Antiviral or antibacterial bio-patch and fabrication method therefor

Abstract

The present invention relates to an antiviral or antibacterial bio-patch and a fabrication method therefor, and provides: an antibacterial or antiviral bio-patch comprising polydopamine; and a bio-patch fabrication method comprising a step of mixing dopamine hydrochloride, deionized water, and a Tris buffer to prepare a polydopamine solution.

Description

Antiviral or antimicrobial biopatch and method of manufacturing the same

[0001] The present invention relates to an antiviral or antibacterial biopatch containing polydopamine and a method for manufacturing the same.

[0002] The skin forms an effective barrier between the inside and outside of an organism and performs various protective functions. The epidermis protects the individual from physical threats such as mechanical injections and UV irradiation, regulates permeability, and prevents excessive moisture loss.

[0003] Among the various barrier functions of the skin, its function as a biological immune barrier plays a crucial role as it is directly related to life; the skin barrier prevents the penetration of pathogens and can influence the attachment and proliferation of organic cells.

[0004] The skin barrier, particularly the epidermis, can be easily damaged and its function impaired by various factors ranging from physical attacks such as scratches or abrasions to pathological conditions such as dermatitis and psoriasis. Exposure of internal tissues due to epidermal damage not only increases the risk of disease caused by external infectious agents such as bacteria, fungi, and viruses, but also triggers various health problems, including inflammatory responses and chronic skin diseases.

[0005] The background description of the invention is provided to facilitate a better understanding of the present invention. The matters described in the background description should not be construed as an acknowledgment that they exist as prior art.

[0006] When the epidermis is damaged due to various physical or chemical attacks, surface modification of the epidermis can mitigate the risk of disease and substantially improve public health by supporting the epidermal biological barrier function or providing protection against various microbial contamination.

[0007] Meanwhile, conventional surface modification methods such as chemical vapor deposition (CVD), self-assembled monolayers (SAM), and polymer brush coating can successfully modify the physicochemical properties of surfaces and impart unique functions such as anti-fouling, self-cleaning, and water repellency. However, solution processes such as SAM and polymer brush coating are difficult to apply to living organisms because they use carcinogenic organic solvents such as hexane and toluene, and existing deposition technologies such as CVD and atomic layer deposition have the problem of low versatility because they require a strictly controlled environment such as a vacuum.

[0008] Accordingly, the inventors recognized the need to develop a material that possesses excellent biocompatibility for direct application to biological surfaces, particularly human skin, and can impart antimicrobial contamination properties to the surface of the epidermis. They aimed to develop a novel skin surface modification material that protects biological surfaces, particularly the human epidermis, from various pathogens, supports the biological barrier function of the epidermis, or provides various antimicrobial contamination functions.

[0009] Furthermore, it was noted that the polydopamine surface modification technology utilizes dopamine, the smallest monomer containing both catechol and amine, and exhibits strong adhesion by mimicking the adhesion mechanism of mussel adhesive protein, which is one of the natural wet adhesives with very strong underwater adhesion.

[0010] As a result, the inventors of the present invention have discovered that by manufacturing a biopatch by directly forming a polydopamine (PDA) layer on the surface of the skin, it can be uniformly applied to the surface of an organism having various morphological characteristics and surface energy, and that the biopatch can provide a function to prevent microbial contamination by having antibacterial properties against cellular microorganisms and anti-adsorption properties against non-cellular microorganisms.

[0011] Accordingly, the problem that the present invention aims to solve is to provide an antibacterial or antiviral biopatch containing polydopamine.

[0012] In addition, another problem that the present invention aims to solve is to provide a composition for skin surface modification comprising polydopamine.

[0013] In addition, another problem that the present invention aims to solve is to provide a method for manufacturing a biopatch using polydopamine.

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

[0015] In order to solve the problem described above, an antibacterial or antiviral biopatch comprising polydopamine according to one embodiment of the present invention is provided.

[0016] According to a feature of the present invention, the biopatch may further include an antibiotic.

[0017] According to another feature of the present invention, the antibiotic may comprise at least one selected from the group consisting of aminoglycoside antibiotics, β-lactam antibiotics, tetracycline antibiotics, macrolide antibiotics, glycopeptide antibiotics, quinolone antibiotics, and sulfonamide antibiotics.

[0018] According to another feature of the present invention, the aminoglycoside antibiotic may comprise at least one selected from the group consisting of tobramycin, gentamicin, streptomycin, kanamycin, neomycin, amikacin, spectinomycin, dibekacin, isokanamycin, ribostamycin, and paromycin.

[0019] According to another feature of the present invention, the antibacterial agent may be antibacterial activity against Escherichia coli.

[0020] According to another feature of the present invention, the antiviral may have anti-adsorption activity against SARS-CoV-2 virus.

[0021] According to another feature of the present invention, the biopatch may have a thickness of 1 nm to 100 nm.

[0022] According to another feature of the present invention, the biopatch may serve as a skin barrier that maintains homeostasis of the epidermal surface.

[0023] According to another feature of the present invention, the biopatch may be a forming biopatch.

[0024] According to another feature of the present invention, the polydopamine may be polydopamine in liquid form.

[0025] According to another feature of the present invention, the biopatch may be formed to closely adhere to the skin's micro-topography by mimicking the natural microstructure of the epidermis.

[0026] In order to solve the problem described above, a skin surface modification composition comprising polydopamine according to another embodiment of the present invention is provided.

[0027] According to a feature of the present invention, the skin surface modification composition may have antibacterial or antiviral properties.

[0028] To solve the problem described above, a method for manufacturing a biopatch is provided, comprising the step of preparing a polydopamine solution by mixing dopamine hydrochloride, deionized water, and Triss buffer according to another embodiment of the present invention.

[0029] According to the features of the present invention, the method may further include the step of forming a polydopamine layer on the skin.

[0030] Since this invention utilizes dopamine, a harmless organic substance extracted from living organisms, it is harmless and safe to the human body, allowing for direct application to the human body unlike conventional surface modification technologies.

[0031] The biopatch according to the present invention has excellent tissue adhesion (Mucoadhesive or Bioadhesive) by strongly adhering to the skin surface through various physicochemical bonds between the polydopamine layer and the epidermis, and by modifying the epidermal surface of the organism through these interactions, it imparts anti-biological contamination properties, thereby effectively preventing infection by cellular and non-cellular microorganisms.

[0032] In addition, the biopatch according to the present invention has excellent biocompatibility, so it is effective in maintaining skin barrier function for a long time even in environments that change chronically due to various internal secretions such as sweat and sebum.

[0033] In addition, the biopatch according to the present invention is an ultra-thin film of 20 nm or less that adheres closely to the skin, providing excellent comfort and responding flexibly to movement. It can be manufactured in various shapes without being limited to a specific shape, and can also be applied to curved or uneven surfaces.

[0034] The effects according to the present invention are not limited to those exemplified above, and various other effects are included in this specification.

[0035] FIG. 1a illustrates a schematic diagram showing the process of surface modification of human epidermis with an ultrathin mussel-derived polydopamine layer according to one embodiment of the present invention.

[0036] FIG. 1b illustrates the results of human epidermal surface modification according to the polymerization time of a polydopamine layer according to one embodiment of the present invention.

[0037] FIG. 1c illustrates the results of a Raman spectroscopic spectrum analysis of a polydopamine layer or a polydopamine layer combined with tobramycin (TOB) according to one embodiment of the present invention.

[0038] FIG. 1d exemplarily illustrates the appearance of pores and body hair present on the human epidermis in a state of surface modification with an ultrathin polydopamine layer according to one embodiment of the present invention.

[0039] FIG. 1e illustrates the results of optical microscopy observation of a pore surface-modified with a polydopamine layer according to one embodiment of the present invention.

[0040] FIG. 1f shows the results of optical microscope and scanning electron microscope observations of body hair surface-modified with a polydopamine layer according to one embodiment of the present invention.

[0041] FIG. 2a illustrates the results of optical microscopy observation over time of pig skin modified into a polydopamine layer using a static method according to one embodiment of the present invention.

[0042] FIG. 2b illustrates the results of observing the transmission characteristics of RGB light through a polydopamine layer according to the modification time in one embodiment of the present invention.

[0043] FIG. 2c illustrates the results of an analysis of surface energy changes of a polydopamine-treated epidermis based on the water contact angle according to one embodiment of the present invention.

[0044] FIG. 2d illustrates the results of roughness analysis of a tomato surface and an orange surface treated with polydopamine according to one embodiment of the present invention.

[0045] FIG. 2e illustrates the results of Raman spectroscopic spectrum analysis of a tomato surface and an orange surface treated with polydopamine according to one embodiment of the present invention.

[0046] FIG. 2f illustrates the surface energy analysis results of a tomato surface, an orange surface, an apple surface, pig skin, and chicken skin based on whether the polydopamine layer surface is modified according to the water contact angle according to one embodiment of the present invention.

