hydrogel adhesive layer excellent in adhesiveness and light conductivity. At this time, R in the chemical formula 1 1 may be a functional group that reacts with the amino group of the amino group-containing biocompatible polymer described later.

[0030] According to one embodiment of the present invention, the pyrogallol-based compound can include at least one of 2,3,4-trihydroxybenzaldehyde, 2,4,5-trihydroxybenzaldehyde, 3,4,5-trihydroxybenzaldehyde, and 2,4,6-trihydroxybenzaldehyde. The pyrogallol-based compound can react with the biocompatible polymer to form an adhesive layer excellent in adhesiveness and light conductivity. Specifically, the pyrogallol-based compound can react with the amino group-containing biocompatible polymer to form a hydrogel adhesive layer excellent in adhesiveness and light conductivity.

[0031] 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 amino group-containing biocompatible polymer, the amino group-free biocompatible polymer, and the pyrogallol-based compound.

[0032] According to one embodiment of the present invention, based on 100 parts by weight of the composition for producing the adhesive layer, the content of the biocompatible polymer may be 1 part by weight or more and 30 parts by weight or less. When the content of the biocompatible polymer is within the above-described range, biological harmfulness can be effectively reduced when the adhesive layer adheres to an object, and the adhesive layer can effectively maintain its adhesive ability even when moisture is present on the surface of the object to be adhered.

[0033] According to one embodiment of the present invention, based on 100 parts by weight of the composition for producing the adhesive layer, the content of the amino group-containing biocompatible polymer is 0.5 part by weight or more and 15 parts by weight or less, and the content of the amino group-free biocompatible polymer may be 0 part by weight or more and 15 parts by weight or less. When the contents of the amino group-containing biocompatible polymer and the amino group-free biocompatible polymer are within the above-described ranges, biological harmfulness can be effectively reduced when the adhesive layer adheres to an object, and the adhesive layer can effectively maintain its adhesive ability even when moisture is present on the surface of the object to be adhered.

[0034] According to one embodiment of the present invention, the content ratio of the amino group-free biocompatible polymer to the amino group-containing biocompatible polymer may be 1:0.5 to 1:5. Specifically, the content of the amino group-containing biocompatible polymer may be greater than the content of the amino group-free biocompatible polymer. When the content ratio of the amino group-containing biocompatible polymer to the amino group-free biocompatible polymer is within the above-described range, biological harmfulness can be effectively reduced when the adhesive layer adheres to an object, and the adhesive layer can effectively maintain its adhesive ability even when moisture is present on the surface of the object to be adhered.

[0035] According to one embodiment of the present invention, the reaction product can contain 0.3 parts by weight or more and 30 parts by weight or less of the pyrogallol-based compound with respect to 100 parts by weight of the biocompatible polymer. That is, the content of the pyrogallol-based compound may be 0.3 parts by weight or more and 30 parts by weight or less with respect to 100 parts by weight of the total content of the amino group-containing biocompatible polymer and the amino group-free biocompatible polymer contained in the composition for producing the adhesive layer. On the other hand, the content of the pyrogallol-based compound may be a content that can react with all of the amino groups contained in the amino group-containing biocompatible polymer. Specifically, R of the pyrogallol-based compound represented by the chemical formula 1 1 The content of the pyrogallol-based compound represented by the chemical formula 1 can be set so that it can react with the amino group contained in the amino group-containing biocompatible polymer in a ratio of 1:1. When the contents of the biocompatible polymer and the pyrogallol-based compound for forming the reaction product are within the ranges described above, the adhesive layer can stably adhere with a strong adhesive force to the surface of the organic substance. Further, by adjusting the contents of the biocompatible polymer and the pyrogallol-based compound to the ranges described above, the light guiding physical properties of the adhesive layer can be effectively improved. That is, the adhesive layer can be stably adhered to the surface of the organic substance and can effectively transmit light to the surface of the organic substance.

[0036] According to one embodiment of the present invention, the adhesive layer can further contain an antioxidant. By including the antioxidant in the adhesive layer, it is possible to effectively prevent the light guiding efficiency of the adhesive layer from decreasing. As the antioxidant, antioxidants used in the art can be used, for example, vitamin B, vitamin C, and the like can be used.

