Active polypeptide, composition and use thereof

Abstract

Disclosed are an active polypeptide, composition, and use thereof, relating to the field of polypeptide technology. The peptide or its salt has the structure represented by formula (I): R1-Tyr-X1-Lys-Leu-Gln-Val-R2 (I). The disclosed peptide or its salt, or composition thereof, has multiple effects, including soothing, moisturizing, repairing, firming, anti-aging, oil control, and acne treatment, and can be used for skin or mucous membrane care.

Description

Technical Field

[0001] The present disclosure relates to the field of polypeptide technology, and in particular to an active polypeptide and its composition and use. Background Art

[0002] As the largest organ in the human body, the skin undertakes multiple physiological functions, including barrier protection, immune regulation, and sensory transmission. However, factors such as age, diet, stress, environmental pollution, ultraviolet radiation, and endocrine disorders have led to increasingly prominent skin problems such as impaired barrier function, collagen loss, and imbalanced skin oil secretion. Hyaluronic acid is closely related to the skin's barrier function, and hyaluronidase is a hydrolase that degrades hyaluronic acid. Increased hyaluronidase activity leads to a decrease in hyaluronic acid, which damages the skin's barrier function and causes water loss within the skin. The loss of a large amount of collagen weakens the skin's support, which in turn manifests as sagging skin. Excessive oil secretion in the skin blocks the ducts of the sebaceous glands in the hair follicles, causing skin problems such as acne and acne.

[0003] Skin care has garnered widespread attention in recent years, and active peptides are a core ingredient in skin care products. However, traditional peptides are often used to improve only a single skin concern. When multiple skin concerns arise, peptides with different targets are often combined. Currently, there are relatively few peptide compounds with multiple benefits, necessitating the research of more active peptides. Summary of the Invention

[0004] The present disclosure relates to active polypeptides. These active polypeptides and compositions containing these active polypeptides have the effects of caring for skin or mucous membranes.

[0005] In one aspect, the present disclosure provides a peptide represented by formula (I), or a stereoisomer thereof, or a mixture of stereoisomers thereof, or a salt thereof,

[0006] R1-Tyr-X1-Lys-Leu-Gln-Val-R2(I)

[0007] In formula (I),

[0008] X1 is selected from -Asp- or -Gln-;

[0009] R1 is selected from: H or R3-CO-, wherein R3 is selected from: substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl;

[0010] R2 is selected from: -NR4R5 or -OR4, wherein each R4 and R5 are independently selected from: H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl;

[0011] The alkyl group refers to a saturated aliphatic linear or branched alkyl group having 1 to 24 carbon atoms (or 1 to 16 carbon atoms; or 1 to 14 carbon atoms; or 1 to 12 carbon atoms; or 1, 2, 3, 4, 5 or 6 carbon atoms); in some embodiments, the alkyl group is selected from: methyl, ethyl, isopropyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl, decyl, dodecyl, tetradecyl, hexadecyl, octadecyl, 2-ethylhexyl, 2-methylbutyl or 5-methylhexyl;

[0012] The alkenyl group refers to a straight or branched alkenyl group having 2 to 24 carbon atoms (or 2 to 16 carbon atoms; or 2 to 14 carbon atoms; or 2 to 12 carbon atoms; or 2, 3, 4, 5 or 6 carbon atoms); the alkenyl group has one or more carbon-carbon double bonds, and in some embodiments, the alkenyl group has 1, 2 or 3 conjugated or non-conjugated carbon-carbon double bonds; the alkenyl group is bonded to the rest of the molecule through a single bond; in some embodiments, the alkenyl group is selected from: vinyl, oleyl or linoleyl;

[0013] In some embodiments, the substituents in the "substituted alkyl" and "substituted alkenyl" are selected from C1-C4 alkyl; hydroxy; C1-C4 alkoxy; amino; C1-C4 aminoalkyl; C1-C4 carbonyloxy; C1-C4 oxycarbonyl; halogen (such as fluorine, chlorine, bromine, and iodine); cyano; nitro; azide; C1-C4 alkylsulfonyl; thiol; C1-C4 alkylthio; C6-C 30 Aryloxy such as phenoxy; -NR b (C=NR b )NR b R c , where R b and R c are independently selected from: H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C 10 Cycloalkyl, C6-C 18 Aryl, C7-C 17 an aralkyl group, a three- to ten-membered heterocyclic group, or a protecting group for an amino group.

[0014] In some embodiments, R1 is selected from: H, acetyl, tert-butyryl, hexanoyl, 2-methylhexanoyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl or linoleoyl; R4 and R5 are independently selected from: H, methyl, ethyl, hexyl, dodecyl or hexadecyl;

[0015] In some embodiments, R1 is selected from H, acetyl, lauroyl, myristoyl, or palmitoyl; R4 is H and R5 is selected from H, methyl, ethyl, hexyl, dodecyl, or hexadecyl;

[0016] In some embodiments, R1 is selected from H, acetyl, lauroyl, myristoyl, or palmitoyl; and R2 is -OH or -NH2.

[0017] In some embodiments, the peptide represented by formula (I), or a stereoisomer thereof, or a mixture of stereoisomers thereof, or a salt thereof, is selected from peptides (1) to (16):

[0018] (1) H-Tyr-Asp-Lys-Leu-Gln-Val-NH2;

[0019] (2)H-Tyr-Asp-Lys-Leu-Gln-Val-OH;

[0020] (3) Ac-Tyr-Asp-Lys-Leu-Gln-Val-NH2;

[0021] (4) Ac-Tyr-Asp-Lys-Leu-Gln-Val-OH;

[0022] (5) Palm-Tyr-Asp-Lys-Leu-Gln-Val-NH2;

[0023] (6) Palm-Tyr-Asp-Lys-Leu-Gln-Val-OH;

[0024] (7) Myr-Tyr-Asp-Lys-Leu-Gln-Val-NH2;

[0025] (8) Myr-Tyr-Asp-Lys-Leu-Gln-Val-OH;

[0026] (9)H-Tyr-Gln-Lys-Leu-Gln-Val-NH2;

[0027] (10)H-Tyr-Gln-Lys-Leu-Gln-Val-OH;

[0028] (11) Ac-Tyr-Gln-Lys-Leu-Gln-Val-NH2;

[0029] (12) Ac-Tyr-Gln-Lys-Leu-Gln-Val-OH;

[0030] (13) Palm-Tyr-Gln-Lys-Leu-Gln-Val-NH2;

[0031] (14) Palm-Tyr-Gln-Lys-Leu-Gln-Val-OH;

[0032] (15)Myr-Tyr-Gln-Lys-Leu-Gln-Val-NH2;

[0033] (16)Myr-Tyr-Gln-Lys-Leu-Gln-Val-OH.

[0034] The peptides of the present invention contain a large number of asymmetric carbon atoms. It is understood by those skilled in the art that the peptides of the present invention have stereoisomers and can exist as stereoisomers or mixtures of stereoisomers, and therefore it is possible to obtain isomeric mixtures and racemic mixtures or diastereomeric mixtures, or pure diastereomers or enantiomers, depending on the number of asymmetric carbons and the isomers or isomeric mixtures present. In some embodiments, the peptides of the present invention are pure isomers, that is, enantiomers or diastereomers. In some embodiments, the structure of the peptides of the present invention is the L-isomer.

[0035] The present disclosure also includes all suitable isotopic variants of the above-mentioned peptides. Isotopic variants of the peptides of the present disclosure are understood herein to mean compounds in which at least one atom in the peptides of the present disclosure is replaced by another atom of the same atomic number, but the atomic mass of the other atom is different from the atomic mass usually or predominantly found in nature. Examples of isotopes that can be incorporated into the peptides of the present disclosure are those of hydrogen, carbon, nitrogen or oxygen, e.g. 2 H (deuterium), 3 H (tritium), 13 C. 14 C. 15 N. 17 O or 18 O. Certain isotopic variants of the peptides disclosed herein (particularly those into which one or more radioactive isotopes have been incorporated) may be useful, for example, for examining the mechanism of action or distribution of the active compound in vivo; due to their relative ease of preparation and detectability, particularly with 3 H or 14Compounds labeled with a C isotope are suitable for this purpose. In addition, due to the greater metabolic stability of the compound, the incorporation of an isotope (e.g., deuterium) can produce specific therapeutic benefits, such as an extension of the in vivo half-life or a reduction in the required active dose. Isotopic variants of the peptides of the present disclosure can be prepared by methods known to those skilled in the art, for example, by the methods further described below and in the examples, by using corresponding isotopic modifications of the respective reagents and / or starting materials.

[0036] The term "salt" refers to a salt approved for use in animals, and more specifically, humans, including metal salts of the peptides of the present disclosure, the metals including, but not limited to, lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc or aluminum; including salts formed between the peptides of the present disclosure and organic bases, the organic bases including, but not limited to, ethylenediamine, ethanolamine, arginine, lysine, histidine or piperazine; including salts formed between the peptides of the present disclosure and inorganic or organic acids, the organic acids including, but not limited to, acetic acid, citric acid, lactic acid, malonic acid, maleic acid, tartaric acid, fumaric acid, benzoic acid, aspartic acid, glutamic acid, succinic acid, oleic acid, trifluoroacetic acid, oxalic acid, pamoate or gluconic acid; the inorganic acids including, but not limited to, hydrochloric acid, sulfuric acid, boric acid or carbonic acid.

[0037] The nature of the salt is not critical and salts of the disclosed peptides may be obtained by conventional methods well known in the art.

