Composition for treating psoriasis diseases using nano-graphene oxide

Abstract

The present invention relates to a composition for treating psoriasis diseases using nano-graphene oxide. It was confirmed that the nano-graphene oxide of the present invention regulates inflammatory immune cell subtypes and tissue-resident memory cells, which are psoriasis-pathogenic immune cells. In addition, in an acute psoriasis animal model, it was confirmed that skin thickness, scaling, and erythema were reduced, and the thickness of the epidermal layer was decreased. Furthermore, it was confirmed that immune cells are regulated by reducing psoriasis-pathogenic immune cells and increasing immunoregulatory cells in splenocytes. Moreover, it was confirmed that mitochondrial functions are regulated by increasing mitochondrial ROS and oxygen consumption rates in psoriasis-pathogenic immune cells.

Description

Composition for treating psoriasis using nano-graphene oxide

[0001] The present invention relates to a composition for treating psoriasis using nano-graphene oxide.

[0002] Psoriasis is a very common inflammatory skin disease affecting approximately 100 million people worldwide, with about 1–2% of the current population. It is an autoimmune disease. When psoriasis spreads significantly from localized areas, it can cover almost the entire body. Although the exact cause of psoriasis is not yet fully understood, genetic factors and the Koebner phenomenon—where localized psoriasis develops upon skin damage—are known to play a role. Furthermore, various environmental factors are suggested to exacerbate the condition. These include stress, the discontinuation of invasive corticosteroids, and other environmental factors. While psoriasis is not life-threatening, it causes psychological distress, loss of self-confidence, and depression, and requires long-term treatment.

[0003] In psoriasis, unlike a normal immune system, T cells become activated and secrete cytokines even in the absence of any antigens on the skin. These cytokines act on normal skin cells, which normally regenerate and mature over a cycle of approximately 28 days, causing them to regenerate and mature very rapidly over a cycle of 3 to 4 days. Skin cells that have regenerated and matured at such a rapid rate migrate to the skin surface, where dead cells accumulate in layers to form grayish-white scales. Additionally, blood vessels dilate and blood flow increases, causing the skin to turn red. Regarding T cell activation in psoriasis, it has been reported that Th-1 cells trigger the condition, and that the use of IL-10, which inhibits Th-1 cell activity, alleviates psoriasis symptoms. Furthermore, cytokines such as IL-1β, IL-6, IL-8, GM-CSF, and TNF-α induce psoriasis triggering, and increased concentrations of VEGT and Substances P have also been reported to be associated with psoriasis.

[0004] Common treatments for psoriasis include topical medications, phototherapy, and oral medications. Topical treatments include steroids, coal tar, anthralin, vitamin D3 and its analogues, retinoids, and sun exposure; however, these treatments carry side effects such as skin thinning, stretch marks, burns, irritation, and photosensitivity. Phototherapy involves the administration of psoralen in combination with ultraviolet B or ultraviolet A rays, but it has the disadvantages of accelerated skin aging and an increased risk of skin cancer. Oral medications, applied to the most severe cases of psoriasis, include methotrexate, oral retinoids, and cyclosporine. However, cyclosporine requires careful monitoring as it can cause kidney damage and blood pressure issues. While methotrexate has the advantage of being effective for both psoriasis and psoriatic arthritis, it must be used with caution as cumulative use can lead to liver cirrhosis or fibrosis. Additionally, the use of oral retinoids must be carefully controlled due to the potential for serious complications during childbirth in women. As such, conventional drugs used to treat psoriasis have side effects or drawbacks. Furthermore, drugs such as methotrexate and cyclosporine, which inhibit T-cell activity, are highly toxic. Consequently, biologics with fewer side effects than these drugs have been developed, including alefacept (Amevive), itanercept (Enbrel), infliximab (Remicade), and ipalizumab (Raptiva). Therefore, there is an urgent need for a psoriasis treatment that is not only effective but also highly safe, free from issues of side effects or toxicity.

[0005] Accordingly, the inventors confirmed that nano-sized graphene oxide improves psoriasis and completed the present invention.

[0006] The object of the present invention is to provide a composition for the prevention or treatment of skin diseases comprising nano-sized graphene oxide as an active ingredient.

[0007] Another objective of the present invention is to provide a cosmetic composition for the prevention or improvement of skin diseases comprising nano-sized graphene oxide as an active ingredient.

[0008] Another objective of the present invention is to provide a patch composition for the prevention or improvement of skin diseases comprising nano-sized graphene oxide as an active ingredient.

[0009] Another objective of the present invention is to provide a method for treating a skin disease comprising the step of administering a pharmaceutically effective amount of nano-sized graphene oxide to an individual.

[0010] To achieve the above objective, the present invention provides a composition for the prevention or treatment of skin diseases comprising nano-sized graphene oxide as an active ingredient.

[0011] In addition, the present invention provides a cosmetic composition for the prevention or improvement of skin diseases comprising nano-sized graphene oxide as an active ingredient.

[0012] In addition, the present invention provides a patch composition for the prevention or improvement of skin diseases comprising nano-sized graphene oxide as an active ingredient.

[0013] In addition, the present invention provides a method for treating a skin disease comprising the step of administering a pharmaceutically effective amount of nano-sized graphene oxide to an individual.

[0014] It was confirmed that the nano-graphene oxide of the present invention regulates inflammatory immune cell subtypes and tissue-resident memory cells, which are pathogenic immune cells of psoriasis. Furthermore, in an animal model of acute psoriasis, it was confirmed that it reduces skin thickness, keratinization, and erythema, and decreases the thickness of the epidermal layer. Additionally, it was confirmed that it regulates immune cells by reducing pathogenic immune cells of psoriasis and increasing immune regulatory cells in splenocytes. Moreover, since it regulates mitochondrial function by increasing mitochondrial ROS and oxygen respiration in pathogenic immune cells of psoriasis, it can be usefully utilized in related industries.

[0015] Figure 1 is a figure confirming the characteristics of the nano-graphene oxide of the present invention (A: TEM analysis result, B: confirmation of average particle distribution, C: FTIR analysis result).

