Skin adhesive patch for negative pressure stimulation and manufacturing method thereof

Abstract

One embodiment of the present invention provides a skin adhesive patch for negative pressure stimulation and a method for manufacturing the same, the skin adhesive patch imitating an octopus-like suction cup adhesive structure in a raised shape which can be stably attached and removed even in an environment in which the skin is dry or moisture exists, according to the present invention, an adhesive cup part having a freely deformable curvature is provided so that the adhesive cup can include a wide area when the adhesive cup adheres to the skin, thereby locally inducing a negative pressure on the skin when the adhesive cup adheres to the skin, and improving the efficiency of delivering an active ingredient through the skin without an external power source.

Description

Technical Field

[0001] The present invention relates to a skin adhesive patch, and to a skin adhesive patch for negative pressure stimulation and a manufacturing method thereof. The skin adhesive patch improves the efficiency of delivering active ingredients through the skin by locally inducing negative pressure without an external power source. Background Art

[0002] With the rapid growth of the transdermal drug delivery system market, the development of adhesive patch fabrication technologies based on microstructures that can adhere to the skin without irritation and systems that can induce local negative pressure on the skin without an external power source have high application potential in medical wearable devices and drug delivery therapeutic patches.

[0003] In recent years, with the technological advancement of wearable drug delivery systems, transdermal drug delivery devices that can deliver drugs by attaching to the skin have attracted widespread attention.

[0004] Transdermal drug delivery is a system that delivers drugs into the body through absorption through the skin and can be applied to a variety of drugs and diseases.

[0005] Compared with oral administration, transdermal drug delivery systems have fewer side effects and can improve bioavailability because they do not undergo liver metabolism. They are also simpler than injection administration, thus improving patient compliance and convenience.

[0006] However, in order to achieve effective transdermal drug delivery, the mechanical defense of the stratum corneum, which is the main transdermal barrier, must be overcome to improve drug delivery and absorption rate.

[0007] To this end, commercial drug delivery devices have been developed to date to induce physical perforation of the stratum corneum by electrical stimulation, invasive drug delivery using microneedles, drug delivery by photothermal stimulation, and chemical enhancer technology for improving delivery rates.

[0008] As an example of transdermal drug delivery technology, a technology that uses strong pressure from a magnet to induce microperforations in the skin layer and thereby improves drug delivery efficiency can be cited. In this case, the strong pressure used to induce perforations may cause skin irritation. In addition, in order to apply sufficient pressure, the magnet must be attached for a long time, which also has the problem of being difficult to commercialize.

[0009] As another example of transdermal drug delivery technology, there is a technology that uses near-infrared photothermal effect to induce partial erosion of the skin layer. In this case, compared with the use of chemical enhancers, a higher drug delivery efficiency is shown. However, drug delivery through photothermal stimulation has the problem of secondary side effects that may be caused by skin damage caused by removing the stratum corneum of the skin.

[0010] As another example of transdermal drug delivery technology, there is a technology that uses a suction cup to induce pressure after injecting the drug to improve drug delivery efficiency. In this case, there are the following problems: a vacuum pump is required to induce pressure, and the additional use of the vacuum pump increases the inconvenience of use, and negative pressure must be applied for a long time.

[0011] As another example of transdermal drug delivery technology, there are transdermal drug delivery products in the form of patches. In this case, there is a problem that since it includes a drug layer and an adhesive layer, and most adhesive layers use chemical adhesive materials, it may leave residues on the skin or induce irritation.

[0012] That is, the transdermal drug delivery technology still has the following problems.

[0013] First, when applying electrical stimulation, there is a problem of requiring an external power source. Second, there is a problem of the possibility of secondary skin damage due to electrical stimulation. Third, due to the invasive method of microneedles, there is a risk of bacterial infection. Fourth, the use of chemical adhesive materials to achieve close contact between the drug delivery material and the skin interface may be accompanied by side effects such as skin rash, peeling, and redness.

[0014] That is, the prior art technologies for improving the efficiency of transdermal drug delivery have technical and material limitations, concerns about skin damage, and require an external power source, and cannot ensure sufficient skin adhesion and stability.

[0015] Therefore, there is a need to develop a technology that can solve the above-mentioned problems existing in the prior art for transdermal drug delivery.

[0016] Prior art literature

[0017] Korean Patent Publication No. 10-2018-0065848 (published on June 18, 2018) Summary of the invention

[0018] Technical issues

[0019] In order to solve the above-mentioned problems of the prior art, the present invention aims to provide a skin adhesive patch for negative pressure stimulation and a method for manufacturing the same, which improves the efficiency of delivering active ingredients through the skin by locally inducing negative pressure without an external power source.