[0037] According to one embodiment of the present invention, the core layer may be a hydrogel containing a cured product of a composition containing a compound containing a photoreactive group and a photoinitiator. The core layer can protect the adhesive layer and at the same time play a role in efficiently transmitting 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 adhesion site of the adhesive layer can be improved, and the durability of the adhesive patch portion and the like can be improved.

[0038] According to one embodiment of the present invention, the compound containing a photoreactive group can include at least one of polyethylene glycol di(meth)acrylate, (meth)acrylated hyaluronic acid, (meth)acrylated alginate, and (meth)acrylated gelatin. Specifically, the compound containing a photoreactive group can include at least one of polyethylene glycol diacrylate and polyethylene glycol dimethacrylate. Further, the molecular weight of the compound containing a photoreactive group may be 500 g / mol or more and 3,000 g / mol or less. By using the compound containing a photoreactive group of the above-described type, the light transmission efficiency of the core layer can be improved, and a core layer having excellent mechanical properties can be manufactured.

[0039] According to one embodiment of the present invention, as the photoinitiator, those that can be used as photoinitiators in the art can be used without limitation. For example, the photoinitiator can be a propiophenone-based photoinitiator, a benzoin and its alkyl ether photoinitiators, an acetophenone photoinitiator, an anthraquinone photoinitiator, a thioxanthone photoinitiator, a ketal photoinitiator, a benzophenone photoinitiator, an α-aminoacetophenone photoinitiator, an acylphosphine oxide photoinitiator, a ketone photoinitiator, a phenylphosphine oxide photoinitiator, a thioxanthone photoinitiator, an oxime ester photoinitiator, etc., but the type of the photoinitiator is not limited.

[0040] According to one embodiment of the present invention, the core layer can be manufactured using a composition for manufacturing the core layer. That is, the core layer can include a photocured product of the composition for manufacturing the core layer. The composition for manufacturing the core layer can include the photoreactive group-containing compound and a photoinitiator.

[0041] According to one embodiment of the present invention, based on 100 mL of the composition for manufacturing the core layer, the content of the photoreactive group-containing compound may be 5 g or more and 90 g or less. That is, the content of the photoreactive group-containing compound may be 5 w / v% or more and 90 w / v% or less. When the content of the photoreactive group-containing compound is within the above-described range, a core layer excellent in light transmission efficiency can be formed.

[0042] According to one embodiment of the present invention, based on 100 mL of the composition for manufacturing the core layer, the content of the photoinitiator may be 0.01 g or more and 5 g or less. That is, the content of the photoreactive group-containing compound may be 0.01 w / v% or more and 5 w / v% or less. When the content of the photoinitiator is within the above-described range, the photocuring reaction of the cured product is stably performed. Further, by adjusting the content of the photoinitiator to the above-described range, it is possible to control the mechanical properties of the core layer and easily manufacture an adhesive patch portion having desired physical properties.

[0043] According to one embodiment of the present invention, the light guide layer may be a hydrogel light guide layer including at least one of alginate, hyaluronic acid, chitosan, and gelatin. The hydrogel light guide layer is provided on the adhesive portion and can guide the light flowing in from the light transmission portion onto the adhesive portion. Thereby, the adhesive portion can more stably transmit light on the surface of the organic substance. Further, by providing the light guide layer containing the above-described substances on the adhesive portion, when a non-uniform or uniform external force is applied to the adhesive patch portion, the external force is dispersed so that the adhesive portion can be adhered more stably.

[0044] According to an 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-described range, the adhesive layer can stably adhere to the surface of the organic material and can effectively disperse the external force applied to the adhesive portion.

[0045] According to an embodiment of the present invention, the thickness ratio of the adhesive portion to the light guide layer may be 1:0.1 to 1:2. That is, the thickness ratio of the light guide layer may be 1:0.1 to 1:2 with respect to the total thickness of the adhesive layer and the core layer. When the thickness ratio of the adhesive portion to the light guide layer is within the above-described range, the adhesive patch portion can effectively transmit light to the surface of the organic material. Further, by adjusting the thickness ratio of the adhesive portion to the light guide layer to the above-described range, the light guide layer can disperse the external force and further improve the adhesion stability of the adhesive portion.