[0016] Figure 2 is a figure confirming the structure and characteristics of the nano-oxidized graphene of the present invention.

[0017] A: Check average size of graphene nanooxide

[0018] B: Confirmation of nano-graphene (daNGO) peaks

[0019] C: Confirmation of Oxygen Peak in Nano-Graphene Oxide

[0020] D: Confirmation of carbon peak in nano-oxidized graphene

[0021] Figure 3 is a figure showing the analysis of IL-17-expressing immune cell subtypes in vitro following treatment with the nano-oxidized graphene of the present invention (A: CD4 positive cell analysis result, B: CD8 positive cell analysis result).

[0022] Figure 4 is a figure showing the analysis of subtypes of tissue-resident memory T cells in vitro following treatment with nano-graphene oxide of the present invention (A: CD4 positive cell analysis result, B: CD8 positive cell analysis result).

[0023] Figure 5 illustrates the process of preparing an acute psoriasis animal model of the present invention.

[0024] Figure 6 is a figure confirming the psoriasis activity and psoriasis index in an acute psoriasis animal model following the administration of nano-graphene oxide of the present invention (A: visual observation of psoriasis activity, B: quantification of psoriasis-related index).

[0025] Figure 7 shows the epidermal layer thickness confirmed by H&E staining in an animal model of acute psoriasis following the administration of nano-graphene oxide of the present invention (A: staining result, B: quantification of staining result).

[0026] Figure 8 is a figure confirming the regulation of psoriasis pathogenic cells in splenocytes of an acute psoriasis animal model following the administration of nano-graphene oxide of the present invention by flow cytometry (A: quantification of CD4-positive cells, B: quantification of CD8-positive cells).

[0027] Figure 9 is a figure showing the identification of immune regulatory cells in splenocytes of an acute psoriasis animal model following the administration of nano-graphene oxide of the present invention by flow cytometry.

[0028] Figure 10 is a figure confirming the regulation of tissue-resident memory cells in splenocytes of an acute psoriasis animal model following the administration of nano-graphene oxide of the present invention by flow cytometry (A: CD4 TRM quantification, B: CD8 TRM quantification).

[0029] Figure 11 is a figure confirming the mitochondrial function regulating effect of the nano-oxidized graphene of the present invention in mouse splenocytes.

[0030] A: Flow cytometry results

[0031] B: MitoROS Quantification

[0032] C: OCR Analysis Results

[0033] D: Quantification of OCR analysis results

[0034] Figure 12 is a figure confirming the mitochondrial function regulating effect of the nano-oxidized graphene of the present invention in immune cells derived from psoriasis patients.

[0035] A: PBMC flow cytometry results and quantification

[0036] B: CD8 TRM Flow Cytometry Results and Quantification

[0037] C: OCR Analysis Results

[0038] Embodiments of the present invention will be described in detail below with reference to the attached drawings. In the following description, detailed descriptions of technologies well known to those skilled in the art may be omitted. Furthermore, in describing the present invention, detailed descriptions of related known functions or configurations may be omitted if it is determined that such descriptions would unnecessarily obscure the essence of the present invention. Additionally, the terminology used in this specification is used to appropriately express preferred embodiments of the present invention, and may vary depending on the intent of the user or operator, or the conventions of the field to which the present invention belongs.

[0039] Therefore, the definitions of these terms should be based on the content throughout this specification. Throughout the specification, when a part is described as "comprising" a certain component, this means that, unless specifically stated otherwise, it does not exclude other components but may include additional components.

[0040] The present invention provides a composition for the prevention or treatment of skin diseases comprising nano-sized graphene oxide as an active ingredient.

[0041] The term "graphene" in the present invention is a compound word formed by combining "graphite," meaning graphite, and the suffix "-ene," which in chemistry denotes a molecule having a carbon double bond. The graphene has a hexagonal honeycomb structure in which carbon atoms are connected infinitely. That is, it is a thin film structure in the form of a two-dimensional planar layer with a thickness of 0.35 nm, consisting of a single layer of carbon atoms. Although graphene has a simple structure, it exhibits excellent physicochemical properties in various dimensions, such as high electrical and thermal conductivity, high mechanical strength and hardness, unique optical properties, and chemical stability. The intracellular absorption of graphene is relatively limited due to its thin film form. Therefore, in terms of cell safety, it has advantages over carbon nanotubes, which are absorbed into cells through various pathways such as phagocytosis and membrane surface adsorption.

[0042] Furthermore, "graphene oxide" refers to a form in which oxygen is attached to graphene as it oxidizes and intervenes between carbon bonds. For example, when strong acids such as sulfuric acid are added to graphite and reacted, the graphene oxidizes and is replaced by oxygen, which is referred to as "graphene oxide." Since oxidizing graphene increases its elasticity and it retains electrical conductivity even when stretched or folded, it is a material attracting attention in the field of nanomaterials. Additionally, graphene oxide exhibits a relatively wide particle size range, ranging from tens of micrometers to as small as tens of nanometers, and graphene oxide with a size of tens of nanometers is designated as "nano-graphene oxide."

[0043] The term "prevention" as used in this invention refers to any act of suppressing the symptoms of a specific disease or delaying its progression through the administration of the composition of this invention.

[0044] The term "treatment" as used in this invention refers to any act of improving or beneficially altering the symptoms of a specific disease through the administration of the composition of this invention.

[0045] The pharmaceutical composition of the present invention may additionally include an adjuvant in addition to the active ingredient. Any adjuvant known in the art may be used without limitation, but, for example, Freund's complete or incomplete adjuvant may be further included to increase the effect.

[0046] The pharmaceutical composition according to the present invention may be prepared in a form in which an active ingredient is incorporated into a pharmaceutically acceptable carrier. Here, the pharmaceutically acceptable carrier includes carriers, excipients, and diluents commonly used in the pharmaceutical field. Pharmaceutically acceptable carriers that can be used in the pharmaceutical composition of the present invention are not limited to these, but may include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

[0047] The pharmaceutical composition of the present invention may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external formulations, suppositories, or sterile injectable solutions, each according to conventional methods.

