Skin-improving cosmetic composition

Abstract

The present disclosure relates to a cosmetic composition for improving skin conditions, which contains a peptide for improving skin conditions. The peptide for improving skin conditions of the present disclosure or a derivative thereof exhibits a significantly excellent effect of improving skin conditions. The peptide or a derivative thereof can be used as an active ingredient in a functional cosmetic composition or a topical skin preparation composition that can be used on the skin.

Description

[Technical Field]

[0001] This application claims priority based on Korean Application No. 10-2022-0172978 filed on December 12, 2022, and Korean Application No. 10-2023-0100598 filed on August 1, 2023, and the contents disclosed in the specifications and drawings of those applications are incorporated herein in their entirety.

[0002] The present disclosure relates to a cosmetic composition for improving skin conditions, which contains a peptide for improving skin conditions. [Background technology]

[0003] Skin wrinkles are generally caused by strong muscle contractions or by maintaining a posture that causes strong muscle contractions for a long period of time. Today, wrinkles that appear when making facial expressions (expression lines) and wrinkles associated with aging are often treated with Botox (botulinum toxin type A). Botox improves skin wrinkles by paralyzing the muscles around the eyes and forehead. However, Botox has drawbacks, such as limited use because it must be administered by a doctor via subcutaneous injection, high cost, and high toxicity. Furthermore, the effects of Botox only last for about three to six months, requiring repeated treatments.

[0004] The mechanism of action of Botox is to paralyze muscles by selectively blocking the release of acetylcholine at the neuromuscular synapse. This is achieved by cleaving a protein called SNAP-25. The N-terminal amino acid sequence of SNAP-25 (H-Glu-Glu-Met-Gln-Arg-Arg-NH2) also blocks Ca release at the synapse. ++It induces muscle relaxation by inhibiting the secretion of α-dependent neurotransmitters. The topically applicable compound developed from this, Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, marketed under the trade name Argirelline™, is 5,000 times weaker than Botox, making it easy to administer and virtually non-toxic. However, its muscle relaxant effect is very weak and inconsistent, its wrinkle-reducing effect is unsatisfactory, and its proteolytic stability is insufficient.

[0005] Small peptides or peptide compounds are formed by enzymatic degradation within the skin's extracellular matrix. These peptides or peptide compounds, called "matrikines," possess important signaling functions and can regulate cellular activity. Therefore, various peptides or peptide compounds obtained by extraction or synthesis have been proposed as active ingredients in cosmetics. Examples include the lipid peptides Pal-KTTKS and Pal-GHK / Pal-GQPR mixtures, which are commercially available under the trade name MATRIXYL™ and correspond to collagen fragments. In vitro experiments have measured their collagen synthesis stimulating effects, and in vivo experiments have measured improvements in skin firmness, elasticity, density, thickness, and microrelief (wrinkles and fine lines). Novel peptide compounds that can correct skin defects and improve skin condition are promising active ingredients in the cosmetics industry.

[0006] Drug delivery devices that transdermal delivery are convenient and are used in a variety of fields and forms. While drugs that pass through the skin are primarily intended to be delivered to the systemic circulatory system via the skin, they are also used to directly deliver active ingredients to the skin's own organs, such as in atopic dermatitis treatments and whitening or anti-wrinkle cosmetics.

[0007] Recently, peptides have been developed that have a similar effect to Botox in the skin, but in a non-paralyzing manner, reducing muscle contractions without the side effects of toxins. These peptides reduce the formation of wrinkles by temporarily blocking the secretion of neurotransmitters such as acetylcholine, which are responsible for muscle cell contraction. However, there are limitations to their use, such as the risk of side effects from excessive use of these peptides and their limited effectiveness in areas with high nerve density. Summary of the Invention [Problem to be solved by the invention]

[0008] The problem to be solved by the present disclosure is to overcome the drawbacks of conventional skin-improving peptides and provide a composition that has excellent skin-improving effects and is safe for the human body. [Means for solving the problem]

[0009] The inventors of the present invention have worked to improve skin conditions by addressing the problems associated with conventionally used peptides for improving skin conditions, such as side effects and precautions for use, and have devoted themselves to developing compositions that are safe for human use and have excellent skin condition-improving effects without drawbacks such as weak effects. As a result, the inventors have discovered a specific peptide sequence that exhibits skin condition-improving effects. The inventors have surprisingly found that applying a peptide consisting of a specific amino acid sequence whose effectiveness has been stabilized by mutation and sequence optimization to the skin significantly improves skin condition, leading to the completion of the present invention.

[0010] The present disclosure provides a peptide or derivative thereof comprising the amino acid sequence of Formula I: The peptide or derivative thereof of the present disclosure can be used to improve the condition of the skin, preferably the appearance of the skin. <Chemical formula I> X1-X2-X3-(SSCF)-Y1-Y2-Y3

[0011] In the amino acid sequence of Formula I, X1 can be K or absent, X2 can be G or absent, X3 can be R or absent, Y1 can be V or absent, Y2 can be D or absent, and Y3 can be C or absent.

[0012] In one embodiment of the present disclosure, the amino acid sequence of Chemical Formula I may preferably include at least one amino acid sequence of X1 to X3 and Y1 to Y3.

[0013] In one embodiment of the present disclosure, the amino acid sequence of Formula I can be the amino acid sequence of any one of the following SEQ ID NOs: Sequence number 1: KGRSSCFVDC SEQ ID NO: 2: KGRSSCFVD SEQ ID NO: 3: KGRSSCF SEQ ID NO: 4: KGRSSCFV SEQ ID NO: 5: RSSCFVDC SEQ ID NO: 6: SSCFVDC SEQ ID NO: 7: GRSSCFVD SEQ ID NO: 8: RSSCFVD SEQ ID NO: 9: SSCFVD SEQ ID NO: 10: KGSSCFVDC SEQ ID NO: 11: KGRSSCFDC SEQ ID NO: 12: KGRSSCFVC SEQ ID NO: 13: RSSCF

[0014] The present disclosure provides a cosmetic, topical skin preparation, or pharmaceutical composition for improving skin conditions, which comprises a peptide or a derivative thereof comprising an amino acid sequence of chemical formula I selected from the amino acid sequences of any one of SEQ ID NOs: 1 to 13. Preferably, the composition for improving skin conditions may be a cosmetic composition.

