Biodegradable adhesive patch and manufacturing method thereof

Abstract

The present invention provides a biodegradable adhesive patch comprising: a substrate; and a plurality of embossed portions arranged on the substrate, wherein a fine wrinkle layer is disposed on the upper surfaces of the embossed portions.

Description

Biodegradable adhesive patch and method for manufacturing the same

[0001] This specification claims the benefit of Korean Patent Application No. 10-2024-0018279, filed with the Korean Intellectual Property Office on February 6, 2024, the entire contents of which are incorporated herein by reference.

[0002] The present invention relates to a biodegradable adhesive patch and a method for manufacturing the same.

[0003] This invention is a result of research conducted as part of the 3-stage Industry-Academia-Research Cooperation Leading University Development Project (LINC 3.0) supported by funds from the Ministry of Education and the National Research Foundation of Korea.

[0004] Recently, multiscale structures using physically based adhesives based on in vivo adhesion mechanisms have been shown to achieve stable adhesion on human surfaces. For example, a gecko-derived adhesive film using micropillars demonstrated enhanced adhesion due to van der Waals forces. However, van der Waals forces have lower adhesion efficiency under wet or flowing water conditions.

[0005] Furthermore, numerous studies on the wet adhesion mechanisms of amphibians, such as tree frogs, have demonstrated stable fixation and movement on wet surfaces, driven by oil (mucus)-assisted capillary and viscous forces. For example, research is underway on adhesive films derived from frog toes with multiscale structures, demonstrating robust and stable adhesion performance. Furthermore, research is underway to develop a frog-shaped adhesive system coated with high-viscosity oil.

[0006] To address the limitations of conventional closure methods using sutures and staplers, which cause various problems (scarring, inflammation, redness, etc.), bioadhesives have been intensively studied to alleviate the need for invasive procedures. Bioadhesives, primarily used as sealants and hemostatic agents in surgical procedures, cover wounds with minimal tissue damage at the application site. Typically, chemical adhesives such as cyanoacrylate and fibrin glue are used in surgical procedures. However, these adhesives can exhibit loss of adhesion in wet conditions and may leave chemical residues on the bonded biomaterial surface.

[0007] To overcome these issues, a bioadhesive using DOPA (l-3,4-dihydroxyphenylalanine), inspired by mussels, has been proposed. The tissue adhesion achieved by utilizing the catechol group in DOPA resulted in an adhesive that adheres well to various wet surfaces without losing biocompatibility.

[0008] For hemostatic sealants and tissue repair materials, various studies have been conducted to develop hydrogel-based adhesives (e.g., chitosan, polyallylamine, poly(ethylene glycol) diacrylate, polyethyleneimine, and polyacrylic acid) that exhibit adhesive properties on various tissue surfaces. While these adhesives exhibit high adhesive strength and biocompatibility, they may require additional surgical removal or pose the risk of contamination.

[0009] Biodegradable polymers are attracting significant attention in the medical field (e.g., tissue engineering, drug delivery, biosignal detection) because they can be safely degraded within the body without producing toxic substances and can be eliminated without additional procedures such as surgery. Specifically, for use as adhesive film layers, biodegradable materials must possess a ductile modulus that prevents physical damage to tissue surfaces and maintains their mechanical properties even in humid environments.

[0010] Meanwhile, it is necessary to develop a patch that is not affected by the chemical effects of microorganisms and saliva when attached to the oral mucosa, and a moisture-resistant adhesive ability is required to attach the patch to the oral mucosa wet with saliva.

[0011] However, as mentioned above, various studies on chemical wet patches using biomimetic mussel proteins are being conducted, but there were some parts that were difficult to remove from the patches.

[0012] Therefore, there is a need to develop a patch technology that allows sufficient drug delivery and easy removal after wet adhesion is achieved.

[0013] The present invention relates to a biodegradable adhesive patch and a method for manufacturing the same.

[0014] However, the problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.

[0015] In order to solve the above-mentioned conventional problems, according to one embodiment of the present invention, a biodegradable adhesive patch is provided, which includes a substrate and a plurality of relief portions arranged on the substrate, and a fine wrinkle layer is arranged on the upper surface of the relief portions.

[0016] The above fine wrinkle layer is characterized by having a plurality of linear structures.

[0017] The plurality of linear structures of the above-mentioned fine wrinkle layer can be arranged randomly.

[0018] The adhesive force of the surface of the above-mentioned relief portion is characterized by a capillary force determined by the surface tension and Laplace pressure of the surface boundary of the above-mentioned relief portion.