[0046] According to an embodiment of the present invention, the light transmission portion may be provided in contact with one surface of the adhesive layer, and may include a core that guides light to the adhesive patch portion and a coating layer provided on the surface of the core. Referring to FIGS. 1A and 1B, one end of the core 210 is provided in contact with one surface (for example, a side surface) of the adhesive portion 130, and a light source may be provided at the other end of the core 210. Further, the coating layer 220 may be provided in a form surrounding the entire surface of the core 210 along the outer peripheral surface of the core 210. Furthermore, one end of the coating layer 220 is provided in contact with one surface (for example, a side surface) of the adhesive portion 130 and one surface (for example, a side surface) of the light guide layer 140, and a light source may be provided at the other end of the coating layer 220.

[0047] According to an 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 can protect the core and at the same time can play a role of assisting in transmitting 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.

[0048] According to one embodiment of the present invention, the core can include a cured product of a composition containing a compound containing a photoreactive group and a photoinitiator. That is, the core may be a photocured product of a composition for producing a core containing the compound containing a photoreactive group and the photoinitiator.

[0049] According to one embodiment of the present invention, the compound containing a photoreactive group can include at least one of polyethylene glycol di(meth)acrylate, (meth)acrylated hyaluronic acid, (meth)acrylated alginate, and (meth)acrylated gelatin. Specifically, the compound containing a photoreactive group can include at least one of polyethylene glycol diacrylate and polyethylene glycol dimethacrylate. Further, the molecular weight of the compound containing a photoreactive group may be 500 g / mol or more and 3,000 g / mol or less. By using the compound containing a photoreactive group of the above-described type, the light transmission efficiency of the core can be improved, and a core excellent in mechanical physical properties can be produced.

[0050] According to one embodiment of the present invention, as the photoinitiator, those that can be used as photoinitiators in the art can be used without limitation. For example, the photoinitiator can be a propiophenone-based photoinitiator, a benzoin and its alkyl ether photoinitiator, an acetophenone photoinitiator, an anthraquinone photoinitiator, a thioxanthone photoinitiator, a ketal photoinitiator, a benzophenone photoinitiator, an α-aminoacetophenone photoinitiator, an acylphosphine oxide photoinitiator, a ketone photoinitiator, a phenylphosphine oxide photoinitiator, a thioxanthone photoinitiator, an oxime ester photoinitiator, etc., but the type of the photoinitiator is not limited.

[0051] 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 may be 5 g or more and 90 g or less. That is, the content of the photoreactive group-containing compound may be 5 w / v% or more and 90 w / v% or less. When the content of the photoreactive group-containing compound is within the above-described range, a core with excellent light transmission efficiency can be formed.

[0052] According to one embodiment of the present invention, based on 100 mL of the core manufacturing composition, the content of the photoinitiator may be 0.01 g or more and 5 g or less. That is, the content of the photoreactive group-containing compound may be 0.01 w / v% or more and 5 w / v% or less. When the content of the photoinitiator contained in the core manufacturing composition is within the above-described range, the photocuring reaction of the cured product can be stably performed. Further, by adjusting the content of the photoinitiator to the above-described range, the mechanical properties of the core can be controlled so that the light transmission portion is flexible and can be bent well.

[0053] According to one embodiment of the present invention, the coating layer can include one or more hydrogel layers containing at least one of alginate, hyaluronic acid, chitosan, and gelatin. Specifically, the coating layer can include one or more hydrogel layers containing the above-described substances, and the two or more hydrogel layers may be formed of the same substance or different substances. Also, the two or more hydrogel layers contained in the coating layer may have the same or different thicknesses. By providing the coating layer containing the above-described substances on the core, it is possible to assist the transmission of light through the core and prevent damage to the core layer.

[0054] According to an embodiment of the present invention, the thickness ratio of the core to the coating layer may be from 1:0.2 to 1:4. When the thickness ratio of the core to the coating layer is within the above-mentioned range, the light transmission part can effectively transmit light to the adhesive patch part. Further, damage to the light transmission part can be prevented, and deformation of the light transmission part can be facilitated. That is, the light transmission part can be bent without damage, thereby improving the usability of the light guiding adhesive patch.

