PEPTIDE, COSMETIC COMPOSITION AND FOOD COMPOSITION TO IMPROVE SKIN CONDITION AND USE OF THE PEPTIDE

BR112025021465A2Pending Publication Date: 2026-09-08

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Patent Information

Application Number: BR112025021465
Authority / Receiving Office: BR · BR
Patent Type: Applications
Publication Date: 2026-09-08

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Description

1 / 19 PEPTIDE, COSMETIC COMPOSITION AND FOOD COMPOSITION TO IMPROVE SKIN CONDITION AND USE OF THE PEPTIDE Field of Technique

[0001] The present disclosure relates to peptides that have the activity to improve the condition of the skin and their uses. Background of the Technique

[0002] Human skin is constantly subject to changes, the most representative of which is the deterioration of skin function and the decrease in visual beauty due to aging. Aging causes the formation of wrinkles on the skin, and typical factors for wrinkle formation include exposure to ultraviolet rays and decreased collagen biosynthesis, etc. Skin aging can be broadly categorized into intrinsic aging, which is caused by genetic factors, and extrinsic aging, which is caused by external environmental factors such as solar radiation. Among these, in the case of extrinsic aging, it is known that aging can be prevented, treated, or delayed by the removal of reactive oxygen species, fibroblast proliferation, promotion of collagen biosynthesis, etc.

[0003] On the other hand, collagen, an important component of the extracellular matrix, is the main matrix protein produced by fibroblasts in the skin. Collagen forms the majority of the organic matter in the skin, tendons, bones, and teeth, with its content being particularly high in bones and skin (dermis). This collagen decreases with age and photoaging due to ultraviolet radiation, which is known to be closely related to wrinkle formation. Petition 870250090437, dated 03 / 10 / 2025, page 13 / 41 2 / 19 in the skin. Furthermore, collagen plays an important role in wound healing, and by stimulating collagen synthesis in damaged epithelium, wounds can be repaired quickly and without leaving scars. Additionally, it has been reported that as collagen biosynthesis is promoted, the density of the basal layer, etc., increases, the concentration of melanin pigment per unit of skin density decreases, and a skin tone lightening effect can be expected.

[0004] In this technical context, multifaceted studies are being conducted to improve skin condition through mechanisms such as promoting collagen biosynthesis and increasing fibroblast proliferation and activity (Registered Patent No. KR 10-1043081), but they are still insufficient. Disclosure of the Invention; Problem of the Technique

[0005] One aspect is to provide a peptide consisting of the amino acid sequence of SEQ ID NO: 1.

[0006] Another aspect is to provide a cosmetic composition to improve the skin condition, which includes the above peptide as an active ingredient.

[0007] Other objectives and advantages of this application will become apparent from the following detailed description, together with the accompanying claims and drawings. Any matter not described in this document will be sufficiently recognized and inferred by those skilled in the art of this application or similar art, and the description is hereby omitted. Petition 870250090437, dated 03 / 10 / 2025, p. 14 / 41 3 / 19 Solution to the Problem

[0008] Each of the descriptions and embodiments disclosed in this application can be applied to other descriptions and embodiments. Consequently, all combinations of the various elements disclosed in this application are covered by the scope of this application. Furthermore, the scope of this application should not be considered limited by the specific description presented below.

[0009] One aspect provides a peptide consisting of the amino acid sequence of SEQ ID NO: 1.

[0010] As used in this document, the term peptide may refer to a linear molecule formed by the combination of amino acid residues with each other by peptide bonds. The peptide above can be prepared according to chemical synthesis methods known in the art, particularly solid-phase synthesis techniques (Merrifield, J. Amer. Chem. Soc. 85:2149-54 (1963)) or liquid-phase synthesis techniques (US Patent No. 5,516,891).

[0011] As a result of diligent efforts to develop a peptide with biologically effective activity, the inventors of the present disclosure have identified a peptide consisting of the amino acid sequence SEQ ID NO: 1. Herein, the biologically effective activity may be one or more selected from: (a) promoting the proliferation of human dermal fibroblasts; and (b) increasing the expression of a selected dermal extracellular matrix from type 1 collagen, fibronectin, or elastin. Therefore, the above peptide can be used to improve skin conditions.