[0019] The above-described substrate and the plurality of relief portions arranged on the above-described substrate may include a biodegradable material.

[0020] The above-described substrate and the plurality of relief portions arranged on the above-described substrate may include a mixture of gelatin and polyacrylamide (PAAm).

[0021] The mixture of the above gelatin and polyacrylamide (PAAm) may be included in a weight ratio of 1:1 to 1:2.

[0022] Another embodiment of the present invention provides a method for manufacturing a biodegradable adhesive patch, comprising the steps of: manufacturing a polymer master mold having a plurality of raised pillar-shaped patterns on a surface and micro-grooves between the plurality of raised pillar-shaped patterns, and having wrinkles formed on the upper surface of the micro-grooves; and filling a biodegradable precursor material into the micro-grooves of the polymer master mold, attaching a substrate to cover the upper portion, and curing the substrate; wherein a micro-wrinkle layer is formed on the upper surface of the raised portion.

[0023] The step of manufacturing the above polymer master mold may be performed by: manufacturing a structure having a plurality of relief pillar-shaped patterns on a surface and micro-grooves between the plurality of relief pillar-shaped patterns; forming a micro-wrinkle layer by stamping on the upper surface of the plurality of relief pillar-shaped patterns of the structure; and applying and curing a polymer material to the structure.

[0024] The step of manufacturing the polymer master mold may be performed by: manufacturing a structure having a plurality of relief pillar-shaped patterns on a surface and micro-grooves between the plurality of relief pillar-shaped patterns; applying a polymer material to the structure and partially curing it; and separating the partially cured structure and forming a micro-wrinkle layer in the micro-grooves between the relief pillar-shaped patterns.

[0025] According to one embodiment of the present invention, a biodegradable adhesive patch comprises a plurality of raised portions arranged on a substrate, imitating the structure of a frog's tongue, and has a structure in which a fine wrinkle layer is arranged on the upper surface of the raised portions, so that the adhesive force is excellent while minimizing irritation to the skin adhesion surface, and thus the adhesive force is excellent and material transfer is possible without causing damage to the skin.

[0026] In addition, the biodegradable adhesive patch has strong adhesive strength even in moisture or water, so it can adhere even when saliva is present in the mouth, and it can maintain adhesive strength and not come off even when the mouth moves.

[0027] In addition, according to one embodiment of the present invention, since the biodegradable adhesive patch is manufactured by including a biodegradable polymer, it can be safely decomposed without generating toxic substances in the body or on the surface of the human body.

[0028] In particular, the biodegradable adhesive patch has a soft modulus so that the biodegradable material can maintain its mechanical properties even in a wet environment without causing physical damage to the tissue surface when used as an adhesive film layer.

[0029] Figure 1 is a schematic diagram and a partially enlarged view of a biodegradable adhesive patch according to one embodiment of the present invention.

[0030] FIG. 2 is a drawing illustrating the structure of a frog's tongue for simulating the structure of a biodegradable adhesive patch according to one embodiment of the present invention.

[0031] Figure 3 is a graph showing biodegradability according to the biodegradable material included in the biodegradable adhesive patch according to one embodiment of the present invention.

[0032] Figure 4 is a schematic diagram showing a first embodiment of manufacturing a biodegradable adhesive patch according to one embodiment of the present invention.

[0033] Figure 5 is a schematic diagram showing a second embodiment of manufacturing a biodegradable adhesive patch according to one embodiment of the present invention.

[0034] Figure 6 is a graph showing the coefficient of friction according to an embodiment and a comparative example of the present invention.

[0035] In this specification, when a part is said to "include" a certain component, this does not mean that it excludes other components, but rather that it may include other components, unless otherwise specifically stated.

[0036] In this specification, when it is said that a member is located “on” another member, this includes not only cases where the member is in contact with the other member, but also cases where another member exists between the two members.

[0037] In this specification, the terms “step of” and “step of” do not mean “step for”.

[0038] The specific details for implementing the present invention will be described in detail with reference to the attached drawings below.

[0039] Figure 1 is a schematic diagram and a partially enlarged view of a biodegradable adhesive patch according to one embodiment of the present invention.

[0040] FIG. 2 is a drawing illustrating the structure of a frog's tongue for simulating the structure of a biodegradable adhesive patch according to one embodiment of the present invention.

[0041] Referring to FIGS. 1 and 2, according to one embodiment of the present invention, a biodegradable adhesive patch is provided, which includes a substrate and a plurality of relief portions arranged on the substrate, and a fine wrinkle layer is arranged on the upper surface of the relief portions.