[0047] FIG. 3a illustrates a schematic diagram showing a PDA layer according to one embodiment of the present invention acting as a barrier layer that maintains homeostasis on the surface of the epidermis.

[0048] FIG. 3b illustrates a schematic diagram of a stacked wearable device stacked on a PDA layer according to one embodiment of the present invention.

[0049] FIG. 3c illustrates an optical image of an impedance measuring device attached to a control group epidermis according to one embodiment of the present invention.

[0050] FIG. 3d illustrates an optical image of an impedance measuring device attached to a PDA modified skin according to one embodiment of the present invention.

[0051] FIG. 3e illustrates the results of an analysis of impedance changes according to frequency and time of a control group epidermis according to one embodiment of the present invention.

[0052] FIG. 3f illustrates the results of an analysis of impedance changes according to frequency and time of a PDA-modified epidermis according to one embodiment of the present invention.

[0053] FIG. 4a illustrates a schematic diagram showing the antibacterial mechanism of a PDA layer modified on a skin surface according to one embodiment of the present invention.

[0054] FIG. 4b illustrates the results of observing E. coli colonies at various concentrations using the injection plate method on an untreated, PDA layer, or TOB-PDA layer-modified epidermis according to one embodiment of the present invention. Dip inoculation (DI) 1, 2, and 3 indicate the number of dilutions.

[0055] FIG. 4c shows the results of measuring the number of live E. coli after culture by injection plate method on an untreated, PDA layer, or TOB-PDA layer modified epidermis according to one embodiment of the present invention.

[0056] FIG. 4d illustrates the results of an evaluation of antibacterial activity against Escherichia coli using the disk diffusion method in a PDA solution, a TOB-PDA solution, and a hand disinfectant gel according to one embodiment of the present invention.

[0057] FIG. 4e illustrates a schematic diagram of PDA modification of nose hair according to one embodiment of the present invention.

[0058] FIG. 4f illustrates the results of measuring the water contact angle of nose hairs treated with PDA according to one embodiment of the present invention.

[0059] FIG. 4g shows the results of scanning electron microscopy observation after bacterial attachment analysis on nasal hairs modified with an untreated, PDA layer, or TOB-PDA layer according to one embodiment of the present invention.

[0060] FIG. 5a illustrates a schematic diagram of virus adsorption before and after water washing on a PDA or TOB-PDA modified epidermis according to one embodiment of the present invention.

[0061] FIG. 5b shows the cryo-transmission electron microscope (cryo-TEM) observation results (left) and electron microscope observation results (right) of SARS-CoV-2 virus on PDA or TOB-PDA modified epidermis according to one embodiment of the present invention.

[0062] FIG. 5c illustrates the results of virus adsorption evaluation on untreated, PDA, and TOB-PDA modified epidermis after water washing according to one embodiment of the present invention.

[0063] FIG. 5d illustrates the results of a study on ACE-2-dependent SARS-CoV-2 virus adsorption according to one embodiment of the present invention.

[0064] Figure 5e shows the results of fluorescence microscopy observation of untreated, PDA, and TOB-PDA modified epidermis after the introduction of a quantum dot-coupled anti-spike protein according to one embodiment of the present invention.

[0065] The advantages and features of the present invention and the methods for achieving them will become clear by referring to the embodiments described below in detail together with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below but may be implemented in various different forms. These embodiments are provided merely to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the invention, and the present invention is defined only by the scope of the claims.

[0066] In the following, terms used within this specification are explained for clarity of explanation.

[0067] In this document, expressions such as "have," "can have," "include," or "can include" refer to the existence of the relevant feature (e.g., numerical values, functions, actions, or components, etc.) and do not exclude the existence of additional features.

[0068] In this document, "or" means "and / or" unless otherwise noted. Expressions such as "A or B," "at least one of A or / and B," or "one or more of A or / and B" may include all possible combinations of items listed together. For example, "A or B," "at least one of A and B," or "at least one of A or B" may refer to cases including (1) at least one A, (2) at least one B, or (3) both at least one A and at least one B.

[0069] The term “polydopamine” as used in this invention refers to a polymer material formed by the oxidation of a compound called dopamine; it is a chemically synthesized polymer developed inspired by the adhesive proteins of marine mussels. It is primarily utilized in various fields, such as biomaterials and coating agents.

[0070] The term “patch” as used in the present invention refers to a thin, flexible structure designed for drug delivery, protection, cosmetic, sensor functions, etc., which is a material that adheres to the surface of the skin and remains there for a certain period of time.

[0071] The term “Bio-patch” as used in the present invention refers to a thin, flexible structure that is biocompatible and functional, capable of being attached to skin or tissue to provide therapeutic effects or perform specific functions. This patch is typically used for drug delivery, wound healing, skin protection, or skin regeneration, and may include biomaterials or physiologically active substances.

[0072] The term “forming bio patch” as used in this invention refers to a functional protective layer that self-forms on a biological surface through physical and chemical reactions after being applied in a liquid state.

[0073] The term “skin” as used in the present invention refers to tissue exposed to the outside of a living organism. In this case, said tissue includes skin, mucous membranes, scales, feathers, corneas, fingernails, toenails, hair follicles, surfaces of external organs, etc. For example, the skin of mammals, the skin of amphibians, the skin of reptiles, the feathers of birds, or areas where the skin is exposed are included. Preferably, it may be the skin of mammals such as humans or non-human primates, mice, rats, dogs, cats, horses, and cattle, and more preferably, it may be human skin, but is not limited thereto.

[0074] The term “skin surface” as used in this invention refers to the epidermal layer of the skin. Skin is generally composed of the epidermis, dermis, and subcutaneous tissue, and the epidermal layer serves to protect from the external environment and provide sensory reception functions. Furthermore, the skin surface may show differences in function and structure among various animals.

[0075] The term “antimicrobial” as used in the present invention refers to a characteristic that inactivates microorganisms, particularly bacteria, and said inactivation means inhibiting or stopping the activity of bacteria through various mechanisms, such as inhibiting bacterial cell wall synthesis, interfering with protein synthesis, and altering cell membrane function.

[0076] The term “antiviral” as used in this invention refers to a characteristic that prevents a virus from infecting a host cell, and in this invention, refers to a characteristic that prevents a virus from adsorbing or binding to the skin surface by binding to the surface proteins or glycosylated structures of the virus.

[0077] The term “ultrathin film” used in the present invention refers to a film or layer with a thickness of 100 nm or less, preferably a film or layer with a thickness of 20 nm or less.

[0078] The term “skin barrier” as used in this invention refers to a structure that performs an important function of protecting the skin’s external environment and internal tissues. It plays a crucial role in maintaining the homeostasis of the epidermis by preventing moisture loss and blocking the penetration of harmful substances, pathogens, chemicals, etc., thereby protecting the skin from external stimuli.

[0079] The term “skin surface modification” as used in this invention refers to changing the surface characteristics of the skin through physical or chemical methods. In this invention, it refers to polydopamine forming a functional protective layer on the epidermis through chemical bonding.

[0080] In one aspect, the present invention relates to an antibacterial or antiviral biopatch comprising polydopamine.

[0081] In one embodiment of the present invention, the biopatch may further include an antibiotic.

[0082] In one embodiment of the present invention, the antibiotic may comprise at least one selected from the group consisting of aminoglycoside antibiotics, β-lactam (β) antibiotics, tetracycline antibiotics, macrolide antibiotics, glycopeptide antibiotics, quinolones antibiotics, and sulfonamide antibiotics, but is not limited thereto.

[0083] In this case, aminoglycoside antibiotics containing an amine group (-NH2) can bind to polydopamine through covalent bonding and electrostatic interactions with the catechol group (-OH) of polydopamine. β-lactam antibiotics containing a carboxyl group (-COOH) can bind to polydopamine through covalent bonding with the amine group (-NH2) of polydopamine and ππ interactions with phenol and aryl rings (benzyl). Tetracycline antibiotics can bind to polydopamine through chelation bonding and ππ stacking interactions with the catechol group (-OH). Macrolide antibiotics containing hydrophilic functional groups (-OH, -OCH3) can bind to polydopamine through hydrogen bonding with the catechol group (-OH) of polydopamine. Glycopeptide antibiotics can bind to polydopamine through hydrogen bonding with the catechol group (-OH) of polydopamine and ππ interactions with the phenyl group, by including a hydroxyl group (-OH). Quinolone antibiotics can bind to polydopamine through covalent bonding with the amine group (-NH2) of polydopamine and ππ interactions with the quinolone ring, by including a carboxyl group (-COOH). Sulfonamide antibiotics can bind to polydopamine through hydrogen bonding between the electrophilic properties of the sulfonamide group and the catechol group (-OH) of polydopamine, and covalent bonding with the amine group (-NH2).

[0084] In one embodiment of the present invention, the aminoglycoside antibiotic may comprise at least one selected from the group consisting of tobramycin, gentamicin, streptomycin, kanamycin, neomycin, amikacin, spectinomycin, dibekacin, isokanamycin, ribostamycin, and paromycin, and preferably may be tobramycin, but is not limited thereto.