[0038] The synthesis of the peptides of the present invention, or their stereoisomers, or mixtures of stereoisomers, or salts thereof can be carried out according to conventional methods known in the art, such as solid phase synthesis, liquid phase synthesis, or a combination of solid phase and liquid phase methods. They can also be prepared by biotechnological methods aimed at producing the desired sequence, or by controlled hydrolysis of proteins of animal, fungal, or plant origin.

[0039] For example, a method of obtaining the peptides of the present disclosure comprises the following steps:

[0040] - coupling an amino acid having a protected N-terminus and a free C-terminus with an amino acid having a free N-terminus and a C-terminus that is protected or bound to a solid support;

[0041] - Elimination of the group protecting the N-terminus;

[0042] - repeating this coupling sequence and eliminating the group protecting the N-terminus until the desired peptide sequence is obtained;

[0043] - Elimination of the group protecting the C-terminus or cleavage from the solid support.

[0044] In some embodiments, the C-terminus is bound to a solid support and the method is performed on a solid phase, comprising coupling an amino acid having a protected N-terminus and a free C-terminus to an amino acid having a free N-terminus and a C-terminus bound to a polymer support; eliminating the group protecting the N-terminus; and repeating this sequence as many times as required to thereby obtain a peptide of the desired length, followed by cleavage of the synthesized peptide from the initial polymer support.

[0045] The functional groups of the amino acid side chains remain fully protected with temporary or permanent protecting groups throughout the synthesis and can be deprotected simultaneously or orthogonally to the process of cleavage of the peptide from the polymer support.

[0046] In some embodiments, solid phase synthesis can be performed by a convergent strategy of coupling a dipeptide or tripeptide to a polymer support or to a dipeptide or amino acid previously bound to a polymer support.

[0047] The functional groups at the termini can be modified by deprotecting the N- and C-termini and / or cleaving the peptide from the polymer support in an undefined order using standard conditions and methods known in the art. Optional modifications of the N- and C-termini can be performed on the peptide while bound to the polymer support, or after the peptide has been cleaved from the polymer support.

[0048] Due to the application outside the body of a mammal, the peptides of the present disclosure can form part of various types of compositions. Therefore, another aspect of the present disclosure provides a composition comprising an effective amount of the above-mentioned peptide, or a stereoisomer thereof, or a mixture of stereoisomers thereof, or a salt thereof, and at least one excipient and optionally an adjuvant. The composition can be prepared by conventional methods known to those skilled in the art.

[0049] In some embodiments, the adjuvant includes, but is not limited to: analgesics, agents that inhibit PAR-2 ​​activity, collagen synthesis stimulators, agents that regulate PGC-1α synthesis, agents that regulate PPARγ activity, agents that increase or decrease the triglyceride content of adipocytes, agents that stimulate or delay adipocyte differentiation, lipolytic agents or agents that stimulate lipolysis, lipogenic agents, inhibitors of acetylcholine receptor aggregation, agents that inhibit muscle contraction, anticholinergic agents, elastase inhibitors, matrix metalloproteinase inhibitors, melanin synthesis stimulators or inhibitors, whitening agents or depigmenting agents, pigmentation promoting agents, self-tanning agents, NO-synthase inhibitors, 5α-reductase inhibitors, lysyl hydroxy inhibitors of hydroxylase and / or prolyl hydroxylase, antioxidants, anti-air pollution agents, anti-glycation agents, antihistamines, antiparasitic agents, emollients, organic solvents, liquid propellants, moisture retaining substances, alpha hydroxy acids, beta hydroxy acids, epidermal hydrolases, vitamins, amino acids, proteins, pigments, biopolymers, gelling polymers, thickeners, surfactants, adhesives, preservatives, anti-wrinkle agents, agents capable of reducing or treating under-eye bags, keratolytic agents, antimicrobial agents, agents that stimulate elastin synthesis, agents that stimulate decorin synthesis, agents that stimulate laminin synthesis, agents that stimulate defensin synthesis, agents that stimulate chaperone protein synthesis, agents that stimulate cAMP synthesis, Agents that stimulate hyaluronic acid synthesis, agents that stimulate fibronectin synthesis, agents that stimulate sirtuin synthesis, agents that stimulate the synthesis of lipids and stratum corneum components, ceramides, fatty acids, agents that inhibit collagen degradation, agents that inhibit elastin degradation, agents that inhibit serine proteases, agents that stimulate fibroblast proliferation, agents that stimulate keratinocyte proliferation, agents that stimulate adipocyte proliferation, agents that stimulate melanocyte proliferation, agents that stimulate keratinocyte differentiation, agents that inhibit acetylcholinesterase, skin relaxants, agents that stimulate glycosaminoglycan synthesis, anti-hyperkeratosis agents, comedolytic agents, antipsoriatic agents, anti-eczema agents, DNA repair agents, DNA protective agents, stabilizers, antipruritic agents, firming agents agents, tightening agents, restructuring agents, agents regulating sebum production, antiperspirants, agents stimulating healing, agents assisting healing, agents stimulating re-epithelialization, agents assisting re-epithelialization, cytokines, sedatives, anti-inflammatory agents, agents acting on capillary circulation and / or microcirculation, agents stimulating angiogenesis, agents inhibiting vascular permeability, agents of venous tension, agents acting on cellular metabolism, agents for improving the dermal-epidermal junction, agents inducing hair growth, agents inhibiting or retarding hair growth, fragrances, chelating agents, plant extracts, essential oils, marine extracts, agents obtained from biological fermentation processes, inorganic salts, cell extracts, and organic or inorganic photoprotective agents effective against ultraviolet A and / or UVB rays, or mixtures thereof.

[0050] The effective amount of the disclosed peptides to be administered, and their dosage, will depend on a number of factors, including the age, condition of the user, severity of the condition, route and frequency of administration, and the specific nature of the peptide to be used.

[0051] "Effective amount" means a non-toxic amount of one or more peptides of the present disclosure that is sufficient to provide the desired effect. The peptides of the present disclosure are used in the compositions of the present disclosure at concentrations effective to achieve the desired effect. In some embodiments, the concentration is between 0.00000001% (by weight) and 20% (by weight) relative to the total weight of the composition; in some embodiments, the concentration is between 0.000001% (by weight) and 15% (by weight) relative to the total weight of the composition; in some embodiments, the concentration is between 0.0001% (by weight) and 10% (by weight) relative to the total weight of the composition; in some embodiments, the concentration is between 0.0001% (by weight) and 5% (by weight) relative to the total weight of the composition.

[0052] Another aspect of the present disclosure provides a delivery system or sustained-release system for achieving better penetration of active ingredients, which comprises an effective amount of the above peptide, or its stereoisomer, or its mixture of stereoisomers, or its salt, or the above composition.

[0053] The term "delivery system" refers to a diluent, adjuvant, excipient or carrier to be administered with the peptides of the present invention, selected from the group consisting of water, oil or surfactant, including those of petroleum origin, animal origin, plant origin, or synthetic origin, such as, but not limited to, peanut oil, soybean oil, mineral oil, sesame oil, castor oil, polysorbates, sorbitan esters, ether sulfates, sulfates, betaines, glucosides, maltosides, fatty alcohols, nonoxynol ether, poloxamers, polyoxyethylene, polyethylene glycol, dextrose, glycerol, digitonin and the like. Those of ordinary skill in the art are aware of the diluents, adjuvants, excipients or carriers that can be used in different delivery systems for administering the peptides of the present invention.

[0054] The term "sustained release" is used in its conventional sense to refer to a delivery system that provides for the gradual release of a compound over a period of time. In some embodiments, a sustained release system has a relatively constant level of compound release over a period of time.

[0055] Examples of delivery systems or sustained-release systems include, but are not limited to, liposomes, oleosomes, ethosomes, millicapsules, microcapsules, nanocapsules, nanostructured lipid carriers, sponges, inclusion compounds, lipid vesicles, micelles, millispheres, microspheres, nanospheres, lipid spheres, microemulsions, nanoemulsions, milliparticles, microparticles, or nanoparticles.

[0056] Another aspect of the present disclosure provides a cosmetic comprising an effective amount of the above peptide, or its stereoisomer, or its mixture of stereoisomers, or its salt, or the above composition, or the above delivery system or sustained-release system.

[0057] In some embodiments, the dosage form of the cosmetic comprises ointment, cream, emulsion, aqueous solution, oil, gel, powder, tablet, mud, patch, film, aerosol, spray, freeze-dried preparation or nano preparation.

[0058] Another aspect of the present disclosure provides a use of the above-mentioned peptide, or its stereoisomer, or its mixture of stereoisomers, or its salt, or the above-mentioned composition, or the above-mentioned delivery system or sustained-release system in preparing a composition for caring for skin or mucous membranes.

[0059] Another aspect of the present disclosure provides a use of the above-mentioned peptide, or its stereoisomer, or its mixture of stereoisomers, or its salt, or the above-mentioned composition, or the above-mentioned delivery system or sustained-release system in the preparation of a composition for soothing, moisturizing, repairing, firming, anti-aging, oil control or acne treatment.

[0060] Another aspect of the present disclosure provides a use of the above-mentioned peptide, or its stereoisomer, or its mixture of stereoisomers, or its salt, or the above-mentioned composition, or the above-mentioned delivery system or sustained-release system in preparing a composition for inhibiting hyaluronidase activity; or in preparing a composition for increasing the content of hyaluronic acid; or in preparing a composition for repairing the skin barrier; or in preparing a composition for promoting the expression of loricrin and / or filaggrin; or in preparing a composition for promoting collagen production; or in preparing a composition for increasing skin elasticity and / or improving skin firmness; or in preparing a composition for inhibiting skin oil synthesis or secretion.