[0015] In one embodiment of the present disclosure, the peptide or derivative thereof may comprise an amino acid sequence having at least 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of Formula I. Preferably, the peptide or derivative thereof may comprise an amino acid sequence having 80% or more sequence identity to the amino acid sequence of Formula I.

[0016] In one embodiment of the present disclosure, the peptide or derivative thereof may comprise an amino acid sequence having at least 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 1 to 13. Preferably, the peptide or derivative thereof may comprise an amino acid sequence having 80% or more sequence identity to the amino acid sequence of any one of SEQ ID NOs: 1 to 13.

[0017] In one embodiment of the present disclosure, the peptide or its derivative comprising the amino acid sequence of Chemical Formula I may be contained in an amount of 0.0001 to 50 wt %, preferably 0.001 to 30 wt %, more preferably 0.001 to 1 wt %, based on the total weight of the composition. When the content of the peptide or its derivative is within the above range, the skin condition improving effect may be more excellent.

[0018] In one embodiment of the present disclosure, the peptide comprising the amino acid sequence of formula I or a derivative thereof may be used to improve skin conditions, preferably for treating skin wrinkles, skin elasticity, or skin sebum.

[0019] In one embodiment of the present disclosure, the term "peptide" refers to both natural and synthetic peptides containing 15 or fewer amino acids, and may include naturally occurring or commercially available peptides, including derivatives, isomers, or complexes with metal ions thereof.

[0020] In one embodiment of the present disclosure, the peptide comprising the amino acid sequence of Formula I can be a pure peptide, an L-isomer, a D-isomer, or a mixture thereof, preferably the naturally occurring L-isomer.

[0021] In one embodiment of the present disclosure, the peptide comprising the amino acid sequence of formula I may be in the form of a salt, preferably any salt commonly used in cosmetic or pharmaceutical compositions, such as a hydrochloride or acetate salt.

[0022] In one embodiment of the present disclosure, a derivative of a peptide comprising the amino acid sequence of Formula I refers to a peptide in which a chemical functional group is modified or added, but the carbon skeleton remains unchanged. The derivative includes a peptide chemically modified at the N-terminus, C-terminus, or the like, or a peptide modified by the addition, substitution, or deletion of an amino acid. The peptide derivative may be a lipophilic derivative, such as a palmitoyl derivative. The peptide derivative may also be a derivative in which a dansyl group is attached. The peptide derivative may also be a derivative in which an acetyl group is attached.

[0023] In one embodiment of the present disclosure, the peptide can exhibit a skin condition-improving effect even when it contains amino acids having a reverse sequence of the amino acids of Chemical Formula I. Preferably, the amino acid sequence having the reverse sequence may be any one of the amino acid sequences of SEQ ID NOs: 14 to 16 below. SEQ ID NO: 14: CDVFCSSRGK SEQ ID NO: 15: DVFCSSRGK SEQ ID NO: 16: FCSSRGK

[0024] In one embodiment of the present disclosure, the peptides comprising the amino acid sequence of Formula I include analogs with modified and / or added chemical functional groups and additional changes to the carbon backbone. Furthermore, the peptides may include peptides with sequences that differ from the wild-type amino acid sequence by one or more amino acid groups. Amino acid exchanges in proteins and polypeptides that do not change the overall activity of the molecule are known in the art. Common exchanges include exchanges between amino acid residues Ala / Ser, Val / Ile, Asp / Glu, Thr / Ser, Ala / Gly, Ala / Thr, Ser / Asn, Ala / Val, Ser / Gly, Thy / Phe, Ala / Pro, Lys / Arg, Asp / Asn, Leu / Ile, Leu / Val, Ala / Glu, or Asp / Gly. The peptides may also include peptides with increased structural stability or activity, such as against heat or pH, due to mutations or modifications in the amino acid sequence.

[0025] The peptides may be produced by conventional chemical peptide synthesis methods, or by amplifying a gene encoding the peptide by PCR or synthesizing it by known methods, and then cloning it into an expression vector and expressing it. The peptides also include complexes with metal ions, such as copper, zinc, manganese, and magnesium. When chemically synthesizing the peptides using machinery, the peptides can be synthesized using an automated peptide synthesizer using convergent solution phase synthesis or solid phase peptide synthesis.

[0026] The present disclosure further provides a polynucleotide encoding a peptide or derivative thereof comprising the amino acid sequence of Formula I. The polynucleotide may be mutated by substitution, deletion, insertion, or a combination thereof of one or more bases. When the nucleotide sequence is produced by chemical synthesis, synthesis methods well known in the art, such as those described in Engels and Uhlmann, Angew., Chem Int Ed Engl., 37:73-127, 1988, can be used. Synthesis can also be performed by triester, phosphite, phosphoramidite, and H-phosphate methods, PCR and other autoprimer methods, oligonucleotide synthesis on a solid support, etc.

[0027] The present disclosure provides polynucleotides of SEQ ID NOs: 17 to 19 that encode the amino acid sequence of any one of SEQ ID NOs: 1 to 3. The polynucleotide of SEQ ID NO: 17 encodes the amino acid sequence of SEQ ID NO: 1, the polynucleotide of SEQ ID NO: 18 encodes the amino acid sequence of SEQ ID NO: 2, and the polynucleotide of SEQ ID NO: 19 encodes the amino acid sequence of SEQ ID NO: 3. -SEQ ID NO:17:AAA GGC CGC AGC AGC TGC TTT GTG GAT TGC -SEQ ID NO:18:AAA GGC CGC AGC AGC TGC TTT GTG GAT -SEQ ID NO:19:AAA GGC CGC AGC AGC TGC TTT

[0028] The present disclosure also provides an expression vector containing the polynucleotide, a transformant containing the expression vector, and a method for producing the skin condition-improving peptide or a derivative thereof using the transformant.

[0029] In this disclosure, the term "expression vector" refers to a recombinant vector capable of expressing a target peptide in a host cell, a genetic construct containing the necessary regulatory elements operably linked to express a gene insert. The expression vector contains expression regulatory elements such as an initiation codon, a termination codon, a promoter, and an operator. The initiation codon and termination codon are generally considered to be part of the nucleotide sequence encoding a polypeptide, and must function in an individual when the genetic construct is administered, and must be in frame with the coding sequence. The promoter may be constitutive or inducible.

