Peptide having preventive or therapeutic activity against atopic dermatitis

Abstract

The present invention relates to a peptide exhibiting anti-inflammatory function, a fusion compound containing the same, and a medicine, cosmetic, food, medical device, etc. containing the same. [Solution] The present invention has revealed that the RMSP1 peptide of sequence number 1 and its variants not only exhibit low cytotoxicity and significantly reduce the cellular inflammatory response induced by lipopolysaccharides, but also exhibit wound healing efficacy.

Description

[Technical field]

[0001] The present invention relates to a peptide exhibiting activity for preventing and / or treating atopic dermatitis and a composition containing the same, and relates to application of the peptide to medicines, quasi-drugs, medical devices, cosmetics, etc. [Background technology]

[0002] Atopic dermatitis is a chronic skin disease accompanied by dry skin, keratinization, and itching, which affects 0.5-1% of the total population, especially 5-10% of children, and the number of patients is increasing in recent years. In the affected area of ​​atopic dermatitis, the infiltration of immune-related cells such as macrophages, mast cells, and Th lymphocytes increases significantly. In patients with atopic dermatitis, the blood IgE concentration increases significantly because the number of Th2 cells increases and the IL-4 secreted by these cells stimulates B lymphocytes to promote the secretion of IgE. Therefore, atopic dermatitis is classified as a Th2-type skin disease associated with abnormalities in the immune system. Atopic dermatitis causes physical and mental pain to patients, as well as a lot of economic damage, and no specific medicine has been found to treat this disease to date. Currently, steroids, antihistamines, etc. are used as treatments for atopic dermatitis. However, long-term use of these drugs can cause serious side effects, and alternative drugs are therefore needed. Summary of the Invention [Problem to be solved by the invention]

[0003] An object of the present invention is to provide a novel peptide for preventing and / or treating atopic dermatitis, which is safe and stable for the living body and can be used in cosmetics, pharmaceuticals, etc. Another object of the present invention is to provide cosmetics, pharmaceutical compositions, medical devices, foods, etc., which contain peptides for the prevention and / or treatment of atopic dermatitis. [Means for solving the problem]

[0004] In order to solve the above-mentioned problems of the present invention, the present inventors have selected and tested a number of candidate peptides derived from humans, and have found that a peptide consisting of 5 to 25 consecutive amino acids selected from 31 amino acids 5'-DVENNSTLEKHSGKRRKKRKRRHRSKVNGLQRG-3' (SEQ ID NO: 40) from amino acids 519 to 549 derived from human SP100 protein shows low cytotoxicity and significantly reduces the inflammatory response of cells induced by lipopolysaccharide, and also shows efficacy in wound healing and improvement of atopic dermatitis. The activity of the molecule does not change overall due to the above mutation.

[0005] The inventors have referred to this peptide consisting of 15 amino acids, LEKHSGKRRKKRRRHR (SEQ ID NO: 1; a peptide consisting of amino acids 526 to 540 of human SP100 protein), as "RMSP1" or "RMSP1 peptide" in the following description of the present invention, and have represented 12 representative sequences among other peptides consisting of consecutive amino acids as RMSP1-1 to RMSP1-12, respectively, and have tested that peptides of various lengths and sequences have the effect of reducing or treating cellular inflammatory responses, and show efficacy in wound treatment and improvement of atopic dermatitis.

[0006] Furthermore, the peptides according to the present invention can be modified by phosphorylation, sulfation, acylation, glycosylation, methylation, panesylation, and the like.

[0007] The peptide or a fragment thereof of the present invention can be conjugated with a biocompatible polymer or a fatty acid to form a conjugate. The biocompatible polymer can be one or more selected from the group consisting of starch, dextran, chitosan, glycol chitosan, pullulan, chondroitin sulfate, hyaluronic acid, pectin, polylactic acid (PLA), polyglycolide (PGA), polycaprolactone (PCL), poly(caprolactone-lactide) random copolymer (PCLA), etc., but is not limited thereto. The fatty acid can be one or more selected from the group consisting of hexanoic acid, caprylic acid, capric acid, lauric acid, palmitic acid, stearic acid, and cholesterol, but is not limited thereto.