[0061] Another aspect of the present disclosure provides use of the above-mentioned peptide, or its stereoisomer, or its mixture of stereoisomers, or its salt, or the above-mentioned composition, or the above-mentioned delivery system or sustained-release system in preparing cosmetics.

[0062] In the present disclosure, the term "skin" is understood to include the multiple layers comprising it, from the uppermost layer or stratum corneum to the lowermost layer or subcutaneous tissue, both ends inclusive. These layers are composed of different types of cells, such as keratinocytes, fibroblasts, melanocytes, and / or adipocytes. In the present disclosure, the term "skin" includes the scalp.

[0063] The term "skin care" refers to the maintenance and care of the skin, improving the condition of the skin, making the skin delicate, smooth, tender and healthy.

[0064] The present disclosure has the following advantages and effects:

[0065] Compared with the reference peptide, the peptide disclosed in the present invention achieves unexpected technical effects of soothing, moisturizing, repairing, firming, anti-aging, oil control, and acne removal, and can be used to care for the skin or mucous membranes. BRIEF DESCRIPTION OF THE DRAWINGS

[0066] In order to more clearly illustrate the technical solution of the present disclosure, the following briefly introduces the drawings required for use in the description of the present disclosure. Obviously, the drawings described below are only some embodiments of the present disclosure. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0067] Figure 1 This is the mass spectrum of peptide (3) Ac-Tyr-Asp-Lys-Leu-Gln-Val-NH2.

[0068] Figure 2 This is the mass spectrum of peptide (11) Ac-Tyr-Gln-Lys-Leu-Gln-Val-NH2. DETAILED DESCRIPTION

[0069] To make the objectives, features, and advantages of the present disclosure more readily apparent, the present disclosure is further described below in detail with reference to the accompanying drawings and examples. It should be understood that the described embodiments are only a portion of the embodiments of the present disclosure, and not all of them. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present disclosure without inventive effort are intended to fall within the scope of protection of the claims appended to the present disclosure.

[0070] In the present disclosure, abbreviations used for amino acids follow the rules specified by the IUPAC-IUB Commission of Biochemical Nomenclature in Eur. J. Biochem. 1984, 138: 9-37.

[0071] Unless otherwise specified, the experimental reagents and materials used in this disclosure can be obtained commercially. The following are the abbreviations of some reagents and materials:

[0072] Amide Resin: a starting resin for peptide synthesis (cross-linking degree 1%, substitution degree 1.56 mmol / g, particle size 100-200 mesh); Wang Resin: a starting resin for peptide synthesis (Wang resin); Fmoc-Linker: 4-[(2,4-dimethoxyphenyl)(Fmoc-amino)methyl]phenoxyacetic acid; DCM: dichloromethane; Ac2O: acetic anhydride; DMF: N,N-dimethylformamide; DIPEA: diisopropylethylamine; DIC: diisopropylcarbodiimide; piperidine: piperidine; HOBt: 1-hydroxybenzotriazole; DMAP: 4-dimethoxybenzotriazole Methylaminopyridine; TFA: trifluoroacetic acid; TIS: triisopropylsilane; Tyr: tyrosine; Asp: aspartic acid; Lys: lysine; Leu: leucine; Gln: glutamine; Val: valine; Fmoc: 9-fluorenylmethoxycarbonyl; Boc: tert-butyloxycarbonyl; tBu: tert-butyl; OtBu: tert-butoxy; Trt: trityl; Ac-: acetyl (CH3-CO-); Palm-: palmitoyl (CH3-(CH2) 14 -CO-); Myr-: myristoyl (CH3-(CH2) 12 -CO-); Lauroyl-: lauroyl (CH3-(CH2) 10 -CO-).

[0073] Example 1 Preparation of Ac-Tyr-Asp-Lys-Leu-Gln-Val-NH2

[0074] 1.1 Preparation of Fmoc-Linker-Amide Resin

[0075] Weigh 5 g of Amide Resin into a solid phase synthesis reaction column, pour in 20 mL of DCM and swell for 30 min, wash the resin, and remove the solvent.

[0076] Weigh 7 g of Fmoc-Linker and 2 g of HOBt into a dry Erlenmeyer flask. Dissolve in DMF and prefreeze at -20°C for 10 min. Activate with 3 mL of DIC for 10 min.

[0077] The activated Fmoc-Linker was added to the swollen resin and reacted for 3 h. The reaction solution was removed, the resin was washed, and the solvent was removed.

[0078] Ac2O and DIPEA were added to cap the resin for 2 h, and the resin was washed and the solvent was removed.

[0079] 1.2 Fmoc removal

[0080] De-Fmoc the Fmoc-Linker-Amide Resin twice with 20% piperidine / DMF for 10 min each. Samples were taken for K-test, and the color developed dark blue. The resin was washed seven times with DMF, and the solvent was removed.

[0081] 1.3 Feeding reaction

[0082] Weigh 6g of Fmoc-Val-OH and 2.8g of HOBt into a dry Erlenmeyer flask. Dissolve in DMF, seal, and freeze at -18°C for 30 minutes. Activate with 4mL of DIC for 10 minutes. Add the activated amino acid to the deprotected resin and react for 1 hour. Aspirate the reaction solution. A colorless, transparent resin on the K-test indicates a complete reaction.

[0083] The N-terminal Fmoc group was deprotected, and 10.7 g of activated Fmoc-Gln(Trt)-OH was coupled to the peptidyl resin in the presence of 2.8 g of HOBt and 4 mL of DIC using DMF as the solvent. The reaction was continued for 1 hour. The resin was then washed and the Fmoc group deprotection treatment was repeated to couple the next amino acid. In each coupling, 6.2 g of Fmoc-Leu-OH, 9.4 g of Fmoc-Lys(Boc)-OH, 8.3 g of Fmoc-Asp(OtBu)-OH, and then 9.2 g of Fmoc-Tyr(tBu)-OH were sequentially coupled in the presence of 2.8 g of HOBt and 4 mL of DIC using DMF as the solvent. After the reaction was complete, the resin was washed and the solvent was removed.

[0084] The N-terminal Fmoc group of the peptidyl resin was deprotected using 20% ​​piperidine / DMF for two 10-min cycles. Samples were taken for K-test, and the color developed to be dark blue. The resin was washed seven times with DMF, and the solvent was removed.

[0085] In the presence of 0.9 mL of DIPEA, 2.3 mL of Ac2O was coupled to the peptidyl resin using DMF as solvent. The reaction was continued for 1 h. The resin was washed, the solvent was removed, and the resin was shrunk to dryness to obtain 18.3 g of Ac-Tyr(tBu)-Asp(OtBu)-Lys(Boc)-Leu-Gln(Trt)-Val-Linker-Amide Resin.

[0086] 1.4 Lysis

[0087] Measure 114 mL of TFA, 3 mL of TIS and 3 mL of water, mix and stir evenly to obtain a lysis solution, seal the container and place it in a -20°C refrigerator for later use; place isopropyl ether in a -20°C refrigerator for later use.

[0088] Weigh 18.3 g of Ac-Tyr(tBu)-Asp(OtBu)-Lys(Boc)-Leu-Gln(Trt)-Val-Linker-Amide Resin into a round-bottom flask, add the frozen lysate, and stir for 2 h. Filter, collect the filtrate, concentrate to 60 mL, add 500 mL of isopropyl ether, and allow to settle. Wash the mixture five times with isopropyl ether by centrifugation and vacuum drying to obtain 6.2 g of crude Ac-Tyr-Asp-Lys-Leu-Gln-Val-NH2 peptide.

[0089] 1.5 Purification

[0090] Weigh 6.2 g of crude Ac-Tyr-Asp-Lys-Leu-Gln-Val-NH2 peptide and dissolve it in 90 mL of methanol: acetic acid: water (V:V:V = 2:1:6). Ultrasonicate and filter the solution. Load the sample and purify it by reverse-phase HPLC. The purification gradient is shown in Table 1:

[0091] Table 1

[0092] Time (min) Flow rate (mL / min) A% (acetonitrile) B% (0.1% acetic acid + pure water) 0 15 2 98 10 15 2 98 18 15 5 95 40 15 5 95

[0093] The sample was injected for purification, and the fractions were collected, concentrated, and lyophilized to obtain peptide (3) Ac-Tyr-Asp-Lys-Leu-Gln-Val-NH2 with a purity greater than 95%.

[0094] The molecular weight of peptide (3) was determined, and the mass spectrum was as follows Figure 1 The results showed that [M+H] + The mass-to-charge ratio (m / z) of the quasi-molecular ion peak was 806.5584, and the molecular weight measured by mass spectrometry was 805.56.

[0095] Example 2 Preparation of Ac-Tyr-Gln-Lys-Leu-Gln-Val-NH2

[0096] 2.1 Preparation of Fmoc-Linker-Amide Resin

[0097] Weigh 5 g of Amide Resin into a solid phase synthesis reaction column, pour in 20 mL of DCM and swell for 30 min, wash the resin, and remove the solvent.

[0098] Weigh 7 g of Fmoc-Linker and 2 g of HOBt into a dry Erlenmeyer flask. Dissolve in DMF and prefreeze at -20°C for 10 min. Activate with 3 mL of DIC for 10 min.

[0099] The activated Fmoc-Linker was added to the swollen resin and reacted for 3 h. The reaction solution was removed, the resin was washed, and the solvent was removed.

[0100] Ac2O and DIPEA were added to cap the resin for 2 h, and the resin was washed and the solvent was removed.

[0101] 2.2 Fmoc removal

[0102] De-Fmoc the Fmoc-Linker-Amide Resin twice with 20% piperidine / DMF for 10 min each. Samples were taken for K-test, and the color developed dark blue. The resin was washed seven times with DMF, and the solvent was removed.