[0030] The expression vector may contain a signal sequence for polypeptide export to facilitate isolation of the protein from the cell culture medium. A specific initiation signal may be required for efficient translation of the inserted nucleic acid sequence. The signal includes the ATG initiation codon and adjacent sequences. In some cases, it may be necessary to provide exogenous translational control signals, which may include the ATG initiation codon. These exogenous translational control signals and initiation codons may be of various natural and synthetic origins. Expression efficiency may be improved by the introduction of appropriate transcriptional or translational enhancing factors.

[0031] The expression vector may further include a protein tag that can be removed using an endopeptidase to facilitate detection of the peptide or its derivative. The term "tag" refers to a molecule that exhibits a quantifiable activity or characteristic, and may be a fluorescent molecule, including a chemiluminescent substance such as fluorescein, a polypeptide fluorescent substance such as fluorescent protein (GFP) or related proteins, or an epitope tag, such as a Myc tag, Flag tag, histidine tag (His tag), leucine tag, IgG tag, or streptavidin tag. When an epitope tag is used, the epitope tag may be a peptide tag, preferably consisting of six or more amino acid residues, more preferably consisting of 8 to 50 amino acid residues.

[0032] In the present disclosure, the expression vector may comprise a nucleotide sequence encoding the peptide or a derivative thereof. The expression vector is not particularly limited as long as it is capable of producing the peptide or a derivative thereof. Preferably, plasmid DNA or phage DNA can be used, and more preferably, commercially developed plasmids (pUC18, pBAD, pIDTSAMRT-AMP, etc.), Escherichia coli-derived plasmids (pYG601BR322, pBR325, pUC118, pUC119, etc.), Bacillus subtilis-derived plasmids (pUB110, pTP5, etc.), yeast-derived plasmids (YEp13, YEp24, YCp50, etc.), phage DNA (Charon4A, Charon21A, EMBL3, EMBL4, λgt10, λgt11, λZAP, etc.), animal virus vectors (retrovirus, adenovirus, vaccinia virus, etc.), insect virus vectors (baculovirus, etc.), etc. can be used. The expression vectors vary in the amount of protein expressed depending on the host cell, so it is preferable to select and use the host cell that is most suitable for the purpose.

[0033] In the present disclosure, the transformant can be prepared by introducing the expression vector into a host and transforming it. The transformant can be used to express the polynucleotide contained in the expression vector to produce the peptide or its derivative for improving skin conditions. The transformation can be performed by various methods, including, but not limited to, CaCl precipitation, the Hanahan method in which the efficiency of CaCl precipitation is increased by using a reducing agent, dimethyl sulfoxide (DMSO), electroporation, calcium phosphate precipitation, protoplast fusion, agitation using silicon carbide fibers, Agrobacterium-mediated transformation, polyethylene glycol (PEG)-mediated transformation, dextran sulfate-mediated transformation, lipofectamine-mediated transformation, and desiccation / repression-mediated transformation. In addition, hosts used to prepare the transformants include, but are not limited to, bacterial cells such as Escherichia coli (E. coli), Streptomyces, and Salmonella typhimurium; yeast cells such as Saccharomyces cerevisiae and Schizosaccharomyces pombe; fungal cells such as Pichia pastoris; insect cells such as Drosophila and Armyworm Sf9 cells; animal cells such as CHO, COS, NSO, 293, and Bowes melanoma cells; or plant cells.

[0034] The transformant can also be used in a method for producing the peptide or a derivative thereof. Specifically, the method for producing the peptide or a derivative thereof of the present disclosure may include: (a) culturing the transformant to obtain a culture; and (b) recovering the peptide or a derivative thereof of the present disclosure from the culture.

[0035] In the present disclosure, "cultivation" refers to a method of growing a microorganism under appropriate artificially controlled environmental conditions. The method of culturing the transformant can be carried out using a method well known in the art. Specifically, the culture can be carried out by a batch process or a continuous culture using a fed batch or repeated fed batch process.

[0036] The medium used for the culture must meet the requirements of the specific strain in an appropriate manner by adjusting the temperature, pH, etc. under aerobic conditions in a standard medium containing appropriate carbon sources, nitrogen sources, amino acids, vitamins, etc. Usable carbon sources include a mixed sugar of glucose and xylose as the main carbon source, as well as sugars and carbohydrates such as sucrose, lactose, fructose, maltose, starch, or cellulose; oils and fats such as soybean oil, sunflower oil, castor oil, or coconut oil; fatty acids such as palmitic acid, stearic acid, and linoleic acid; glycerol; alcohols such as ethanol; and organic acids such as acetic acid. These substances can be used individually or as a mixture. Usable nitrogen sources include inorganic nitrogen sources such as ammonia, ammonium sulfate, ammonium chloride, ammonium acetate, ammonium phosphate, ammonium carbonate, and ammonium nitrate; and organic nitrogen sources such as amino acids (e.g., glutamic acid, methionine, glutamine), peptone, NZ-amine, meat extract, yeast extract, malt extract, corn steep liquor, casein hydrolysate, fish or its hydrolyzed products, and defatted soybean cake or its hydrolyzed products. These nitrogen sources can be used alone or in combination. The medium may contain potassium monophosphate, potassium diphosphate, and the corresponding sodium salts as phosphorus sources. Inorganic compounds such as sodium chloride, calcium chloride, iron chloride, magnesium sulfate, iron sulfate, manganese sulfate, and calcium carbonate may also be used. Essential growth substances such as other amino acids and vitamins may also be used.

[0037] Furthermore, precursors suitable for the culture medium may be used in the culture medium. The raw materials may be added to the culture by an appropriate method during the culture process, such as batch, fed-batch, or continuous methods, but are not limited to these. The pH of the culture may be adjusted using a basic compound such as sodium hydroxide, potassium hydroxide, or ammonia, or an acidic compound such as phosphoric acid or sulfuric acid, in an appropriate manner. Foam formation may also be suppressed using an antifoaming agent such as a fatty acid polyglycol ester. To maintain an aerobic state, oxygen or an oxygen-containing gas (e.g., air) is injected into the culture medium. The culture temperature is typically 27°C to 37°C, preferably 30°C to 35°C. The culture may be continued until the maximum amount of the peptide or its derivative is obtained; for this purpose, the culture may be typically performed for 10 to 100 hours.