[0048] When formulating, the product may be prepared using diluents or excipients such as commonly used fillers, volume expanders, binders, wetting agents, disintegrants, and surfactants. Solid dosage forms for oral administration include tablets, pills, powders, granules, and capsules, and such solid dosage forms may be prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc., with the active ingredient. In addition, lubricants such as magnesium stearate and talc may also be used in addition to simple excipients. Liquid dosage forms for oral administration include suspensions, liquid formulations, emulsions, and syrups, and may contain various excipients, such as wetting agents, sweeteners, flavoring agents, and preservatives, in addition to commonly used diluents such as water and liquid paraffin. Preparations for parenteral administration include sterile aqueous solutions, water-insoluble solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Water-insoluble solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Bases for suppositories may include Witepsol, Tween 61, cocoa paste, laurin paste, glycerogelatin, etc.

[0049] The pharmaceutical composition according to the present invention may be administered to an individual by various routes. Any mode of administration may be anticipated, for example, by oral, intravenous, intramuscular, subcutaneous, or intraperitoneal injection.

[0050] The dosage of the pharmaceutical composition according to the present invention is selected by taking into consideration the age, weight, gender, physical condition, etc. of the individual. It is obvious that the concentration of the active ingredient included in the pharmaceutical composition can be selected in various ways depending on the subject, and preferably, it is included in the pharmaceutical composition at a concentration of 0.01 to 5,000 μg / mL. If the concentration is less than 0.01 μg / mL, pharmaceutical activity may not appear, and if it exceeds 5,000 μg / mL, it may exhibit toxicity to the human body.

[0051] According to one embodiment of the present invention, the nano-oxidized graphene may have a particle size of 1 to 100 nm.

[0052] According to one embodiment of the present invention, the nano-oxidized graphene may regulate immune cells, and the immune cells may be cells selected from the group consisting of Th1, Th2, Th17, Tc1, Tc2, Tc17 and Treg, and may be tissue-resident memory cells (TRMs).

[0053] According to one embodiment of the present invention, the tissue-resident memory cells may be CD4-positive TRM, CD4-positive TRM17, CD8-positive TRM, and CD8-positive TRM17.

[0054] According to one embodiment of the present invention, regulating the immune cells may involve decreasing the expression of cells selected from the group consisting of Th1, Th2, Th17, Tc1, Tc2, and Tc17, increasing the expression of Treg, and decreasing tissue-resident memory cells.

[0055] According to one embodiment of the present invention, the nano-oxidized graphene may reduce skin thickness, and the nano-oxidized graphene may reduce skin keratinization or erythema.

[0056] According to one embodiment of the present invention, the nano-oxidized graphene may regulate mitochondrial function, and regulating mitochondrial function may reduce mitochondrial ROS and increase mitochondrial respiration.

[0057] According to one embodiment of the present invention, the skin disease may be psoriasis.

[0058] The "psoriasis" of the present invention is a type of skin disease characterized by red, millet-like rashes on the skin and layers of silvery-white, dandruff-like skin scales accumulating on the rashes, with the rashes gradually growing in size. Although the cause of psoriasis is not clearly known, it is known to be a chronic inflammatory disease caused by abnormalities in the body's immune system.

[0059] In addition, the present invention provides a cosmetic composition for the prevention or improvement of skin diseases comprising nano-sized graphene oxide as an active ingredient.

[0060] The term "improvement" as used in the present invention refers to any action that at least reduces parameters related to the condition being treated, such as the degree of symptoms.

[0061] A cosmetic composition containing the active ingredient of the present invention can be used in various ways for the prevention or improvement of skin diseases. Products to which the present composition can be added include, for example, cosmetics such as various creams, lotions, skin toners, essences, etc., as well as shampoos, rinses, cleansers, facial cleansers, soaps, treatments, packs, beauty solutions, etc.

[0062] The cosmetic composition of the present invention comprises a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, high molecular weight polysaccharides, sphingolipids, and seaweed extracts.

[0063] As for water-soluble vitamins, any that can be incorporated into cosmetics may be used, but preferably, examples include vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinamide, folic acid, vitamin C, vitamin H, etc., and their salts (thiamine hydrochloride, sodium ascorbate, etc.) or derivatives (sodium ascorbate-2-phosphate, magnesium ascorbate-2-phosphate, etc.) are also included in the water-soluble vitamins that can be used in the present invention. Water-soluble vitamins can be obtained by conventional methods such as microbial conversion methods, purification methods from microbial cultures, enzymatic methods, or chemical synthesis methods.

[0064] As for the useful vitamin, any that can be incorporated into cosmetics may be used, but preferably, examples include vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol), and their derivatives (ascorbin palmitate, ascorbin stearate, ascorbin dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherol nicotinate, vitamin E, DL-pantotenyl alcohol, D-pantotenyl alcohol, pantotenyl ethyl ether, etc.) are also included in the useful vitamin used in the present invention. The useful vitamin can be obtained by conventional methods such as microbial conversion, purification from microbial cultures, enzymes, or chemical synthesis.

[0065] As for the high molecular weight peptide, any material that can be incorporated into cosmetics may be used, but preferably, collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, keratin, etc. The high molecular weight peptide can be obtained by purification through conventional methods such as purification from a microbial culture medium, enzymatic methods, or chemical synthesis methods, or it can be used by purifying it from natural materials such as the dermis of pigs or cattle, or silk fibers of silkworms.

[0066] As for the high molecular weight polysaccharide, any that can be incorporated into cosmetics may be used, but preferably, hydroxyethylcellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate or its salt (sodium salt, etc.) may be used. For example, chondroitin sulfate or its salt, etc., can be used after purifying it from mammals or fish.

[0067] As for sphingolipids, any that can be incorporated into cosmetics may be used, but preferably, ceramides, phytosphingosines, sphingoglycolipids, etc. Sphingolipids can be obtained by purifying them by conventional methods or by chemical synthesis from mammals, fish, shellfish, yeast, or plants.