[0012] The peptide may have a protecting group attached to the N- or C-terminal of the peptide to acquire stability. Petition 870250090437, dated 03 / 10 / 2025, page 15 / 41 4 / 19 chemical, improved pharmacological properties (half-life, absorption, titer, effect, etc.), altered specificity (e.g., broad spectrum of biological activity) or reduced antigenicity. Consequently, the peptide can be used to include either the peptide itself or a protected derivative thereof in which a protecting group is introduced. In one embodiment, an N-terminal of the peptide can be linked to any protecting group selected from the group consisting of an acetyl group, a fluoroylmethoxycarbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, a butoxycarbonyl group (Boc), an allyloxycarbonyl group (Alloc) and polyethylene glycol (PEG); and / or the C-terminal of the peptide can be linked to any protecting group selected from the group consisting of an amino group (NH2), a tertiary alkyl group and an azide (-NHNH2).In addition, the peptide may optionally include a bleaching sequence, a label, labeled residues, or an amino acid sequence prepared for the specific purpose of increasing the half-life or stability of the peptide.

[0013] The peptide above is artificially synthesized or unnaturally occurring or genetically modified, and “unnaturally occurring or genetically modified” refers to a state that is not in its natural state but is created by artificial modification. Here, artificial modification may include the artificial synthesis of an amino acid sequence mimicking a plurality of amino acid structures or manipulating it to acquire chemical stability, enhanced pharmacological properties, Petition 870250090437, dated 03 / 10 / 2025, page 16 / 41 5 / 19 altered specificity or reduced antigenicity, as described above.

[0014] As used in this document, the term stability can refer not only to in vivo stability, which protects the peptide from attack by proteolytic enzymes in vivo, but also to storage stability (e.g., storage stability at room temperature).

[0015] Another aspect provides a cosmetic composition to improve skin conditions, which includes, as an active ingredient, a peptide consisting of the amino acid sequence SEQ ID NO: 1.

[0016] In the description of the peptide above, the terms or elements mentioned are the same as those already mentioned.

[0017] As used in this document, the term improve may refer to any act that at least reduces a parameter associated with the relief or treatment of a condition, for example, the severity of a symptom.

[0018] As used in this document, the term “improve skin condition” can broadly refer to the process or effect of treating, reducing, or alleviating skin damage, etc., caused by endogenous or exogenous skin factors, such as, for example, showing improvement in wrinkles, improvement in skin elasticity, or recovery from injuries, but without limitation to the same.

[0019] As used in this document, improving wrinkles, improving skin elasticity, and wound recovery can refer to all actions that increase the total amount of extracellular matrix factors, including promoting collagen synthesis, etc. Petition 870250090437, dated 03 / 10 / 2025, page 17 / 41 6 / 19

[0020] Although previous functional peptides have effective biological activity, they have had disadvantages, such as not being able to effectively enter the target tissue or cell due to the size of the peptide itself, or disappearing from the body in a short period of time due to their short half-life. In contrast, the cosmetic composition according to one example includes, as an active ingredient, a peptide consisting of 10 or fewer amino acids and, consequently, the penetration rate, etc., of the active ingredient into the skin is very excellent, and the skin condition can be effectively improved, for example, when applied topically to the skin.

[0021] According to one example, the peptide showed the effect of promoting the proliferation of human dermal fibroblasts; and increasing the expression of the selected dermal extracellular matrix among type 1 collagen, fibronectin or elastin. Thus, the peptide can be used as an active ingredient in a cosmetic composition to improve skin conditions.

[0022] The cosmetic composition may include a cosmetically effective amount of the peptide; and / or a cosmetically acceptable carrier, but without limitation to the same.

[0023] As used in this document, the term cosmetically effective quantity may refer to a quantity sufficient to achieve the skin condition-improving effect of the cosmetic composition.

[0024] The weight ratio between the peptide and a cosmetically acceptable carrier may be, for example, 500:1 to 1:500, for example, the weight ratio may be 450:1 to 1:450, 400:1 to 1:400, 350:1 to 1:350, 300:1 to 1:300, 250:1 to Petition 870250090437, dated 03 / 10 / 2025, page 18 / 41 7 / 19 1:250, 200:1 to 1:200, 150:1 to 1:150, 100:1 to 1:100, 80:1 to 1:80, 60:1 to 1:60, 40:1 to 1:40, 20:1 to 1:20, 10:1 to 1:10, 8:1 to 1:8, 6:1 to 1:6, 4:1 to 1:4 or 2:1 to 1:2, but without limitation to the same.

[0025] The cosmetic composition may be prepared in any formulation commonly prepared in the art, for example, it may be formulated as a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleanser, an oil, a powder base, an emulsion base, a wax base, and a spray, etc., but without limitation thereto. For example, the cosmetic composition may be prepared in the form of a softening lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, mask, spray, or powder.

[0026] If the cosmetic composition formulation is a paste, cream or gel, the carrier component may be an animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide, etc.

[0027] If the cosmetic composition formulation is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component and, for example, if the formulation is a spray, it may additionally include a propellant such as chlorofluorohydrocarbon, propane / butane or dimethyl ether.