[0055] According to an embodiment of the present invention, the ratio of the area of the adhesive part to the cross-sectional area of the core may be from 1:0.004 to 1:0.04. That is, the ratio of the area of the adhesive layer to the cross-sectional area of the core may be from 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 from 1:0.004 to 1:0.04. Referring to FIG. 1A, the area of the adhesive part may mean the cross-sectional area of the adhesive part in the x-y plane, and the cross-sectional area of the core may mean the cross-sectional area of the core in the y-z plane. At this time, light may be irradiated in the x-axis direction (a direction perpendicular to the y-z plane) with respect to the core. When the ratio of the area of the adhesive part to the cross-sectional area of the core is within the above-mentioned range, light emitted from the light source can stably reach the adhesive patch part through the light transmission part.

[0056] An embodiment of the present invention provides a method for manufacturing a light guiding adhesive patch, including a step of manufacturing an adhesive patch part and a step of manufacturing a light transmission part.

[0057] The method for manufacturing a light guiding adhesive patch according to an embodiment of the present invention can stably adhere to the surface of an organic substance and can easily manufacture a light guiding adhesive patch capable of effectively transmitting light to an attachment site.

[0058] The manufacturing method of the light guide adhesive patch is a method for manufacturing the light guide adhesive patch according to the above-described embodiment. In the manufacturing method of the light guide adhesive patch according to the present embodiment, the adhesive layer, the core layer, the adhesive portion, the light guide layer, the adhesive patch portion, the core, the coating layer, and the light transmission portion may be the same as the adhesive layer, the core layer, the adhesive portion, the light guide layer, the adhesive patch portion, the core, the coating layer, and the light transmission portion in the light guide adhesive patch according to the above-described embodiment.

[0059] According to an embodiment of the present invention, the step of manufacturing the adhesive patch portion may include the step of manufacturing the adhesive layer, the step of manufacturing the core layer, and the step of manufacturing the light guide layer.

[0060] The step of manufacturing the adhesive layer can manufacture the adhesive layer using a composition for manufacturing an adhesive layer containing the biocompatible polymer and the pyrogallol-based compound. Specifically, the composition for manufacturing the adhesive layer can be dried at a temperature of 20°C or higher and 40°C or lower to manufacture an adhesive layer in the form of a film, and can be shaped into a desired form.

[0061] The step of manufacturing the core layer can manufacture the core layer using a composition for manufacturing a core layer containing the photo-reactive group-containing compound and the photoinitiator. Specifically, the composition for manufacturing the core layer is put into a mold and irradiated with ultraviolet rays of 1 mW / cm 2 or more and 100 mW / cm 2 or less for 5 minutes or more and 10 minutes or less to cure the composition for manufacturing the core layer and manufacture the core layer.

[0062] In order to manufacture the adhesive portion, the adhesive layer can be attached onto the manufactured core layer to manufacture the adhesive portion. At this time, the core layer is attached to one surface of the adhesive layer, and a release film can be attached to the other surface of the adhesive layer exposed to the outside.

[0063] The step of manufacturing the light guide layer can manufacture the light guide layer using a hydrogel precursor solution. At this time, the hydrogel precursor solution can contain at least one of alginate, hyaluronic acid, chitosan, and gelatin. Specifically, the hydrogel precursor solution can be applied onto one surface of the core layer of the adhesive part and immersed in a reactive solution to form a light guide layer on the core layer. At this time, the reactive solution can contain a reactive substance capable of reacting with the compound contained in the hydrogel precursor solution to form a hydrogel. For example, the reactive substance may be calcium chloride.

[0064] According to an embodiment of the present invention, the step of manufacturing the light transmission part can include the step of manufacturing a core and the step of manufacturing a coating layer.

[0065] The step of manufacturing the core can manufacture the core using a core manufacturing composition containing the photo-reactive group-containing compound and the photoinitiator. Specifically, the core manufacturing composition is placed in a mold and irradiated with ultraviolet light of 1 mW / cm 2 or more and 100 mW / cm 2 or less for a time of 5 minutes or more and 10 minutes or less to cure the core manufacturing composition and manufacture the core.