[0020] In addition, another problem that the present invention aims to solve is to provide a skin adhesive patch for negative pressure stimulation and a method for manufacturing the same, wherein the skin adhesive patch imitates an embossed octopus suction cup adhesive structure that can be stably attached and removed even in an environment where the skin is dry or moisture is present, and has an adhesive cup portion with a curvature that can be freely deformed so that the adhesive cup can cover a wider area when attached to the skin.

[0021] Another problem to be solved by the present invention is to provide a skin adhesive patch for negative pressure stimulation, which minimizes skin irritation and side effects caused by a transdermal drug delivery material, and a method for producing the same.

[0022] Another problem to be solved by the present invention is to provide a skin adhesive patch for negative pressure stimulation and a method for producing the same, wherein the skin adhesive patch induces local negative pressure through an adhesive cup based on stable skin adhesive properties, thereby providing improved drug delivery efficiency.

[0023] The technical problems to be solved by the present invention are not limited to the technical problems mentioned above, and a person skilled in the art in the art to which the present invention belongs should be able to clearly understand other technical problems not mentioned based on the following description.

[0024] Solution to the problem

[0025] In order to achieve the above technical problems, one embodiment of the present invention provides a skin adhesive patch for negative pressure stimulation, characterized in that it includes: a base portion 10, which is flexible; and a plurality of adhesive cup portions 20, wherein a plurality of the base portion 10 is arranged on the skin adhesive surface.

[0026] The base surface portion 10 and the adhesive cup portion 20 can be made of a flexible polymer material, and the flexible polymer material is one or more selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester (Ecoflex), polyurethane (PU), polyaniline (PANI) and styrene ethylene-butylene styrene (Styrene Ethylene / Butylene Styrene, SEBS).

[0027] The adhesive cup portion 20 may include: a cup column portion 21, which has a negative pressure groove 22 formed on the skin adhesive surface; an adhesive flange portion 23, which is extended from the upper edge area of ​​the negative pressure groove 22 along the side of the cup column portion 21; and a dome portion 25, which is protruding from the bottom surface of the negative pressure groove 22 in the form of an embossment.

[0028] The cup-column portion 21 may be formed in an arc shape in which a side generatrix portion is recessed toward a direction perpendicular to the central axis of the cup-column portion 210 to have a columnar shape with a recessed side surface.

[0029] The adhesive cup portion 20 may further include a polymer precursor coating 50 formed on the upper surface of the adhesive flange portion 23 to smooth the surface roughness and improve the adhesive force.

[0030] The polymer precursor forming the polymer precursor coating 50 may include one or more selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester (Ecoflex), polyurethane (PU), polyaniline (PANI) and styrene ethylene-butylene styrene (SEBS).

[0031] In order to achieve the above-mentioned technical problems, another embodiment of the present invention may include: a 3D mold model design step, which designs a 3D mold model with an intaglio shape corresponding to a plurality of adhesive cup portions 20 to realize the molding and production of the above-mentioned skin adhesive patch for negative pressure stimulation of the skin; a 3D mold production step, which produces a 3D mold 30 according to the above-mentioned 3D mold model design; a molding step, which molds and produces a skin adhesive patch 1 having a base surface 10 and a plurality of adhesive cup portions 20 by depositing a flexible polymer material on the 3D mold 30 that has been surface-treated and solidifying it; a demolding step, which separates the above-mentioned skin adhesive patch 1 molded above from the above-mentioned 3D mold 30; and a polymer precursor coating forming step, which forms a polymer precursor coating 50 on the skin adhesive surface of the above-mentioned skin adhesive patch 1.

[0032] The 3D mold making step may further include a step of performing surface treatment on the 3D mold.

[0033] The above-mentioned molding step can be implemented by using a solution process of a flexible polymer material.

[0034] In the above-mentioned molding step, the above-mentioned flexible polymer material can be one or more selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester (Ecoflex), polyurethane (PU), polyaniline (PANI) and styrene ethylene-butylene styrene (Styrene Ethylene / Butylene Styrene, SEBS).

[0035] The polymer precursor coating layer forming step may be an embossing process step in which the polymer precursor coating layer 50 and the adhesive flange portion 23 are formed by laminating a polymer precursor on the skin adhesive surface of the skin adhesive patch 1 and then performing an embossing process.

[0036] The polymer precursor coating layer forming step may be a spray coating step. In the spray coating step, the polymer precursor coating layer 50 is formed by spraying a polymer precursor onto the skin adhesive surface of the skin adhesive patch 1 .

[0037] In the above-mentioned polymer precursor coating forming step, the above-mentioned polymer precursor may include one or more selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester (Ecoflex), polyurethane (PU), polyaniline (PANI) and styrene ethylene-butylene styrene (Styrene Ethylene / Butylene Styrene, SEBS).