[0028] If the cosmetic composition formulation is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component and may include, for example, water, ethanol, isopropanol, ethyl carbonate, Petition 870250090437, dated 03 / 10 / 2025, page 19 / 41 8 / 19 ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, aliphatic glycerol esters, polyethylene glycol or sorbitan fatty acid esters.

[0029] If the cosmetic composition formulation is a suspension, the carrier component may include a liquid diluent, such as water, ethanol or propylene glycol, a suspending agent, such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum meta-hydroxide, bentonite, agar or tragacanth, etc.

[0030] If the cosmetic composition formulation is a surfactant-containing cleanser, the carrier component may include 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, lanolin derivative, or ethoxylated glycerol fatty acid ester, etc.

[0031] The peptide can be incorporated into a nanosome or nanoparticle to further improve skin penetration or solve stability problems. For example, the nanosome can be prepared by a microfluidizer using lecithin as a feedstock and can be incorporated into lecithin particles. Any method of nanosome preparation can be used, provided it is known. The nanosome particle size is preferably 30 to 200 nm. If the nanosome particle size is smaller than 30 nm, skin penetration may be compromised. Petition 870250090437, dated 03 / 10 / 2025, page 20 / 41 9 / 19 progresses very rapidly, resulting in side effects on the skin, and if the size is larger than 200 nm, penetration into the skin may not be easy, hindering the achievement of the effect of using the nanosome structure.

[0032] The ingredients included in the cosmetic composition include, in addition to peptides and carrier components as active ingredients, components commonly used in cosmetic compositions and may include, for example, common adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances.

[0033] The peptide content as an active ingredient in the cosmetic composition may be appropriately selected without limitation depending on the product form, intended use, etc., and may be added, for example, from 0.01 to 15% by weight of the total weight of the cosmetic composition. In addition, for example, the cosmetic composition may include the peptide in an amount of 1.0% by weight to 3.0% by weight, preferably from 2.0% by weight to 3.0% by weight, based on the total weight.

[0034] Another aspect provides a method for improving the skin condition, which involves applying a cosmetic composition that includes a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient to a subject's skin.

[0035] In the description above of the cosmetic composition, the terms or elements mentioned are the same as those already mentioned.

[0036] As used in this document, the terms apply, administer, and apply are used interchangeably and may refer to causing at least the partial localization of a composition according to an example. Petition 870250090437, dated 03 / 10 / 2025, p. 21 / 41 10 / 19 in a desired location, or to place a composition according to an example in a subject via administration.

[0037] Another aspect provides a pharmaceutical composition to improve skin conditions, which includes, as an active ingredient, a peptide consisting of the amino acid sequence SEQ ID NO: 1.

[0038] In the description of the peptide above, the terms or elements mentioned are the same as those already mentioned.

[0039] According to one example, the peptide showed the effect of promoting the proliferation of human dermal fibroblasts; and increasing the expression of the selected dermal extracellular matrix among type 1 collagen, fibronectin or elastin. Thus, the peptide can be used as an active ingredient in a pharmaceutical composition to improve skin conditions.

[0040] The pharmaceutical composition may include a pharmaceutically effective amount of the peptide; and / or a pharmaceutically acceptable carrier, but without limitation to the same.

[0041] As used in this document, the term pharmaceutically effective quantity refers to an amount sufficient to achieve the efficacy of the pharmaceutical composition in the prevention or treatment of skin diseases.

[0042] Pharmaceutically acceptable carriers are commonly used in formulations and include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil, etc. Carriers and formulations Petition 870250090437, dated 03 / 10 / 2025, page 22 / 41 Pharmaceutically acceptable 11 / 19 compounds are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

[0043] The weight ratio between the peptide and a pharmaceutically acceptable carrier may be, for example, 500:1 to 1:500, for example, the weight ratio may be 450:1 to 1:450, 400:1 to 1:400, 350:1 to 1:350, 300:1 to 1:300, 250:1 to 1:250, 200:1 to 1:200, 150:1 to 1:150, 100:1 to 1:100, 80:1 to 1:80, 60:1 to 1:60, 40:1 to 1:40, 20:1 to 1:20, 10:1 to 1:10, 8:1 to 1:8, 6:1 to 1:6, 4:1 to 1:4 or 2:1 to 1:2, but without limitation to the same.

[0044] In addition to the above ingredients, the pharmaceutical composition may also include, but is not limited to, lubricants, humectants, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc.