[0008] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the art to which this invention belongs.

[0009] The present invention relates to a) an RMSP1 peptide consisting of SEQ ID NO: 40; b) a peptide for preventing or ameliorating atopic dermatitis selected from RMSP1 mutant peptides containing one or more of the following mutations in the RMSP1 peptide: amino acid substitution, amino acid addition, and amino acid deletion, the amino acid deletion including 10 or less, or 9 or less, or 8 or less, or 7 or less, or 6 or less, or 5 or less, or 4 or less, or 3 or less, or 2 or less, or 1 amino acid deletion.

[0010] The present invention also relates to a peptide for preventing or ameliorating atopic dermatitis, characterized in that the peptide for preventing or ameliorating atopic dermatitis has an efficacy in treating wounds.

[0011] The present invention also relates to a peptide for preventing or ameliorating atopic dermatitis, wherein the amino acid substitution in b) above is a conservative amino acid substitution.

[0012] The present invention also relates to a peptide for preventing or ameliorating atopic dermatitis, characterized in that the conservative amino acid substitutions are such that the arginine residue positions of SEQ ID NO: 1 are independently substituted with lysine residues or are substituted and the lysine residue positions of SEQ ID NO: 1 are substituted with arginine residues.

[0013] The present invention also relates to a peptide for preventing or ameliorating atopic dermatitis, wherein the amino acid deletion of b) is a deletion of 1 to 10 arginine and lysine residues among the amino acids of the RMSP1 peptide.

[0014] The present invention also relates to a peptide for preventing or ameliorating atopic dermatitis, which comprises one or more of the following: i) an RMSP1 peptide; ii) an amino acid substitution sequence of the RMSP1 peptide; iii) a sequence in which amino acids are deleted from the RMSP1 peptide sequence; iv) a sequence in which amino acids are added to the RMSP1 peptide sequence; v) a sequence in which amino acid substitutions and deletions have been made in the RMSP1 peptide; vi) a sequence in which amino acid substitutions, additions and deletions have been made in the RMSP1 peptide; vii) a sequence in which amino acid substitutions and additions have been made in the RMSP1 peptide; and viii) a sequence in which amino acid substitutions and additions have been made in the RMSP1 peptide. In addition, the peptides i) to viii) may be repeated two or more times, and other examples include peptides or proteins for preventing or ameliorating atopic dermatitis that are composed of a sequence in which one or more peptides from i) to viii) are combined and / or repeated. However, it will be obvious to a person having ordinary skill in the art to which the present invention pertains that the peptides or proteins for preventing or ameliorating atopic dermatitis of the present invention are not limited to those exemplified above.

[0015] The present invention also relates to a peptide for preventing or ameliorating atopic dermatitis, characterized in that the peptide for preventing or ameliorating atopic dermatitis is composed of two or more, preferably 2 to 100, more preferably 2 to 50, peptides having the same sequence or different sequences bound together.

[0016] The present invention also relates to a fusion compound comprising a peptide for preventing or ameliorating atopic dermatitis, in which a functional molecule is bound to one or more of the N-terminus and C-terminus of the peptide for preventing or ameliorating atopic dermatitis.

[0017] The present invention also relates to a fusion compound containing a peptide for preventing or improving atopic dermatitis, characterized in that the functional molecule is a therapeutic peptide such as a hormone, a growth factor, a neurotransmitter, or an ion channel ligand, or a therapeutic protein such as various enzymes including superoxide dismutase, albumin, or an antibody.

[0018] The present invention also relates to a fusion compound comprising a peptide for preventing or ameliorating atopic dermatitis, characterized in that the functional molecule is, for example, a molecule exhibiting an antioxidant function such as peroxiredoxin, an anti-inflammatory function such as interleukin, or a molecule exhibiting a wound healing function.

[0019] The present invention also relates to a pharmaceutical composition for preventing or treating a disease, comprising the peptide for preventing or improving atopic dermatitis, or a fusion compound in which a functional molecule is bound to one or more of the N-terminus and C-terminus of the peptide for preventing or improving atopic dermatitis. The disease includes, but is not limited to, inflammation of the skin, such as atopic dermatitis. In particular, the pharmaceutical composition of the present invention is useful for preventing and treating dermatitis, particularly atopic dermatitis, and wounds and inflammation caused by trauma, such as cuts, wounds, and abrasions on the skin.