[0038] Effects of the Invention

[0039] One embodiment of the present invention described above provides the following effects: solving the problems of drug delivery system requiring external power source, use of structure and materials that may induce secondary diseases such as skin infection, rash, redness, etc., and adhesive properties for stable skin adhesion.

[0040] In addition, one embodiment of the present invention described above provides the effect of improving the efficiency of delivering an active ingredient through the skin by locally inducing negative pressure without an external power source.

[0041] In addition, one embodiment of the present invention provides the following effects: by imitating an octopus suction cup adhesive structure with a relief shape that can be stably attached and removed even in an environment where the skin is dry or moisture exists, and having a freely deformable curvature so that the adhesive cup can cover a wider area when attached to the skin, the softening of the skin keratin and the drug absorption capacity are enhanced.

[0042] In addition, one embodiment of the present invention described above provides the following effect: it is possible to provide negative pressure stimulation that minimizes skin irritation and side effects caused by a transdermal drug delivery material.

[0043] In addition, one embodiment of the present invention described above provides the following effect: by combining existing transdermal drug delivery technology with various delivery components or electronic materials, it is possible to provide original technology for high-performance medical patch systems such as drug delivery systems and skin interface sensors.

[0044] It should be understood that the effects of the present invention are not limited to the above-mentioned effects, but include all effects that can be inferred from the inventive constitutions described in the detailed description of the present invention or the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 1 is a perspective view of a skin adhesive patch 1 for negative pressure stimulation and an enlarged partial cross-sectional view of an adhesive cup portion 20 according to an embodiment of the present invention.

[0046] Figure 2 It is a large-area patch photograph, cross-sectional view and design drawing showing the structure of an octopus-like adhesive cup including a micro-dome structure and a curved relief morphology.

[0047] Figure 3 It is a schematic diagram showing the process for producing the adhesive patch of one example of the present invention.

[0048] Figure 4 It is a graph showing data of vertical adhesive force measured based on the size of the adhesive structure (diameter: 2, 3, 5, 10 mm) in a dry / moisture-presence environment.

[0049] Figure 5 In the figure, based on the different outer diameters of the skin contact surface of the adhesive cup portion 20, (a) is a photograph showing the increased area of ​​the adhesive cup portion 20 during preload and (b) is a graph showing the coverage ratio of the adhesive cup portion 20 (the outer diameters of the skin adhesive surface of the adhesive cup portion 2 are (i) 2 mm, (ii) 3 mm, (iii) 5 mm, (iv) 10 mm)).

[0050] Figure 6The adhesion performance of the patch on the porcine skin substitute is shown, and the graphs show (a) vertical adhesion performance based on preload, (b) horizontal and peel adhesion performance of the octopus-like adhesion structure (d-SCC) and the patch without this structure (flat), and (c) 100-cycle adhesion performance of d-SCC.

[0051] Figure 7 In the figure, (a) is a schematic diagram of when d-SCC was applied and when it was not applied, (b) is data of measuring the delivery depth of fluorescent particles (rhodamine b) based on the time (5, 10, 20, 30 minutes) of applying the above d-SCC on pig skin for each of the above cases, and (c) is a photograph showing the traces of fluorescent particles (rhodamine b) delivered into the skin based on the time (5, 10, 20, 30 minutes) of applying the above d-SCC.

[0052] Figure 8 In the figure, (a) is a schematic diagram when d-SCC is removed, (b) is data of measuring the delivery depth of fluorescent particles (rhodamine b) based on the time (5, 10, 20, 30 minutes) after the above d-SCC was applied to pig skin for 30 minutes and removed, and (c) is a photograph showing the traces of fluorescent particles (rhodamine b) delivered based on the time (5, 10, 20, 30 minutes) after the above d-SCC was applied for 30 minutes and removed.

[0053] FIG. 9 shows data obtained by measuring the enhanced delivery depth of fluorescent particles by d-SCC using various skin types (pig skin, human skin, and artificial skin).

[0054] Fig.10 The images show the degree of deformation of the stratum corneum of skin (pig) due to pre-pressure.

[0055] Fig.11a is a graph showing the degree of improvement in the delivery depth of various drugs each having a different molecular weight on porcine skin by d-SCC, and Fig.11b are photographs showing the traces of various drugs delivered based on the above-mentioned conditions.

[0056] Fig.12a The present invention is a graph comparing the skin irritation when the trial products (surgical plastic tape, chlorhexidine gluconate film) and the d-SCC patch of one embodiment of the present invention were applied to various human skins.

[0057] Fig.13a are photographs showing the progress of skin recovery in mice with atopic dermatitis by applying various drugs together with d-SCC, and Fig.13b This is a graph showing the transepidermal water loss of the skin over time when the above-mentioned various drugs and d-SCC are applied together. DETAILED DESCRIPTION

[0058] The present invention is described below with reference to the accompanying drawings. However, the present invention can be implemented in various forms and is not limited to the embodiments described herein. In addition, in order to clearly illustrate the present invention in the accompanying drawings, parts not related to the description are omitted, and similar parts are given similar reference numerals throughout the specification.