[0103] 2.3 Feeding reaction

[0104] Weigh 6g of Fmoc-Val-OH and 3.8g of HOBt into a dry Erlenmeyer flask. Dissolve in DMF, seal, and freeze at -18°C for 30 minutes. Activate with 4mL of DIC for 10 minutes. Add the activated amino acid to the deprotected resin and react for 1 hour. Aspirate the reaction solution. A colorless, transparent resin on the K-test indicates a complete reaction.

[0105] The N-terminal Fmoc group was deprotected, and 10.7 g of activated Fmoc-Gln(Trt)-OH was coupled to the peptidyl resin in the presence of 2.8 g of HOBt and 4 mL of DIC using DMF as the solvent. The reaction was continued for 1 hour. The resin was then washed and the Fmoc group deprotection treatment was repeated to couple the next amino acid. In each coupling, 6.2 g of Fmoc-Leu-OH, 9.4 g of Fmoc-Lys(Boc)-OH, 12.2 g of Fmoc-Gln(Trt)-OH, and then 9.2 g of Fmoc-Tyr(tBu)-OH were sequentially coupled in the presence of 2.8 g of HOBt and 4 mL of DIC using DMF as the solvent. After the reaction was complete, the resin was washed and the solvent was removed.

[0106] The N-terminal Fmoc group of the peptidyl resin was deprotected using 20% ​​piperidine / DMF for two 10-min cycles. Samples were taken for K-test, and the color developed to be dark blue. The resin was washed seven times with DMF, and the solvent was removed.

[0107] In the presence of 0.9 mL of DIPEA, 2.3 mL of Ac2O was coupled to the peptidyl resin using DMF as solvent. The reaction was continued for 1 h. The resin was washed, the solvent was removed, and the resin was shrunk to dryness to obtain 21.2 g of Ac-Tyr(tBu)-Gln(Trt)-Lys(Boc)-Leu-Gln(Trt)-Val-Linker-Amide Resin.

[0108] 2.4 Lysis

[0109] Measure 114 mL of TFA, 3 mL of TIS and 3 mL of water, mix and stir evenly to obtain a lysis solution, seal it and place it in a -20°C refrigerator for later use; place isopropyl ether in a -20°C refrigerator for later use.

[0110] Weigh 21.2 g of Ac-Tyr(tBu)-Gln(Trt)-Lys(Boc)-Leu-Gln(Trt)-Val-Linker-Amide Resin into a round-bottom flask, add the frozen lysate, and stir for 2.5 hours. Filter, collect the filtrate, concentrate to 50 mL, add 500 mL of isopropyl ether, and allow to settle. Wash the mixture four times with isopropyl ether by centrifugation and vacuum drying to obtain 8.8 g of crude Ac-Tyr-Gln-Lys-Leu-Gln-Val-NH2 peptide.

[0111] 2.5 Purification

[0112] 8.8 g of crude peptide Ac-Tyr-Gln-Lys-Leu-Gln-Val-NH2 was weighed and dissolved in 140 mL of methanol: acetic acid: water (V:V:V = 3:6:5). The solution was dissolved and filtered by ultrasonication, and the sample was loaded and purified by reverse phase HPLC. The purification gradient is shown in Table 2:

[0113] Table 2

[0114] Time (min) Flow rate (mL / min) A% (acetonitrile) B% (0.1% acetic acid + pure water) 0 15 5 95 7 15 10 90 15 15 20 80 25 15 28 72 35 15 32 68

[0115] The sample was injected for purification, and the fractions were collected, concentrated, and lyophilized to obtain peptide (11) Ac-Tyr-Gln-Lys-Leu-Gln-Val-NH2 with a purity greater than 95%.

[0116] The molecular weight of peptide (11) was determined, and the mass spectrum was as follows Figure 2 The results showed that [M+H] + The mass-to-charge ratio (m / z) of the quasi-molecular ion peak was 819.5517, and the molecular weight measured by mass spectrometry was 818.55.

[0117] Example 3 Preparation of Ac-Tyr-Asp-Lys-Leu-Gln-Val-OH

[0118] 3.1 Resin swelling

[0119] 10 g of Wang Resin was weighed and placed in a solid phase synthesis reaction column, swollen with DCM, the resin was washed, and the solvent was removed.

[0120] 3.2 Feeding reaction

[0121] Weigh 8g of Fmoc-Val-OH and 4g of HOBt into a dry Erlenmeyer flask. Dissolve in DMF and cool in an ice-water bath for 10 minutes. Activate with 5.5mL of DIC for 10 minutes. Add the activated Fmoc-Val-OH and 1.1g of DMAP to the swollen resin and allow to react for 2.5 hours. Remove the reaction mixture, wash the resin, and remove the solvent. Continue capping with AcO, DMAP, and DIPEA for 2.5 hours. Wash the resin and remove the solvent to obtain Fmoc-Val-Wang Resin.

[0122] Fmoc-Val-Wang Resin was depolymerized twice with 20% piperidine / DMF for 10 min each time. Samples were taken for K-test, and the color developed to be dark blue. The resin was washed seven times with DMF, and the solvent was removed.

[0123] Weigh 10.5 g of Fmoc-Gln(Trt)-OH and 3 g of HOBt into a dry Erlenmeyer flask. Dissolve in DMF, seal, and freeze at -18°C for 30 min. Activate with 4 mL of DIC for 7 min. Add the activated amino acid to the deprotected resin and react for 4 h. Aspirate the reaction solution. A colorless, transparent resin on K-test indicates a complete reaction.

[0124] The N-terminal Fmoc group was deprotected, and 6 g of activated Fmoc-Leu-OH was coupled to the peptidyl resin using DMF as a solvent in the presence of 3 g of HOBt and 4 mL of DIC. The reaction was continued for 2.3 h. The resin was then washed and the Fmoc group deprotection treatment was repeated to couple the next amino acid. In each coupling, 8 g of Fmoc-Lys(Boc)-OH, 7 g of Fmoc-Asp(OtBu)-OH, and then 8 g of Fmoc-Tyr(tBu)-OH were sequentially coupled in the presence of 3 g of HOBt and 4 mL of DIC using DMF as a solvent. After the reaction was complete, the resin was washed and the solvent was removed.

[0125] The N-terminal Fmoc group of the peptidyl resin was deprotected using 20% ​​piperidine / DMF for two 10-min cycles. Samples were taken for K-test, and the color developed to be dark blue. The resin was washed six times with DMF, and the solvent was removed.

[0126] In the presence of 1.5 mL of DIPEA, 3.5 mL of Ac2O was coupled to the peptidyl resin using DMF as solvent. The reaction was continued for 1 h. The resin was washed, the solvent was removed, and the resin was shrunk to dryness to obtain 25 g of Ac-Tyr(tBu)-Asp(OtBu)-Lys(Boc)-Leu-Gln(Trt)-Val-Wang Resin.

[0127] 3.3 Cracking

[0128] 142.5 mL of TFA, 3.75 mL of TIS, and 3.75 mL of water were measured, mixed, and stirred evenly to obtain a cleavage solution, which was sealed and placed in a -18°C refrigerator for later use; isopropyl ether was placed in a -18°C refrigerator for later use.

[0129] Weigh 25g of Ac-Tyr(tBu)-Asp(OtBu)-Lys(Boc)-Leu-Gln(Trt)-Val-Wang Resin into a round-bottom flask. Add the chilled lysate and stir for 2.5h. Filter, collect the filtrate, concentrate it to 90mL, add isopropyl ether, stir, centrifuge and wash six times, and vacuum dry to obtain 7.2g of crude Ac-Tyr-Asp-Lys-Leu-Gln-Val-OH peptide.

[0130] 3.4 Purification

[0131] 7.2 g of crude Ac-Tyr-Asp-Lys-Leu-Gln-Val-OH peptide was weighed and dissolved in 350 mL of a mixed solution of acetic acid, acetonitrile, and water. The solution was filtered through a 0.45 μm microporous filter membrane to obtain a clear and transparent solution. The solution was purified by reverse-phase HPLC using the following purification gradient:

[0132] Table 3

[0133] Time (min) Flow rate (mL / min) A% (acetonitrile) B% (0.1% acetic acid + pure water) 0 40 20 80 15 40 30 70 30 40 45 55 60 40 60 40 80 40 80 20 100 40 80 20

[0134] The sample was injected for purification, and the fractions were collected, concentrated, and lyophilized to obtain peptide (4) Ac-Tyr-Asp-Lys-Leu-Gln-Val-OH with a purity of >95%.

[0135] Example 4 Preparation of Ac-Tyr-Gln-Lys-Leu-Gln-Val-OH

[0136] 4.1 Resin swelling

[0137] 10 g of Wang Resin was weighed and placed in a solid phase synthesis reaction column, swollen with DCM, the resin was washed, and the solvent was removed.

[0138] 4.2 Feeding reaction

[0139] Weigh 8g of Fmoc-Val-OH and 4g of HOBt into a dry Erlenmeyer flask. Dissolve in DMF and cool in an ice-water bath for 10 minutes. Activate with 5.5mL of DIC for 10 minutes. Add the activated Fmoc-Val-OH and 1.1g of DMAP to the swollen resin and allow to react for 2.5 hours. Remove the reaction mixture, wash the resin, and remove the solvent. Continue capping with AcO, DMAP, and DIPEA for 2.5 hours. Wash the resin and remove the solvent to obtain Fmoc-Val-Wang Resin.

[0140] Fmoc-Val-Wang Resin was depolymerized twice with 20% piperidine / DMF for 10 min each time. Samples were taken for K-test, and the color developed to be dark blue. The resin was washed seven times with DMF, and the solvent was removed.