[0068] Any seaweed extract that can be incorporated into cosmetics may be used, but preferably, brown algae extract, red algae extract, green algae extract, etc., may be used. Additionally, calagenan, arginic acid, sodium alginate, potassium alginate, etc., purified from these seaweed extracts are also included in the seaweed extract used in the present invention. The seaweed extract can be obtained by purifying seaweed by conventional methods.

[0069] In addition to the essential ingredients mentioned above, the cosmetic composition of the present invention may also include other ingredients that are conventionally incorporated into cosmetic compositions as needed. Other ingredients that may be added include oil components, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, UV absorbers, preservatives, disinfectants, antioxidants, plant extracts, pH adjusters, alcohols, colorants, fragrances, blood circulation promoters, cooling agents, antiperspirants, purified water, etc. Examples of oil components include ester-based oils, hydrocarbon-based oils, silicone-based oils, fluorinated-based oils, animal oils, plant oils, etc.

[0070] As ester-based oils, tri-2-ethylhexanoate glyceryl, 2-ethylhexanoate cetyl, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, butyl stearate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, diisopropyl adipice, isoalkyl neopentanoate, tri(capryl, capric acid)glyceryl, tri-2-ethylhexanoate trimethylolpropane, triisostearate trimethylolpropane, tetra-2-ethylhexanoate pentaelislitol, cetyl caprylate, decyl lauricate, Hexyl laurate, Decyl myristate, Myristyl myristate, Cetyl myristate, Stearyl stearate, Decyl oleate, Cetyl lisinooleate, Isostearyl laurate, Isotridecyl myristate, Isocetyl palmitate, Octyl stearate, Isocetyl stearate, Isodecyl oleate, Octyldodecyl oleate, Octyldodecyl linoleate, Isopropyl isostearate, Cetostearyl 2-ethylhexanoate, Stearyl 2-ethylhexanoate, Hexyl isostearate, Ethylene glycol dioctanoate, Ethylene glycol dioleate, Propylene glycol dicaprine, Di(Capryl, Capric acid)propylene glycol, Propylene glycol dicaprylate, Neopentyl glycol dicaprine, Neopentyl glycol dioctanoate, Glyceryl tricaprylate, Glyceryl triundecylate, Glyceryl triisopalmitate, Glyceryl triisostearate, Octyldodecyl neopentanoate, Isostearyl octanoate, Octyl isononanoate, Hexyldecyl neodecanoate, Octyldodecyl neodecanoate, Isocetyl isostearate, Isostearyl isostearate, Octyldecyl isostearate, Polyglycerin oleic acid ester, Polyglycerin isostearic acid ester, Triisocetyl citrate, Triisoalkyl citrate, Triisooctyl citrate, Lauryl lactate, Myristyl lactate, Cetyl lactate, Octyldecyl lactate, Triethyl citrate, Acetyltriethyl citrate, Acetyltributyl citrate, Trioctyl citrate, Diisostearyl malate, Hydroxystearic acid 2-ethylhexyl, di2-ethylhexyl succinate, diisobutyl adipicate, diisopropyl sebacicate,Examples include ester systems such as dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, pitsteryl isostearate, pitsteryl oleate, isocetyl 12-stealloylhydroxystearate, stearyl 12-stealloylhydroxystearate, and isostearyl 12-stealloylhydroxystearate.

[0071] Examples of hydrocarbon oils include squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, and Vaseline.

[0072] Examples of silicone-based oils include polymethylsilicon, methylphenylsilicon, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane and methylcetyloxysiloxane copolymer, dimethylsiloxane and methylstealoxysiloxane copolymer, alkyl-modified silicone oil, amino-modified silicone oil, etc.

[0073] Examples of fluorinated oils include perfluoropolyethers.

[0074] Examples of animal or plant oils include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, safflower oil, soybean oil, corn oil, rapeseed oil, apricot kernel oil, palm kernel oil, palm oil, castor oil, sunflower oil, grapeseed oil, cottonseed oil, coconut oil, cucurbit oil, wheat germ oil, rice germ oil, shea butter, laurel oil, macadamia nut oil, meadowsweet oil, egg yolk oil, beef tallow, horse oil, mink oil, orange raffia oil, jojoba oil, candelilla wax, carnaba wax, liquid lanolin, hydrogenated castor oil, etc.

[0075] Examples of moisturizers include water-soluble low-molecular-weight moisturizers, oil-soluble molecular moisturizers, water-soluble polymers, and oil-soluble polymers.

[0076] Examples of water-soluble low molecular weight moisturizers include serine, glutamine, sorbitol, mannitol, pyrrolidone-sodium carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B (degree of polymerization n = 2 or more), polypropylene glycol (degree of polymerization n = 2 or more), polyglycerin B (degree of polymerization n = 2 or more), lactic acid, lactate, etc.

[0077] Examples of fat-soluble low-molecular-weight moisturizers include cholesterol and cholesterol esters.

[0078] Examples of water-soluble polymers include carboxyvinyl polymer, polyaspartate, tragacanth, xanthan gum, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, water-soluble chitin, chitosan, dextrin, etc.

[0079] Examples of fat-soluble polymers include polyvinylpyrrolidone and eicocene copolymers, polyvinylpyrrolidone and hexadecene copolymers, nitrocellulose, dextrin fatty acid esters, and polymeric silicones. Examples of emollients include long-chain acylglutamic acid cholesteryl esters, hydroxystearate cholesteryl, 12-hydroxystearate, stearic acid, rosin acid, and lanolin fatty acid cholesteryl esters.

[0080] Examples of surfactants include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants.

[0081] Examples of nonionic surfactants include self-emulsifying monostearate glycerin, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE (polyoxyethylene) sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor oil, POE and POP (polyoxyethylene and polyoxypropylene) copolymer, POE and POP alkyl ether, polyether-modified silicone, alkanolamide lauric acid, alkylamine oxide, hydrogenated soybean phospholipid, etc.