[0059] Throughout the specification, when it is stated that a certain part is "connected (connected, in contact with, combined with) to another part, this includes not only the case of "direct connection" but also the case of "indirect connection" with other components interposed in between. In addition, when it is stated that a certain part "includes" a certain constituent element, unless there is a special statement to the contrary, it means that it may further include other constituent elements, rather than excluding other constituent elements.

[0060] The terms used in this specification are only used to illustrate specific embodiments and are not intended to limit the present invention. Unless the context clearly indicates otherwise, singular expressions include plural expressions. In this specification, it should be understood that terms such as "comprising" or "having" are intended to specify the existence of features, numbers, steps, operations, constituent elements, parts or combinations thereof recorded in the specification, and do not preclude the existence or additional possibility of one or more other features, numbers, steps, operations, constituent elements, parts or combinations thereof.

[0061] Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.

[0062] Figure 1 1 is a perspective view of a skin adhesive patch 1 for negative pressure stimulation and an enlarged partial cross-sectional view of an adhesive cup portion 20 according to an embodiment of the present invention.

[0063] like Figure 1 As shown, the skin adhesive patch 1 may include a flexible base surface portion 10 and a plurality of adhesive cup portions 20 .

[0064] Figure 2 It is a large-area patch photograph, cross-sectional view and design drawing showing the structure of an octopus-like adhesive cup including a micro-dome structure and a curved relief morphology.

[0065] The adhesive cup has a cup structure including micro-domes, and is attached to a surface using negative pressure by maximizing the volume change inside the cup.

[0066] Reference Figure 1 A, you can see the actual photo of the large-area patch, refer to Figure 1 From b to c, it is possible to confirm the actual octopus adhesive cup and the cross-sectional view and design drawing of the adhesive cup structure. Figure 1 The mechanism of the above-mentioned adhesion structure can be confirmed.

[0067] The base surface portion 10 may be made flexible.

[0068] The plurality of adhesive cup portions 20 may be formed so as to be arranged in plurality on the skin adhesive surface of the base surface portion 10 .

[0069] The base surface portion 10 and the adhesive cup portion 20 can be made of a flexible polymer material, and the flexible polymer material is one or more selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester (Ecoflex), polyurethane (PU), polyaniline (PANI) and styrene ethylene-butylene styrene (Styrene Ethylene / Butylene Styrene, SEBS).

[0070] The adhesive cup portion 20 may include a cup column portion 21 , an adhesive flange portion 23 and a slightly domed portion 25 .

[0071] The cup-column portion 21 may be formed in an arc shape in which a side generatrix portion is recessed toward a direction perpendicular to the central axis of the cup-column portion 210 to have a columnar shape with a recessed side surface.

[0072] The cup column portion 21 may form a negative pressure groove 22 on the skin adhesive surface.

[0073] The adhesive flange portion 23 may be formed by extending from the upper edge region of the negative pressure groove 22 along the lateral direction of the cup column portion 21 to expand the adhesive surface in contact with the skin and improve the adhesive force.

[0074] The dome portion 25 may be formed in relief on the bottom surface of the negative pressure groove 22. The dome portion 25 maintains uniform air volume distribution inside the negative pressure groove 22. Therefore, when the skin adhesive patch 1 of the embodiment of the present invention is adhered to the skin, the negative pressure distribution is uniform by making the air volume inside the negative pressure groove 22 for providing adhesive force uniform, thereby improving the adhesive force.

[0075] The adhesive cup portion 20 may further include a polymer precursor coating 50 formed on the upper surface of the adhesive flange portion 23 to smooth the surface roughness and improve the adhesive force.

[0076] The outer diameter of the skin adhesive surface of the adhesive cup portion 20 can be 2 mm to 10 mm. In this case, in order to effectively increase the coverage area ratio of the adhesive cup portion 20, the outer diameter of the skin adhesive surface of the adhesive cup portion 20 can be 2 mm to 5 mm. More preferably, the outer diameter of the skin adhesive surface of the adhesive cup portion 20 can be 2 mm to 3 mm.

[0077] The polymer precursor forming the polymer precursor coating 50 may include one or more selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester (Ecoflex), polyurethane (PU), polyaniline (PANI) and styrene ethylene-butylene styrene (SEBS).

[0078] The skin adhesive patch 1 according to one embodiment of the present invention having the above-mentioned configuration provides van der Waals force and negative pressure effect in a dry environment and provides capillary force and negative pressure effect in a wet environment due to the structure of the adhesive cup portion 20 .