[0141] Weigh 10.5 g of Fmoc-Gln(Trt)-OH and 3 g of HOBt into a dry Erlenmeyer flask. Dissolve in DMF, seal, and freeze at -18°C for 30 min. Activate with 4 mL of DIC for 7 min. Add the activated amino acid to the deprotected resin and react for 4 h. Aspirate the reaction solution. A colorless, transparent resin on K-test indicates a complete reaction.

[0142] The N-terminal Fmoc group was deprotected, and 6 g of activated Fmoc-Leu-OH was coupled to the peptidyl resin using DMF as a solvent in the presence of 3 g of HOBt and 4 mL of DIC. The reaction was continued for 2.3 h. The resin was then washed and the Fmoc group deprotection treatment was repeated to couple the next amino acid. In each coupling, 8 g of Fmoc-Lys(Boc)-OH, 10.5 g of Fmoc-Gln(Trt)-OH, and then 8 g of Fmoc-Tyr(tBu)-OH were sequentially coupled in the presence of 3 g of HOBt and 4 mL of DIC using DMF as a solvent. After the reaction was complete, the resin was washed and the solvent was removed.

[0143] The N-terminal Fmoc group of the peptidyl resin was deprotected using 20% ​​piperidine / DMF for two 10-min cycles. Samples were taken for K-test, and the color developed to be dark blue. The resin was washed six times with DMF, and the solvent was removed.

[0144] In the presence of 1.5 mL of DIPEA, 3.5 mL of Ac2O was coupled to the peptidyl resin using DMF as solvent. The reaction was continued for 1 h. The resin was washed, the solvent was removed, and the resin was shrunk to dryness to obtain 25 g of Ac-Tyr(tBu)-Gln(Trt)-Lys(Boc)-Leu-Gln(Trt)-Val-Wang Resin.

[0145] 4.3 Lysis

[0146] Measure 165 mL of TFA, 4.5 mL of TIS and 4.5 mL of water, mix and stir evenly to obtain a lysis solution, seal the container and place it in a -18°C refrigerator for later use; place isopropyl ether in a -18°C refrigerator for later use.

[0147] Weigh 25g of Ac-Tyr(tBu)-Gln(Trt)-Lys(Boc)-Leu-Gln(Trt)-Val-Wang Resin into a round-bottom flask. Add the chilled lysate and stir for 2.5h. Filter, collect the filtrate, concentrate it to 90mL, add isopropyl ether, stir, and centrifuge six times. Vacuum dry to obtain 8.5g of crude Ac-Tyr-Gln-Lys-Leu-Gln-Val-OH peptide.

[0148] 4.4 Purification

[0149] 8.5 g of crude peptide Ac-Tyr-Gln-Lys-Leu-Gln-Val-OH was weighed and dissolved in a mixture of acetic acid, methanol, and water. The solution was filtered through a 0.22 μm microporous filter membrane to obtain a clear and transparent solution. The solution was purified by reverse-phase HPLC using the following purification gradient:

[0150] Table 4

[0151] Time (min) Flow rate (mL / min) A% (acetonitrile) B% (0.1% acetic acid + pure water) 0 40 50 50 7 40 50 50 15 40 60 40 30 40 70 30 45 40 80 20 80 40 90 10 100 40 90 10

[0152] The sample was injected for purification, and the fractions were collected, concentrated, and lyophilized to obtain peptide (12) Ac-Tyr-Gln-Lys-Leu-Gln-Val-OH with a purity of >95%.

[0153] Example 5

[0154] Other peptides disclosed herein can be prepared using a polypeptide solid phase synthesis method similar to that of Examples 1-4, including but not limited to:

[0155] H-Tyr-Asp-Lys-Leu-Gln-Val-NH2;

[0156] H-Tyr-Asp-Lys-Leu-Gln-Val-OH;

[0157] Palm-Tyr-Asp-Lys-Leu-Gln-Val-NH2;

[0158] Palm-Tyr-Asp-Lys-Leu-Gln-Val-OH;

[0159] Myr-Tyr-Asp-Lys-Leu-Gln-Val-NH2;

[0160] Myr-Tyr-Asp-Lys-Leu-Gln-Val-OH;

[0161] Lauroyl-Tyr-Asp-Lys-Leu-Gln-Val-NH2;

[0162] Lauroyl-Tyr-Asp-Lys-Leu-Gln-Val-OH;

[0163] H-Tyr-Gln-Lys-Leu-Gln-Val-NH2;

[0164] H-Tyr-Gln-Lys-Leu-Gln-Val-OH;

[0165] Palm-Tyr-Gln-Lys-Leu-Gln-Val-NH2;

[0166] Palm-Tyr-Gln-Lys-Leu-Gln-Val-OH;

[0167] Myr-Tyr-Gln-Lys-Leu-Gln-Val-NH2;

[0168] Myr-Tyr-Gln-Lys-Leu-Gln-Val-OH;

[0169] Lauroyl-Tyr-Gln-Lys-Leu-Gln-Val-NH2;

[0170] Lauroyl-Tyr-Gln-Lys-Leu-Gln-Val-OH.

[0171] Example 6 Hyaluronidase inhibition experiment

[0172] 6.1 Reagents and Materials

[0173] Sodium acetate buffer (pH=5.6), hyaluronidase, calcium chloride, sodium hyaluronate, acetylacetone solution, anhydrous ethanol, sodium hydroxide solution, P-DAB color developer [prepared by uniformly mixing p-dimethylaminobenzaldehyde (0.8 g), concentrated hydrochloric acid (15 mL) and an equal amount of glacial acetic acid].

[0174] 6.2 Instruments

[0175] Microplate reader, electronic balance, and gas bath constant temperature oscillator.

[0176] 6.3 Samples to be tested and grouping

[0177] 6.3.1 Samples to be tested

[0178] Peptide (3), peptide (11), reference peptide (Ac-YEKLQV-NH2), and dipotassium glycyrrhizate as a positive control. The test concentrations of the samples were 50 ppm, 200 ppm, and 500 ppm.

[0179] 6.3.2 Grouping

[0180] Sample group: test sample, hyaluronidase, sodium hyaluronate;

[0181] Sample zero adjustment group: test sample, sodium acetate buffer;

[0182] Blank control group: distilled water, hyaluronidase, sodium hyaluronate;

[0183] Blank zero adjustment group: distilled water, sodium acetate buffer.

[0184] 6.4 Experimental Methods

[0185] Hyaluronidase and sodium hyaluronate were dissolved in sodium acetate buffer.

[0186] In a 96-well plate, 25 μL of the test sample and 25 μL of hyaluronidase (500 U / mL) were added to the sample group; 25 μL of the test sample and 25 μL of sodium acetate buffer were added to the sample zero adjustment group; 25 μL of distilled water and 25 μL of hyaluronidase (500 U / mL) were added to the blank control group; and 25 μL of distilled water and 25 μL of sodium acetate buffer were added to the blank zero adjustment group. After shaking in a 37°C constant temperature air bath for 20 minutes, 5 μL of calcium chloride solution (2.5 mol / L) was added to each well and the plates were shaken in a 37°C constant temperature air bath for 20 minutes. 25 μL of sodium hyaluronate (1 mg / mL) was added to the sample and blank control groups. 25 μL of sodium acetate buffer was added to the sample and blank zero adjustment groups. The plates were shaken in a 37°C constant temperature air bath for 40 minutes and then allowed to stand at room temperature for 10 minutes. Then, 25 μL of distilled water, 5 μL of sodium hydroxide solution (5 mol / L), and 25 μL of acetylacetone solution were added to each well and placed in a boiling water bath for 15 minutes, followed by an ice bath for 10 minutes, and finally placed at room temperature for 10 minutes. 50 μL of P-DAB was added to each well, followed by 100 μL of anhydrous ethanol, and the cells were placed at room temperature for 30 minutes. The OD was measured at 570 nm. 570 value.

[0187] Hyaluronidase inhibition rate (%) =

[0188] Where: A1 is the OD of the sample zeroing group 570 value, A2 is the sample group OD 570 A3 is the OD of the blank zero adjustment group. 570 A4 is the OD of the blank control group. 570 value.

[0189] 6.5 Experimental Results

[0190] Hyaluronidase activity is closely linked to type I allergic reactions. Inhibiting hyaluronidase activity can exert soothing and anti-allergic effects, and is therefore often used as an evaluation indicator for soothing and anti-allergic effects. Furthermore, hyaluronidase is a hydrolase that degrades hyaluronic acid. A reduction in hyaluronic acid can disrupt the skin's barrier function and lead to water loss. Inhibiting hyaluronidase activity can reduce hyaluronic acid degradation in cells and increase their content, thereby increasing hydration of the skin or mucous membranes, repairing the skin barrier, and exerting moisturizing, soothing, and repairing effects.

[0191] Sodium hyaluronate is a substrate for hyaluronidase. Under the catalytic action of hyaluronidase, sodium hyaluronate is degraded to produce glucuronic acid and N-acetylglucosamine. Under the action of P-DAB, it develops color and absorbs visible light at a wavelength of 570 nm. In this experiment, the test sample was treated with hyaluronidase, and the reaction amount of sodium hyaluronate was measured to determine whether the test sample disclosed herein could inhibit the activity of hyaluronidase.

[0192] The results of hyaluronidase activity inhibition rates of different test samples are shown in Table 5.