[0045] The pharmaceutical composition can be administered orally or parenterally, preferably parenterally, and if administered parenterally, it can be administered by, but not limited to, intramuscular injection, intravenous injection, subcutaneous injection, intraperitoneal injection, topical administration, transdermal administration, etc.

[0046] The dosage of the pharmaceutical composition may be, but is not limited to, 0.0001 to 1000 μg (micrograms), 0.001 to 1000 μg, 0.01 to 1000 μg, 0.1 to 1000 μg or 1.0 to 1000 μg per day, and may be varied by factors such as formulation method, mode of administration, patient age, weight, sex, medical condition, diet, administration time, route of administration, excretion rate and sensitivity response. Petition 870250090437, dated 03 / 10 / 2025, page 23 / 41 12 / 19

[0047] The pharmaceutical composition may be formulated, with a pharmaceutically acceptable carrier and / or excipient, according to a method that can be easily practiced by a person skilled in the art to which the present disclosure pertains, and the composition may be prepared in a unit dose form or may be contained in a multidose container.

[0048] The formulation may be in the form of a solution, suspension or emulsion in an oily or aqueous medium, or in the form of an extract, powder, granule, tablet or capsule, and may additionally include a dispersant and / or stabilizer.

[0049] Another aspect provides a food composition to improve the condition of the skin, which includes, as an active ingredient, a peptide consisting of the amino acid sequence of SEQ ID NO: 1.

[0050] In the description of the peptide above, the terms or elements mentioned are the same as those already mentioned.

[0051] The peptide content as an active ingredient in the food composition can be appropriately selected without limitation depending on the food form, intended use, etc., and can be added, for example, from 0.01 to 15% by weight of the total weight of the food. Furthermore, for example, the composition of the healthy drink can be added at a rate of 0.02 to 10 g, preferably 0.3 to 1 g, based on 100 ml. Advantageous Effects of the Invention

[0052] According to one aspect, the peptide can be applied to improve skin conditions, including wrinkle reduction, improved skin elasticity, and wound healing, etc., by promoting fibroblast proliferation. Petition 870250090437, dated 03 / 10 / 2025, page 24 / 41 13 / 19 human dermal cells or increasing the expression of the dermal extracellular matrix, such as collagen, fibronectin, or elastin. Brief Description of the Drawings

[0053] Figure 1 shows the results of measuring the growth-promoting effect on fibroblast cells of a peptide consisting of the amino acid sequence SEQ ID NO: 1.

[0054] Figure 2 shows the results of measuring the effect of a peptide consisting of the amino acid sequence SEQ ID NO: 1 on increasing the expression of the skin extracellular matrix. Method for the Invention

[0055] Hereafter in this document, the present disclosure will be described in more detail with reference to examples. However, these examples are intended to illustrate the present disclosure by way of example, and the scope of the present disclosure is not limited to these examples. Example 1: Peptide Synthesis

[0056] A peptide with the amino acid sequence of SEQ ID NO: 1 listed in Table 1 below was synthesized using an automated peptide synthesizer (Milligen 9050, Millipore, USA), and the synthesized peptide was purified by reverse-phase C18 high-performance liquid chromatography (HPLC) (Waters Associates, USA). The column used was an ACQUITY UPLC BEH300 C18 (2.1 mm X 100 mm, 1.7 μm, Waters Co, USA). [Table 1] SEQ ID NO: Sequence (N terminal ^ C terminal) 1 AERRREKCRC Petition 870250090437, dated 03 / 10 / 2025, page 25 / 41 14 / 19 Example 2: Confirmation of Fibroblast Proliferation Effect

[0057] To confirm the effect of a peptide consisting of the amino acid sequence of SEQ ID NO: 1 in promoting fibroblast proliferation. Specifically, human dermal fibroblasts were seeded in a 96-well plate at a density of 5x10³ cells / well and cultured for 24 hours. After replacement with serum-free mesenchymal stem cells, the cells were cultured for 24 hours. The above peptide was treated at concentrations of 10 μM, 50 μM, or 100 μM, respectively, and incubated at 37 °C for 72 hours. As a positive control group, 50 nM of recombinant human FGF protein was treated. After completion of the culture, the culture supernatant was removed and the cells were fixed using ethanol. After washing with PBS, staining was performed by treatment with SRB solution. After washing with % acetic acid, the cells were observed under a microscope and decolorized by treatment with a 20 mM Tris solution.Cell viability was measured by measuring absorbance at a wavelength of 560 nm using a spectrophotometer (SpectraMax iD3, Molecular Devices (USA, CA)).