[0066] The step of manufacturing the coating layer can manufacture the coating layer using a hydrogel precursor solution. At this time, the hydrogel precursor solution can contain at least one of alginate, hyaluronic acid, chitosan, and gelatin. Specifically, after the manufactured core is immersed in the hydrogel precursor solution, it can be immersed in a reactive solution to form a coating layer on the core. At this time, the reactive solution can contain a reactive substance capable of reacting with the compound contained in the hydrogel precursor solution to form a hydrogel. For example, the reactive substance may be calcium chloride.

[0067] According to an embodiment of the present invention, a light-conducting adhesive patch can be manufactured by attaching a light-transmitting part manufactured on one side of the manufactured adhesive patch part. In order to attach the adhesive patch part and the light-transmitting part, an adhesive or an adhesive film harmless to the human body used in the art can be used. Further, by positioning the light-transmitting part on one side of the adhesive patch part and using a hydrogel precursor solution and a reactive solution, the adhesive patch part and the light-transmitting part can be bonded to manufacture a light-conducting adhesive patch. Furthermore, by positioning a core manufactured on one side of an adhesive part including an adhesive layer and a core layer and using a hydrogel precursor solution and a reactive solution, a light-conducting layer and a coating layer can be formed together. Thereby, a light-conducting adhesive patch in which the adhesive patch part and the light-transmitting part are integrally provided can be manufactured.

[0068] Hereinafter, examples will be given for a specific description of the present invention. However, the examples according to the present invention can be deformed into various different forms, and the scope of the present invention is not construed as being limited to the examples described below. The examples in this specification are provided to more fully explain the present invention to those having average knowledge in the art.

Example

[0069] A light-conducting adhesive patch having the form shown in Fig. 1A was manufactured by the following method.

[0070] 1) Manufacture of the bonding patch part (1) Manufacture of core layer Polyethylene glycol diacrylate having a molecular weight of 700 g / mol, which is a compound containing a photoreactive group, and 2-Hydroxy-4’-(2-hydroxyethoxy)-2-methylpropiophenone (Sigma Aldrich) as a photoinitiator were mixed in distilled water to manufacture a composition for manufacturing a core layer.

[0071] At this time, based on 100 mL of the composition for manufacturing the core layer, the content of polyethylene glycol diacrylate was 80 g (80 w / v%). Also, the content of the photoinitiator was 1 g (1 w / v%) based on 100 mL of the composition for manufacturing the core layer.

[0072] Thereafter, the composition for manufacturing the core layer was put into a mold and irradiated with ultraviolet light of 5 mW / cm 2 for 300 seconds. Finally, a core layer having a width of 15 mm, a length of 15 mm, and a thickness of 2 mm was manufactured.

[0073] (2) Manufacture of the adhesive layer Hyaluronic acid - adipic acid dihydrazide was prepared with an amine group - containing biocompatible polymer, and 2,3,4 - Trihydroxybenzaldehyde was prepared with a pyrogallol - type compound.

[0074] Thereafter, hyaluronic acid - adipic acid dihydroxy group, 2,3,4 - Trihydroxybenzaldehyde, and distilled water were mixed to manufacture a composition for manufacturing the adhesive layer. At this time, based on 100 parts by weight of the composition for manufacturing the adhesive layer, the content of hyaluronic acid - adipic acid dihydrazide was 1 part by weight. On the other hand, the amount of 2,3,4 - Trihydroxybenzaldehyde was adjusted so that the amine group of the 6 - branched polyethylene glycol amine and the aldehyde group of 2,3,4 - Trihydroxybenzaldehyde corresponded to 1:0, 1:1, and 1:5. At this time, based on 100 parts by weight of the total content of hyaluronic acid - adipic acid dihydrozide, the contents of 2,3,4 - Trihydroxybenzaldehyde were 0, 10, and 50 parts by weight, respectively.

[0075] Thereafter, the composition for manufacturing the adhesive layer was dried at room temperature to manufacture an adhesive layer in the form of a film, and it was shaped to manufacture an adhesive layer having a width of 15 mm, a length of 15 mm, and a thickness of 0.1 mm. Thereafter, the adhesive layer manufactured on one surface of the core layer manufactured above was attached to manufacture an adhesive part.

[0076] (3) Fabrication of the light guide layer A 2 w / v% alginate solution and a 100 mM calcium chloride solution were prepared.