[0193] Table 5 Hyaluronidase activity inhibition rate of test samples (Mean±SD, n=4)

[0194]

[0195] The results showed that the peptides (3) and (11) disclosed herein can significantly inhibit the activity of hyaluronidase, and compared with the reference peptide, the inhibitory effect of the peptides disclosed herein on hyaluronidase activity is greatly improved, achieving unexpected technical effects. It can be seen that the peptides disclosed herein have excellent inhibitory effects on hyaluronidase activity, can be used to repair the skin barrier, and have the effects of repairing, soothing, and moisturizing.

[0196] Example 7 Determination of hyaluronic acid content

[0197] 7.1 Reagents and Materials

[0198] Fetal bovine serum, DMEM medium, phosphate buffered saline, trypsin, hyaluronic acid detection kit, RIPA lysis buffer, BCA protein kit.

[0199] 7.2 Instruments

[0200] Microplate reader, CO2 incubator, clean bench, and gas bath constant temperature oscillator.

[0201] 7.3 Cell lines

[0202] Human keratinocytes (HaCaT).

[0203] 7.4 Samples to be tested and grouping

[0204] 7.4.1 Samples to be tested

[0205] Peptide (3) and peptide (11) were tested at a concentration of 20 ppm.

[0206] 7.4.2 Grouping

[0207] Experimental group: UV radiation + tested sample;

[0208] Blank control group: PBS;

[0209] UV group: UV radiation + PBS.

[0210] 7.5 Experimental Methods

[0211] Take a bottle of HaCaT cells in good exponential growth phase, add 0.25% trypsin digestion solution, digest to make the adherent cells fall off, and count (1-4)×105 cells / mL to prepare a cell suspension.

[0212] The diluted cell suspension was inoculated into a 12-well plate and cultured in a CO2 incubator for 24 hours. The complete culture medium in the well was aspirated, and each group was repeatedly washed with an appropriate amount of PBS until colorless. The blank control group was added with 100 μL PBS and the complete culture medium was replenished to 1000 μL without UV irradiation. The UV group and the experimental group were added with 200 μL PBS and placed in 80 mJ / cm 2 Irradiate under UV light for 15 minutes. After irradiation, discard the PBS. Add 100 μL of PBS to the UV group and replenish the volume with complete culture medium to 1000 μL. Add 100 μL of the test sample to the experimental group and replenish the volume with complete culture medium to 1000 μL. Incubate the blank control, UV, and experimental groups in a 37°C, 5% CO2 incubator for 48 hours.

[0213] After the culture, the cells were collected and centrifuged to discard the supernatant. RIPA lysis buffer was added and the cells were shaken three times with a vortexer (30 s / time, 3 min interval). The cells were centrifuged at 12000 rpm for 10 min. The supernatant was aspirated and tested according to the instructions of the hyaluronic acid detection kit. The total protein concentration of the supernatant was detected using a BCA protein quantification kit.

[0214] 7.6 Experimental Results

[0215] Hyaluronic acid (HA) is an acidic mucopolysaccharide with important physiological functions. It plays a unique role in protecting the skin, keeping it moisturized, smooth, delicate, tender, and elastic. It has moisturizing, soothing, beauty-enhancing, and restoring effects on the skin's physiological functions. A reduction or destruction of HA content in the skin can cause water loss and epidermal aging, leading to its reputation as an anti-aging factor. This experiment measured the effect of the disclosed peptides on HA content to determine whether they could increase HA content and thereby exert moisturizing, anti-aging, and repairing effects.

[0216] The results of the effects of the test samples on the hyaluronic acid content are shown in Table 6.

[0217] Table 6 Effects of test samples on hyaluronic acid content (n=4)

[0218] Group Relative content of hyaluronic acid (Mean±SD, %) Blank control group 100.00±12.19 UV Group <![CDATA[37.72±10.11 ### ]]> 20ppm Peptide (3) Group <![CDATA[116.48±7.76 *** ]]> 20ppm Peptide (11) Group <![CDATA[106.60±16.74 *** ]]>

[0219] Note: Compared with the blank control group, ### P <0.001; compared with the UV group, *** P <0.001.

[0220] The results showed that compared with the blank control group, the hyaluronic acid content in the UV group showed an extremely significant decrease, indicating that the modeling was successful; compared with the UV group, the peptide (3) and peptide (11) disclosed in the present invention were able to extremely significantly increase the hyaluronic acid content.

[0221] It can be seen from this that the peptide disclosed in the present invention can increase the content of hyaluronic acid, thereby repairing the skin barrier, replenishing moisture on the skin surface, making the skin surface hydrated and smooth, and has the effects of moisturizing, anti-aging and repairing.

[0222] Example 8 Collagen I content test

[0223] 8.1 Reagents and Materials

[0224] Fetal bovine serum, DMEM medium, phosphate buffered saline (PBS), trypsin, RIPA lysis buffer, collagen I ELISA kit, BCA protein kit.

[0225] 8.2 Instruments

[0226] Microplate reader, CO2 incubator, clean bench, and gas bath constant temperature oscillator.

[0227] 8.3 Cell lines

[0228] Human skin fibroblasts (HSF).

[0229] 8.4 Samples to be tested and grouping

[0230] 8.4.1 Samples to be tested

[0231] Peptide (3), peptide (11), and reference peptide (Ac-YEKLQV-NH2) were tested at a concentration of 25 ppm.

[0232] 8.4.2 Grouping

[0233] Experimental group: UV radiation + tested sample;

[0234] Blank control group: PBS;

[0235] UV group: UV radiation + PBS.

[0236] 8.5 Experimental methods.

[0237] Take HSF fibroblasts in good exponential growth phase, add 0.25% trypsin digestion solution, digest to make the adherent cells fall off, and count (1-4)×10 6 cells / mL to prepare a cell suspension.

[0238] Appropriate dilution to take 10 5Cell suspensions were seeded in 6-well plates, and the UV experimental model was established when the cells grew to about 80%. After repeated washing with appropriate amounts of PBS until colorless, the blank control group added 100 μL PBS and supplemented with complete culture medium to 1000 μL without UV irradiation; the UV group and experimental group added 200 μL PBS and placed in 80 mJ / cm 2 Irradiate under UV light, with the lamp source 15 cm away from the culture flask. After irradiation, discard the PBS. Add 100 μL of PBS to the UV group and replenish the culture medium to 1000 μL. Add 100 μL of the test sample to the experimental group and replenish the culture medium to 1000 μL. Incubate the blank control, UV, and experimental groups in a 37°C, 5% CO2 incubator for 48 hours.

[0239] After the culture was completed, the cells were collected and centrifuged to discard the supernatant. RIPA lysis buffer was added and the cells were shaken three times with a vortexer (30 s / time, 3 min interval). The cells were centrifuged at 12000 rpm for 10 min. The supernatant was aspirated and tested according to the collagen I ELISA operating instructions. The total protein concentration of the supernatant was detected using a BCA protein quantification kit.

[0240] 8.6 Experimental Results

[0241] Type I collagen is the most abundant collagen in the human body. It occurs in thick, tightly packed bundles and possesses strong tensile strength, providing a strong structural support and strength for the skin, giving it elasticity and toughness. Therefore, increasing type I collagen content is crucial for preventing aging and increasing skin elasticity and firmness. This experiment used test samples to treat cells exposed to ultraviolet radiation and measured the type I collagen content in the cells to determine whether the disclosed peptides could promote type I collagen production.

[0242] The results of the effects of the test samples on the collagen I content are shown in Table 7.

[0243] Table 7 Effects of test samples on collagen I content (n=3)

[0244] Group Relative content of collagen I (Mean±SD, %) Percent increase relative to the reference peptide Blank control group 100.00±15.85 / UV Group 51.70±5.65 / Reference peptide group 75.17±16.98 / Peptide (3) group 121.70±23.54 61.90% Peptide (11) group 114.82±28.83 52.75%

[0245] The results showed that compared with the blank control group, the collagen I content in the UV group was significantly reduced, indicating that the modeling was successful; compared with the UV group, the peptide (3) and peptide (11) disclosed in the present invention could significantly increase the collagen I content and promote collagen production, and compared with the reference peptide, the peptide disclosed in the present invention had a greatly improved promoting effect on collagen production, achieving unexpected technical effects.

[0246] It can be seen from this that the peptide disclosed in the present invention can significantly increase collagen content, promote collagen production, and can be used to increase skin elasticity, improve skin firmness, delay skin aging, and have a firming and anti-aging effect.

[0247] Example 9 Determination of Loricrin Content

[0248] 9.1 Reagents and Materials

[0249] Fetal bovine serum, DMEM medium, phosphate-buffered saline (PBS), trypsin, RIPA lysis buffer, loricrin (LOR) ELISA kit, BCA protein kit.

[0250] 9.2 Instruments

[0251] Microplate reader, CO2 incubator, clean bench, and gas bath constant temperature oscillator.

[0252] 9.3 Cell lines

[0253] Human keratinocytes (HaCaT) were purchased from the Kunming Cell Bank of the Committee of Type Culture Collection of the Chinese Academy of Sciences.

[0254] 9.4 Samples to be tested and grouping

[0255] 9.4.1 Samples to be tested

[0256] Peptide (3), peptide (11), and reference peptide (Ac-YEKLQV-NH2) were tested at a concentration of 1 ppm.

[0257] 9.4.2 Grouping

[0258] Experimental group: UV radiation + tested sample;

[0259] Blank control group: PBS;

[0260] UV group: UV radiation + PBS.

[0261] 9.5 Experimental Methods

[0262] Take a bottle of HaCaT cells in good exponential growth phase, add 0.25% trypsin digestion solution, digest to make the adherent cells fall off, and count (1-4)×10 5 cells / mL to prepare a cell suspension.