[0079] Thus, the above-mentioned skin adhesive patch 1 is attached to the skin and the local part where the negative pressure groove 22 is formed is kept in a vacuum state. Thus, negative pressure stimulation is provided to the skin to stimulate the stratum corneum of the skin. Thus, the efficiency of the permeation of various substances including drugs through the skin is improved by a non-invasive method. Furthermore, the developed skin adhesive patch 1 can be applied to various forms of drugs as a high-performance therapeutic patch because the efficiency of substance delivery is improved by negative pressure.

[0080] A method for manufacturing a skin adhesive patch for skin negative pressure stimulation according to an embodiment of the present invention may include a 3D mold model design step, a 3D mold manufacturing step, a molding step, a demolding step, and a polymer precursor coating formation step.

[0081] The 3D mold model designing step may be a step of designing a 3D mold model having an intaglio shape corresponding to a plurality of adhesive cup portions 20 to realize the molding and manufacturing of the skin adhesive patch for the skin negative pressure stimulation.

[0082] The 3D mold making step may be a step of making a 3D mold 30 for injection molding of the skin adhesive patch 1 according to the 3D mold model design.

[0083] The 3D mold making step may further include a step of performing surface treatment on the 3D mold.

[0084] The above-mentioned step of surface treating the mold can be performed in order to use the 3D mold as a casting mold to mold the flexible polymer material. Specifically, it can be performed by immersing the 3D mold in a solution capable of forming a monomolecular layer, which can have the effect of easily separating the flexible polymer material from the 3D mold.

[0085] The molding step may be a step of depositing a flexible polymer material on the 3D mold 30 that has undergone the surface treatment and curing the material to mold the skin adhesive patch 1 having the base surface 10 and a plurality of adhesive cup portions 20 .

[0086] The above-mentioned molding step can be implemented by a solution process. In the above-mentioned solution process, the flexible polymer material is formed into a solution by using an organic solvent or the like, and then deposited on the above-mentioned 3D mold 30 by using a method such as spin coating or inkjet printing.

[0087] In the above-mentioned molding step, the above-mentioned flexible polymer can be one or more selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester (Ecoflex), polyurethane (PU), polyaniline (PANI) and styrene ethylene-butylene styrene (Styrene Ethylene / Butylene Styrene, SEBS).

[0088] The demoulding step may be a step of separating the skin adhesive patch 1 manufactured by the molding from the 3D mold 30 .

[0089] The polymer precursor coating layer forming step may be an embossing process step in which a polymer precursor is laminated on the skin adhesive surface of the skin adhesive patch 1 and then an embossing process is performed to form the polymer precursor coating layer 50 and the adhesive flange portion 23 .

[0090] In addition, the polymer precursor coating layer forming step may be a spray coating step in which a polymer precursor is sprayed onto the skin adhesive surface of the skin adhesive patch 1 to form the polymer precursor coating layer 50 .

[0091] The polymer precursor coating forming step may further include a step of thinly laminating the polymer precursor by embossing or spraying and then thermally curing the laminate.

[0092] Figure 3 It is a schematic diagram which shows the process for manufacturing the adhesive patch of one Example of this invention.

[0093] Reference Figure 3It can be confirmed that the adhesive patch preparation process of one embodiment of the present invention is carried out through the following steps: a step of pretreating a master mold for a molding process produced by 3D printing, etc.; a step of using a flexible polymer and preparing a patch through a molding process; and a step of preparing a flexible attachment surface by coating a polymer precursor.

[0094] The polymer precursor coating layer 50 provides the following effects: the roughness of the surface of the adhesive flange portion 50 of the adhesive cup portion 20 is increased, thereby increasing the skin adhesion and minimizing skin irritation.

[0095] Furthermore, the adhesive flange 50 provides an effect of increasing the skin adhesive area to enhance the adhesive force.

[0096] In the above-mentioned polymer precursor coating forming step, the above-mentioned polymer precursor may include one or more selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester (Ecoflex), polyurethane (PU), polyaniline (PANI) and styrene ethylene-butylene styrene (Styrene Ethylene / Butylene Styrene, SEBS).

[0097] Figure 4 It is a graph showing data of vertical adhesive force measured based on the size of the adhesive structure (diameter: 2, 3, 5, 10 mm) in a dry / moisture-presence environment.

[0098] Reference Figure 4 It can be confirmed that when a pre-pressure of 1N / cm2 is applied, the octopus suction cup adhesive structure with a diameter of 3mm has the highest vertical adhesive force.

[0099] At this time, 1N / cm 2 The pre-compression is the level of pressure that will not cause damage to the skin.

[0100] Figure 5 In the figure, based on the different outer diameters of the skin contact surface of the adhesive cup 20, (a) is a photograph showing the increased area of ​​the adhesive cup 20 during preload (N / cm2) and (b) is a graph showing the coverage ratio of the adhesive cup 20 (outer diameters of the adhesive cup ((i) 2 mm, (ii) 3 mm, (iii) 5 mm, (iv) 10 mm).