[0077] Thereafter, after applying the alginate solution onto the other surface of the core layer where the adhesive layer did not adhere, it was immersed in the calcium chloride solution to form an alginate hydrogel. That is, a light guide layer containing the alginate hydrogel was formed on the other surface of the core layer. At this time, the light guide layer was formed on the core layer in a form with a horizontal dimension of 15 mm, a vertical dimension of 15 mm, and a thickness of 1 mm. Thereby, the adhesive patch portion was finally fabricated.

[0078] 2) Manufacture of the light transmission part (1) Fabrication of the core Example 1-1 (photoinitiator 0.2 w / v%) Polyethylene glycol diacrylate with a molecular weight of 700 g / mol, which is a photo-reactive group-containing compound, and 2-hydroxy-4’-(2-hydroxyethoxy)-2-methylpropiophenone (2-Hydroxy-4’-(2-hydroxyethoxy)-2-methylpropiophenone) (Sigma Aldrich) as a photoinitiator were mixed in distilled water to produce a core fabrication composition. At this time, based on 100 mL of the core fabrication composition, the content of polyethylene glycol diacrylate was 80 g (80 w / v%). Also, the content of the photoinitiator was 0.2 g (0.2 w / v%) based on 100 mL of the core fabrication composition.

[0079] Thereafter, the core fabrication composition was put into a mold and irradiated with ultraviolet light of 5 mW / cm 2 for 300 seconds. Finally, a core having a diameter of 2 mm and a length of 30 mm was fabricated.

[0080] Example 1-2 (photoinitiator 0.6 w / v%) The core of the light transmission part was fabricated in the same manner as in Example 1-1, except that the content of the photoinitiator was adjusted to 0.6 w / v% in Example 1-1.

[0081] Example 1-3 (photoinitiator 1 w / v%) The core of the light transmission part was manufactured in the same manner as in Example 1-1, except that the content of the photoinitiator was adjusted to 1 w / v% in Example 1-1.

[0082] Example 1-4 (photoinitiator 1 w / v%, 50 mW / cm 2 ) The core of the light transmission part was manufactured in the same manner as in Example 1-1, except that the content of the photoinitiator was adjusted to 1 w / v% and the ultraviolet intensity was adjusted to 50 mW / cm 2 in Example 1-1.

[0083] (2) Manufacture of the coating layer A 2 w / v% alginate solution and a 100 mM calcium chloride solution were prepared.

[0084] Thereafter, the manufactured core was immersed in the alginate solution and then in the calcium chloride solution to form an alginate hydrogel. That is, a coating layer containing the alginate hydrogel was formed on the surface of the core. At this time, the thickness of the coating layer was 0.5 mm and the length was 30 mm. Thus, the light transmission part was finally manufactured.

[0085] Thereafter, a light guide adhesive patch having a form in which the light transmission part was connected to one side of the adhesive patch part was manufactured.

Example

[0086] A light guide adhesive patch having the form shown in Fig. 1B was manufactured by the following method.

[0087] 1) Manufacture of the bonding patch part (1) Manufacture of the core layer A core layer having a diameter of 8 mm and a thickness of 2 mm was manufactured in the same manner as in Example 1.

[0088] (2) Manufacture of the adhesive layer In the same manner as in Example 1, an adhesive layer with a diameter of 8 mm and a thickness of 0.1 mm was manufactured. Subsequently, the manufactured adhesive layer was attached onto one surface of the manufactured core layer to manufacture an adhesive portion.

[0089] (3) Manufacture of the light guide layer In the same manner as in Example 1, a light guide layer with a diameter of 8 mm and a thickness of 1 mm was formed on the other surface of the core layer. Thereby, the adhesive patch portion was finally manufactured.

[0090] 2) Manufacture of the light transmission part (1) Manufacture of the core In the same manner as in Example 1, a core of a light transmission portion with a diameter of 2 mm and a length of 30 mm was manufactured.

[0091] (2) Manufacture of the coating layer In the same manner as in Example 1, a coating layer with a thickness of 0.5 mm was manufactured on the surface of the manufactured core. Thereby, the light transmission portion was finally manufactured.

[0092] Subsequently, a light guide adhesive patch having a form in which the light transmission portion was connected to one side of the adhesive patch portion was manufactured.