[0038] Furthermore, the step of recovering the peptide or its derivative from the culture can be carried out by methods known in the art, including, but not limited to, centrifugation, filtration, extraction, spraying, drying, evaporation, precipitation, crystallization, electrophoresis, differential dissolution (e.g., ammonium sulfate precipitation), or chromatography (e.g., ion exchange, affinity, hydrophobic, and size exclusion).

[0039] In one aspect of the present disclosure, the topical skin preparation refers to a solid, semi-solid, or liquid topical preparation that can be easily applied to the skin by mixing an active ingredient with various bases such as oils, petrolatum, lanolin, glycerol, etc. The topical dosage form is not particularly limited, but is preferably a powder, gel, ointment, cream, liquid, or aerosol dosage form.

[0040] In one embodiment of the present disclosure, the pharmaceutical composition may further comprise, in addition to the peptide or derivative thereof consisting of the amino acid sequence of Formula I, a drug to be introduced into the body through the skin or delivered (transmitted) to an organ in the skin itself. The pharmaceutical composition may further comprise a suitable carrier, excipient, or diluent commonly used in the art.

[0041] The pharmaceutical composition may be in any one of the following dosage forms: tablets, pills, powders, granules, capsules, suspensions, oral solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories, and may be in various oral or parenteral dosage forms. When formulated, it is prepared using commonly used diluents or excipients, such as fillers, extenders, binders, wetting agents, disintegrants, or surfactants. Solid formulations for oral administration include tablets, pills, powders, granules, or capsules, and are prepared by mixing one or more compounds with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, or gelatin. In addition to simple excipients, lubricants, such as magnesium stearate and talc, are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, syrups, etc., which may contain various excipients such as wetting agents, sweeteners, flavorings, preservatives, etc. in addition to commonly used simple diluents such as water and liquid paraffin. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, etc. Non-aqueous solvents and suspensions that can be used include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.

[0042] In one embodiment of the present disclosure, the pharmaceutical composition can be administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" refers to an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to any medical treatment. The effective dose level can be determined based on factors including the type and severity of the individual, age, sex, type of disease, drug activity, drug sensitivity, administration time, administration route and excretion rate, treatment duration, concomitant medications, and other factors well known in the medical field. The composition of the present disclosure can be administered as an individual therapeutic agent, in combination with other therapeutic agents, or sequentially or simultaneously with conventional therapeutic agents. It can be administered in single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that provides maximum efficacy at the minimum dose without side effects, which can be easily determined by one skilled in the art. The preferred dosage of the composition of the present disclosure varies depending on the patient's condition and weight, the severity of the disease, the drug form, the route and duration of administration, and the appropriate total daily dose can be determined by the treating physician within the scope of sound medical judgment. Generally, however, the dosage is 0.001 to 1000 mg / kg, preferably 0.05 to 200 mg / kg, and more preferably 0.1 to 100 mg / kg, administered once a day or in divided doses. The subject of administration of the composition is not particularly limited. For example, the composition can be administered to any individual, including non-human animals such as monkeys, dogs, cats, rabbits, guinea pigs, rats, mice, cattle, sheep, pigs, and goats, as well as humans. The administration method can be any method commonly used in the art, without limitation. For example, transdermal administration, such as topical application, can be used, but is not limited thereto.

[0043] In one embodiment of the present disclosure, the cosmetic composition may comprise conventional adjuvants, such as fatty substances, organic solvents, solubilizers, thickeners, gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or non-ionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, blocking agents, moisturizing agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, or lipid vesicles, as well as adjuvants commonly used in the cosmetic or dermatological fields.

[0044] In one embodiment of the present disclosure, the cosmetic composition may be a functional cosmetic. Functional cosmetics are products with specialized functionality that incorporate specialized therapeutic functions of pharmaceuticals and emphasize physiologically active efficacy and effects, including products that help whiten the skin, reduce wrinkles, and tan or protect the skin from UV rays. The functional cosmetics may exhibit skin-improving effects through, for example, promoting the synthesis of functional substances such as collagen, elastin, laminin, or HAS2. The dosage form is not particularly limited, and may be prepared in the form of, for example, a solution, emulsion, suspension, paste, cream, lotion, gel, powder, spray, surfactant-containing cleanser, oil, soap, liquid cleanser, bath additive, foundation, makeup base, essence, toner, foam, pack, softening lotion, sunscreen cream, or sun oil, and preferably, it may be prepared in the form of an ointment for external use on the skin, softening lotion, nourishing lotion, nourishing cream, massage cream, essence, pack, emulsion, or oil gel, and the carrier used may be selected depending on the dosage form of the cosmetic.

[0045] In one embodiment of the present disclosure, there is provided a method for improving skin condition, comprising transdermally administering to a subject in need of improvement of skin condition an effective amount of a composition comprising the peptide or a derivative thereof having the amino acid sequence of Formula I. Preferably, the improvement of skin condition can be improvement of skin wrinkles or improvement of skin lipid secretion.

[0046] In one embodiment of the present disclosure, the method for improving skin condition may include the steps of: preparing a subject in need of improvement in skin wrinkles or skin lipid secretion; transdermally administering 1 ml of the composition for 4 weeks; and improving the skin condition of the subject. Preferably, the improvement in skin condition may be improvement in skin wrinkles or skin lipid secretion.

[0047] In one embodiment of the present disclosure, the composition for improving skin conditions may contain a physiologically acceptable medium. Such a physiologically acceptable medium refers to, but is not limited to, an aqueous or hydroalcoholic solution, a water-in-oil emulsion, an oil-in-water emulsion, a microemulsion, an aqueous gel, an anhydrous gel, a serum, a vesicular dispersion, or a powder. The term "physiologically acceptable" means that the composition is suitable for topical or transdermal application when it comes into contact with the mucous membranes, appendages (nails, hair), scalp, and skin of mammals, particularly humans. The composition may be ingestible or injectable into the skin without toxicity, incompatibility, instability, allergic reactions, or other risks. Such a "physiologically acceptable medium" may be a common excipient of the composition.