[0020] The present invention also relates to a cosmetic composition comprising the peptide for preventing or improving atopic dermatitis, or a fusion compound in which a functional molecule is bound to at least one of the N-terminus and C-terminus of the peptide for preventing or improving atopic dermatitis. The cosmetic composition can alleviate inflammation and improve wounds when there is a wound on the skin, and has the effect of preventing and improving atopic dermatitis. The cosmetic of the present invention can include basic cosmetics such as lotion, cream, essence, oil-in-water or water-in-oil emulsion, ointment, and also color cosmetics such as foundation, lipstick, eye shadow, etc.

[0021] The present invention also relates to a food composition that exhibits the function of preventing or improving atopic dermatitis and / or the function of wound healing, which comprises one or more of the above-mentioned peptides for preventing or improving atopic dermatitis, or a fusion compound in which a functional molecule is bound to one or more of the N-terminus and C-terminus of the above-mentioned peptides for preventing or improving atopic dermatitis.

[0022] In addition, the present invention relates to a medical device selected from a wound dressing, a filler, or a composite filler, which comprises one or more of the peptides for preventing or improving atopic dermatitis, or a fusion compound in which a functional molecule is bound to one or more of the N-terminus and C-terminus of the peptides for preventing or improving atopic dermatitis.

[0023] As used herein, "conservative substitution" refers to a modification of a cargo molecule transport domain that involves replacing one or more amino acids with amino acids having similar biochemical properties that do not result in loss of biological or biochemical function of the cargo molecule transport domain.

[0024] As used herein, a "conservative amino acid substitution" refers to a substitution in which an amino acid residue is replaced with an amino acid residue having a similar side chain. Classes of amino acid residues having similar side chains have been defined and are well known in the art. These classes include amino acids having basic side chains (e.g., lysine, arginine, histidine), amino acids having acidic side chains (e.g., aspartic acid, glutamic acid), amino acids having uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), amino acids having non-polar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), amino acids having β-branched side chains (e.g., threonine, valine, isoleucine), and amino acids having aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine).

[0025] The peptides for preventing or ameliorating atopic dermatitis according to the present invention are understood to include variants in which one or more amino acids from the RMSP1 peptide have been mutated by substitution, deletion and / or addition.

[0026] Furthermore, the variants of the peptides for preventing or improving atopic dermatitis according to the present invention are understood to include variants of the cargo molecule transport domain or fragments thereof that have substantially the same function and / or effect as the cargo molecule transport domain of the present invention and have an amino acid sequence homology of 80% or 85% or more, preferably 90% or more, and more preferably 95% or more.

[0027] Furthermore, even if the peptide of the present invention for preventing or ameliorating atopic dermatitis has conservative amino acid substitutions, amino acid deletions, or amino acid additions, it is expected that it will still have activity for preventing or ameliorating atopic dermatitis.

[0028] The present invention is also characterized in that the functional molecule is selected from the group consisting of proteins, peptides, nucleic acids such as oligonucleotides and polynucleotides, carbohydrates, lipids, and mixtures of one or more of these.

[0029] The present invention is also characterized in that the chemical bond between the functional molecule and the peptide for preventing or improving atopic dermatitis is a covalent bond or a non-covalent bond, preferably a covalent bond. The chemical bond may be a covalent bond or a non-covalent bond. Non-covalent bonds may include ionic bonds or bonds due to electrostatic attraction, or bonds due to hydrophobic interactions. The substance capable of binding to the anti-inflammatory peptide by ionic bonds or electrostatic attraction may be a charged substance such as DNA or RNA.

[0030] The peptides for preventing or ameliorating atopic dermatitis of the present invention are not limited to those represented by SEQ ID NOs: 1 to 13, but representative peptides are exemplified in Table 1 for convenience of experiments.