[0085] In one embodiment of the present invention, the tobramycin may be included at a concentration of 1 to 5 mg / ml, preferably at a concentration of 1 to 3 mg / ml, but is not limited thereto.

[0086] In one embodiment of the present invention, the antibacterial activity may be antibacterial activity against Escherichia coli, but is not limited thereto.

[0087] In one embodiment of the present invention, the antiviral may have anti-adsorption activity against SARS-CoV-2 virus, but is not limited thereto.

[0088] In one embodiment of the present invention, the biopatch may have a thickness of 1 nm to 100 nm, and preferably may be an ultrathin film with a thickness of 1 nm to 20 nm, but is not limited thereto.

[0089] In one embodiment of the present invention, the biopatch may serve as a skin barrier that maintains homeostasis on the surface of the epidermis, but is not limited thereto.

[0090] In one embodiment of the present invention, the biopatch may be a forming biopatch, but is not limited thereto.

[0091] In one embodiment of the present invention, the polydopamine may be included in the biopatch in various forms, such as solid or liquid, regardless of the state of the material. However, when the biopatch of the present invention is used as a forming biopatch, it is preferable to include polydopamine in a solution form, but is not limited thereto.

[0092] In one embodiment of the present invention, the biopatch may be formed to adhere to a skin microtopography including pores, body hair, wrinkles, sweat gland outlets, keratin protrusions, skin protrusions, scar tissue, etc. by mimicking the natural microstructure of the epidermis, but is not limited thereto and may be formed to adhere to various biological surfaces having three-dimensional curvature.

[0093] In one embodiment of the present invention, the biopatch may further include an adhesive material known in the art to improve adhesiveness. For example, the adhesive material may include various types of adhesives, such as acrylic adhesives, rubber adhesives, silicone adhesives, polyurethane adhesives, water-soluble adhesives, latex adhesives, polyvinyl alcohol adhesives, hexamethylenediamine adhesives, and fluorinated rubber adhesives, although not limited thereto. Preferred examples may include poly(alkyl acrylate), poly(methyl methacrylate), poly(ethyl acrylate), poly(isobutyl acrylate), natural rubber, synthetic rubber, butyl rubber, neoprene, styrene-butadiene rubber, NBR (nitrile rubber), polydimethylsiloxane, silicone rubber, cyclosiloxane, polysiloxane, polyurethane, alkyl polyurethane, diphenylmethane diisocyanate, toluene diisocyanate, polyvinyl alcohol, acrylate resin, carrageenan, gelatin, hybrid polymer, natural latex, synthetic latex, styrene-butadiene latex, ethylene-vinyl acetate latex, polyvinyl alcohol, cross-linked PVA, cross-linked polyvinyl alcohol, hexamethylenediamine, hexamethylenediamine-based polyurethane, PTFE (polytetrafluoroethylene), FPM (fluorinated rubber), Viton, Teflon, etc.

[0094] In one embodiment of the present invention, the biopatch can be used for various purposes, such as a drug delivery patch, a cosmetic patch, a protective patch, or a sensor patch, and can include both water-soluble and oil-soluble active ingredients without limitation, so any substance capable of being delivered transdermally depending on the application can be included without limitation. For example, when used as a drug delivery patch that releases drugs into the body through the skin, it may further include drugs (e.g., hormones such as nicotine, estradiol, and testosterone; analgesics such as fentanyl and buprenorphine; motion sickness preventive agents such as lolapitant and scopolamine; acne treatments such as benzoyl peroxide, salicylic acid, azelaic acid, and clindamycin), and may provide skin moisturization and wrinkle improvement. When used as a cosmetic patch providing functions such as whitening, it may additionally contain skin active ingredients (e.g., moisturizers such as hyaluronic acid, glycerin, and ceramide; whitening agents such as vitamin C, arbutin, and niacinamide; anti-wrinkle agents such as retinol, peptides, and adenosine; sunscreens such as titanium dioxide, avobenzone, and oxybenzone; exfoliating agents such as salicylic acid, glycolic acid, and lactic acid; sebum-reducing agents such as salicylic acid, niacinamide, and green tea extract); when used as a protective patch to aid in skin protection and wound healing, it may additionally contain healing aid ingredients (e.g., wound healing promoters such as aloe vera, panthenol, and madecassoside; antibacterial agents such as tea tree oil, chlorhexidine, and triclosan; anti-inflammatory agents such as allantoin, chamomile extract, and azulene; pain relievers such as lidocaine and menthol); and when used as a sensor patch for monitoring body temperature, blood sugar, etc. In some cases, a sensing sensor (e.g., a biosensor such as an enzyme, antibody, or ion-sensing substance; an electrochemical sensor such as an electrode or conductive polymer; an optical sensor such as a fluorescent substance or color change-sensing substance; a physical sensor such as a temperature sensor, a pressure sensor, or a humidity sensor) may be further included.

[0095] In one embodiment of the present invention, the biopatch may further include a skin penetration promoter to promote skin penetration of an active ingredient, such as N-cyclohexyl-2-pyrrolidone, 1-butyl-3-dodecyl-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone, 1-ethyl-2-pyrrolidone, 1-hexyl-4-methyloxycarbonyl-2-pyrrolidone, and 1-hexyl-2-pyrrolidone. 1-(2-hydroxyethyl)pyrrolidone, 3-hydroxy-N-methyl-2-pyrrolidone, 1-lauryl-4-methyloxycarbonyl-2-pyrrolidone, N-methyl-2-pyrrolidone, N-caprylyl-2-pyrrolidone, N-dodecyl-2-pyrrolidone, glycerol lauryl alcohol, oleyl alcohol, isopropyl myristrate, sorbitan mono-oleate, Propylene monolaurate, propylene mono-oleate, oleylmacrogolglyceride, oleic acid, lauroylmacrogglyceride, linoleoylmacrogglyceride,It may optionally include one or more selected from the group consisting of propylene glycol caprylate / caprate, sorbitan monostearate mono-oleate, glycerol monolaurate, propylene glycol monolaurate, propylene glycol monocaprylate, sorbitan monolaurate, lauryl lactate, caprylic / capric triglyceride, corn oil PEG-8 ester, corn oil PEG-6 ester, or triacetin.

[0096] In one embodiment of the present invention, the biopatch may further include a preservative. The preservative may be any biocompatible component known in the art that can prevent deterioration of the included active ingredient, and such components may be used without limitation.

[0097] In one embodiment of the present invention, the biopatch may additionally include other additives such as preservatives, fragrances, pH adjusters, auxiliary thickeners, auxiliary adhesives, skin irritation allergens, and colorants as needed.

[0098] In one embodiment of the present invention, a static method may be used as the method for manufacturing the biopatch of the present invention, but is not limited thereto, and any polymer coating method known in the art may be used without limitation.

[0099] In one aspect, the present invention relates to a composition for modifying the skin surface comprising polydopamine.

[0100] In one embodiment of the present invention, the skin surface modification composition may have antibacterial or antiviral properties, but is not limited thereto.

[0101] In one embodiment of the present invention, additional skin active ingredients may be included. Additionally, depending on the skin active ingredients, beneficial characteristics may be imparted, such as removing dead skin cells and preventing keratinization to improve roughness of the skin surface, promoting blood flow to make the skin look brighter (improving skin tone), providing radiance, nutritional supplementation of the skin and scalp, elasticity, softness, or smoothness, thereby beautifying the skin, increasing attractiveness, changing appearance, imparting fragrance or suppressing body odor, preventing or improving skin troubles such as itching or atopy, promoting hair growth, preventing acne, shrinking pores, promoting penetration of active ingredients, improving retention time, providing moisture to the skin, or blocking ultraviolet rays. As a skin surface modification effect, it can produce effects such as improving skin wrinkles, increasing skin moisturizing power, providing skin nutrition, maintaining skin moisture homeostasis, exfoliating and reducing skin dead skin cells, preventing skin troubles, preventing skin aging, providing skin antioxidants, preventing scalp dandruff, promoting skin blood circulation, improving skin radiance and elasticity, and preventing skin roughness and cracking.

[0102] In one embodiment of the present invention, the skin active ingredient may be, but is not limited to, an antioxidant ingredient; a conditioning ingredient; a moisturizing ingredient; a whitening ingredient; a UV blocking ingredient; a fragrance ingredient; an anti-wrinkle or anti-wrinkle ingredient; an exfoliation ingredient; an anti-dandruff or itching or anti-wrinkle ingredient; a hair growth or hair growth promoting ingredient; an anti-acne or antibacterial ingredient; a body odor suppressing ingredient; an atopic dermatitis care ingredient; a pore care ingredient; a hair removal ingredient; a dye; a powder; a nail care ingredient; or a biocompatible ingredient.