[0082] Examples of anionic surfactants include fatty acid soaps, alpha-acylsulfonates, alkylsulfonates, alkylallylsulfonates, alkylnaphthalenesulfonates, alkyl sulfates, POE alkyl ether sulfates, alkylamide sulfates, alkyl phosphates, POE alkyl phosphates, alkylamide phosphates, alkylloylalkyl taurine salts, N-acyl amino acids, POE alkyl ether carboxylates, alkyl sulfosuccinates, sodium alkyl sulfoacetate, acylated hydrolyzed collagen peptide salts, perfluoroalkyl phosphate esters, etc.

[0083] Examples of cationic surfactants include alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride, diethylaminoethylamide stearate, dimethylaminopropylamide stearate, and quaternary ammonium salts of lanolin derivatives. Examples of amphoteric surfactants include carboxybetaine type, amidebetaine type, sulfobetaine type, hydroxysulfobetaine type, amidesulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amideamine type, etc.

[0084] Organic and inorganic pigments include inorganic pigments such as silica, anhydrous silica, magnesium silicate, talc, sericite, mica, kaolin, bengala, clay, bentonite, titanium-coated mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, aluminum oxide, calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, ultramarine, chromium oxide, chromium hydroxide, calamine, and complexes thereof; Examples include polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenolic resin, fluoropolymer, silicone resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene and styrene copolymer, silk powder, cellulose, CI pigment yellow, CI pigment orange, and other organic pigments, as well as composite pigments of inorganic pigments and organic pigments.

[0085] As organic powders, metal soaps such as calcium stearate; metal alkyl phosphate salts such as sodium zinc cetylphosphate, zinc laurylphosphate, and calcium laurylphosphate; polyvalent metal salts of acyl amino acids such as calcium lauroyl-beta-alanine, zinc lauroyl-beta-alanine, and calcium lauroylglycine; polyvalent metal salts of amide sulfonic acids such as calcium lauroyl-taurine and calcium palmitoyl-taurine; N-acyl basic amino acids such as N-epsilon-lauroyl-L-lysine, N-epsilon-palmitoyllysine, N-alpha-palitoylolnitine, N-alpha-lauroylarginine, and N-alpha-hydrogenated beef tallow fatty acid acylarginine; and N-acyl polypeptides such as N-lauroylglycylglycine. Alpha-amino fatty acids such as alpha-aminocaprilic acid and alpha-aminolauric acid; polyethylene, polypropylene, nylon, polymethyl methacrylate, polystyrene, divinylbenzene and styrene copolymers, tetrafluoroethylene, etc. are examples.

[0086] As ultraviolet absorbers, para-aminobenzoic acid, ethyl para-aminobenzoate, amyl para-aminobenzoate, octyl para-aminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomentyl salicylate, benzyl cinnamonate, paramethoxycinnamate-2-ethoxyethyl paramethoxycinnamate, octyl paramethoxycinnamate, mono-2-ethylhexaneglyceryl diparamethoxycinnamate, isopropyl paramethoxycinnamate, mixture of diisopropyl and diisopropyl cinnamonate esters, urocanic acid, ethyl urocanicate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenonesulfonic acid and its salts, dihydroxymethoxybenzophenone, sodium dihydroxymethoxybenzophenonedisulfonate, dihydroxybenzophenone, tetrahydroxybenzophenone, Examples include 4-tert-butyl-4'-methoxydibenzoylmethane, 2,4,6-trianilino-p-(carbo-2'-ethylhexyl-1'-oxy)-1,3,5-triazine, 2-(2-hydroxy-5-methylphenyl)benzotriazole, etc.

[0087] Examples of disinfectants include hinokitiol, triclosan, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcinol, isopropylmethylphenol, azulene, salicylic acid, zincphyllithion, benzalkonium chloride, photosensitive element 301, mononitroguaiacol sodium, undecylenic acid, etc.

[0088] Examples of antioxidants include butylhydroxyanisole, propyl gallic acid, and elisorbic acid.

[0089] Examples of pH adjusters include citric acid, sodium citrate, malic acid, sodium malate, fumaric acid, sodium fumarate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogen phosphate, etc.

[0090] Examples of alcohols include higher alcohols such as cetyl alcohol.

[0091] In addition, the ingredients that may be added are not limited to those mentioned above, and any of the above ingredients may be incorporated within a range that does not impair the purpose and effects of the present invention.

[0092] The cosmetic composition of the present invention may take the form of a solution, an emulsion, a viscous mixture, etc.

[0093] The ingredients included in the cosmetic composition of the present invention may include ingredients commonly used in cosmetic compositions as active ingredients, and include, for example, conventional auxiliary agents and carriers such as stabilizers, solubilizers, vitamins, pigments, and fragrances.

[0094] The cosmetic composition for preventing or improving skin diseases according to the present invention can be prepared in any formulation commonly manufactured in the art, such as a lotion, cream, lotion, pack, foundation, lotion, beauty serum, hair cosmetic, etc.

[0095] Specifically, the cosmetic composition of the present invention includes formulations of skin lotion, skin softener, skin toner, milk lotion, astringent, lotion, moisture lotion, nourishing lotion, massage cream, nourishing cream, moisture cream, hand cream, foundation, essence, nourishing essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, hair lotion, hair tonic, hair essence, hair shampoo, hair rinse, hair treatment, body lotion, and body cleanser.

[0096] In the case where the formulation of the present invention is a paste, cream, or gel, animal fibers, plant fibers, wax, paraffin, starch, tracanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide may be used as carrier components.

[0097] In the case where the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, it may additionally include a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

[0098] In the case where the formulation of the present invention is a solution or emulsion, a solvent, a solvating agent, or an emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan.

[0099] In the case where the formulation of the present invention is a suspension, liquid diluents such as water, ethanol, or propylene glycol, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracant may be used as carrier components.

[0100] In the case where the formulation of the present invention is a surfactant-containing cleansing agent, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, linolin derivative, or ethoxylated glycerol fatty acid ester, etc. may be used as a carrier component.

[0101] In addition, the present invention provides a patch composition for the prevention or improvement of skin diseases comprising nano-sized graphene oxide as an active ingredient.

[0102] In addition, the present invention provides a method for treating a skin disease comprising the step of administering a pharmaceutically effective amount of nano-sized graphene oxide to an individual.