[0042] The above-mentioned substrate is not particularly limited and may be, for example, a substrate or a film. Specifically, the substrate may include a biodegradable material.

[0043] According to one embodiment of the present invention, the substrate can be manufactured from a biodegradable material, so that automatic detachment and decomposition are possible after drug delivery.

[0044] The biodegradable material is not particularly limited and may be, for example, one or more selected from the group consisting of cellulose, chitin, PAAm, PHA, PCL, PGA, PLLA, PBS, PHB, and gelatin.

[0045] A biodegradable adhesive patch according to one embodiment of the present invention includes a plurality of raised portions arranged on the substrate.

[0046] The above-mentioned plurality of raised parts correspond to parts that imitate the fungiform papillae structure in the structure of a frog's tongue, as shown in Fig. 2.

[0047] The above-described plurality of relief portions may include a biodegradable material. The biodegradable material is not particularly limited and may be, for example, at least one selected from the group consisting of cellulose, chitin, PAAm, PHA, PCL, PGA, PLLA, PBS, PHB, and gelatin.

[0048] According to one embodiment of the present invention, the plurality of raised portions can be manufactured from a biodegradable material, so that automatic detachment and decomposition are possible after drug delivery.

[0049] According to one embodiment of the present invention, the planar shape of the plurality of relief portions may be circular or polygonal. In addition, the planar shapes of the plurality of relief portions may be different from each other or may be the same shape.

[0050] In a biodegradable adhesive patch according to one embodiment of the present invention, a fine wrinkle layer is arranged on the upper surface of the raised portion.

[0051] The structure in which a fine wrinkle layer is arranged on the upper surface of the above-mentioned relief portion corresponds to a part that imitates the filiform papillae structure of the frog tongue, as shown in Fig. 2.

[0052] The above-described fine wrinkle layer is characterized by having a plurality of linear structures. In addition, the plurality of linear structures of the fine wrinkle layer can be randomly arranged.

[0053] According to one embodiment of the present invention, a biodegradable adhesive patch has a micro-wrinkle layer arranged on the upper surface of the raised portion, and since the micro-wrinkle layer has a plurality of linear structures, adhesive strength can be improved.

[0054] The adhesive force of the surface of the above-mentioned relief portion is characterized by a capillary force determined by the surface tension and Laplace pressure of the surface boundary of the above-mentioned relief portion.

[0055] In the case of water, the viscous force can be neglected compared to the capillary force, so the total wetting adhesive force on the surface of the above-mentioned relief can be basically expressed as the sum of two components: the surface tension of the fluid and the Laplace pressure.

[0056] σ capillary can be expressed as follows.

[0057]

[0058] Here n area The number of reliefs per unit area (~180 # cm -2 ), A H is the area of ​​the circular relief, γ is the surface tension of water (~0.072 J m -2 ), θ1 is the contact angle of deionized water (DI) on the sample (PGS; ~64.5°), θ2 is the contact angle of deionized water on the substrate (silicon wafer; ~65.3°), h is the height of the liquid film, and l is the perimeter of the circular relief.

[0059] According to one embodiment of the present invention, a biodegradable adhesive patch comprises a plurality of raised portions arranged on a substrate, imitating the structure of a frog's tongue, and has a structure in which a fine wrinkle layer is arranged on the upper surface of the raised portions, so that the adhesive force is excellent while minimizing irritation to the skin adhesion surface, and thus the adhesive force is excellent and material transfer is possible without causing damage to the skin.

[0060] In addition, the biodegradable adhesive patch has strong adhesive strength even in moisture or water, so it can adhere even when saliva is present in the mouth, and it can maintain adhesive strength and not come off even when the mouth moves.

[0061] As described above, according to one embodiment of the present invention, the substrate and the plurality of relief portions arranged on the substrate may include a biodegradable material.

[0062] Figure 3 is a graph showing biodegradability according to the biodegradable material included in the biodegradable adhesive patch according to one embodiment of the present invention.

[0063] Referring to FIG. 3, in the case where a biodegradable adhesive patch is manufactured using a mixture of gelatin and polyacrylamide (PAAm) as in one embodiment of the present invention, it can be seen that the biodegradability increases by more than three times compared to the case where acrylate or acrylamide is used alone.

[0064] Another embodiment of the present invention provides a method for manufacturing a biodegradable adhesive patch, comprising the steps of: manufacturing a polymer master mold having a plurality of raised pillar-shaped patterns on a surface and micro-grooves between the plurality of raised pillar-shaped patterns, and having wrinkles formed on the upper surface of the micro-grooves; and filling a biodegradable precursor material into the micro-grooves of the polymer master mold, attaching a substrate to cover the upper portion, and curing the substrate; wherein a micro-wrinkle layer is formed on the upper surface of the raised portion.