[0093] Experimental example Measurement of the mechanical properties of the core of the light transmission portion Using Discovery Hybrid Rheometer2 (TA Instrument), the mechanical properties of the cores of the light transmission portions manufactured in Examples 1-1 to 1-4 were measured. Specifically, the storage modulus (G’), loss modulus (G”), and Tan(δ) value of the cores of the light transmission portions were measured at a frequency of 1 Hz.

[0094] Figure 2 is a diagram showing the results of measuring the mechanical properties of the core of the light transmission portion manufactured in Example 1 of the present invention. Specifically, the measured storage modulus (G’), loss modulus (G”), and Tan(δ) value of the cores of the light transmission portions manufactured in Examples 1-1 to 1-4 are shown.

[0095] Referring to Fig. 2, it can be seen that by adjusting the content of the photoinitiator contained in the composition for manufacturing the core, the mechanical properties of the manufactured core can be controlled.

[0096] Ex vivo Adhesion Strength Evaluation of the Adhesive Layer Using a Universal testing machine (UTM; 34SC-1, Instron), the adhesion strength of the adhesive layer manufactured in the same manner as in Example 1 was measured. Specifically, first, a PET film was attached as a backing substrate to a porcine skin tissue processed to 1 cm × 2 cm. The adhesive layer was shaped to 1 cm × 1 cm and pasted between two porcine skin tissues. After 5 minutes, it was pulled at a speed of 20 mm / min, and the adhesion strength (kPa) was calculated as the maximum load (N) divided by the area ratio of the film-attached surface.

[0097] Fig. 3 shows the results of measuring the adhesion strength of the adhesive layer manufactured in Example 1 of the present invention. Specifically, the adhesion strength (kPa) of the adhesive layer manufactured in Example 1 is shown.

[0098] Referring to Fig. 3, it can be seen that by adjusting the content of 2,3,4-trihydroxybenzaldehyde, which is a pyrogallol-based compound, the adhesion strength of the adhesive layer can be controlled.

[0099] Light Transmission Evaluation It was evaluated whether the light incident from the outside was well transmitted to the light transmission part manufactured in the above example.

[0100] Specifically, an Avalight-LED (Avantes) was prepared as a light irradiation device with adjustable light wavelength. One end of the light transmission parts manufactured in Example 1 and Example 2 was coupled to the light irradiation device, and the light irradiation device was driven to confirm whether the light transmission parts could transmit light.

[0101] Fig. 4 is a photograph of the light transmission part manufactured in Example 1 of the present invention transmitting light, and Fig. 5 is a photograph of the light transmission part manufactured in Example 2 of the present invention transmitting light.

[0102] Referring to FIGS. 4 and 5, it was confirmed that the light transmission parts manufactured in Example 1 and Example 2 transmitted the light flowing into one end well to the other end. In particular, referring to FIG. 5, it was confirmed that even when the light transmission part was bent, the light flowing into one end was transmitted well to the other end.

[0103] Also, with respect to the light guide adhesive patch manufactured in the above example, it was evaluated whether the light incident from the outside was transmitted well.

[0104] FIG. 6 is a photograph of the light guide adhesive patch manufactured in Example 1 of the present invention, and FIG. 7 is a photograph of the light guide adhesive patch manufactured in Example 1 of the present invention transmitting light. FIG. 8 is a photograph of the light guide adhesive patch manufactured in Example 2 of the present invention, and FIG. 9 is a photograph of the light guide adhesive patch manufactured in Example 2 of the present invention transmitting light.

[0105] Referring to FIGS. 7 and 9, it was confirmed that the light guide adhesive patches manufactured in Example 1 and Example 2 transmitted the light flowing in from the end of the light transmission part well to the adhesive patch part. In particular, referring to FIG. 9, it was confirmed that even when the light transmission part was bent, the light flowing in from the end of the light transmission part was transmitted well to the adhesive patch part.

[0106] Confirm the light transmission rate improvement effect In order to improve the light transmission rate of the existing brown bioadhesive patch (without anti-oxidant, w / o A-O) having the color as in Example 1 and Example 2, an antioxidant (anti-oxidant, A-O) was added to the adhesive layers of Example 1 and Example 2 to produce a light guide adhesive patch that was made transparent, and the improvement in its light transmission rate was measured.