[0048] In one aspect of the present disclosure, the peptide or derivative thereof can be dissolved in a lipophilic or hydrophilic matrix, optionally with the use of a solubilizing agent, depending on the application. The peptides can be combined at effective concentrations with other active ingredients that can act synergistically or additively to reinforce and achieve the desired effects described in this disclosure, such as formulations of: anti-aging, anti-fine lines and anti-wrinkles, whitening, pro-pigmenting, hydrating, moisturizing, slimming, exfoliating, anti-acne, anti-redness, anti-inflammatory, antioxidant / radical scavenger, complexion brightener, anti-glycation, volumizing, restructuring, anti-carbonylation, skin soothing, anti-hair regrowth, acting on the stratum corneum, skin-epidermal junction, heat shock protein (HSP) production, firmness, elasticity and skin tone, hair growth (eyelashes and eyebrows), eye contour (dark circles and bags under the eyes), promoting blood circulation, other peptides, or vitamins. These active ingredients are derived from plant materials such as traditional plant extracts or products of plant cell culture or fermentation.

[0049] In one embodiment of the present disclosure, the composition may be provided in any conventional form or carrier in the form of a solution, dispersion, emulsion, paste, or powder. The composition may also be applied as a premix in a vehicle or vector, such as in the form of macro-, micro-, or nano-capsules; macro-, micro-, or nano-spheres; liposomes, oleosomes, or chylomicrons; macro-, micro-, or nano-sponges; or micro- or nano-emulsions; or absorbed onto organic polymer powders, talc, bentonite, spores, or exosporiums, and other inorganic or organic supports.

[0050] In one embodiment of the present disclosure, the composition can be used for skin protection or makeup applications on the face, body, hair, and other body hair. The peptide or its derivative can be delivered topically by contacting the skin with fabrics, natural or synthetic fibers, wool, clothing materials, handkerchiefs, etc.

[0051] In one embodiment of the present disclosure, the composition may contain, in addition to the peptide or derivative thereof, additional active agents, including, but not limited to, a wide range of cosmetic and pharmaceutical ingredients commonly used in the skin care industry, as listed in the CTFA (International Cosmetic Ingredient Dictionary & Handbook (15th Edition, 2014) published by the Personal Care Products Council, ex-the Cosmetic, Toiletry, and Fragrance Association, Inc., Washington, DC). The additional active ingredients include betaine, glycerol, ActimoistBio2™ (active organics) (Active organics), AquaCacteen™ (Mibelle AG Cosmetics), Aquaphyline™ (Silab), AquaregulK™ (Solabia), Carciline™ (Greentech), Codiavelane™ (Biotech Marine), Dermaflux™ (Arch Chemicals, Inc.), Hydra'Flow™ (Sochibo), Hydromoist L (Hydromoist L™ (Symrise), RenovHyal™ (Soliance), Seamoss™ (Biotech Marine), Argireline™ (Lipotec's trade name for acetyl hexapeptide-3), extract of Acmella oleracea known as spilanthol or the trade name Gatuline Expression™, Boswellia serrata known as Boswellin™,serrata extract, Deepaline PVB™ (Seppic), Syn-AKE™ (Pentapharm), Ameliox™, Bioxilift™ (Silab), PhytoCellTec™, Argan (Mibelle), Papilactyl D™ (Silab), Preventhelia™ (Lipotec), Subliskin™ (Sederma), Venuceane™ (Sederma), Moist 24™ (Sederma), Vegesome Moist 24 24) (Trademark) (Sederma), Essenskin (Trademark) (Sederma), Juvinity (Trademark) (Sederma), Revidrat (Trademark) (Sederma), Resistem (Trademark) (Sederma), Chronodyn (Trademark) (Sederma), Kombuchka (Trademark) (Sederma), Chromocare (Trademark) (Sederma), Calmosensine (Trademark) (Sederma), Glycokin factor S S)™ (Sederma), Biobustyl™ (Sederma), Idealift™ (Sederma), Ceramide 2™, Ceramide A™ et. al., Ceramide HO3™ (Sederma), Legance™ (Sederma), Intenslim™ (Sederma), Prodizia™ (Sederma), Beautifeye™ (Sederma), NG-Shea Butter UnsaponifiablesBeurre de Karite (Natural Grade) (Sederma), Zingerslim™ (Sederma), Meiritage™ (Sederma), Senestem™ (Sederma), Sebuless™ (Sederma), Majestem™ (Sederma), Apiscalp™ (Sederma), Rubistem™ (Sederma), or mixtures thereof. The additional active substances also include ivy, in particular English ivy (Hedera Helix), manchuria (Bupleurum chinensis), Bupleurum falcatum, arnica (Arnica Montana L), rosemary (Rosmarinus officinalis N), marigold (Calendula officinalis), sage (Salvia officinalis L), ginseng (Panax ginseng), ginkgo biloba, St. John's wort (Hyperycum perforatum), butcher's broom (Ruscus aculeatus L), European meadowsweet (European Meadowsweet (Filipendula ulmaria L), big-flowered Jarva tea (Orthosiphon stamineus benth), algae (Bladderwrack (Fucus Vesiculosus)), birch (Betula alba), green tea, cola nuts (Cola nipida), horse chestnut, bamboo, Centella asiaticaasiatica, heather, fucus, willow, mouse-ear, escin, cangzhu, chrysanthellum indicum, plants of the Armeniacea genus, Atractylodis Platicodon, Sinnomenum, Pharbitidis, Flemingia, Coleus, where Coleus is, for example, C. forskohlii, C. blumei, C. esquiroli, esquirolii, C. scutellaroides, C. xanthantu and C. Barbatus, an extract of C. barbatus being, for example, an extract of the root of Coleus barbatus, Ballote, Guioa, Davallia, Terminalia, Barringtonia, Trema, antirobia, cecropia, argania, Dioscoreae, where Dioscoreae is, for example, an extract of Dioscorea opposita or Mexican visnaga, Siegesbeckia, where Siegesbeckia is in particular Siegesbeckia orientalis extract, vegetable extracts of the Ericaceae family, in particular bilberry (Vaccinium angustifollium) extract or bearberry (Arctostaphylos uva ursi), aloe vera, extracts of plants containing sterols (e.g., phytosterols), Manjistha (Rubia), plants of the genus Rubia, in particular Rubia cordifoliaCordifolia), and Guggal (extracted from Commiphora, especially Commiphora Mukul), kola extract, chamomile, red clover, kava (Piper methysticum) extract (Kava Kava®, SEDERMA), Bacopa monieri extract (Bacocalmine®, SEDERMA), sea whip extract, Glycyrrhiza glabra extract, mulberry extract, Melaleuca (tea tree) extract, Larrea dibarricatum extract, divaricata, Rabdosia rubescens, Euglena gracilis, Fibraurea recisa Hirudinea, Chaparral Sorghum extract, Sunflower extract, Enantia chlorantha, Mitracarpe of Spermacocea genus, Buchu barosma, Henna L (Lawsonia inermis L), Capillus-veneris L (Adiantium Capillus-veneris L), Celandine (Chelidonium majus), Luffa cylindrica, Japanese Mandarin (Citrus reticulata Blanco var. unshiu), Tea plant (Camelia sinensis), Imperata cylindrica, Horned poppy (Glaucium flavum), Cypress (Cupressus sempervirens), Solomon's seal (Polygonatum multiflorum), Lovely Hemsleya (lovelyhemsleya, Elderberry (Sambucus Nigra), Lima bean (Phaseolus lunatus), Centaurium japonica (Centaurium), Duckweed (Macrocystis Pyrifera), Turnera diffusa (Turnera Diffusa), Flower sedge (Anemarrhena asphodeloides), Portulaca pilosa, Hops (Humulus lupulus), Arabica coffee (Coffea Extracts of plants such as Albizzia julibrissin, Albizzia arabica, Ilex paraguariensis, Globularia cordifolia, Albizzia julibrissin, Oxydendron arboretum, Zingimber zerumbet Smith, Astragalus membranaceus, Atractylodes macrocephalae, Plantago lanceolata, Leontopodium alpinum, Mirabilis jalapa, or Apium graveolens can be used.