[0101] The above-mentioned pre-pressure means a force applied to make the skin adhesive patch 1 adhere to the skin.

[0102] Reference Figure 5It can be seen that when the skin adhesive patch 1 having adhesive cup portions 20 with outer diameters of (i) 2 mm, (ii) 3 mm, (iii) 5 mm, and (iv) 10 mm on the skin adhesive surface is adhered to the skin and pre-pressure is applied, the area of ​​the adhesive cup portion 20 increases.

[0103] At this time, the coverage ratio of the adhesive cup 20 increases as the preload increases. In addition, it is confirmed that as the outer diameter of the skin contact surface of the adhesive cup 20 decreases, the coverage ratio of the adhesive cup 20 increases. Therefore, the outer diameter of the skin adhesive surface of the adhesive cup 20 can be 2 mm to 10 mm.

[0104] In this case, in order to effectively increase the coverage area ratio of the adhesive cup part 20, the outer diameter of the skin adhesive surface of the adhesive cup part 20 may be 2 mm to 5 mm.

[0105] More preferably, the outer diameter of the skin adhesive surface of the adhesive cup portion 20 may be 2 mm to 3 mm.

[0106] Figure 6 The adhesion performance of the patch on the porcine skin substitute is shown, and the graphs show (a) vertical adhesion performance based on preload, (b) horizontal and peel adhesion performance of the octopus-like adhesion structure (d-SCC) and the patch without this structure (flat), and (c) 100-cycle adhesion performance of d-SCC.

[0107] Reference Figure 6 (a) shows that, whether in a wet state or a dry state, the vertical adhesion performance is improved as the force applied to make the skin adhesive patch 1 adhere to the skin, i.e., the preload, increases. In addition, it can be confirmed that in the entire preload region, the vertical adhesion performance in the wet state is higher than that in the dry state.

[0108] Here, the dry environment refers to a general skin surface state in which no liquid or the like exists, and the wet environment refers to a state in which the skin surface is sufficiently wetted with liquid.

[0109] Generally speaking, for existing adhesives, liquids such as moisture or water will reduce the surface energy of the attachment surface and make adhesion more difficult, but the adhesive cup of one embodiment of the present invention has the characteristics and advantages that the adhesive performance of the skin surface in a wet environment is enhanced due to cross-sectional sealing and capillary force.

[0110] Reference Figure 6(b), it can be confirmed that the octopus-like adhesive structure (d-SCC) of one embodiment of the present invention has significantly better effects than the patch (flat surface) without the above structure in both horizontal adhesive performance and peeling adhesive performance. In addition, it can be confirmed that the octopus-like adhesive structure (d-SCC) of one embodiment of the present invention has better performance in a wet state than in a dry state.

[0111] Reference Figure 6 (c) shows that the adhesive performance of the octopus-like adhesive structure (d-SCC) of one embodiment of the present invention at 100 cycles is superior to that of the dry state in the entire region.

[0112] Figure 7 In the figure, (a) is a schematic diagram of when d-SCC was applied and when it was not applied, (b) is data of measuring the delivery depth of fluorescent particles (rhodamine b) based on the time (5, 10, 20, 30 minutes) of applying the above d-SCC on pig skin for each of the above cases, and (c) is a photograph showing the traces of fluorescent particles (rhodamine b) delivered into the skin based on the time (5, 10, 20, 30 minutes) of applying the above d-SCC.

[0113] Reference Figure 7 It was confirmed that when the d-SCC was applied for 30 minutes, the delivery depth of the fluorescent particles (rhodamine b) was the deepest, which was about 130 μm.

[0114] Furthermore, it was confirmed that when the d-SCC was applied for 30 minutes, the delivery depth of the fluorescent particles (rhodamine b) was increased by 44% compared to the case of simply coating and delivering the fluorescent particles (w / o patch).

[0115] Figure 8 In the figure, (a) is a schematic diagram when d-SCC is removed, (b) is data of measuring the delivery depth of fluorescent particles (rhodamine b) based on the time (5, 10, 20, 30 minutes) after the above d-SCC was applied to pig skin for 30 minutes and removed, and (c) is a photograph showing the traces of fluorescent particles (rhodamine b) delivered based on the time (5, 10, 20, 30 minutes) after the above d-SCC was applied for 30 minutes and removed.

[0116] Reference Figure 8 It was confirmed that the delivery depth of the fluorescent particles (rhodamine b) was the deepest, reaching a value of about 150 μm or more, 30 minutes after the d-SCC was applied for 30 minutes and then removed.

[0117] Furthermore, it was confirmed that 30 minutes after the d-SCC was applied for 30 minutes and then removed, the delivery depth of the fluorescent particles (rhodamine b) was increased by 36% compared to the case of simply applying the fluorescent particles for delivery (w / o type patch).