[0103] The treatment method of the present invention comprises administering the above-mentioned nano-graphene oxide to an individual in a therapeutically effective amount. It is preferable to apply a specific therapeutically effective amount for a specific individual differently depending on various factors, including the specific composition (such as the type and degree of the response to be achieved and whether other preparations are used in some cases), the individual's age, body weight, general health status, gender and diet, time of administration, route of administration and secretion rate of the composition, duration of treatment, and drugs used together or concurrently with the specific composition, as well as similar factors well known in the pharmaceutical field. The daily dosage is 0.0001 to 100 mg / kg based on the amount of the pharmaceutical composition of the present invention, preferably 0.01 to 100 mg / kg, and may be administered 1 to 6 times a day. However, it is obvious to those skilled in the art that the dosage or administration amount of each active ingredient must be such that it does not contain an excessively high content of each active ingredient to cause side effects. Therefore, it is preferable to determine the effective amount of the composition suitable for the purpose of the present invention by considering the aforementioned matters.

[0104] The above-mentioned individual is applicable to any mammal, and said mammal includes not only humans and primates, but also livestock such as cattle, pigs, sheep, horses, dogs, and cats.

[0105] The nano-graphene oxide of the present invention can be administered to mammals, such as rats, mice, livestock, and humans, via various routes. All modes of administration are expected, for example, orally, rectally or intravenously, intramuscularly, subcutaneously, intrathecally, or intracerebroventricularly.

[0106] The present invention will be explained in more detail below through examples. These examples are merely for the purpose of explaining the present invention more specifically, and it will be obvious to those skilled in the art that the scope of the present invention is not limited to these examples.

[0107] <Example 1> Preparation and Characterization of Nano-graphene Oxide

[0108] <1-1> Preparation of Nano-Graphene Oxide

[0109] The nano-sized graphene oxide (daNGO) of the present invention was prepared. Specifically, graphite (Qingdao Kropfmuehl, China) was used as the carbon structure, and graphene oxide was synthesized using the Couette-Tayler flow method, in which a vortex is generated in a container containing a graphite mixture to allow sulfuric acid to penetrate the graphite layer and promote a chemical reaction. Sulfuric acid (H2SO4), sodium nitrate (NaNO3), and potassium permanganate (KMnO4) were all purchased from Samjeon Sunyak. Graphite and sulfuric acid (H2SO4) were mixed in a ratio of 1:40 to 70, and sodium nitrate (NaNO3), which lowers the viscosity of the mixed solution to facilitate stirring, was mixed into the mixture in a ratio of 1:0.2 to 0.7 relative to the weight of graphite (mixture). At this time, sulfuric acid (H2SO4) is inserted between the interlayer structures of graphite, expanding the interlayer spacing.

[0110] After that, the above mixture was mixed at 150 rpm to 500 rpm for 1 to 3 hours, and then the mixture and potassium permanganate (KMnO4) were mixed in a ratio of 1:5 to 15, and a rotational force of 1,200 rpm to 5,000 rpm was applied for 1 to 72 hours to perform interlayer expansion and separation of graphite.

[0111] At this time, appropriately controlling the reaction time and rotational force through the control of the oxidation reaction is important for controlling the interlayer spacing and fabricating single-layer graphene oxide. The graphene oxide fabricated by the above process was subjected to nano-densification by applying ultrasound ranging from 10 to 900 W. The nano-densification conditions were varied according to the size of the graphene oxide being nano-densified.

[0112] To enhance the frictional force of the obtained graphene oxide, distilled water or PBS solvent was added at a volume 50 to 100 times that of the solid graphene oxide. A certain amount of graphene oxide mixed in the solvent was introduced into a nanofabrication device utilizing physical methods to reduce the particle size of the graphene oxide. Furthermore, the ratio of each material applied during the production of the graphene oxide was set to a ratio that promotes the nanofabrication of the graphene oxide. In this experiment, the nanofabrication of graphene oxide was separated using physical methods in the nanofabrication device. Additionally, the graphene can be separated by size through a centrifugation process, with a centrifugation speed of 8,000 to 20,000 rpm applied depending on the size.

[0113] <1-2> Characterization of Nano-Graphene Oxide

[0114] The characteristics of the nano-graphene oxide prepared in Example 1-1 above were confirmed. Specifically, the morphology of the nano-graphene oxide was confirmed using a transmission electron microscope (TEM). Specifically, the nano-graphene oxide was loaded onto a 400-mesh carbon-coated copper grid and analyzed using a Cs-corrected HRTEM (JEM-ARM200F, Cold FEG, JEOL Ltd, Japan). In addition, particle size analysis (CPS Disc Centrifuge; CPS Instruments, USA) was used to confirm the average particle size. At this time, the nano-graphene oxide was separated by size using centrifugal precipitation in a liquid medium, and the precipitate was stabilized by a slight density gradient within the liquid.

[0115] In addition, the NGO prepared on the sapphire wafer was inspected using a non-contact atomic force microscope (XE-100, Park Systems, Korea). Furthermore, to confirm the chemical bonding characteristics, Fourier transform infrared spectroscopy (FTIR) spectra were analyzed using a Platinum FTIR Spectrometer (ALPHA II, Bruker Corp., USA) to examine the FTIR peak CO (1045 cm⁻¹) of the nano-graphene oxide. -1 ), C=O(1630cm -1 , 1729cm -1 ), CH(2859cm -1 The OH Peak generated during the ) and nano-process was analyzed. The bonding type and constituent elements of nano-graphene oxide were confirmed using X-ray photoelectron spectroscopy (AXIS-His, Kratos, USA).