[0031] In addition, the pharmaceutical composition containing the peptide for preventing or improving atopic dermatitis of the present invention or the fusion compound of the peptide for preventing or improving atopic dermatitis and a functional molecule as an active ingredient can be formulated with a carrier generally accepted in the pharmaceutical field and formulated in various forms such as skin external preparations, oral preparations, sprays, patches, or injections by a general method. For example, oral compositions include tablets and gelatin capsules, which contain, in addition to the active ingredient, diluents (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and / or glycine), lubricants (e.g., silica, talc, stearic acid and its magnesium or calcium salt, and / or polyethylene glycol), and tablets further contain binders (e.g., magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone), and optionally contain disintegrants (e.g., starch, agar, alginic acid or its sodium salt) or boiling mixtures and / or absorbents, colorants, flavors, and sweeteners. The compositions for injection are preferably isotonic aqueous solutions or suspensions, and the compositions mentioned are sterilized or sterilized and contain auxiliary substances (e.g., preservatives, stabilizers, wetting agents or emulsifiers, dissolution promoters, salts for regulating osmotic pressure and / or buffers). They may also contain other therapeutically useful substances.

[0032] The pharmaceutical preparation thus prepared can be administered orally or parenterally, i.e., intravenously, subcutaneously, intraperitoneally, or topically, depending on the purpose. The dosage can be 0.0001 to 100 mg / kg per day, administered once or in several divided doses. The dosage for a particular patient can be changed depending on the patient's weight, age, sex, health condition, administration time, administration method, excretion rate, severity of disease, etc.

[0033] The term "food" as used in the present invention means a natural or processed product containing one or more nutrients, preferably a product that has been processed to a certain degree and is ready to be eaten directly, and in the usual sense includes all of foods, food additives, functional foods, health functional foods, dietary supplements, and beverages. The food composition of the present invention can be produced in the form of various beverages, gums, teas, sweets, vitamin complexes, dietary supplements, and the like, but is not limited thereto. The preferred intake amount of the food composition of the present invention varies depending on the condition, weight, and severity of symptoms of the person taking it, the form of the food, and the intake period, and can be appropriately selected. It is preferable to take the food composition of the present invention at 0.2 mg / kg to 200 mg / kg of active ingredient per day in order to obtain optimal effects.

[0034] In addition, the pharmaceutical composition for preventing or treating a disease, which contains the peptide for preventing or improving atopic dermatitis or the fusion composition in which the peptide for preventing or improving atopic dermatitis is bound to a functional molecule as an active ingredient, is characterized in that it is a skin topical preparation for treating skin inflammation. The liniment containing the peptide for preventing or improving atopic dermatitis of the present invention or the fusion composition to which a functional molecule is added as an active ingredient can be easily produced in any form by a normal manufacturing method. As an example, when producing a cream-type liniment, the anti-inflammatory composition of the present invention is added to a general oil-in-water (O / W) or water-in-oil (W / O) cream base, and fragrances, chelating agents, pigments, antioxidants, preservatives, etc. are used as necessary, while synthetic or natural materials such as proteins, minerals, and vitamins can be used in combination for the purpose of improving physical properties.

[0035] In addition, unless otherwise specified, the terms used in this specification, claims, and drawings are used in the meaning commonly used by a person having ordinary knowledge in the technical field to which the present invention belongs.

[0036] [Table 1] Effect of the Invention

[0037] The anti-inflammatory peptide of the present invention not only exhibits low cytotoxicity and significantly reduces cellular inflammatory responses induced by polysaccharides, but also exhibits efficacy in wound healing and atopy treatment. Therefore, peptides for preventing and / or improving atopic dermatitis and compounds containing the same can be used in medicines, cosmetics, food compositions for preventing or alleviating inflammation, wound healing agents, fillers or composite fillers, etc., which are applied to inflammation including dermatitis. [Brief description of the drawings]