[0118] FIG. 9 shows data obtained by measuring the enhanced delivery depth of fluorescent particles by d-SCC using various skin types (pig skin, human skin, and artificial skin).

[0119] Reference Figure 9b It can be confirmed that in the case of pig skin, 30 minutes after applying the patch of one embodiment of the present invention, the delivery depth of the fluorescent particles (Rhodamine B) is increased by up to 44% compared with the case where the fluorescent particles are simply coated for delivery (W / O type patch). 30 minutes after removing the patch of one embodiment of the present invention, the delivery depth of the fluorescent particles (Rhodamine B) is increased by up to 36% compared with the case where the fluorescent particles are simply coated for delivery (W / O type patch).

[0120] In the case of human skin, it was confirmed that 30 minutes after applying the patch of one embodiment of the present invention, the delivery depth of the fluorescent particles (rhodamine b) was increased by 56% compared with the case of simply coating the fluorescent particles for delivery (w / o type patch).

[0121] 30 minutes after the patch of one embodiment of the present invention was removed, the delivery depth of the fluorescent particles (rhodamine b) was increased by up to 31% compared with the case where the fluorescent particles were simply coated for delivery (w / o type patch).

[0122] In the case of artificial skin, it was confirmed that 30 minutes after applying the patch of one embodiment of the present invention, the delivery depth of the fluorescent particles (rhodamine b) was increased by as much as 138% compared to the case of simply coating the fluorescent particles for delivery (w / o type patch).

[0123] 30 minutes after the patch of one embodiment of the present invention was removed, the delivery depth of the fluorescent particles (rhodamine b) was increased by up to 95% compared to the case where the fluorescent particles were simply coated for delivery (w / o type patch).

[0124] Fig.10 The images show the degree of deformation of the stratum corneum of skin (pig) due to pre-pressure.

[0125] Reference Fig.10It can be confirmed that when applying the patch by applying pre-pressure, the distance between the stratum corneum increases and deformation occurs. In addition, it can be confirmed that as the pre-pressure increases, a greater negative pressure is transmitted to the skin, thereby increasing the degree of deformation of the stratum corneum. Such results show that the application of the patch can significantly affect the stratum corneum of the skin and can improve the efficiency of delivering substances through the skin.

[0126] Fig.11a is a graph showing the degree of improvement in the delivery depth of various drugs each having a different molecular weight on porcine skin by d-SCC, and Fig.11b are photographs showing the traces of various drugs delivered based on the above-mentioned conditions.

[0127] Reference Fig.11a It can be confirmed that when the octopus-like adhesive structure (d-SCC) of one embodiment of the present invention and the maltol drug are used simultaneously, the optimal delivery depth is achieved.

[0128] Furthermore, it was confirmed that when the octopus-like adhesive structure (d-SCC) of one embodiment of the present invention was used simultaneously with retinol as a fat-soluble substance and maltol, ramoplanin, hyaluronic acid, and ovalbumin as water-soluble substances, excellent delivery depth was achieved even in substances with various solubilities.

[0129] Fig.12a The present invention is a photograph of various human skins on which the trial products (surgical plastic tape, chlorhexidine gluconate film) and the d-SCC patch of one embodiment of the present invention were applied, and a graph comparing the skin irritation when the trial products and the d-SCC patch of one embodiment of the present invention were applied.

[0130] In FIG12 , the redness caused by stimulation was evaluated using the intensity of the RGB components 1 minute after the removal of each of the trial products and the patch of one example of the present invention, and it was confirmed that the change in the RGB components was the smallest when the d-SCC patch of one example of the present invention was used compared with the other trial products, namely, the surgical plastic tape and the chlorhexidine gluconate film. This indicates that the irritation was the smallest when the d-SCC patch of one example of the present invention was used compared with the other trial products, namely, the surgical plastic tape and the chlorhexidine gluconate film.

[0131] Fig.13a are photographs showing the progress of skin recovery in mice with atopic dermatitis by applying various drugs together with d-SCC, and Fig.13bThis is a graph showing the transepidermal water loss of the skin over time when the above-mentioned various drugs and d-SCC are applied together.

[0132] 13 , it can be confirmed that when the atopic therapeutic drug maltol and the d-SCC patch of one embodiment of the present invention are applied simultaneously, the transepidermal water loss (TEWL) of the skin is restored to be closest to that of normal skin (control).

[0133] The above description of the present invention is intended to be illustrative, and a person skilled in the art of the present invention can understand that it can be easily transformed into other specific forms without changing the technical ideas or essential features of the present invention. Therefore, it should be understood that the embodiments described above are illustrative in all aspects and not restrictive. For example, the constituent elements described as a whole can also be implemented in a dispersed manner, and similarly, the constituent elements described in a dispersed manner can also be implemented in a combined form.