[0103] The above-mentioned antioxidant components may include, but are not limited to, antioxidant active ingredients having the ability to significantly reduce or prevent the destruction and depletion of skin functions and structures damaged by oxidation, such as extracts derived from natural products like animals, plants, and minerals, fermented extracts, amino acids, peptides, and proteins. For example, they may be one or more selected from the group consisting of acetylcysteine, ascorbic acid, curcumin, caffeic acid, arbutin, epigallocatechin gallate, resveratrol, glutathione, kojic acid, quercetin, picetanol, hydroquinone, magnesium ascorbate, vitamin E, and niacinamide.

[0104] The above conditioning ingredient may include, but is not limited to, conditioning active ingredients capable of filling damaged areas of the skin, such as extracts derived from natural products like animals, plants, and minerals, amino acids, peptides, and proteins. For example, it may be one or more selected from the group consisting of polymers, silicones, fatty alcohols, fatty acids, waxes, esters, hydrocarbons, alkylglyceryl esters, polyhydric alcohols, sugars, surfactants, powders and dyes, polyethylene, polypropylene, ceramides, vitamins, alkylamines, alkylamidoamines, and derivatives thereof.

[0105] The above moisturizing ingredients may include, but are not limited to, moisturizing ingredients capable of filling damaged areas of the skin, such as extracts derived from natural products like animals, plants, and minerals, amino acids, peptides, proteins, sugars, and vitamins.For example, PPG-arginine, glycerin, propylene glycol, butylene glycol, dipropylene glycol, caprylyl glycol, diglycerin, methylgluceth, ethoxydiglycol, glycereth, propanediol, diethoxydiglycolpyrrolidone carboxylic acid, sodium lactate, sodium PCA, mineral oil, petroleum jelly, lanolin, jojoba oil, olive oil, glycosphingolipid, phospholipid, lipid mixture, isononyl isononanoate, betaine, carboxymethyl chitin, ceramide, glucosylceramide, glycosaminoglycan, alpha-glucan, hyaluronic acid, hydrolyzed hyaluronic acid, betaine, chitosan, chitosan succinamide, vitamin E (tocopherol), urea, hydroxyethylurea, Glucosides, Gamma PGA, Xylitylglucoside, Xylitol, Pentaerythrityl Tetraisostearate, Sodium Chondroitin Sulfate, Chondroitin-4-Sulfate, Atelocollagen, Beta-glucan, PEG, Pyridoxine Tris-Hexyl Decanoate, Potassium PCA, Sodium Polygamma-Glutamate, Polyglutamic Acid, Glyceryl Polyacrylate, Galactoarabinan, Polyglycerin-3 Crosspolymer, Sodium Hyaluronate, Bis-PEG-18 Methyl Ether Dimethylsilane, Bis-Ethoxydiglycol Succinate, Lecithin, Ascorbyl Tetraisopalmitate, Glycosyl Trehalose, Hydrogenated Starch Hydrolysate, 1,2-Hexanediol, Mannitol, Arginine, Serine, Sucrose, PCA, It may be one or more selected from the group consisting of citrulline, glycogen, histidine HCl, alanine, threonine, glutamic acid, lysine HCl, phosphate-buffered seline, creatine, cholesteryl isostearate, cholesteryl chloride, cholesteryl nonanoate, BHT, sodium dilauramidoglutamide lysine, maltodextrin, polyquaternium-39, cholecalciferol PEG-12 ether, saccharide isomerate, sorbitol, and derivatives thereof, but is not limited thereto.

[0106] The above whitening ingredient may include, but is not limited to, whitening active ingredients capable of improving areas damaged by melanin pigmentation of the skin, such as extracts derived from natural products like animals, plants, and minerals, amino acids, hormones, and vitamins. For example, it may be one or more selected from the group consisting of kojic acid, niacinamide, ascorbyl glucoside, magnesium ascorbyl phosphate, acetyltyrosine, fullerene, oryzanol, methoxyPEG-7 ascorbic acid, methylundecenoyl leucine, diacetylbenzoylatrol, protocatechuic aldehyde, alpha-bisabolol, dihydroxymethoxychalcone, acetylphytosphingosine, polydatin, diosmetin, azelaic acid, mace's lignan, ginseng extract, red ginseng extract, black ginseng extract, Lithospermum root extract, Triosteum extract, Agrimony extract, Indocanthus root extract, Jeju bamboo extract, Sophora extract, Coix extract, Atractylodes extract, wheat germ extract, Atractylodes oil, and European plum extract.

[0107] The above-mentioned UV blocking ingredient may include UV absorbers such as p-aminobenzoic acid derivatives, cinnamon acid derivatives, salicylic acid derivatives, and benzophenone derivatives; UV scattering agents such as titanium oxide and zinc oxide; resins such as cellulose-based, PVP / alpha olefin-based polymers, acrylic acid polymers, silicone resins, and fluorine-modified silicone resins; and polymer film-forming agents. Ingredients that actually possess UV blocking functions include, for example, cinnamic acid, glyceryl faba, drometrizole, digallol trioleate, 3-(4-methylbenzylidene)camphor, menthyl anthranilate, benzophenone-3, benzophenone-4, benzophenone-8, butyl methoxybenzoyl methane, cinoxate, adenine riboside, octocrylene, octyl dimethyl faba, octyl methoxycinnamate, octyl salicylate, octyl triazone, para-aminobenzoic acid, 2-benzimidazole-5-sulfonic acid, homosalate, zinc oxide, titanium dioxide, isoamyl-p-methoxycinnamate, bisethylhexyloxyphenol methoxyphenyl triazine, disodium phenyldibenzimidazole tetrasulfonate, amodi-drometrizole trisiloxane. It may be one or more selected from the group consisting of diethylhexyl butamidotriazone, polysilicon-15 (dimethicodiethylbenzalmalonate), methylenebis-benzotriazoleyltetramethylbutylphenol, terephthalidendicamposulfonic acid and salts thereof.

[0108] The above fragrance components may specifically include, for example, aldehydes, phenols, alcohols, ethers, esters, hydrocarbons, ketones, lactones, musc, fragrances having a terpene backbone, natural fragrances, animal fragrances, etc. Examples may include undecylenaldehyde, laurylaldehyde, aldehyde C-12MNA, miracaldehyde, α-amylcinnamaldehyde, cyclamenaldehyde, ethyl vanillin, heliotropin, anisaldehyde, etc. Additionally, phenols may include eugenol and isoeugenol, alcohols may include bakdanol, dihydromyrcenol, linalool, nerol, and santhalol, and ethers may include cedramba and grisalva. Examples of esters include cis-3-hexenylacetate, p-crezylacetate, amylacetate, benzyl salicylate, and geranyl acetate. Hydrocarbons may include myrcene, and ketones may include α-ionone, β-ionone, and methyl-β-naphthyl ketone. Lactones include γ-decaractone and coumarin, while muscovates include cyclopentadecanolide and ethylene brasylate. Fragrances with a terpene backbone include geraniol, linalool, citral, citronellol, and mint, while natural fragrances include orange oil, lemon oil, lavender oil, and peppermint oil. Examples of animal-derived fragrances include musk, civet, and harley.

[0109] The above anti-wrinkle or improving ingredients may include extracts derived from natural products such as animals, plants, and minerals, amino acids, hormones, vitamins, etc. Examples include vitamin A (retinoid), vitamin E (tocopherol), flavonoids, polyphenols, SOD (Superoxide dismutase), coenzyme Q10, alpha-lipoic acid, acetyl hexapeptide, retinol, retinyl palmitate, retinyl acetate, adenosine, vitamin C, collagen, hexapeptide 3, skin cell growth factor (EGF), kinetin, snail mucus, aquanomide, ceramide, glycerin, hyaluronic acid, betaine, chitosan, urea, and derivatives thereof.

[0110] The above exfoliating ingredients may include, but are not limited to, alpha hydroxy acids (lactic acid, citric acid, mandelic acid, glycolic acid, tartaric acid, etc.), beta hydroxy acids (salicylic acid), propanoic acid, hydroxypropionic acid, carnitine, retinoid derivatives, vitamin A derivatives, black soybean extract, black bean powder, sugarcane extract, rice hull powder, palm seed powder, nephrite powder, hydrolyzed cactus flower extract, thioglycolic acid, etc.

[0111] The above ingredients for preventing or improving dandruff and itching may include, but are not limited to, extracts derived from natural products such as animals, plants, and minerals, amino acids, hormones, vitamins, etc. For example, moisturizing ingredients such as ceramide, glycerin, hyaluronic acid, betaine, chitosan, vitamin E (tocopherol), and urea; hair growth agents including vasodilators, hair growth agents, female hormone agents, and hair root revitalizers; anti-inflammatory and keratolytic agents such as d-panthenol, sulfur, resorcinol, serine chloride, allantoin, AHA, and salicylic acid; agents for preventing skin damage such as astringents, cooling agents, vitamins, hormones, and antihistamines; sebum inhibitors; fungicides such as trichlorocarbamide, tocopherol acetate, zinc pyrithione, benzalkonium chloride, benzethonium chloride, chlorhexidine, hinothiol, phenol, and isopropylmethylphenol; anti-seborrheic agents such as pyridoxine and its derivatives; glycyrrhizic acid and its derivatives; hydrocotison acetate; and hydrocotison succinate. It may be one or more selected from the group consisting of anti-inflammatory agents such as prednisolone, antipruritic agents such as diphenhydramine chloride, chlorophenylamine maleate, camphor, and menthol, and other alanine glutamine, bisabolol, allantoin, coenzyme Q10, SG (Stearyl Glycyrrhetinate) / DPG (dipotassium Glycyrrhizinate), phytosphingosine and derivatives thereof.