[0052] In one embodiment of the present disclosure, the following ingredients can be used as the additional active substance: Vialox™ (INCI name: Pentapeptide-3 (synthetic peptide containing alanine, arginine, isoleucine, glycine, and proline)), Syn-Aake™ (β-Ala-Pro-Dab-NH-Bzl) or Syn-Coll™ (Pal-Lys-Val-Lys-OH), sold by Pentapharm; Argireline™ (Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 (INCI name: Acetyl hexapeptide-3)), Leuphasyl™ (Tyr-D-Ala-Gly-Phe-Leu), Aldenine™ (Gly-His-Lys), Trylagen™ (INCI name: Pseudoalteromona), sold by Lipotec wheat ferment extract, hydrolyzed wheat protein, hydrolyzed soy protein, tripeptide-10 citrulline (reaction product of citrulline and tripeptide-10 (a synthetic peptide consisting of aspartic acid, isoleucine, and lysine)), tripeptide-1), Eyeseryl™ (Ac-β-Ala-His-Ser-His), Serilesine™ (Ser-Ile-Lys-Val-Ala-Val) (SEQ ID NO 23) or Decorinyl™ (INCI name: Tripeptide-10 Citrulline = reaction product of citrulline and tripeptide-10 (a synthetic peptide consisting of aspartic acid, isoleucine, and lysine)); Collaxyl™ (Gly-Pro-Gln-Gly-Pro-Gln) or Quintescine™ (Cys-Gly), sold by Vincience; Cytokinol™ LS (casein hydrolysate), sold by Les Laboratoires Serobiologiques / Cognis; Kollaren™ (Gly-His-Lys), IP2000™ (Pal-Val-Tyr-Val) or Meliprene™ (INCI name: Monofluoroheptapeptide-1, a synthetic peptide containing acetic acid and arginine, glycine, glutamic acid, histidine, norleucine, p-fluorophenylalanine and tryptophan) sold by the European Biotechnology Institute; Neutrazen™ (Pal-His-D-Phe-Arg-NH2), available from Introvations; or BONT-L-Peptide™ (INCI name: Palmitoyl hexapeptide-19, reaction product of palmitic acid with hexapeptide-19 (a synthetic peptide consisting of asparagine, aspartic acid, lysine and methionine)), Timp-Peptide™ (INCI name: Acetyl hexapeptide-20, reaction product obtained by acetylation of hexapeptide-20 (a synthetic peptide consisting of alanine, glycine, lysine, valine and proline)), or ECM Moduline™ (INCI name: Palmitoyl tripeptide-28, reaction product of palmitic acid with tripeptide-28 (a synthetic peptide consisting of arginine, lysine and phenylalanine)), sold by Infinitec Activos.

[0053] In one embodiment of the present disclosure, the composition may include, as an additional active substance, at least one of a compound selected from a vitamin B3 compound, a compound such as niacinamide or tocopherol, a retinoid compound such as retinol, hexamidine, alpha-lipoic acid, resveratrol or DHEA, or hyaluronic acid.

[0054] The present disclosure provides a use of a peptide or a derivative thereof comprising the amino acid sequence of Formula I for the manufacture of a composition for improving skin condition. The peptide or a derivative thereof can be used to improve the condition of the skin and its appendages by inducing the synthesis of at least one molecule within the skin matrix.

[0055] In one aspect of the present disclosure, improvement of skin condition comprehensively refers to the process or effect of reducing, alleviating, or healing skin damage caused by intrinsic or extrinsic factors. For example, improvement of skin condition may include improvement of skin wrinkles, skin moisturizing, skin whitening, maintenance or improvement of skin elasticity, wound healing, anti-aging, improvement of lipid secretion, or alleviation or improvement of dermatitis. Furthermore, improvement of skin condition may include overall anti-aging, anti-wrinkle and microsurface improvement (skin softening, wrinkle filling), improvement of skin mechanical properties such as firmness and elasticity, increased skin density (skin restructuring effect), increased skin volume (plumping effect), improvement of stretch marks, anti-spot treatment, improvement of skin uniformity and luster, or improvement of skin pigmentation. Preferably, the improvement of skin condition refers to improvement of skin wrinkles or sebum secretion.