[0116] As a result, as shown in FIGS. 1 and 2, the hexagonal carbon structure of the nano-graphene oxide of the present invention was confirmed, and the average particle size was confirmed to be 15.9 nm. In addition, the Fourier Transform Infrared Spectroscopy (FTIR) spectrum of the NGO showed 3428 cm⁻¹ corresponding to the stretching vibrations of the OH, C=O, and CO bonds, respectively. -1 , 1720cm -1 and 1049cm -1A peak was observed at (see Fig. 1c). Based on the above results, it was confirmed that hydroxyl, carboxyl, and epoxy groups are present in nanographene oxide. According to atomic force microscopy analysis, the atomic thickness of nanographene oxide was less than 1 nm, which suggests that nanographene oxide consists of fewer than two monolayers. The surface composition of nanographene oxide was analyzed using X-ray photoelectron spectroscopy and found that it exhibits the typical bonding pattern of graphene oxide (similar peak shape). A relatively strong CC peak was observed, and it was confirmed that CC bonding is higher than CO bonding due to the influence of nanoscale graphene oxide (Fig. 2).

[0117] <Example 2> Confirmation of Immune Cell Subtype Regulation by Nano-Graphene Oxide

[0118] <2-1> Confirmation of IL-17 expression regulation in cell subtypes

[0119] To confirm that the nano-graphene oxide of the present invention improves psoriasis, it was determined in vitro whether it regulates IL-17 cell subtypes, which are immune cells causative of psoriasis. Specifically, single cells isolated from the spleen of BALB / C mice were cultured under stimulation conditions of CD3 (2 μg / ml) and LPS (100 ng / ml), and 5 μg of the nano-graphene oxide (Graphene, Grp) prepared in Example 1 was added according to size (15.9 nm or 35.1 nm), after which IL-17-positive CD4 or CD8 T cells were analyzed by flow cytometry. As controls, an untreated control group (Nil group) and a negative control group (-) treated with an equal amount of solvent under IL-17 stimulation conditions were used.

[0120] As a result, as shown in Figure 3, compared to the Nil group, IL-17-positive CD4 T cells (Th17) were significantly increased in the negative control group, but the increased Th17s were significantly decreased in the group treated with nano-graphene oxide. In addition, IL-17-positive CD8 T cells (Tc17) were also significantly increased in the negative control group, but were significantly decreased with treatment with nano-graphene oxide, confirming that nano-graphene oxide regulates immune cells that cause psoriasis.

[0121] <2-2> Confirmation of tissue-resident memory T cell subtype regulation

[0122] In order to confirm that the nano-oxidized graphene of the present invention improves psoriasis, it was determined in vitro whether it regulates tissue-resident memory T cell (TRM) subtypes, which are immune cells causative of psoriasis. Specifically, under the same conditions as in Example 2-1 above, the expression of tissue-resident memory cell subtypes, CD4 TRM, CD4 TRM 17, CD8 TRM, and CD8 TRM 17, was analyzed by flow cytometry.

[0123] As a result, as shown in Figure 4, CD4-positive TRM was significantly increased in the negative control group compared to the Nil group, but it was confirmed that the increased CD4-positive TRM was significantly reduced in the group treated with nano-graphene oxide. In addition, regarding CD8-positive TRM, it was confirmed that CD8-positive TRM was significantly reduced in the group treated with nano-graphene oxide compared to the negative control group.

[0124] <Example 3> Confirmation of Acute Psoriasis Improvement Effect

[0125] <3-1> Preparation of an Acute Dry Skin Animal Model

[0126] To confirm whether the nano-graphene oxide of the present invention improves psoriasis, an acute psoriasis animal model was constructed. Specifically, the dorsal hair of SKG mice, known to readily form an autoimmune environment, was removed. One day later, imiquimod, a psoriasis-inducing substance, was applied to the dorsal skin of the mice at a dose of 62.5 mg daily for six days. Additionally, on days 2, 4, and 6 following the application of imiquimod, 15.9 nm nano-graphene oxide was diluted in saline to a concentration of 6.7 mpk and injected intraperitoneally. Thickness score, scaling score, and redness score were measured from the time of psoriasis induction until the end of the experiment. At the end of the experiment, mice were humanely sacrificed, skin tissues were obtained and sectioned, and the epidermal thickness was measured by staining with hematoxylin & eosin (H&E). As a control group, a vehicle group was used in which acute psoriasis was induced and an equal amount of solvent was injected. The specific process of constructing the animal model is shown in Figure 5.

[0127] As a result, as shown in Figure 6, compared to the Vehicle group, it was visually confirmed that the pathological activity of psoriasis was reduced in the group treated with nano-graphene oxide, and from the start to the end of the experiment, the skin thickness index, keratin index, and erythema index were significantly reduced compared to the Vehicle group.

[0128] In addition, as shown in Figure 7, it was confirmed that the thickness of the epidermal layer was significantly reduced in the group treated with nano-graphene oxide compared to the vehicle group, confirming that nano-graphene oxide improves skin conditions in a psoriasis animal model.

[0129] <3-2> Confirmation of Immune Cell Subtype Regulation

[0130] To confirm whether the nano-oxidized graphene of the present invention improves psoriasis, it was determined whether it regulates immune cell subtypes in an animal model of acute psoriasis. Specifically, spleen tissue was obtained from the mouse sacrificed in Example 3-1 above, and spleen cells were isolated from it. Then, the cells were stimulated with PMA-lonomycin for 2 hours, and after 2 hours, a Golgi apparatus stop was performed for 2 hours, and the activity of T cells expressing each cytokine was analyzed via flow cytometry.

[0131] As a result, as shown in Fig. 8A, compared to the Vehicle group, it was confirmed that CD4-positive Th1, Th2, and Th17 cells, which are inflammatory immune cell subtypes, were reduced in the group treated with nano-graphene oxide, with Th1 and Th17 cells being particularly significantly reduced. In addition, compared to the Vehicle group, it was confirmed that CD8-positive Tc1, Tc2, and Tc17 cells were significantly reduced (Fig. 8B).

[0132] In addition, as shown in Figure 9, it was confirmed that Treg cells, which are immune regulatory cells, significantly increased in the group treated with nano-graphene oxide compared to the Vehicle group, thereby confirming that nano-graphene oxide reduces autoimmune pathogenic cell subtypes and increases immune regulatory cells in an acute psoriasis animal model.