[0112] The above hair growth promoting ingredients may include, but are not limited to, hair growth promoting ingredients capable of filling damaged areas of the skin or hair, such as extracts derived from natural products like animals, plants, and minerals, amino acids, peptides, proteins, sugars, and vitamins. For example, Angelica extract, capronium chloride, cepharanthin, benzyl nicotinate, L-menthol, estradiol, ethinylestradiol, pyridoxine hydrochloride, salicylic acid, resorcinol, benzalkonium chloride, benzethonium chloride, isopropyl methylphenol, piroctone olamine, climbazole, pantothenic acid, placenta extract, biotin, mononitroguaiacol, photosensitive compounds, glycerides of pentadecanoate, glycyrrhetinic acid, potassium or ammonium salts of glycyrrhetinic acid, allantoin, minoxidil, steroids, estradiol benzoate, estrone, hydrocortisone (acetic acid), prednisolone, diphenhydramine hydrochloride, dipotassium glycyrrhizinate, pyridoxine dicaprylate, tricosaccharides, tocopherol / tocopherol acetate, It may be one or more selected from the group consisting of hinokitiol, dexpanthenol, pantothenyl ethyl ether, sodium / calcium pantothenate, isopropyl ethylphenol, mononitroguaiacol, chlorhexidine gluconate solution, ethyl nicotinate, nicotinamide, chili pepper tincture, lysogen, cholesterol, swerthiol, soluble cystine, Sophora flavescens tincture, Asarum sieboldii tincture, Lepidium macranthum extract, Citrus aurantium extract, cephalanthin, gamma-oryzarol, cantharis tincture, ginger tincture, benzyl nicotinate ester, vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin E, cystine, cysteine, methionine, leucine, tryptophan, glycerin, pyrrolidone carboxylic acid, and camphor.

[0113] The above-mentioned acne-preventing or antibacterial ingredients may include, but are not limited to, ingredients with acne-preventing and antibacterial action capable of improving areas damaged by melanin pigmentation of the skin, such as extracts derived from natural products like animals, plants, and minerals, amino acids, hormones, and vitamins. For example, they may be one or more selected from the group consisting of: sebum inhibitors such as estradiol, estrone, and ethinylestradiol; exfoliating and dissolving agents such as sulfur, salicylic acid, and resorcin; disinfectants such as benzalkonium chloride, benzethonium chloride, harocalban, and 2,4,4-trichloro-2-hydroxyphenol; disinfectants for cosmetics such as triclosan, trichlorocarbitol, isopropylmethylphenol, and pinion; anti-inflammatory agents such as allantoin, ε-aminocapriic acid, and glycyrrhic acid; and keratolytic agents such as glycolic acid.

[0114] The above body odor-inhibiting ingredients may be one or more selected from the group consisting of, for example, aluminum compounds such as chlorohydroxy aluminum, allantoin chlorohydroxy aluminum, allantoin dihydroxy aluminum, aluminum chloride, and potassium aluminum sulfate, benzethonium chloride, halocaran, chlorhexidine hydrochloride, zinc oxide, zinc p-phenolsulfonate, benzalkonium chloride, triclosan, thiram, Psoralea corylifolia extract, Pueraria lobata extract, honeysuckle extract, bamboo extract, sweet flag extract, ginkgo leaf extract, Paeonia lactiflora bark extract, licorice extract, Polygonum multiflorum extract, Houttuynia cordata extract, Portulaca oleracea extract, wood vinegar, bamboo salt, grapefruit extract, green tea extract, and peony extract.

[0115] The above-mentioned atopic care ingredients may include, but are not limited to, ingredients for atopic or skin trouble care that have the ability to significantly reduce or prevent atopic dermatitis or skin trouble through functions such as skin soothing and regeneration, and strengthening immunity, such as natural products derived from animals, plants, minerals, fermented extracts, herbal ingredients, and vitamins. For example, they may be one or more selected from the group consisting of ceramide, peptide, hyaluronic acid, glycerin, tacrolimus, pimecrolimus, clindamycin, erythromycin, tretinoin, adaphalene, benzoyl peroxide, glycyrrhizic acid, EGF (Epidermal Growth Factor), peanut oil, macadamia seed oil, propolis, olive leaf extract, Acanthopanax senticosus extract, Houttuynia cordata extract, arnica extract, and Sophora flavescens tincture. The above peptides may specifically be wheat peptides, wheat hydrolysate peptides, keratin peptides, keratin hydrolysate peptides, collagen peptides, collagen hydrolysate peptides, etc., but are not limited thereto.

[0116] The above pore care ingredients may include, but are not limited to, niacinamide, polyethoxylated retinamide, adenosine, menthol, witch hazel extract, ascorbic acid, kaolin, retinol, grape root extract, clays, asiaticoside, artichoke leaf extract, glycosyl trehalose, hydrogenated starch hydrolysate, lecithin, tocopherol, charcoal powder, etc.

[0117] The above hair removal ingredients may include, but are not limited to, thioglycolic acid, beeswax, narcissus bulb extract, papaya extract, oak bush extract, etc.

[0118] The above dye may include, but is not limited to, one or more atomic groups selected from the group consisting of -NO2, -N=N-, C=O, C=C, C=N-, C=S, -N=O, and -N=NO as chromophores. Additionally, the above dye may include, but is not limited to, one or more atomic groups selected from the group consisting of -OCH3, -N(CH3)2, -NH(CH3), -NO2, -CF3, -OH, -OCH3, -Cl, and -NH2 as auxiliary chromophores. Additionally, the above dye may include, but is not limited to, one or more reactive groups selected from the group consisting of -COONa, -COOK, -COOH, -NH2, -NHR, -NR2, -Cl, -Br, -I, and -F. Additionally, the above dye may be a natural dye or a synthetic dye used on hair, skin, etc., and the above natural dye may be purpurin, munjistin, melanin, or a melanin precursor, but is not limited thereto, and the above synthetic dye may be Red 3, Red 104, Red 105, Red 201, Red 202, Red 220, Red 227, Black 401, Red 230, Red 231, Red 232, Red 401, Red 405, Yellow 4, Yellow 202, Violet 207, Red 106, Red 213, Red 214, Red 215, Yellow 404, Yellow 405, Blue 403, Disperse Blue 1, Disperse It may be Disperse Violet 1, Disperse Orange 3, Disperse Black 9, HC Blue 2, HC Red 3, HC Yellow 5, or HC Red 1, Basic Orange 1, Basic Orange 2, but is not limited thereto.

[0119] The above powder may be titanium dioxide, hydroxyapatite, triethoxycaprylylsilane, aluminum hydroxide, zinc oxide, talc, mica, yellow iron oxide, red iron oxide, black iron oxide, silica, acrylate copolymer, guanine, guaiazulene, copper powder, aluminum stearate, orthoclase, zinc stearate, bronze powder, gardenia blue pigment, gardenia extract, gardenia yellow pigment, caramel, carmine, carbon, carbon black, copper chlorophyll, henna leaf extract, henna extract, grape powder, grape skin extract, wine extract, grape juice extract, red clay, etc., but is not limited thereto.

[0120] The above nail care ingredients may include, but are not limited to, mistletoe extract, Commelina communis leaf / flower / stem extract, dimethyltolylamine, methacryloylethyl phosphate, myrrh extract, butyl methacrylate, AMP-isostearoyl hydrolyzed silk, Echiacea root extract, Lycium chinense extract, urea peroxide, calcium peroxide, keratin, potassium hydroxide, hydrogen peroxide, hydrolyzed keratin, hydrolyzed collagen, etc.

[0121] The above biocompatible components may include fibrin, albumin, glucosamine, n-acetylglucosamine, alginate, hydrogel, growth factors, physiologically active factors, necrotic tissue removers, hair adhesives, antimicrobial coatings, etc. Examples of the above growth factors may include FGF (Fibroblast Growth Factor), KGF (Keratinocyte Growth Factor), VEGF (Vascular Endothelial Growth Factor), EGF (Epidermal Growth Factor), PDGF-AA (Platelet Derived Growth Factor AA), PDGF-AB (Platelet Derived Growth Factor AB), PDGF-BB (Platelet Derived Growth Factor BB), TGF-α (Transforming Growth Factor-α), TGF-βIGF (Insulin-like Growth Factor), TNF (Tumor Necrosis Factor), GM-CSF (Granulocyte Macrophage Colony Stimulating Factor), NGF (Nerve Growth Factor), etc. The above physiologically active factors may include interferon, erythropoietin, IL-1 (interleukin-1), IL-2, IL-6, IL-8, etc. The above Zimo conjugate may include N-(4-carboxy-3-hydroxy-phenyl)maleimide, transglutaminase, etc. The above antimicrobial coating agent may include benzalkonium chloride, benzethonium chloride, harocalban, 2,4,4-trichloro-2-hydroxyphenol, triclosan, trichlorocalbi, isopropylmethylphenol, pinion, allantoin, ε-aminocaproic acid, glycyrrhic acid derivatives, etc.