[0056] In one embodiment of the present disclosure, the composition may contain other peptides or peptide compounds other than the peptide or derivative thereof comprising the amino acid sequence of Formula I. The other peptides or peptide compounds may be present in an amount of 1×10 based on the total weight of the composition. -7 % by weight to 20% by weight, preferably 1×10 -6 % by weight to 10% by weight, more preferably 1×10 5 It may be included in the composition at % to 5% by weight.

[0057] All ingredients described in the present disclosure preferably do not exceed the maximum usage amount specified in relevant laws, regulations, and standards of Korea, China, the United States, Europe, Japan, etc. (e.g., Regulations Concerning Cosmetic Safety Standards, etc. (Korea), Cosmetic Safety Technical Standards (China), Food Code (Korea), Food Additives Code (Korea), Health Functional Food Code (Korea)). That is, preferably, the cosmetic composition, topical skin composition, or pharmaceutical composition according to the present disclosure contains ingredients according to the present disclosure within the content limits permitted by the relevant laws, regulations, and standards of each country. [Effects of the Invention]

[0058] The peptide or its derivative for improving skin conditions of the present disclosure exhibits a significantly excellent effect of improving skin conditions. The peptide or its derivative can be used as an active ingredient in a functional cosmetic composition or a topical skin preparation composition that can be used on the skin. DETAILED DESCRIPTION OF THE INVENTION

[0059] The present invention will be described in detail below with reference to examples to aid in understanding the present invention. However, the examples according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following examples. The examples of the present invention are provided to more completely explain the present invention to those skilled in the art. The raw materials used in the present invention were purchased from companies that sell them for ordinary commercial purposes. Synthesis Example: Method for synthesizing peptides of formula I The peptide of formula I can be synthesized by the following synthesis method. First step: A hydrazine derivative protected with a "9-fluorenylmethoxycarbonyl" (hereinafter referred to as "Fmoc") group is bonded to a carbonyl compound, and then reacted with Link amide resin to activate the N-terminus to prepare a semicarbazide-type resin; The second step is to remove the Fmoc group, which is the protecting group attached to the nitrogen terminus of the Fmoc-azagly-Rink amide resin (azagly: azagly, -NH-NH-CO-) obtained in the first step, by a deprotection reaction using a reaction solvent such as 20% piperidine / DMF (dimethylformamide); Third step: after the second step, Fmoc-Lys, Fmoc-Gly, Fmoc-Arg, Fmoc-Ser, Fmoc-Ser, Fmoc-Cys, Fmoc-Phe, Fmoc-Val, Fmoc-Asp, and Fmoc-Cys, which are amino acid derivatives whose amine termini and side chains are all protected with protecting groups, are added in sequence and reacted; The fourth step: removing the Fmoc group of the peptide by the two-step deprotection reaction to obtain the Fmoc group of the peptide to obtain a peptide resin; Fifth step: adding a weak acid cleavage solution such as 2% TFA (trifluoroacetic acid) / DCM (dichloromethane) to the peptide resin of the fourth step to separate the peptide from the resin, and then removing the resin; Step 6: adding a hydrazine solution to the separated peptide, and then removing the benzyl group, nitro group (NO2) and Cbz (benzyloxycarbonyl) among the side chain protecting groups by catalytic hydrogen transfer reaction using reagents such as pd / c (palladium / catalyst) and cyclohexadiene, and purifying the resulting peptide using a reversed-phase column and an ion exchange resin; The peptide of formula I of the present disclosure can be prepared by carrying out a process comprising:

[0060] Production Example 1: Cosmetic composition for improving skin condition (skin lotion) A skin lotion composition was prepared by a conventional method according to the formulation shown in Table 1 below.

[0061] [Table 1]

[0062] Production Example 2: Cosmetic composition for improving skin condition (scalp lotion) A scalp lotion composition was prepared by a conventional method according to the formulation shown in Table 2 below.

[0063] [Table 2]

[0064] Experimental Example 1: Collagenase activity inhibition by sequence mutation The collagenase used was derived from rat pancreas, and the synthetic substrate, N-(3-[2-Furyl]acryloyl)-Leu-Gly-Pro-Ala, was used as the collagenase substrate. The buffer solution was 50 mM Tricine, 10 mM CaCl₂·H₂O, and 400 mM NaCl (pH 7.5). The synthetic substrate was dissolved in buffer to a concentration of 10 mM and then diluted to a final concentration of 75 μM. Collagenase was dissolved in cold triple-distilled water at 4°C to a concentration of 1 unit / ml and then diluted with buffer to a final concentration of 0.05 unit / ml. Collagenase inhibitor candidates were tested at final concentrations of 25 ppm and 50 ppm. As a positive control, epigallocatechin gallate (EGCG), known to have collagenase inhibitory effects, was used at a final concentration of 50 ppm. The reaction was carried out in a 96-well plate at room temperature for 10 minutes. The absorbance was measured at 345 nm at 1-minute intervals using a spectrophotometer, and the maximum gradient of the absorbance over time was calculated to confirm the enzyme activity inhibition rate (enzyme activity inhibition rate).

[0065] [Table 3]

[0066] Experimental Example 2: Inhibition of collagenase and elastase activity by permutation of sequences To confirm the efficacy of permutation of the peptide sequence, collagenase activity was examined after the sequence mutation as in Experimental Example 1. Human leukocyte-derived elastase was used, and the synthetic substrate MeOSuc-Ala-Ala-Pro-Val-pNA was used as the elastase substrate. A 100 mM Tris (pH 7.5) solution was used as the buffer solution. Elastase was added at a final concentration of 0.2 mU using the buffer. The synthetic elastase substrate was prepared as a 100 mM solution using DMSO and then diluted with the buffer to a final concentration of 0.5 mM. Quercetin, a known elastase inhibitor, was added at a concentration of 10 ppm as a positive control. Potential elastase inhibitors were added to final concentrations of 10 and 20 ppm. The reaction was carried out in a 96-well plate at room temperature for 20 minutes. The absorbance was measured at 405 nm at 1-minute intervals using a spectrophotometer, and the slope of the absorbance over time was calculated to determine the enzyme activity.