[0065] A method for manufacturing a biodegradable adhesive patch according to another embodiment of the present invention first includes a step of manufacturing a polymer master mold having a plurality of raised pillar-shaped patterns on a surface and micro-grooves between the plurality of raised pillar-shaped patterns, and wrinkles formed on the upper surface of the micro-grooves.

[0066] Figure 4 is a schematic diagram showing a first embodiment of manufacturing a biodegradable adhesive patch according to one embodiment of the present invention.

[0067] Referring to FIG. 4, the step of manufacturing the polymer master mold may be performed by the steps of: manufacturing a structure having a plurality of relief pillar-shaped patterns on a surface and micro-grooves between the plurality of relief pillar-shaped patterns; stamping on the upper surface of the plurality of relief pillar-shaped patterns of the structure to form a micro-wrinkle layer; and applying and curing a polymer material to the structure.

[0068] The structure having a plurality of relief pillar-shaped patterns on the surface and micro-grooves between the plurality of relief pillar-shaped patterns is not particularly limited, but can be manufactured, for example, from polydimethylsiloxane (PDMS).

[0069] Next, a plurality of relief pillar-shaped patterns are stamped on the upper surface of the structure to form a fine wrinkle layer.

[0070] Next, a step of applying and curing a polymer material to the structure may be performed. The polymer material applied to the structure is not particularly limited, and may be, for example, polyurethane acrylate (PUA).

[0071] Finally, by separating the cured product from the structure after the curing, a polymer master mold having a plurality of relief pillar-shaped patterns on the surface and micro-grooves between the plurality of relief pillar-shaped patterns, and wrinkles formed on the upper surface of the micro-grooves can be manufactured.

[0072] Figure 5 is a schematic diagram showing a second embodiment of manufacturing a biodegradable adhesive patch according to one embodiment of the present invention.

[0073] Referring to FIG. 5, the step of manufacturing the polymer master mold may be performed by the steps of: manufacturing a structure having a plurality of relief pillar-shaped patterns on a surface and micro-grooves between the plurality of relief pillar-shaped patterns; applying a polymer material to the structure and partially curing it; and separating the partially cured structure and forming a micro-wrinkle layer in the micro-grooves between the relief pillar-shaped patterns.

[0074] The structure having a plurality of relief pillar-shaped patterns on the surface and micro-grooves between the plurality of relief pillar-shaped patterns is not particularly limited, but can be manufactured, for example, from polydimethylsiloxane (PDMS).

[0075] The polymer material applied to the above structure is not particularly limited and may be, for example, polyurethane acrylate (PUA).

[0076] Finally, a step is performed to separate the partially cured structure and form a micro-wrinkle layer in the micro-grooves between the patterns of the relief pillar shapes, and a polymer master mold having wrinkles formed on the upper surface of the micro-grooves can be manufactured.

[0077] A method for manufacturing a biodegradable adhesive patch according to another embodiment of the present invention comprises the steps of filling a biodegradable precursor material into the micro-grooves of the polymer master mold, attaching a substrate to cover the upper portion, and curing the substrate to form a plurality of raised portions arranged on the substrate. As a result, a micro-wrinkle layer is arranged on the upper surface of the raised portions.

[0078] The above biodegradable precursor material is the same as the biodegradable material included in the biodegradable adhesive patch according to one embodiment of the present invention.

[0079] That is, the biodegradable precursor material may include a mixture of gelatin and polyacrylamide (PAAm).

[0080] The mixture of the above gelatin and polyacrylamide (PAAm) is characterized in that it is included in a weight ratio of 1:1 to 1:2.

[0081] Hereinafter, the present invention will be described in detail using examples. However, the examples according to the present invention may be modified in various ways, and the scope of the present invention is not limited to the examples described below. The examples in this specification are provided to more fully explain the present invention to those of ordinary skill in the art.

[0082] Example

[0083] Embodiments of the present invention were fabricated using various methods including photolithography, partial fill techniques, and replica molding.

[0084] Specifically, a structure having a plurality of relief pillar-shaped patterns on the surface and micro-grooves between the plurality of relief pillar-shaped patterns was manufactured using polydimethylsiloxane (PDMS), and a micro-wrinkle layer was formed by stamping the upper surface of the plurality of relief pillar-shaped patterns of the structure. Then, polyurethane acrylate (PUA) was applied to the structure and cured to manufacture a polymer master mold.