[0122] It is preferable to use the above skin active ingredient in an amount of 0.0001 to 50 parts by weight, 0.001 to 30 parts by weight, 0.01 to 10 parts by weight, or 0.1 to 5 parts by weight per 100 parts by weight of the total composition. If the content is less than 0.0001 parts by weight, there is a limit to the effect provided by the active ingredient, and if it exceeds 50 parts by weight, there are problems with formulation and the stability of the formulation over time, and there is a problem of it acting as an ingredient that is not reacted and is lost.

[0123] In one aspect, the present invention relates to a method for manufacturing a biopatch comprising the step of preparing a polydopamine solution by mixing dopamine hydrochloride, deionized water, and Triss buffer.

[0124] In one embodiment of the present invention, the dopamine solution may be a 0.2 wt% to 0.8 wt% dopamine solution, preferably a 0.4 wt% to 0.6 wt% dopamine solution, but is not limited thereto.

[0125] In one embodiment of the present invention, the dopamine hydrochloride, deionized water, and Triss buffer may be mixed in a mass ratio of 0.3:8:0.8 to 0.7:10:1.2, but are not limited thereto.

[0126] In one embodiment of the present invention, the method for manufacturing the biopatch may further include the step of forming a polydopamine layer on the skin, but is not limited thereto.

[0127] The biopatch of the present invention can be used in a form in which a polydopamine layer is formed using a substrate or mold and then attached to the skin, or in a form in which a polydopamine layer is formed directly on the skin by applying a polydopamine solution to the skin, but is not limited thereto. However, it is preferable to manufacture it using the manufacturing method provided in the present invention so that the polydopamine layer can be formed to closely adhere to the shape of pores and body hair by mimicking the natural microstructure of the epidermis.

[0128] The present invention will be explained in more detail below through examples. However, since these examples are merely illustrative of the present invention, the scope of the present invention should not be interpreted as being limited by these examples.

[0129] Preparation Example: Preparation of Samples

[0130] Pork skin (Hypork, Anseong, South Korea), apple (Freshine, South Korea), orange (Sunkist Growers, Valencia, CA, USA), and tomato (Gwangsik's Farm, South Korea) were cut into cubes measuring 1.5 × 1.5 × 0.5 cm. Chicken neck skin (Modern Food, South Korea) was cut into pieces measuring 1.5 × 1.5 × 0.1 cm.

[0131] Example 1: Skin surface modification using a polydopamine layer

[0132] The skin surface was modified into a polydopamine layer by forming a polydopamine (PDA) layer directly on the skin surface.

[0133] Specifically, to prepare a 0.5 wt% dopamine solution, dopamine hydrochloride, deionized water, and Triss buffer were mixed in a mass ratio of 0.5:9:1 to prepare a PDA solution (pH 7.0 ± 0.1). Subsequently, the epidermal sample was immersed in the PDA solution for about one hour to form a PDA layer with a thickness of approximately 10–20 nm on the surface.

[0134] Figure 1a illustrates a schematic diagram showing the process of surface modification of the skin surface with an ultrathin polydopamine layer, and Figure 1b illustrates the results of surface modification of the human epidermis according to the polymerization time of the polydopamine layer.

[0135] As a result, as shown in FIGS. 1a and 1b, it was confirmed that a thicker polydopamine layer is formed as the polydopamine polymerization time increases, and in particular, even if the polymerization time increases, the polydopamine layer is formed only within a designated area (Fig. 1b).

[0136] These results mean that protective films can be provided in user-desired patterns to areas requiring selective application, such as wounds that can serve as routes for biological infection.

[0137] Next, the Raman spectroscopic spectrum of the epidermis treated with polydopamine was analyzed to confirm whether the surface of the epidermis had been modified. Meanwhile, in order to utilize the properties of dopamine, which reacts with various organic species to implement desired functions, the skin was surface modified with a polydopamine layer conjugated with tobramycin (TOB), and then the Raman spectroscopic spectrum of the epidermis treated with polydopamine conjugated with tobramycin (TOB) was analyzed to characterize its properties.

[0138] Skin surface modification using a polydopamine layer bound to tobramycin (TOB) (hereinafter, TOB-PDA layer) was performed by directly forming a polydopamine (PDA) layer on the skin surface in the same manner as above, but by adding 2 mg / ml of tobramycin (TOB) when preparing the polydopamine solution so that a polydopamine layer bound to tobramycin (TOB) is formed. At this time, the amount of tobramycin added can be appropriately adjusted for antibacterial performance.

[0139] Raman spectroscopic analysis was performed using an inVia Qontor Raman microscope (Renishaw, Wotton-under-Edge, UK) with a 532 nm excitation laser at 500-2500 -1 It was performed in the cm range.

[0140] As a result, as shown in Figure 1c, it was confirmed that the Raman peaks detected in the spectra of the epidermis treated with PDA and PDA-TOB matched the intrinsic Raman peaks representing pure PDA. These results indicate that the skin surface (i.e., the epidermis) was successfully modified into a PDA layer by directly forming a PDA layer on the skin surface.

[0141] Furthermore, referring to FIG. 1d, this skin surface modification is not limited to a specific shape and can be produced in various shapes, and can also be applied to curved or uneven surfaces.

[0142] To confirm this, the epidermis treated with a PDA layer was examined using an optical microscope and a scanning electron microscope to observe the morphological changes caused by the PDA layer on the uneven epidermis and hair surface, including the pores.

[0143] As a result, it was confirmed that, as shown in FIGS. 1e and 1f, it is not manufactured in a form that simply covers the epidermis like conventional patches, but is manufactured in a form that mimics the microstructure of the skin and adheres perfectly to the pores (Fig. 1e) and body hair (Fig. 1f) present in the epidermis.

[0144] Example 2: Surface modification of various epidermis using a polydopamine layer

[0145] The surface of pig skin was modified with a polydopamine layer using a static method. Specifically, pig skin samples were immersed in a PDA solution for 0, 30, 60, 120, 180, or 240 minutes to modify the skin surface with a PDA layer, observed under an optical microscope, and the transmittance of red, green, and blue (RGB) light of the epidermis was measured at 60-minute intervals using a colorimetric method. Direct surface modification using this static method can be applied to various organic surfaces that have morphological and energetic characteristics different from those of the epidermis.

[0146] As a result, as shown in Figures 2a and 2b, it was found that as the coating time increased, the thickness of the PDA layer and light absorption increased, making the color darker (Figure 2a), and as the coating time increased, the light transmittance also decreased, and the layer thickness increased over time (Figure 2b and Table 1).

[0147] [Table 1]

[0148]

[0149] Next, the change in surface energy caused by the PDA layer was confirmed by measuring the water contact angle. Specifically, 3-10 μL of distilled water was quantitatively injected onto a substrate with a completed surface coating using a syringe pump (flow rate: 1 μL / s), and the contact angle formed between the water droplet formed on the substrate and the substrate was measured.

[0150] The contact angle was measured as a static contact angle and an advancing / receding contact angle, respectively, and the contact angle was automatically extracted from the outer contour of the water droplet using a high-resolution contact angle analyzer.

[0151] As a result, as shown in Figure 2c, it was found that the water contact angle decreased as the coating time increased.

[0152] PDA can impart hydrophilicity to a substrate regardless of the substrate's surface characteristics. The contact angle between a PDA-coated substrate and a water droplet decreases as polymerization progresses and reaches a saturation state after approximately 10 hours of polymerization. The saturation of the contact angle is attributed to the increase in the thickness of the PDA layer. In the initial stage, an ultrathin film is formed at the monolayer level to preserve the skin effect on surface energy, which is known as wetting transparency. However, as the polymerization time increases, the thickness of the PDA layer increases, and the skin effect on surface energy decreases, leading to a transition to hydrophilicity. Furthermore, the 20° difference between the forward contact angle and the receding contact angle indicates that the thin PDA layer enables uniform and durable surface modification through chemical modification and surface smoothing effects.

[0153] Subsequently, the surfaces of various organic materials (tomatoes, apples, and oranges) with significant differences in morphology and surface energy were modified with a PDA layer, and roughness analysis and Raman spectroscopic analysis were performed to confirm the universality of surface modification using the above static method. Roughness analysis was performed using 3D optical profiling and an optical microscope, and Raman spectroscopic analysis was performed using the same method as described in Example 1.