[0134] The scope of the present invention is determined by the accompanying claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be interpreted as being included in the scope of the present invention.

[0135] Description of Reference Numerals

[0136] 1: Skin adhesive patch,

[0137] 10: base surface,

[0138] 20: Sticking to the cup,

[0139] 21: Cup-column,

[0140] 22: Negative pressure tank,

[0141] 23: Adhesion flange part,

[0142] 25: Dome top,

[0143] 30: 3D mold,

[0144] 40: Flexible polymer materials,

[0145] 50: Polymer precursor coating.

Claims

1. A skin adhesive patch for negative pressure stimulation, characterized in that: Include: a base surface portion (10) having flexibility; and A plurality of adhesive cup portions (20) are arranged on the skin adhesive surface of the base portion (10).

2. The skin adhesive patch for negative pressure stimulation according to claim 1, characterized in that: The base surface portion (10) and the adhesive cup portion (20) are made of a flexible polymer material, and the flexible polymer material is one or more selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester, polyurethane (PU), polyaniline (PANI) and styrene ethylene-butylene styrene (SEBS).

3. The skin adhesive patch for negative pressure stimulation according to claim 1, characterized in that: The adhesive cup portion (20) comprises: A cup column portion (21) having a negative pressure groove (22) formed on the skin adhesive surface; An adhesive flange portion (23) extending from an upper edge region of the negative pressure groove (22) along the lateral direction of the cup column portion (21); as well as A dome portion (25) is formed in relief on the bottom surface of the negative pressure groove (22).

4. The skin adhesive patch for negative pressure stimulation according to claim 3, characterized in that: The cup-column portion (21) is formed into an arc shape in which the side generatrix portion is recessed toward the vertical center axis direction of the cup-column portion (21) so as to have a columnar shape with a recessed side surface.

5. The skin adhesive patch for negative pressure stimulation according to claim 3, characterized in that: The adhesive cup portion (20) further comprises a polymer precursor coating (50) formed on the upper surface of the adhesive flange portion (23) to smooth the surface roughness and improve the adhesive force.

6. The skin adhesive patch for negative pressure stimulation according to claim 5, characterized in that: The polymer precursor forming the polymer precursor coating (50) includes at least one selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester, polyurethane (PU), polyaniline (PANI) and styrene ethylene-butylene styrene (SEBS).

7. A method for manufacturing a skin adhesive patch for negative pressure stimulation, which is the method for manufacturing the skin adhesive patch for negative pressure stimulation (1) according to claim 1, characterized in that it comprises: a 3D mold model designing step, which designs a 3D mold model having an intaglio shape corresponding to the plurality of adhesive cup portions (20); a 3D mold making step, which makes a 3D mold (30) according to the 3D mold model design; A molding step, wherein a flexible polymer material is deposited on the manufactured 3D mold (30) and then cured to mold and manufacture a skin adhesive patch (1) having a base surface (10) and a plurality of adhesive cup portions (20); a demoulding step, which separates the molded skin adhesive patch (1) from the 3D mold (30); and A polymer precursor coating forming step is to form a polymer precursor coating (50) on the skin adhesive surface of the skin adhesive patch (1).

8. The method for producing a skin adhesive patch for negative pressure stimulation according to claim 7, characterized in that: The 3D mold making step also includes a step of surface treating the 3D mold.

9. The method for producing a skin adhesive patch for negative pressure stimulation according to claim 7, characterized in that: The molding step is performed by using a solution process of the flexible polymer material.

10. The method for producing the skin adhesive patch for negative pressure stimulation according to claim 7, characterized in that: In the molding step, the flexible polymer material is one or more selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester, polyurethane (PU), polyaniline (PANI) and styrene ethylene-butylene styrene (SEBS).

11. The method for producing a skin adhesive patch for negative pressure stimulation according to claim 7, characterized in that: The polymer precursor coating forming step is an embossing process step, in which the polymer precursor coating (50) and the adhesive flange (23) are formed by laminating a polymer precursor on the skin adhesive surface of the skin adhesive patch (1) and then performing an embossing process.

12. The method for producing a skin adhesive patch for negative pressure stimulation according to claim 7, characterized in that: The polymer precursor coating layer forming step is a spraying step, in which the polymer precursor coating layer (50) is formed by spraying a polymer precursor onto the skin adhesive surface of the skin adhesive patch (1).

13. The method for producing a skin adhesive patch for negative pressure stimulation according to claim 7, characterized in that: In the polymer precursor coating forming step, the polymer precursor includes at least one selected from the group consisting of polydimethylsiloxane (PDMS), aliphatic aromatic random copolyester, polyurethane (PU), polyaniline (PANI), and styrene ethylene-butylene styrene (SEBS).

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