[0038] [Figure 1] RMSP1 peptide secondary structure prediction diagram (a) shows the secondary structure of the peptide predicted using the Pep-fold3 program, and (b) is a graph showing the peptide Pepfold. [Diagram 2] 1 shows reverse phase HPLC data showing the purity of the RMSP1 peptide. [Diagram 3] Figure 1 shows the wound healing efficacy of SP100 peptide (a) showing the healing of wounds induced by scratch assay over time and (b) showing the extent of wound closure. [Figure 4] FIG. 1 shows the anti-inflammatory efficacy of RMSP1. [Diagram 5] This figure shows the results of evaluating the efficacy of RMSP1 peptide in treating atopy. (a) is a photograph of the untreated control group (Con), the atopy-induced group treated with oxazolone (Oxa), and the group treated with RMSP1 after atopy was induced by oxazolone treatment (RMSP1). (b) shows the weight of ear biopsies of the same area taken in each group. (c) is a photograph of stained longitudinal sections of ear tissue and a graph of the dermal thickness measured using ImageJ. [Figure 6] FIG. 1 shows the results of gene analysis of ear tissue from an atopic animal model. [Figure 7]In order to confirm whether the efficacy of the RMSP1 peptide can be maintained or improved by mutation, substitution, or deletion of amino acids, the anti-inflammatory efficacy of RMSP1 mutants was evaluated in RAW264.7 macrophages. As a result, it was confirmed that the anti-inflammatory efficacy was maintained, and that the anti-inflammatory efficacy of some mutants was increased. [Figure 8] This figure shows a comparison of efficacy when the cell-penetrating peptides AD or MR were attached to the N-terminal portion of RMSP1, and acetylation or palmitoylation was performed. As a result, palmitoylated pal-RMSP1 had the highest inflammation suppression efficacy, and AD-RMSP1, which had the AD cell-penetrating peptide attached, showed a higher suppression efficacy than MR-RMSP1. [Figure 9] This is a diagram confirming the inflammation-suppressing efficacy of a peptide in which the N-terminus of RMSP1 has been palmitoylated using skin cells. After inducing the expression of inflammatory genes in HaCaT cells by treating them with TNF-α and IFN-γ, the inflammation-suppressing efficacy of pal-RMSP1 was tested, and it was confirmed that inflammatory genes were suppressed by TNF-α, IL-8, CCL-5, CCL-17, and CCL-22 at different concentrations. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0039] Hereinafter, the configuration of the present invention will be described in more detail with reference to specific examples. However, it will be obvious to those skilled in the art to which the present invention pertains that the scope of the present invention is not limited to the description of the examples.

[0040] 1. Cell Culturing

[0041] HaCaT and RAW264.7 cells were cultured in cell culture medium containing 10% fetal bovine serum (FBS) and antibiotic solution (100 units / ml penicillin, 100μg / ml streptomycin) in DMEM medium. The cells were cultured at 37℃, 95% humidity, and 5% CO2. When the cells reached 70-80% adhesion to the culture dish, they were subcultured by treating with trypsin-EDTA. HaCaT cells were provided by Professor Kim Tae-yoon's laboratory at the Catholic University of Japan, and RAW264.7 cells were provided by Professor Kim Sang-beom's laboratory at the College of Pharmacy at Samyook University. 2. Synthesis of peptides such as RMSP1 for preventing or treating atopic dermatitis

[0042] The peptides for preventing or treating atopic dermatitis of the present invention, such as RMSP1, were synthesized using 2-chlorotrityl chloride resin and amino acids using standard Fmoc-SPPS (solid phase peptide synthesis) protocols. The peptides were then cleaved from the resin and the side chain protecting groups were removed from the amino acids using TFA acid, water, and triisopropylsilane. Ether was added for precipitation and the peptides were purified using reversed-phase HPLC with a C18 column. Elution was performed with a water-acetonitrile linear gradient (0-75% (v / v) of acetonitrile) containing 0.1% (v / v) TFA. To remove TFA, the peptides were dissolved in water and 100 mM HCl was added to prepare an HCl concentration of 8 mM. The solution was incubated at room temperature for 5 min, frozen in liquid nitrogen, lyophilized overnight to remove all liquid, and the lyophilized powder was redissolved in HCl solution, frozen again, and lyophilized overnight. Lyophilization was repeated to redissolve three times. After the final lyophilization step, the peptides were redissolved in water and the molecular weight of the purified peptides was confirmed using LC / MS. The results are shown in Figure 2.