[0067] For the treatment efficacy component, a peptide sequence consisting of any one of SEQ ID NOs: 14 to 16 was treated at 100 μg / ml, and the peptide sequence RKSLFVD was used as a control peptide sequence. The collagenase activity inhibition rate (%) and elastase activity inhibition rate (%) were calculated as the relative enzyme activity to the control group, and the results are shown in Table 4 below.

[0068] [Table 4]

[0069] As shown in Table 4, the peptides of SEQ ID NOS: 1 to 3 and their reverse sequences, SEQ ID NOS: 14 to 16, all inhibited the activity of collagenase and elastase, confirming that compositions containing the peptides can be used to improve skin wrinkles, improve elasticity, or moisturize the skin.

[0070] Experimental Example 3: Inhibition of collagenase and elastase activity by N- or C-terminal mutations of the sequence To confirm whether or not N-terminal or C-terminal mutation of the peptide sequence had any effect, collagenase and elastase activities were confirmed in the same manner as in Experimental Example 1 after the sequence mutation.

[0071] [Table 5]

[0072] As shown in Table 5, even when the N-terminus or C-terminus of the peptide sequence of SEQ ID NO: 1 was substituted, the collagenase and elastase activities were significantly suppressed.

[0073] Experimental Example 4: Wrinkle improvement effect on skin The wrinkle improvement effect of the composition for improving skin condition of the present disclosure was tested on a total of 25 men and women. The 25 men and women were divided into 5 groups of 5 men each, and the effects of the products on improving wrinkles around the eyes and forehead were tested for a total of 4 weeks using Comparative Example 1 and Examples 1 to 4.

[0074] Effect measurements were conducted before use, one week after use, two weeks after use, and four weeks after use. Furthermore, during the human application test period, the use of cosmetics containing active ingredients other than the test product that could affect the test results (e.g., functional cosmetics for whitening, wrinkle reduction, etc.) was strictly prohibited. The test was conducted based on the use of 1 ml twice a day, morning and night, for four weeks.

[0075] Measurement of eye and forehead wrinkles was performed using a 3D skin imaging device, Antera 3D CS (Miravex Ltd., Ireland), by photographing the same left forehead area of ​​each subject before and after application of the test product. The saved images were converted to Wrinkles Medium mode, and analysis of eye wrinkles was performed by specifying an analysis area including the area using a 10.7 mm diameter circle. Furthermore, analysis of eye wrinkles was performed by analyzing the indentation index value, which represents the average roughness (Ra) of the wrinkles within the area, expressed in AU. Analysis of forehead wrinkles was performed by analyzing the depth value, which represents the average depth of the wrinkles within the area. The reduction rates of eye and forehead wrinkles were expressed as a percentage compared to when the product was not applied. The measurement results are shown in Table 6 below as the reduction rate of wrinkle density.

[0076] [Table 6]

[0077] From the results shown in Table 6, it was confirmed that Examples 1 to 4 containing the peptides of SEQ ID NOs: 1 to 3 or 14 had a significantly excellent anti-wrinkle effect.

[0078] Experimental Example 5: Improving skin lipid secretion The lipid secretion inhibitory effect of the skin condition improving composition of the present disclosure was tested on a total of 50 men and women. The 50 men and women were divided into 5 groups of 10 men and women, and Comparative Example 1 and Examples 1, 3, 5, and 6 were used. Examples 5 and 6 were prepared based on Example 1 in Table 1, with only the type of peptide changed. After washing the face and air drying for 15 minutes, 1 ml of Comparative Example 1 was applied to the left forehead and cheek, and 1 ml of Examples 1, 3, 5, or 6 was applied to the right forehead and cheek. After 1 hour, the lipid production amount was measured. The lipid production amount was measured using a Sebbumeter. The Comparative Example was applied to one cheek and the Examples to the other, and the measurement was performed relative to the Comparative Example. The results are shown in Table 7.

[0079] [Table 7]

[0080] As can be seen from the above results, a high lipid secretion inhibitory effect was observed in Examples 1, 3, 5, or 6, which contain the peptide sequence of SEQ ID NO: 1, 2, 5, or 6. This proves that the composition for improving skin condition of the present disclosure, which contains SEQ ID NO: 1, 2, 5, or 6, can be used very effectively to inhibit lipid secretion.

[0081] It will be obvious to those skilled in the art that the above-mentioned exemplary formulations such as skin lotions are merely examples of the composition for improving skin conditions of the present disclosure, and that the scope of the composition of the present disclosure is not limited to only these formulations.

[0082]

Claims

1. A peptide comprising an amino acid sequence of Formula I below, a derivative thereof, or an isomer thereof: <Chemical formula I> X1-X2-X3-(S-S-C-F)-Y1-Y2-Y3 wherein X1 is K or absent, X2 is G or absent, X3 is R or absent, Y1 is V or absent, Y2 is D or absent, and Y3 is C or absent.

2. The peptide according to claim 1 , wherein the peptide is for improving skin conditions.

3. The peptide according to claim 2, wherein the improvement of skin condition includes any one or more selected from the group consisting of improvement of skin wrinkles, improvement of skin elasticity, improvement of skin moisturizing, inhibition of skin aging, and improvement of skin lipid secretion.

4. A cosmetic composition comprising the peptide according to claim 1 as an active ingredient.

5. The cosmetic composition according to claim 4, which is for improving skin conditions.

6. The peptide of claim 1, wherein the amino acid sequence of formula I is any one selected from the group consisting of amino acid sequences of SEQ ID NOs: 1 to 13.

7. A peptide comprising any one amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOs: 14 to 16, a derivative thereof, or an isomer thereof.

8. The peptide according to claim 7, which is for improving skin conditions.

9. The peptide according to claim 8, wherein the improvement of skin condition includes any one or more selected from the group consisting of improvement of skin wrinkles, improvement of skin elasticity, improvement of skin moisturizing, inhibition of skin aging, and improvement of skin lipid secretion.

10. A peptide having 80% or more sequence identity to the amino acid sequence of Formula I: <Chemical formula I> X1-X2-X3-(S-S-C-F)-Y1-Y2-Y3 wherein X1 is K or absent, X2 is G or absent, X3 is R or absent, Y1 is V or absent, Y2 is D or absent, and Y3 is C or absent.

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