[0263] The diluted cell suspension was inoculated into a 12-well plate and cultured in a CO2 incubator for 24 hours. The complete culture medium in the well was aspirated, and each group was repeatedly washed with an appropriate amount of PBS until colorless. The blank control group was added with 100 μL PBS and the complete culture medium was replenished to 1000 μL without UV irradiation. The UV group and the experimental group were added with 200 μL PBS and placed in 80 mJ / cm2 Irradiate under UV light for 15 minutes. After irradiation, discard the PBS. Add 100 μL of PBS to the UV group and replenish the volume with complete culture medium to 1000 μL. Add 100 μL of the test sample to the experimental group and replenish the volume with complete culture medium to 1000 μL. Incubate the blank control, UV, and experimental groups in a 37°C, 5% CO2 incubator for 48 hours.

[0264] After the culture, the cells were collected and centrifuged to discard the supernatant. RIPA lysis buffer was added and the cells were shaken three times with a vortexer (30 s / time, 3 min interval). The cells were centrifuged at 12000 rpm for 10 min. The supernatant was aspirated and tested according to the instructions of the loricrin detection kit. The total protein concentration of the supernatant was detected using a BCA protein quantification kit.

[0265] 9.6 Experimental Results

[0266] Loricrin (LOR) is a major component of the keratin envelope and plays a crucial role in the normal functioning of the skin barrier. LOR expression plays a crucial role in the repair of the skin barrier, and increased LOR expression is a key marker of skin barrier repair. This experiment used test samples to treat HaCaT cells and measured the levels of LOR synthesized and secreted in HaCaT cells to analyze whether the disclosed peptides could promote loricrin expression.

[0267] The results of the effects of the test samples on the expression of loricrin are shown in Table 8.

[0268] Table 8 Effects of test samples on loricrin expression (n=4)

[0269] Group Relative content of loricrin (Mean±SD, %) Blank control group 100.00±3.74 UV Group <![CDATA[58.47±5.83 ### ]]> Reference peptide group <![CDATA[98.84±6.90 *** ]]> Peptide (3) group <![CDATA[121.17±14.12 *** ]]> Peptide (11) group <![CDATA[116.40±8.13 *** ]]>

[0270] Note: Compared with the blank control group, ### P <0.001; compared with the UV group, *** P <0.001.

[0271] The results showed that compared with the blank control group, the content of loricrin in the UV group was significantly reduced, indicating that the modeling was successful; compared with the UV group, the peptide (3) and peptide (11) disclosed in the present invention were able to extremely significantly promote the expression of loricrin and increase the content of loricrin, and the peptide disclosed in the present invention had a better effect of promoting the expression of loricrin than the reference peptide.

[0272] It can be seen from this that the peptide disclosed in the present invention can promote the expression of loricrin, enhance or repair the skin barrier, and has a repairing effect.

[0273] Example 10 Determination of Filaggrin Content

[0274] 10.1 Reagents and Materials

[0275] Fetal bovine serum, DMEM medium, phosphate-buffered saline (PBS), trypsin, RIPA lysis buffer, filaggrin (FLG) ELISA kit, BCA protein kit.

[0276] 10.2 Instruments

[0277] Microplate reader, CO2 incubator, clean bench, and gas bath constant temperature oscillator.

[0278] 10.3 Cell lines

[0279] Human keratinocytes (HaCaT) were purchased from the Kunming Cell Bank of the Committee of Type Culture Collection of the Chinese Academy of Sciences.

[0280] 10.4 Samples to be tested and grouping

[0281] 10.4.1 Samples to be tested

[0282] Peptide (3) and peptide (11) were tested at a concentration of 20 ppm.

[0283] 10.4.2 Grouping

[0284] Experimental group: UV radiation + tested sample;

[0285] Blank control group: PBS;

[0286] UV group: UV radiation + PBS.

[0287] 10.5 Experimental Methods

[0288] Take a bottle of HaCaT cells in good exponential growth phase, add 0.25% trypsin digestion solution, digest to make the adherent cells fall off, and count (1-4)×10 5 cells / mL to prepare a cell suspension.

[0289] The diluted cell suspension was inoculated into a 12-well plate and cultured in a CO2 incubator for 24 hours. The complete culture medium in the well was aspirated, and each group was repeatedly washed with an appropriate amount of PBS until colorless. The blank control group was added with 100 μL PBS and the complete culture medium was replenished to 1000 μL without UV irradiation. The UV group and the experimental group were added with 200 μL PBS and placed in 80 mJ / cm 2 Irradiate under UV light for 15 minutes. After irradiation, discard the PBS. Add 100 μL of PBS to the UV group and replenish the complete medium to 1000 μL. Add 100 μL of the test sample to the experimental group and replenish the complete medium to 1000 μL. Incubate the blank control, UV, and experimental groups in a 37°C, 5% CO2 incubator for 48 hours.

[0290] After the culture, the cells were collected and centrifuged to discard the supernatant. RIPA lysis buffer was added and the cells were shaken three times with a vortexer (30 s / time, 3 min interval). The cells were centrifuged at 12000 rpm for 10 min. The supernatant was aspirated and tested according to the instructions of the filaggrin detection kit. The total protein concentration of the supernatant was detected using a BCA protein quantification kit.

[0291] 10.6 Experimental Results

[0292] Filaggrin (FLG) is a key factor in the skin barrier. It contributes to the formation of the horny envelope in the outer layer of the epidermis, promoting epidermal differentiation and forming the unique barrier structure of the stratum corneum. It plays a crucial role in maintaining the physical strength of the stratum corneum and reducing transepidermal water loss, contributing to barrier integrity and moisturizing. Therefore, FLG expression can be used as an indicator to evaluate the effectiveness of skin barrier repair. By testing the effect of a substance on FLG expression, its effectiveness in skin barrier repair can be assessed. Increased FLG expression helps repair the skin barrier, improves skin barrier function, and enhances the skin's ability to retain moisture. In this experiment, HaCaT cells were treated with test samples. The levels of FLG synthesized and secreted in HaCaT cells were measured to determine whether the disclosed peptides could promote filaggrin expression, thereby exerting moisturizing and repairing effects.

[0293] The results of the effects of the test samples on the expression of filaggrin are shown in Table 9.

[0294] Table 9 Effects of test samples on filaggrin expression (n=4)

[0295] Group Relative content of filaggrin (Mean±SD, %) Blank control group 100.00±6.65 UV Group <![CDATA[9.87±3.09 ### ]]> 20ppm Peptide (3) Group <![CDATA[64.34±5.45 *** ]]> 20ppm Peptide (11) Group <![CDATA[54.24±3.94 *** ]]>

[0296] Note: Compared with the blank control group, ### P <0.001; compared with the UV group, *** P <0.001.

[0297] The results showed that compared with the blank control group, the content of filaggrin in the UV group was significantly reduced, indicating that the modeling was successful; compared with the UV group, the peptide (3) and peptide (11) disclosed in the present invention were able to extremely significantly promote the expression of filaggrin and increase the content of filaggrin.

[0298] It can be seen from this that the peptide disclosed in the present invention can promote the expression of filaggrin, enhance or repair the skin barrier, and has the effects of repairing and moisturizing.

[0299] Example 11 Oil content test

[0300] 11.1 Reagents and Materials

[0301] Trypsin digestion solution, DMEM culture medium, fetal bovine serum, phosphate buffered saline (PBS), palmitic acid and linoleic acid mixed solution (FFA), Oil Red O staining kit.

[0302] The preparation method of the palmitic acid and linoleic acid mixed solution (FFA) is as follows:

[0303] (1) Prepare palmitic acid solution: Weigh 3.84 mg of palmitic acid, add 0.5 mL of 0.6 mg / mL NaOH solution, heat at 70°C, and after it is completely dissolved, let it stand at room temperature until it solidifies; then add 0.5 mL of isopropanol and continue heating until it dissolves again; finally, add 1 mL of PBS to make a 2 mL solution and set aside;

[0304] (2) Prepare linoleic acid solution: weigh 4.2 mg of linoleic acid, add 0.5 mL of isopropanol, and then add 1.5 mL of PBS, heat to dissolve, and set aside;

[0305] (3) Preparation of FFA: Take 1 mL each of the above linoleic acid solution and palmitic acid solution, mix thoroughly, dilute to 2250 μmol / L, and filter through a 0.22 μm microporous filter membrane.

[0306] 11.2 Instruments

[0307] Microplate reader, CO2 incubator, clean bench, and gas bath constant temperature oscillator.

[0308] 11.3 Cell Lines

[0309] Sebaceous gland cells (SZ-95).

[0310] 11.4 Samples to be tested and grouping

[0311] 11.4.1 Samples to be tested

[0312] Peptide (3) and peptide (11) were tested at a concentration of 20 ppm.

[0313] 11.4.2 Grouping

[0314] Experimental group: test sample, FFA;

[0315] Control group: PBS;

[0316] Model group: PBS, FFA.

[0317] 11.5 Experimental Methods

[0318] Take a bottle of SZ-95 cells in good exponential growth phase, add 0.25% trypsin digestion solution, digest to make the adherent cells fall off, and count (1-4) × 10 5 cells / mL to prepare a cell suspension.

[0319] An appropriate amount of cell suspension was inoculated onto a 12-well plate and placed in a constant temperature CO2 incubator for 24 h.

[0320] Except for the control group which was added with the same amount of PBS, FFA was added to each well of the remaining wells to induce modeling. Then PBS was added to the model group, and the test samples were added to the experimental groups respectively, and the cells were cultured in a constant temperature CO2 incubator for 48 h.

[0321] The culture medium was discarded and oil staining was performed according to the instructions of the Oil Red O staining kit.

[0322] Aspirate the solution from the plate, add isopropanol to dissolve the Oil Red O dye, and measure the absorbance at 492 nm using a microplate reader. Calculate the relative amount of cellular lipid secretion based on the absorbance.