[0154] As a result, as shown in Figs. 2d and 2e, it was confirmed that a uniform coating layer approximately 130 μm thick was observed on the surface of the PDA-treated tomato (left), and irregularities were observed on the surface of the PDA-treated orange (right), with coating layers ranging from a very thin ultrathin film to approximately 180 μm thick (Fig. 2d). In addition, Raman spectroscopic analysis of the two surfaces revealed that both the smooth surface of the tomato and the rough surface of the orange exhibited characteristic peaks corresponding to pure PDA, including peaks associated with C=C bonds at ~1590 cm⁻¹ and phenol or catechol structures at ~1180 cm⁻¹, respectively (Fig. 2e). These results indicate that the PDA layer is successfully attached to the surface of organic materials regardless of the surface roughness of the material.

[0155] Next, the water contact angles were measured on the skin of tomatoes (T), oranges (O), apples (A), pigs (P), and chickens (C) before and after PDA layer modification.

[0156] As a result, as shown in Figure 2f, all five types of surfaces were found to exhibit hydrophilicity with a significant decrease in surface energy difference after being modified with a PDA layer.

[0157] Example 3: Confirmation of the barrier role of the polydopamine layer and maintenance of epidermal surface homeostasis

[0158] FIG. 3a illustrates a schematic diagram showing a PDA layer according to one embodiment of the present invention acting as a barrier layer that maintains homeostasis on the surface of the epidermis.

[0159] FIG. 3b illustrates a schematic diagram of a stacked wearable device stacked on a PDA layer according to one embodiment of the present invention.

[0160] The surface characteristics or impedance of the epidermis change chronically due to various internal secretions such as sweat and sebum. Therefore, to verify whether the epidermis directly modified with a PDA layer can maintain the chemical characteristics and functions of the skin surface despite these chronic changes, a biomedical wearable device integrated with a PDA layer was fabricated, and the impedance was measured using the device.

[0161] The above biomedical wearable device is designed to continuously and accurately monitor health indicators such as impedance.

[0162] As a result, as shown in Figures 3c to 3f, it was confirmed that the device was properly attached to both bare skin (control group) and skin with the PDA applied (Figures 3c and 3d). To verify the effect of the PDA layer on the impedance change of the wearable device, impedance was measured in the frequency range of 0-1 MHz at 30-minute intervals for 270 minutes. In both cases, the impedance increased over time, and a larger change was observed in the low-frequency region (Figures 3e and 3f). At this time, the impedance of the epidermis of bare skin (control group) varied from a minimum of 10 kΩ (at 1 MHz) to a maximum of 50 kΩ (at 1 Hz), whereas, conversely, the epidermis of skin modified with the PDA layer showed less change in impedance, ranging from a minimum of 6 kΩ (at 1 MHz) to a maximum of 25 kΩ (at 1 Hz).

[0163] These results indicate that the PDA layer can suppress impedance changes by minimizing the influence of external factors that interfere with the measurement of wearable devices, suggesting that direct surface modification using PDA is a biocompatible method that can be used to modify the surface characteristics of the human epidermis.

[0164] Example 4: Antimicrobial function of the polydopamine layer

[0165] To determine whether the PDA layer applied to the epidermis exhibits antimicrobial properties against cellular microorganisms, bacterial adhesion analysis, injection plate method, and disk diffusion method were performed on the epidermis modified with the PDA layer to evaluate the antimicrobial activity against Escherichia coli, a representative cellular microorganism.

[0166] FIG. 4a illustrates a schematic diagram showing the antibacterial mechanism of a PDA layer modified on a skin surface according to one embodiment of the present invention.

[0167] Working cultures of E. coli (ATCC 25922; Korean Culture Center of Microorganisms, Seoul, South Korea) were prepared by scraping off some bacteria cultured on tryptic soy agar (TSA, Becton, Dickinson and Company, Franklin Lakes, NJ, USA) and inoculating them into 9 mL of tryptic soy medium (TSB, Becton, Dickinson and Company). Cells were cultured at 37°C for 24 hours, then subcultured with fresh TSB and cultured again at 37°C for 24 hours. The final cultured E. coli concentration ranged from 8.5 to 9.0 log CFU / mL.

[0168] An E. coli suspension at a concentration of 5.7 ± 0.2 log CFU / mL was prepared by inoculating the bacteria into 9 mL of peptone water. The antimicrobial activity was evaluated by immersing the samples in the bacterial suspension for 4 hours.

[0169] The pour plate method and the disk diffusion method were applied to evaluate the bacterial count. In the pour plate method, the initial bacterial growth concentration was 7.1 × 10⁶ 5Live bacteria were counted after incubation for 24 hours under aerobic conditions with a concentration of log CFU / ml. Bacterial counting was performed by diluting the live bacterial suspension in 0.1% (w / v) peptone water. The bacterial suspension was serially diluted in peptone water in three steps, then dropped onto TSA medium and incubated for 24 hours under aerobic conditions at 37°C. In the disk diffusion method, 50 μL of antimicrobial substance was dropped onto a bacterial suspension (5.7 ± 0.2 log CFU / mL) containing TSA medium, and then incubated for 24 hours under aerobic conditions at 37°C.

[0170] As a result, as shown in Figures 4b to 4d, the epidermis modified with a PDA layer or a TOB-PDA layer showed a significant difference in the number of live E. coli cells compared to the untreated epidermis (control group) (Figure 4b). Quantitative analysis of the number of live E. coli cells after 4 hours of incubation showed that the number of live E. coli on the bare epidermis was 6.1 ± 0.5 log CFU / mL, whereas the epidermis treated with PDA or TOB-PDA showed a significant decrease in the number of live E. coli to 4.1 ± 0.5 log CFU / mL and 0 log CFU / mL, respectively, exhibiting antibacterial activity of 98.64% and 99% or higher (Figure 4c). Similarly, the disk diffusion method results showed that the diameters of the areas inhibiting bacterial growth for TOB-PDA, PDA solution, and hand sanitizer gel were 3.13, 1.57, and 1.71 cm, respectively, indicating the highest antibacterial activity when using the TOB-PDA solution.

[0171] Through these results, it was confirmed that the PDA layer has excellent antibacterial activity when applied to the human body, and in particular, the antibacterial effect of the TOB-PDA layer against E. coli was significantly superior to that of PDA alone.

[0172] Various bacteria and viruses can infect not only the epidermis but also the hands and respiratory tract. Recently, many studies have been conducted on suppressing infection by spraying preventive solutions into the nose. In this context, to evaluate the effect of preventing bacterial infection through the respiratory tract, we coated nasal hairs with PDA and performed a bacterial adhesion analysis to confirm the antimicrobial activity against E. coli.

[0173] For the bacterial attachment analysis, a bacterial suspension at a concentration of 5.7 ± 0.2 log CFU / mL was prepared to evaluate the antimicrobial activity of the PDA layer. Nasal hair samples modified with untreated, PDA-layered, or TOB-PDA-layered materials were immersed in 9 mL of E. coli suspension for 4 hours and then removed. Subsequently, E. coli attached to the samples were observed using a scanning electron microscope.

[0174] FIG. 4e illustrates a schematic diagram of PDA modification of nose hair according to one embodiment of the present invention.

[0175] As a result, as shown in Figs. 4f and 4g, applying PDA for a sufficient period of time, despite the curvature level of the nasal hairs, lowers the contact angle similar to the results observed on a flat epidermal surface (Fig. 4f). This indicates that a uniform layer of PDA was formed on the nasal hairs. Furthermore, scanning electron microscopy (SEM) observations revealed that while live bacteria were identified in the control group (untreated, bare nasal hairs), bacterial destruction and dysfunction were observed in nasal hairs whose surfaces were modified with PDA and TOB-PDA (Fig. 4g).

[0176] Example 5: Antiviral function of the polydopamine layer

[0177] To determine whether the PDA layer applied to the epidermis exhibits anti-adsorption properties against non-cellular microorganisms, the anti-adsorption properties against SARS-CoV-2 virus, a representative non-cellular infectious microorganism, were evaluated on the epidermis modified with a PDA layer.

[0178] FIG. 5a illustrates a schematic diagram of virus adsorption before and after water washing on PDA or TOB-PDA modified epidermis, and FIG. 5b illustrates cryo-transmission electron microscope (cryo-TEM) and electron microscope observation results of SARS-CoV-2 virus according to one embodiment of the present invention.

[0179] Among the various infection routes of the SARS-CoV-2 virus, a representative acellular infectious microorganism, the skin-mediated route is often overlooked. The SARS-CoV-2 virus has a long lifespan on various surfaces. The SARS-CoV-2 virus contains a lipid membrane, and spike proteins are also observed on the cell surface (Fig. 5b). Therefore, it must be possible to inhibit the adsorption of the virus to the epidermal surface under various modification conditions.