[0043] 3. Prediction of secondary structure of RMSP1 peptide To predict the peptide structure of RMSP1, the PEP-FOLD3 De novo peptide structure prediction program was used. The amino acid sequence of RMSP1 was input, and the model predicted by the program was visualized as a 2D predicted structure using the PyMOL 2.4 program [Figure 1 (a)]. In the prediction profile used to analyze the prediction of the secondary structure, (a) indicates a helix, (b) indicates an extension, and (c) indicates a coil, from which the secondary prediction model was derived [Figure 1 (b)].

[0044] 4. Evaluation of inflammation suppression To evaluate the anti-inflammatory efficacy of the peptide for preventing or treating atopic dermatitis of the present invention from RAW264.7 macrophages, 5x10 4 A total of 100 RAW264.7 cells were attached to the wells. The cells were then cultured in serum-free medium for 1 hour, and then treated with 10 μM peptide for 2 hours. Each well was then treated with 100 ng / ml LPS (lipopolysaccharide). After 4 hours, the medium was collected and centrifuged at 1,000 g for 10 minutes, after which IL-6 and TNF-α were detected.

[0045] The results of the analysis of IL-6 are shown in FIG. 4 and FIG. 7, and the results of the analysis of TNF-α are shown in FIG.

[0046] 5. Cellular Wound Healing Experiments To confirm the efficacy of the peptide for preventing or treating atopic dermatitis of the present invention in treating wounds using HaCaT skin cells, a scratch assay was performed. HaCaT cells were cultured at 2 × 10 5 After attaching each well, wounds were induced in the rats using a 200μl pipette tip. The cells were then washed twice with serum-free medium and treated with peptides at different concentrations in serum-free medium. After 0 and 24 hours, cell images were taken using a microscope, and the area of ​​the wound was measured and analyzed using the ImageJ program.

[0047] The efficacy of wound healing confirmed using skin cells is shown in Figure 3. (a) is an image showing the efficacy of wound healing over time of the peptide RMSP1 for preventing or treating atopic dermatitis of the present invention. (b) is a graph showing the extent to which the wound was closed.

[0048] 6. Atopic rat animal model The therapeutic effect of atopic dermatitis was evaluated using the peptide RMSP1 of the present invention for preventing or treating atopic dermatitis in an atopic rat animal model. 2% oxazolone was dissolved in a solvent with a ratio of acetone:olive oil = 4:1, and 10 μl of the solution was used for sensitization to the inner ear and outer ear. After 7 days, 10 μl of 0.5% oxazolone was applied to the inner ear and outer ear. In the case of the peptide for preventing or treating atopic dermatitis of the present invention, 10 μg of the peptide was applied to the surface of the outer ear every day for the number of days indicated, starting one day after sensitization.

[0049] On day 10, rats were sacrificed and the weight of the ear tissue was measured using a 5 mm biopsy punch, then fixed in 4% PFA (paraformaldehyde) solution and paraffin sections were prepared at 5 μm in size. Representative photographs were also obtained through H&E staining, and the thickness of the dermis layer was then measured using Caseviewer.

[0050] FIG. 5(a) is a photograph of rat ears treated with the peptide for preventing or treating atopic dermatitis of the present invention after applying oxazolone to the ears in the same manner as above to induce atopy, and FIG. 5(b) shows the results of measuring the weight of the rat ears of the same area. FIG. 5(c) is a photograph of a stained longitudinal section of ear tissue and a graph showing the thickness of the dermis using ImageJ. 7. Genetic analysis of atopic animal models

[0051] For qPCR, ear tissue from an atopic animal model obtained using a 5 mm biopsy punch was used to obtain RNA using the Rneasy kit, followed by cDNA synthesis, and then the expression level of each gene was measured using the primers and SYBR reen reagent listed in Table 2 below. The relative expression level was confirmed using the anti-absent gene β-actin. The results are shown in Figure 6.

[0052] [Table 2]

[0053] 8. Confirmation of the efficacy of Pal-RMSP1 in suppressing inflammation Gene expression of inflammatory cytokines from HaCaT human skin keratinocytes was analyzed. 3x10 HaCaT cells were plated in each well of a 6-well plate. 5 The cells were then washed with serum-free medium, cultured for 16 hours, and treated with 1 and 10 μM peptides for 2 hours. Each well was treated with 10 mg / ml each of TNF-α and IFN-γ and cultured for 6 hours. The cells were washed with PBS, RNA was obtained using the EZ Total RNA Miniprep Kit (Enzynomics), and cDNA was synthesized using the TOPscript cDNA Synthesis Kit (Enzynomics). The expression level of each gene was measured using the primers listed in Table 3 and the PowerUp SYBR Green Master Mix (Applied Biosystems) reagent. The relative expression level was evaluated using the anti-existence gene GADPH.