[0085] A mixture of gelatin and polyacrylamide (PAAm) in a weight ratio of 1:2 was filled into the micro-grooves of the polymer master mold, and a substrate was attached to cover the upper portion, followed by curing to form a plurality of relief portions arranged on the substrate. Thus, a biodegradable adhesive patch having a micro-wrinkle layer arranged on the upper surface of the relief portion was manufactured.

[0086] Comparative Example 1

[0087] An adhesive patch was prepared, which includes a substrate and a plurality of relief portions arranged on the substrate, and on the upper surface of the relief portion, no fine wrinkle layer was arranged.

[0088] Comparative Example 2

[0089] An adhesive patch composed of a flat substrate was prepared.

[0090] Figure 6 is a graph showing the coefficient of friction according to an embodiment and a comparative example of the present invention.

[0091] Referring to FIG. 6, in the case of the embodiment of the present invention, the friction coefficient is 1.1 or more, whereas in the case of the columnar adhesive patch (Comparative Example 1) without a fine wrinkle layer arranged on the surface, the friction coefficient is less than 0.6, and in the case of the adhesive patch composed of a flat substrate (Comparative Example 2), the friction coefficient is about 0.4, which shows that the friction coefficient of the embodiment of the present invention is the best.

[0092] The present invention described above is not limited to the above-described embodiments, as various substitutions and changes can be made within the scope of the technical idea of ​​the present invention by a person having ordinary skill in the art to which the present invention pertains.

Claims

1. Includes a plurality of relief parts arranged on the substrate and the substrate, The upper surface of the above relief portion has a fine wrinkle layer arranged thereon. Biodegradable adhesive patches.

2. In paragraph 1, The above micro-wrinkle layer is a biodegradable adhesive patch having a plurality of linear structures.

3. In paragraph 2, A biodegradable adhesive patch having a plurality of linear structures of the above fine wrinkle layer and arranged randomly.

4. In paragraph 1, A biodegradable adhesive patch characterized in that the adhesive force of the surface of the above-mentioned relief portion is a capillary force determined by the surface tension and Laplace pressure of the surface boundary of the above-mentioned relief portion.

5. In paragraph 1, A biodegradable adhesive patch comprising a biodegradable material, the substrate and a plurality of raised portions arranged on the substrate.

6. In paragraph 5, A biodegradable adhesive patch comprising a mixture of gelatin and polyacrylamide (PAAm) and a plurality of relief portions arranged on the substrate.

7. In paragraph 6, A biodegradable adhesive patch comprising a mixture of the above gelatin and polyacrylamide (PAAm) in a weight ratio of 1:1 to 1:

2.

8. A step of manufacturing a polymer master mold having a plurality of relief pillar-shaped patterns on a surface and micro-grooves between the plurality of relief pillar-shaped patterns, and wrinkles formed on the upper surface of the micro-grooves; and A step of filling a biodegradable precursor material into the micro-grooves of the polymer master mold, attaching a substrate to cover the upper portion, and curing the substrate to form a plurality of relief portions arranged on the substrate; The upper surface of the above relief portion has a fine wrinkle layer arranged thereon. Method for manufacturing a biodegradable adhesive patch.

9. In paragraph 8, The step of manufacturing the above polymer master mold is: A step of manufacturing a structure having a plurality of relief pillar-shaped patterns on a surface and micro-grooves between the plurality of relief pillar-shaped patterns; A step of forming a fine wrinkle layer by stamping a plurality of relief pillar-shaped patterns on the upper surface of the above structure; and A method for manufacturing a biodegradable adhesive patch, comprising the steps of applying a polymer material to the above structure and curing it.

10. In paragraph 8, The step of manufacturing the above polymer master mold is: A step of manufacturing a structure having a plurality of relief pillar-shaped patterns on a surface and micro-grooves between the plurality of relief pillar-shaped patterns; A step of applying a polymer material to the above structure and partially curing it; and A method for manufacturing a biodegradable adhesive patch, comprising the steps of separating the above-mentioned partially cured structure and forming a micro-wrinkle layer in the micro-grooves between the patterns of the relief pillar shapes.

11. In paragraph 8, A method for manufacturing a biodegradable adhesive patch, wherein the biodegradable precursor material comprises a mixture of gelatin and polyacrylamide (PAAm).

12. In paragraph 11, A method for manufacturing a biodegradable adhesive patch, wherein the mixture of gelatin and polyacrylamide (PAAm) is included in a weight ratio of 1:1 to 1:2.

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