[0323] 11.6 Experimental Results

[0324] Oil Red O is a fat-soluble dye that is highly soluble in fat. Its staining mechanism is that Oil Red O specifically adsorbs to neutral triglycerides, lipids, and lipoproteins within tissues and cells, staining fat. FFA is an inducer. Under FFA stimulation, SZ-95 cells secrete large amounts of oil, which is stained by Oil Red O. This experiment used test samples to treat FFA-induced cells and measured the amount of oil secreted by the cells to determine whether the disclosed peptides could inhibit oil secretion.

[0325] The results of the effects of the test samples on the oil secretion of sebaceous gland cells are shown in Table 10.

[0326] Table 10 Relative oil secretion of SZ-95 cells (n=4)

[0327] Group Relative oil secretion (Mean±SD, %) control group 100.00±9.10 Model Group <![CDATA[177.32±6.27 ### ]]> 20ppm Peptide (3) Group <![CDATA[147.83±5.97 ** ]]> 20ppm Peptide (11) Group <![CDATA[153.88±1.89 *** ]]>

[0328] Note: Compared with the control group, ### P <0.001; compared with the model group, ** P <0.01, *** P <0.001.

[0329] The results showed that compared with the control group, the oil secretion of the model group increased significantly, indicating that the modeling was successful. Compared with the model group, the peptide (3) and peptide (11) disclosed in the present invention can significantly reduce the oil secretion and inhibit the oil secretion of sebaceous gland cells.

[0330] It can be seen from this that the peptide disclosed in the present invention can inhibit the synthesis or secretion of oil by sebaceous gland cells, slow down oil deposition, and can be used to improve problems such as excessive oil production of the skin and water-oil imbalance of the skin. It can also reduce the occurrence of acne or acne, and also help the skin recover after acne or acne occurs, and has the effects of oil control, acne removal, and repair.

[0331] In summary, the peptides disclosed herein can inhibit hyaluronidase activity, increase hyaluronic acid content, promote the expression of loricrin and filaggrin, repair the skin barrier, and exert soothing, moisturizing, and repairing effects; can effectively increase collagen content, promote collagen production, increase skin elasticity, improve skin firmness, and delay skin aging; and can also inhibit skin oil synthesis or secretion, exerting oil control, acne removal, and repair effects. The peptides disclosed herein have multiple effects such as soothing, moisturizing, repairing, firming, anti-aging, oil control, and acne removal, and can be used to care for skin or mucous membranes.

[0332] Example 12

[0333] An emulsion is prepared by the following steps, and the specific formula is shown in Table 11 below:

[0334] Table 11

[0335]

[0336] According to the formula and dosage, heat the materials of Phase A to 75-80°C in an oil phase pot and stir to dissolve completely; add the materials of Phase B to an emulsifying pot, stir and heat to 80-85°C and dissolve completely; pump Phase A into Phase B, turn on the vacuum, homogenize for 5 minutes, maintain stirring, and keep warm for 20 minutes; start cooling, cool to 60-65°C, add Phase C and Phase D materials and continue stirring; cool to 35-40°C, add Phase E materials, and stir for 10-15 minutes.

[0337] Example 13

[0338] An essence is prepared by the following steps, and the specific formula is shown in Table 12 below:

[0339] Table 12

[0340]

[0341] According to the formula and dosage, add the materials of Phase A to a stirring pot, stir and heat to 80-85°C; mix the materials of Phase B evenly until there are no powder particles, add to the stirring pot, and continue stirring for 10-15 minutes; start cooling, cool to 60-65°C, add the materials of Phase C; cool to 35-40°C, add the materials of Phase D and Phase E, and stir for 10-15 minutes.

[0342] Example 14

[0343] A cream is prepared by the following steps, and the specific formula is as shown in Table 13:

[0344] Table 13

[0345]

[0346] According to the formula and dosage, heat the Phase D material in a suitable container to 55-60°C, dissolve completely, and set aside; add Phase A to a stirring pot, stir and heat to 80-85°C; add the Phase B materials to the oil phase pot, stir and heat to 75-80°C, and dissolve completely and become transparent; add Phase B to Phase A, start vacuum, homogenize for 5 minutes, maintain stirring, and keep warm for 20 minutes; start cooling, cool to 60-65°C, add Phase C and pre-dissolved Phase D materials, and homogenize for 2 minutes; cool to 35-40°C, add Phase E materials, and stir for 10-15 minutes.

[0347] In this disclosure, relational terms such as first and second, etc., are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variants thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or terminal device comprising a series of elements includes not only those elements, but also other elements not explicitly listed, or elements inherent to such process, method, article, or terminal device. In the absence of further restrictions, an element defined by the statement "comprising a ..." does not exclude the presence of additional identical elements in the process, method, article, or terminal device comprising the element.

[0348] Although the specific embodiments of the present disclosure have been described for illustrative purposes, those skilled in the art may make various modifications or improvements without departing from the spirit and scope of the present disclosure. These modifications or improvements should fall within the scope of the appended claims of the present disclosure.

Claims

1. A peptide represented by formula (I) or a salt thereof, R1-Tyr-X1-Lys-Leu-Gln-Val-R2(I) In formula (I), X1 is selected from -Asp- or -Gln-; R1 is selected from acetyl, lauroyl, myristoyl or palmitoyl; R2 is -OH or -NH2.

2. The peptide or salt thereof according to claim 1, characterized in that Selected from the following peptides (3)-(8), (11)-(16): (3) Ac-Tyr-Asp-Lys-Leu-Gln-Val-NH2; (4) Ac-Tyr-Asp-Lys-Leu-Gln-Val-OH; (5) Palm-Tyr-Asp-Lys-Leu-Gln-Val-NH2; (6) Palm-Tyr-Asp-Lys-Leu-Gln-Val-OH; (7) Myr-Tyr-Asp-Lys-Leu-Gln-Val-NH2; (8) Myr-Tyr-Asp-Lys-Leu-Gln-Val-OH; (11) Ac-Tyr-Gln-Lys-Leu-Gln-Val-NH2; (12) Ac-Tyr-Gln-Lys-Leu-Gln-Val-OH; (13) Palm-Tyr-Gln-Lys-Leu-Gln-Val-NH2; (14) Palm-Tyr-Gln-Lys-Leu-Gln-Val-OH; (15)Myr-Tyr-Gln-Lys-Leu-Gln-Val-NH2; (16)Myr-Tyr-Gln-Lys-Leu-Gln-Val-OH.

3. The peptide or salt thereof according to claim 1 or 2, characterized in that The salts include metal salts of the peptide, wherein the metal includes lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc or aluminum; Alternatively, the salt includes a salt formed by the peptide and an organic base, the organic base including: ethylenediamine, ethanolamine, arginine, lysine, histidine or piperazine; Alternatively, the salt includes a salt formed by the peptide with an inorganic acid or an organic acid, wherein the organic acid includes: acetic acid, citric acid, lactic acid, malonic acid, maleic acid, tartaric acid, fumaric acid, benzoic acid, aspartic acid, glutamic acid, succinic acid, oleic acid, trifluoroacetic acid, oxalic acid, pamoic acid or gluconic acid; and the inorganic acid includes: hydrochloric acid, sulfuric acid, boric acid or carbonic acid.

4. A composition, characterized in that The composition comprises an effective amount of the peptide or salt thereof according to any one of claims 1 to 3, at least one excipient and optionally an adjuvant.

5. A delivery system, characterized in that Comprising an effective amount of the peptide or salt thereof according to any one of claims 1 to 3, or the composition according to claim 4.

6. The delivery system according to claim 5, wherein The delivery system includes liposomes, oleosomes, ethosomes, millicapsules, microcapsules, nanocapsules, sponges, inclusion compounds, lipid vesicles, micelles, microemulsions or nanoemulsions.

7. The delivery system according to claim 5, wherein The delivery system comprises milliparticles, microparticles or nanoparticles.

8. A cosmetic, characterized in that: Comprising an effective amount of the peptide or salt thereof according to any one of claims 1 to 3, or the composition according to claim 4, or the delivery system according to any one of claims 5 to 7.

9. The cosmetic according to claim 8, characterized in that The dosage forms of the cosmetics include ointments, creams, emulsions, aqueous solutions, oils, gels, powders, tablets, muds, patches, films, aerosols, sprays, freeze-dried preparations or nano preparations.

10. Use of the peptide or salt thereof according to any one of claims 1 to 3, or the composition according to claim 4, or the delivery system according to any one of claims 5 to 7 in the preparation of a composition for soothing, moisturizing, repairing, firming, anti-aging, oil control or acne treatment.

11. The use according to claim 10, characterized in that The soothing includes inhibiting hyaluronidase activity.

12. The use according to claim 10, characterized in that The moisturizing includes increasing the hyaluronic acid content.

13. The use according to claim 10, characterized in that The repair includes promoting the expression of loricrin and / or filaggrin.

14. The use according to claim 10, characterized in that The anti-aging effect includes promoting collagen production.

15. Use of the peptide or salt thereof according to any one of claims 1 to 3, or the composition according to claim 4, or the delivery system according to any one of claims 5 to 7 in preparing a composition for repairing the skin barrier; or in preparing a composition for increasing skin elasticity and / or improving skin firmness; or in preparing a composition for inhibiting skin oil secretion.

16. Use of the peptide or salt thereof according to any one of claims 1 to 3, or the composition according to claim 4, or the delivery system according to any one of claims 5 to 7 in the preparation of cosmetics for soothing, moisturizing, repairing, firming, anti-aging, oil control or acne treatment.

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