[0058] The results are illustrated in Figure 1. From the results in Figure 1, it can be confirmed that proliferation was induced in a concentration-dependent manner in the peptide treatment group, increasing up to 1.62 times. Example 3: Confirmation of Effect to Increase Extracellular Matrix Expression

[0059] To confirm the effect of a peptide consisting of the amino acid sequence SEQ ID NO: 1 on increasing Petition 870250090437, dated 03 / 10 / 2025, page 26 / 41 15 / 19 of the expression of the dermal extracellular matrix. Specifically, human dermal fibroblasts were seeded in a 6-well plate at a density of 3x10⁵ cells / well and cultured for 24 hours. After replacement with serum-free mesenchymal stem cells, the cells were cultured for 24 hours. The peptide was treated at concentrations of 10 μM, 50 μM, or 100 μM, respectively, and incubated at 37 °C for 48 hours. Recombinant human FGF protein was treated at 100 nM. After completion of the culture, the culture supernatant was removed and fixed with 4% paraformaldehyde for 30 minutes. After washing with PBS, the cells reacted with 0.5% Triton X-100 for 15 minutes. After reacting with 3% BSA for 1 hour, the primary antibodies against type 1 collagen, fibronectin, and elastin were diluted 1:100 and reacted overnight at 4°C. The secondary antibody—FITC—was diluted 1:500 and reacted at room temperature for 2 hours, followed by DAPI staining and mounting.The expression images of each marker were observed using a confocal microscope (Leica, Germany). The intensity of the green fluorescence was measured using ImageJ.

[0060] The results are illustrated in Figure 2. From the results in Figure 2, it can be confirmed that the expression of type 1 collagen, fibronectin, and elastin, which are dermal extracellular matrices, increases when the peptide is treated. For collagen, it was confirmed that expression increased up to 1.32 times compared to the control group, for fibronectin up to 1.38 times, and for elastin up to 2 times. Petition 870250090437, dated 03 / 10 / 2025, page 27 / 41 16 / 19 Example Formulation 1. Preparation of Peptide Nanosomes

[0061] 50 mg of the peptide from Example 1 above were dissolved in 500 ml of distilled water by sufficient stirring. The composite solution was mixed with 5 g of lecithin, 0.3 ml of sodium oleate, 50 ml of ethanol and a small amount of oil, and the total quantity was adjusted to 1 l with distilled water, and the mixture was then emulsified using a high-pressure conveyor belt to produce peptide nanosomes with a size of approximately 100 nm. Example of Formulation 2. Soothing Lotion

[0065] An essence that includes the peptide according to an example and that consists of the following composition, was prepared using a method known in the art. [Table 5] Component Content (% by weight) Peptide 2.0 Glycerin 10 1,3-butylene glycol 5 PEG 1500 2 Petition 870250090437, dated 03 / 10 / 2025, pages 30 / 41 19 / 19 Allantoin 0.1 DL-Panthenol 0.3 EDTA-2Na 0.02 Hydroxyethylcellulose 0.1 Sodium hyaluronate 8 Carboxvinyl polymer 0.2 Triethanolamine 0.18 Octyldodeceth-16 0.4 Ethanol 6 Preservatives, colorants As needed Fragrance As needed Purified water Remaining Total 100

[0066] The preceding description of the present disclosure is for illustrative purposes only, and anyone of ordinary skill in the art to which the present disclosure pertains will understand that it can be easily adapted to other specific forms without altering the essential technical ideas or features of the present disclosure. Therefore, the examples described above should be understood in all respects as illustrative and not restrictive. Petition 870250090437, dated 03 / 10 / 2025, pages 31 / 41

Claims

1 / 2 CLAIMS 1Peptide characterized by consisting of the amino acid sequence of SEQ ID NO:

1.

2. Peptide, according to claim 1, characterized in that an N-terminal of the peptide is linked to any protective group selected from the group consisting of an acetyl group, a fluoroylmethoxycarbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, a butoxycarbonyl group, an allyloxycarbonyl group and polyethylene glycol (PEG).

3. Peptide, according to claim 1, characterized in that a C-terminal of the peptide is linked to any protecting group selected from the group consisting of an amino group (-NH2), a tertiary alkyl group and an azide group (-NHNH2).

4. Peptide, according to claim 1, characterized in that the peptide exhibits one or more features selected from the following: (a) promotion of human dermal fibroblast proliferation; and (b) increased expression of a skin extracellular matrix selected from type 1 collagen, fibronectin, or elastin.

5. Cosmetic composition for improving skin condition, characterized by comprising, as an active ingredient, a peptide, as defined in any one of claims 1 to 4.

6. Composition, according to claim 5, characterized by improving the condition of the skin, improving wrinkles, improving skin elasticity or healing wounds. Petition 870250090437, dated 03 / 10 / 2025, page 32 / 41 2 / 2