[0107] The light transmittance improvement using an LED in the optical wavelength band of 355 nm to 590 nm or less, which is the optical wavelength range for performing photodynamic therapy (PDT) using a hypericin photosensitizer, was measured below the patch. As confirmed in Fig. 10, although there are differences depending on the optical wavelength, the developed "w / A-O" patch group obtained 36.3 times the maximum light rate statistically significantly transmitted compared to the "w / o A-O" group (Mann-Whitney nonparametric unpaired t-test; *: p-value < 0.05).

[0108] Verification of the effect of wide-area dynamic therapy (PDT) treatment Using the light guide adhesive patch of the present invention with the U87 malignant brain tumor cell line using a 530 ± 15 nm LED that can maximize the improvement of light transmittance, the improvement of PDT efficiency was confirmed.

[0109] Specifically, a WST-1 cell viability assay was used to verify the cancer cell killing efficacy through PDT.

[0110] In the verification of the improvement of PDT efficiency, when first verifying the PDT condition setting and investigating the toxicity of the photosensitizer itself and light irradiation, no specific cell death was observed within the range of a 50 μM Hypericin photosensitizer concentration (2 hours incubation at 37°C) or a light irradiation dose of 30 mJ at 530 nm. However, when the photosensitizer and light irradiation were performed simultaneously, statistically significant cell death (decrease in cell survival) was confirmed (Fig. 11a). Subsequently, when comparing the PDT efficiency using the "w / o A-O" patch and the "w / A-O" patch, it was confirmed that a statistically significant PDT-cell killing efficiency could be obtained (Fig. 11b). When measuring the change in the cell signal for this using qRT-PCR, it was confirmed that the signals of CDK2 and p21 related to the cell cycle had significant changes when PDT was performed using the "w / A-O" patch, and it was also confirmed that it affected the mechanism of cell death (Fig. 11c).

[0111] In addition, the cell-killing ability was confirmed using 3D spheroids, which are closer to the living body compared to 2D cell culture. As a result, as also confirmed in 12, it was observed that in the group using the "w / A-O" patch, compared to the group using the "w / o A-O" patch, the PDT efficiency of the developed "w / A-O" light-guiding adhesive patch was improved by inducing the form of cell death-necrosis in the peripheral part along with cell growth inhibition.

Explanation of Signs

[0112] 1: Light-guiding adhesive patch 100: Adhesive patch part 110: Adhesive layer 120: Core layer 130: Adhesive part 140: Light-guiding layer 200: Light transmission part 210: Core 220: Coating layer

Claims

1. An adhesive patch part including an adhesive part including an adhesive layer and a core layer, and a light guide layer provided on the adhesive part to guide light to the adhesive part; a light transmitting part connected to the adhesive patch part and guiding light entering from the outside to the adhesive patch part.

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

3. 3. The light-guiding adhesive patch of claim 2, wherein the biocompatible polymer comprises at least one of polyethylene glycol, gelatin, polyethylene glycol amine, 4-branched polyethylene glycol amine, 6-branched polyethylene glycol amine, 8-branched polyethylene glycol amine, chitosan, and collagen.

4. The pyrogallol-based compound is a compound represented by the following chemical formula 1 (Chemical Formula 1): 【Chemistry 1】 In the above Chemical Formula 1, R １ is -COOH, -CHO, -NH ２ , -SH, linear or branched alkyl having 1 to 10 carbon atoms, or linear or branched alkenyl having 2 to 10 carbon atoms, R ２ ~R ６ The light-guiding adhesive patch of claim 2 , wherein three of the groups 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 parts by weight to 30 parts by weight of a pyrogallol-based 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 comprising a cured product of a composition containing a photoreactive group-containing compound and a photoinitiator.

7. 7. The light-guiding adhesive patch of 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 of 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 adhesive part to the light-guiding layer is 1:0.1 to 1:

2.

10. The light transmitting portion is A core provided in contact with one surface of the adhesive layer and configured to guide light to the adhesive patch portion; The light-guiding adhesive patch of claim 1 , further comprising: a coating layer provided on a surface of the core.

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

12. 12. The light-guiding adhesive patch of 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 of claim 10 , wherein the covering layer comprises one or more hydrogel layers comprising at least one of alginate, hyaluronic acid, chitosan, and gelatin.

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

4.

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

Images