[0180] Specifically, a virus solution was sprayed onto a prepared epidermis measuring 1 cm x 1 cm, and the epidermis was sealed and left for 30 minutes to allow sufficient adsorption of the virus onto the epidermis. Afterward, the epidermis was washed three times with 5 mL of deionized water, and then immersed in a viral lysis solution (50 mM tris(hydroxymethyl)aminomethane and 0.05% sodium azide) for 30 minutes to decompose the adsorbed virus and release the nucleocapsid protein (N protein) inside the virus. Then, the amount of released N protein was measured using a commercial ELISA kit (ab274341, abcam, Cambridge, UK) to determine the relative amount of adsorbed virus according to the surface treatment method of the epidermis.

[0181] As a result, as shown in Figure 5c, virus adsorption studies using epidermis with different surface conditions showed that the epidermis modified with a PDA layer and a TOB-PDA layer exhibited significantly reduced levels of virus adsorption of 68.39% and 44.33%, respectively, compared to the control group (untreated, bare epidermis), confirming that both possessed excellent anti-adsorption properties. In particular, it was confirmed that PDA alone had a significantly superior anti-adsorption effect against the SARS-CoV-2 virus compared to the TOB-PDA layer.

[0182] To investigate the underlying mechanism of high SARS-CoV-2 virus adsorption on exposed skin, we hypothesized that the SARS-CoV-2 receptor (angiotensin-converting enzyme 2, ACE2) is important for skin adsorption, and performed ELISA using ACE2 as a capture probe at various concentrations to determine whether SARS-CoV-2 virus adsorption depends on the surface density of ACE2.

[0183] Specifically, the degree of virus adsorption was determined using the same method as described above, but this time, the experiment was conducted using ACE2 as a capture probe. To this end, -OH groups were introduced to the glass surface by O2 plasma treatment (70 W for 1 min). Subsequently, amine functional groups were induced on the surface by immersing the glass in a 3-(aminopropyl)-triethoxysilane solution (5 vol% in ethanol) and reacting it at room temperature for one hour. Then, the amine functional groups were substituted with aldehyde groups by placing the glass in a 2.5 vol% glutaraldehyde solution (solvent: 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES)) and reacting it for one hour. After washing three times with PBS, ACE2 was introduced by adding ACE2 solutions at different concentrations and reacting them at room temperature for one hour. Finally, to prevent nonspecific adsorption, the glass was treated with 1M ethanolamine for one hour, immersed in a 3wt% BSA solution, which is mainly used for surface blocking, for one hour, and then washed three times with PBS to prepare the surface for the adsorption experiment.

[0184] As a result, as shown in Figure 5d, it was found that the amount of adsorbed SARS-CoV-2 virus was proportional to the surface density of ACE2.

[0185] Therefore, the higher adsorption of SARS-CoV-2 on the exposed epidermis may be due to the higher ACE2 density on the exposed epidermis.

[0186] Next, adsorption studies were conducted by introducing quantum dot-bound anti-spike proteins to visualize the adsorption of SARS-CoV-2.

[0187] Specifically, a virus-adsorbed epidermal sample was prepared using the same method as described above, and instead of being placed in a lysis solution, an ACE2-biotin molecule that binds to the virus surface Spike protein was attached, and after washing, a Streptavidin-quantum dot solution was added to make the virus fluoresce and visualize the adsorption of SARS-CoV-2.

[0188] As a result, as shown in Figure 5e, a relatively bright red color, indicating the SARS-CoV-2 virus, was observed only in the control group (exposed epidermis). These results indicate that both the PDA layer and the PDA-TOB layer significantly reduce the adsorption of the SARS-CoV-2 virus.

[0189] In summary, since both the PDA layer and the TOB-PDA layer exhibit excellent antibacterial and antiviral properties, they can be usefully employed as comprehensive bio-contamination prevention materials capable of simultaneously preventing infection by cellular and non-cellular microorganisms.

[0190]

[0191] [National R&D projects that supported this invention]

[0192] [Project ID] 2024040037

[0193] [Assignment No.] 2024040037

[0194] [Ministry Name] Ministry of Science and ICT

[0195] [Name of Project Management (Specialized) Agency] (New) National Research Foundation of Korea (Integrated)

[0196] [Research Project Name] Outstanding Young Researcher

[0197] [Project Title] Development of High-Performance Soft Actuators for Micro Flying Robots

[0198] [Name of Project Performing Organization] Daegu Gyeongbuk Institute of Science and Technology

[0199] [Research Period] April 1, 2024 ~ March 31, 2025

[0200]

[0201] [Project ID] 2710016371

[0202] [Assignment No.] 2710016371

[0203] [Ministry Name] Ministry of Science and ICT

[0204] [Name of Project Management (Specialized) Agency] National Research Foundation of Korea

[0205] [Research Project Name] Future Technology Research Lab

[0206] [Research Project Title] Development of Infrared Emissivity Control Materials for Energy Saving in Everyday Environments

[0207] [Name of Project Performing Organization] Yonsei University

[0208] [Research Period] 20240101 ~ 20241231

[0209]

[0210] [Project ID] 2710006244

[0211] [Assignment No.] 2710006244

[0212] [Ministry Name] Ministry of Science and ICT

[0213] [Name of Project Management (Specialized) Agency] National Research Foundation of Korea

[0214] [Research Project Name] Nanomaterial Technology Development (R&D) - Materials Global Young Connect

[0215] [Project Title] Development of a Theramorphic Magnetic Composite Material Platform for Orally Administered All-in-One Soft Robots

[0216] [Name of Project Performing Organization] Ulsan National Institute of Science and Technology

[0217] [Research Period] 20240401 ~ 20241231

[0218]

[0219] [Project ID] 2710018118

[0220] [Assignment No.] 2710018118

[0221] [Ministry Name] Ministry of Science and ICT

[0222] [Name of Project Management (Specialized) Agency] National Research Foundation of Korea

[0223] [Research Project Name] Group Research Support (R&D) - Global Leading Research Center (ERC)

[0224] [Research Project Title] Global Bio-convergence Interfacing Materials Center

[0225] [Name of Project Performing Organization] Korea Advanced Institute of Science and Technology

[0226] [Research Period] 20240801 ~ 20250430

[0227]

[0228] [Project ID] 2710018122

[0229] [Assignment No.] 00452380

[0230] [Ministry Name] Ministry of Science and ICT

[0231] [Name of Project Management (Specialized) Agency] National Research Foundation of Korea

[0232] [Research Project Name] Nanomaterial Technology Development

[0233] [Research Project Title] Development of Nanostructure-Based Materials for Simultaneous Antibacterial and Antifouling Effects

[0234] [Name of Project Performing Organization] Dankook University Industry-Academic Cooperation Foundation

[0235] [Research Period] 20240701 ~ 2024123

Claims

1. An antimicrobial or antiviral biopatch containing polydopamine.

2. In Paragraph 1, Antimicrobial or antiviral biopatch containing additional antibiotics.

3. In Paragraph 2, The above antibiotic is, An antibacterial or antiviral biopatch comprising at least one selected from the group consisting of aminoglycoside antibiotics, β-lactam antibiotics, tetracycline antibiotics, macrolide antibiotics, glycopeptide antibiotics, quinolone antibiotics, and sulfonamide antibiotics.

4. In Paragraph 3, The above-mentioned aminoglycoside antibiotic is, An antimicrobial or antiviral biopatch comprising at least one selected from the group consisting of tobramycin, gentamicin, streptomycin, kanamycin, neomycin, amikacin, spectinomycin, dibekacin, isokanamycin, ribostamycin, and paromycin.

5. In Paragraph 1, The above antibacterial agent is, Antimicrobial or antiviral biopatch having antimicrobial activity against E. coli.

6. In Paragraph 1, The above antiviral is, Antimicrobial or antiviral biopatch having antiadsorption activity against SARS-CoV-2 virus.

7. In Paragraph 1, The above biopatch is, An antibacterial or antiviral biopatch characterized by having a thickness of 1 nm to 100 nm.

8. In Paragraph 1, The above biopatch is, An antibacterial or antiviral biopatch characterized by acting as a skin barrier to maintain homeostasis on the surface of the epidermis.

9. In Paragraph 1, The above biopatch is, Antimicrobial or antiviral biopatch that is a forming biopatch.

10. In Paragraph 9, The above polydopamine is, An antibacterial or antiviral biopatch characterized by being polydopamine in liquid form.

11. In Paragraph 1, The above biopatch is, An antibacterial or antiviral biopatch characterized by being formed to adhere closely to the skin's microtopography by mimicking the natural microstructure of the epidermis.

12. A composition for modifying the skin surface, comprising polydopamine.

13. In Paragraph 12, The above-mentioned skin surface modification composition is a skin surface modification composition having antibacterial or antiviral properties.

14. A method for manufacturing a biopatch comprising the step of preparing a polydopamine solution by mixing dopamine hydrochloride, deionized water, and Triss buffer.

15. In Paragraph 14, The above method is, A method for manufacturing a biopatch, further comprising the step of forming a polydopamine layer on the skin.

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