[0054] As a result, the efficacy of RMSP1 N-terminal palmitoylated peptides in suppressing inflammation was confirmed using skin cells. It was confirmed that inflammatory genes were suppressed by TNF-α, IL-8, CCL-5, CCL-17, and CCL-22 at different concentrations. The results are shown in Figure 9.

[0055] [Table 3]

Claims

1. a) a peptide consisting of SEQ ID NO: 40; b) a deletion peptide of SEQ ID NO: 40 in which 1 to 13 consecutive amino acids are deleted from the N-terminus and / or 1 to 20 consecutive amino acids are deleted from the C-terminus, resulting in a peptide of 5 to 30 amino acids; c) a peptide consisting of sequence number 40 of a) or a substituted peptide of sequence number 40 in which one or more amino acids in the deletion peptide of sequence number 40 of b) are replaced with conservative amino acids.

2. The peptide for preventing or treating atopic dermatitis according to claim 1, characterized in that the conservative amino acid substitutions are / or are independently substituted with lysine residues at the positions of arginine residues and / or substituted with arginine residues at the positions of lysine residues.

3. The peptide for preventing or treating atopic dermatitis according to claim 1, characterized in that the deletion peptide of SEQ ID NO: 40 in b) is any one selected from SEQ ID NO: 1 to SEQ ID NO:

13.

4. A peptide for preventing or treating atopic dermatitis according to any one of claims 1 to 3, characterized in that it is modified by phosphorylation, sulfation, acylation, glycation, methylation or palmitoylation.

5. A fusion compound comprising a peptide for preventing or treating atopic dermatitis according to any one of claims 1 to 3, characterized in that a functional molecule is bound to one or more of the N-terminus and C-terminus.

6. The fusion compound comprising the peptide for preventing or treating atopic dermatitis according to claim 4, characterized in that a functional molecule is bound to at least one of the N-terminus and the C-terminus.

7. The fusion compound comprising a peptide for preventing or treating atopic dermatitis according to claim 5, wherein the functional molecule is a therapeutic peptide or a therapeutic protein.

8. The fusion compound comprising a peptide for preventing or treating atopic dermatitis according to claim 6, wherein the functional molecule is a therapeutic peptide or a therapeutic protein.

9. The fusion compound comprising a peptide for preventing or treating atopic dermatitis according to claim 7, wherein the functional molecule is a molecule exhibiting antioxidant, anti-inflammatory or wound healing functions.

10. The fusion compound comprising a peptide for preventing or treating atopic dermatitis according to claim 8, wherein the functional molecule is a molecule exhibiting an antioxidant, anti-inflammatory or wound healing function.

11. A pharmaceutical composition for preventing or treating skin inflammation, comprising a peptide for preventing or treating atopic dermatitis described in any one of claims 1 to 4, or a fusion compound containing a peptide for preventing or treating atopic dermatitis described in any one of claims 5 to 10.

12. A pharmaceutical composition for preventing or treating a disease, characterized in that the skin inflammation according to claim 11 is atopic dermatitis.

13. A cosmetic composition comprising a fusion compound containing a peptide for preventing or treating atopic dermatitis described in any one of claims 1 to 4, or a peptide for preventing or treating atopic dermatitis described in any one of claims 5 to 10.

14. A food composition comprising a fusion compound containing a peptide for preventing or treating atopic dermatitis described in any one of claims 1 to 4, or a peptide for preventing or treating atopic dermatitis described in any one of claims 5 to 10.

15. A medical device comprising a peptide for preventing or treating atopic dermatitis described in any one of claims 1 to 4, or a fusion compound containing the peptide for preventing or treating atopic dermatitis described in any one of claims 5 to 10, and being selected from a wound dressing, a filler, or a composite filler.

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