[0133] <3-3> Confirmation of tissue-resident memory T cell subtype regulation

[0134] To confirm whether the nano-graphene oxide of the present invention improves psoriasis, it was determined whether it regulates tissue-resident memory T cell subtypes in an acute psoriasis animal model. Specifically, tissue-resident memory T cell subtypes were analyzed by flow cytometry in splenocytes stimulated in the same manner as in Example 3-2.

[0135] As a result, as shown in Figure 10, it was confirmed that CD4-positive TRM1 and TRM17 were significantly reduced in the group administered nano-graphene oxide compared to the Vehicle group. In addition, it was confirmed that CD8-positive TRM1 and TRM17 were significantly reduced in the group administered nano-graphene oxide compared to the Vehicle group.

[0136] <Example 4> Confirmation of the mitochondrial function regulating effect of nano-graphene oxide

[0137] <4-1> Confirmation of Enhanced Mitochondrial Function in Immune Cells

[0138] To confirm whether the nano-graphene oxide of the present invention improves psoriasis, it was determined whether it improves mitochondrial dysfunction in psoriasis-pathogenic immune cells. Specifically, mouse spleen immune cells were examined to determine whether the effect of reducing reactive oxygen species and increasing oxygen respiration, which are major mitochondrial functions, were observed. Single cells derived from mouse spleen were isolated and stimulated by treating them with CD3 antibodies, CD28 antibodies, and IL-6 to induce psoriasis-pathogenic IL-17-positive T cells. Subsequently, nano-graphene oxide was applied at a concentration of 1 or 10 μg / ml, and mitoSOX was measured to analyze ROS (mitoROS) within mitochondria using flow cytometry. Additionally, OCR (Oxygen Consumption Rate) analysis was performed to confirm whether mitochondrial oxygen respiration increased. As controls, an untreated control group (Nil group) and a negative control group treated with an equal amount of solvent instead of nano-graphene oxide were used.

[0139] As a result, as shown in Figures 11A and 11B, it was confirmed that ROS in mitochondria decreased in a concentration-dependent manner in the group treated with the nano-graphene oxide of the present invention. In addition, it was confirmed that OCR significantly increased compared to the negative control group (Figures 11C and 11D), confirming that the nano-graphene oxide of the present invention enhances mitochondrial function in immune cells.

[0140] <4-2> Enhanced Mitochondrial Function Confirmed in Blood Immune Cells of Psoriasis Patients

[0141] To confirm whether the nano-graphene oxide of the present invention improves psoriasis, it was determined whether it regulates mitochondrial function in immune cells derived from psoriasis patients. Specifically, mitochondrial ROS was analyzed by flow cytometry in patient-derived peripheral blood mononuclear cells (PBMCs) and CD8 tissue-resident memory T cells (CD8 TRMs), which are known to induce immunopathology within tissues in immune diseases such as psoriasis, using the same method as in Example 4-2 above. In addition, mitochondrial respiration was confirmed by OCR analysis. The untreated control group, Nil, was used as the control.

[0142] As a result, as shown in Figures 12A and 12B, it was confirmed that ROS was significantly reduced in patient-derived PBMC or CD8 TRM cells by treatment with nano-graphene oxide. In addition, in OCR analysis, it was confirmed that OCR increased by treatment with nano-graphene oxide (Figure 12C), confirming that the nano-graphene oxide of the present invention enhances mitochondrial function in immune cells of actual psoriasis patients.

[0143] Therefore, it was confirmed that the nano-graphene oxide of the present invention regulates inflammatory immune cell subtypes and tissue-resident memory cells, which are pathogenic immune cells of psoriasis. Furthermore, in an animal model of acute psoriasis, it was confirmed that it reduces skin thickness, keratinization, and erythema, and decreases the thickness of the epidermal layer. Additionally, it was confirmed that it regulates immune cells by reducing pathogenic immune cells and increasing immunoregulatory cells in splenocytes. Moreover, it was confirmed that it regulates mitochondrial function by increasing mitochondrial ROS and oxygen respiration in pathogenic immune cells of psoriasis.

Claims

1. A composition for the prevention or treatment of skin diseases comprising nano-sized graphene oxide as an active ingredient.

2. In Paragraph 1, A composition in which the above-mentioned nano-graphene oxide has a particle size of 1 to 100 nm.

3. In Paragraph 1, The above-mentioned nano-graphene oxide is a composition that regulates immune cells.

4. In Paragraph 3, The above immune cell is a composition in which the immune cell is a cell selected from the group consisting of Th1, Th2, Th17, Tc1, Tc2, Tc17, and Treg.

5. In Paragraph 3, A composition in which the immune cells are tissue-resident memory cells (TRMs).

6. In Paragraph 5, A composition in which the tissue-resident memory cells are CD4-positive TRM, CD4-positive TRM17, CD8-positive TRM, and CD8-positive TRM17.

7. In Paragraph 3, A composition in which regulating the above immune cells reduces the expression of cells selected from the group consisting of Th1, Th2, Th17, Tc1, Tc2, and Tc17.

8. In Paragraph 3, A composition that regulates the above immune cells by increasing the expression of Treg.

9. In Paragraph 3, A composition in which regulating the above immune cells reduces tissue-resident memory cells.

10. In Paragraph 1, The above-mentioned nano-oxidized graphene is a composition that reduces skin thickness.

11. In Paragraph 1, The above-mentioned nano-oxidized graphene is a composition that reduces skin keratinization or erythema.

12. In Paragraph 1, The above-mentioned nano-graphene oxide is a composition that regulates mitochondrial function.

13. In Paragraph 12, A composition that regulates the above mitochondrial function by reducing mitochondrial ROS.

14. In Paragraph 12, A composition that regulates the above mitochondrial function, wherein it increases the mitochondrial respiration rate.

15. In Paragraph 1, A composition in which the above skin disease is psoriasis.

16. A cosmetic composition for the prevention or improvement of skin diseases comprising nano-sized graphene oxide as an active ingredient.

17. A patch composition for the prevention or improvement of skin diseases comprising nano-sized graphene oxide as an active ingredient.

18. A method for treating a skin disease comprising the step of administering a pharmaceutically effective amount of nano-sized graphene oxide to an individual.

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