Linear and cyclic hexapeptides, compositions thereof and their use in the care of the skin or mucous membranes

Abstract

Disclosed are linear and cyclic hexapeptides, compositions thereof and application thereof in caring for skin or mucous membranes, relating to the technical field of polypeptides, the linear hexapeptide or salt thereof has a structure shown in formula (I): R1-Tyr-Tyr-Arg-Nle-Glu-Asp-R2 (I). Also related to a cyclic peptide, the structure of the cyclic peptide is Cyclo-[Tyr-Tyr-Arg-Nle-Glu-Asp]. The compound of the present disclosure has the effects of oil control, anti-aging, anti-glycation and the like, and can be used for caring for skin or mucous membranes.

Description

Technical Field

[0001] This disclosure relates to the field of peptide technology, and particularly to linear and cyclic hexapeptides, compositions thereof, and their use in the care of skin or mucous membranes. Background Technology

[0002] As the largest organ in the human body, the skin not only performs physiological functions such as barrier protection and sensing external stimuli, but its condition also directly affects the body's appearance. With age, environmental factors, and unhealthy lifestyle habits, the skin is prone to various problems such as aging, dullness, and abnormal sebum secretion, which seriously affect skin health and appearance.

[0003] Skin aging is a complex physiological process, mainly manifested as increased wrinkles, decreased elasticity, sagging, and dull skin tone. Current research indicates that glycation is a significant contributing factor to skin aging. Glycation refers to the reaction between reducing sugars (such as glucose and fructose) and biological macromolecules like proteins, lipids, or nucleic acids under non-enzymatic conditions, gradually generating a series of stable, irreversible advanced glycation end products (AGEs). In skin tissue, the accumulation of AGEs causes cross-linking of collagen and elastin, leading to structural and functional abnormalities. Macroscopically, this manifests as loss of skin elasticity, wrinkles, and a dull, yellowish complexion—signs of aging. Furthermore, the accumulation of AGEs exacerbates oxidative stress and inflammation, which in turn stimulate excessive sebum secretion, leading to an imbalance of oil and water in the skin. This further damages the integrity of the skin structure, accelerates the internal aging process, and amplifies the damage caused by external factors such as ultraviolet radiation and pollution, further worsening skin aging problems.

[0004] Therefore, in response to the aforementioned skin problems, it is necessary to develop a novel polypeptide that has multiple functions, including inhibiting glycation, regulating sebum secretion, and delaying skin aging, to meet consumers' skin care needs. Summary of the Invention

[0005] This disclosure relates to a linear and cyclic hexapeptide, and compositions containing such peptides, which have effects such as skin care or mucous membrane care.

[0006] On the one hand, this disclosure provides a peptide of formula (I), or a stereoisomer thereof, or a mixture thereof, or a salt thereof.

[0007] R1-Tyr-Tyr-Arg-Nle-Glu-Asp-R2(I)

[0008] In formula (I),

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

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

[0011] The alkyl group refers to a saturated aliphatic straight-chain or branched alkyl group having 1-24 carbon atoms (or 1-16 carbon atoms; or 1-14 carbon atoms; or 1-12 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-chain or branched alkenyl group having 2-24 carbon atoms (or 2-16 carbon atoms; or 2-14 carbon atoms; or 2-12 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 by a single bond; in some embodiments, the alkenyl group is selected from: vinyl, oleyl, or linoleyl;

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

[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 H, acetyl, lauroyl, myristoyl, or palmitoyl; R2 is -OH or -NH2.

[0017] In another aspect, this disclosure provides a peptide, or a stereoisomer thereof, or a mixture thereof, or a salt thereof, wherein the peptide is a cyclic peptide having the structure Cyclo-[Tyr-Tyr-Arg-Nle-Glu-Asp], the structural formula of which is shown below:

[0018] .

[0019] The peptides disclosed herein contain a large number of asymmetric carbon atoms. Those skilled in the art will understand that the peptides of this disclosure have stereoisomers and can exist as stereoisomers or mixtures of stereoisomers. Therefore, it is possible to obtain mixtures of isomers, racemic mixtures, or diastereomer mixtures, or pure diastereomers or enantiomers, depending on the number of asymmetric carbons and the presence of isomers or mixtures of isomers. In some embodiments, the peptides of this disclosure are pure isomers, i.e., enantiomers or diastereomers. In some embodiments, the peptides of this disclosure have an L-isomer structure.

[0020] This disclosure also includes all suitable isotopic variants of the aforementioned peptides. These isotopic variants of the peptides of this disclosure are understood herein to refer to compounds in which at least one atom within the peptide of this disclosure is replaced by another atom of the same atomic number, but said other atom has an atomic mass different from that of atoms commonly or predominantly found in nature. Examples of isotopes that can be incorporated into the peptides of this disclosure are those of hydrogen, carbon, nitrogen, or oxygen, for example… 2 H (deuterium) 3 H (tritium) 13 C 14 C 15 N、 17 O or 18O. Specific isotopic variants of the peptides disclosed herein (especially those that have been incorporated with one or more radioactive isotopes) may be advantageous, for example, in examining mechanisms of action or the distribution of active compounds in vivo; due to their relatively simple prepareability and detectability, especially with 3 H or 14 Compounds labeled with the C isotope are suitable for this purpose. Additionally, the incorporation of isotopes (e.g., deuterium) can produce specific therapeutic benefits, such as prolonged in vivo half-life or reduced required active dose, due to the enhanced metabolic stability of the compounds. Isotopic variants of the peptides disclosed herein can be prepared by methods known to those skilled in the art, such as those further described below and those described in the examples, using respective reagents and / or corresponding isotope modifiers of the starting materials.

[0021] The term "salt" refers to a salt recognized for use in animals, and more precisely in humans, including metal salts of peptides of this disclosure, said metal including, but not limited to: lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc, or aluminum; including salts formed by peptides of this disclosure with organic bases, said organic bases including, but not limited to: ethylenediamine, ethanolamine, arginine, lysine, histidine, or piperazine; including salts formed by peptides of this disclosure with inorganic or organic acids, said 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, pyric acid, or gluconic acid; said inorganic acids including, but not limited to: hydrochloric acid, sulfuric acid, boric acid, or carbonic acid.

[0022] The properties of the salt are not decisive, and the salts of the peptides disclosed herein can be obtained by conventional methods known in the art.

[0023] The synthesis of the peptides, or stereoisomers thereof, or mixtures thereof, or salts thereof disclosed herein 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 and liquid methods. It can also be prepared by biotechnological methods aimed at producing a desired sequence, or by controlled hydrolysis of proteins of animal, fungal, or plant origin.

[0024] For example, a method for obtaining the peptides disclosed herein includes the following steps:

[0025] - Couple amino acids with a protected N-terminus and a free C-terminus to amino acids with a free N-terminus and a protected C-terminus or a C-terminus bound to a solid support.

[0026] - Eliminate the groups protecting the N-terminus;

[0027] - Repeat this coupling sequence and remove the group protecting the N-terminus until the desired peptide sequence is obtained;

[0028] - Eliminate the groups protecting the C-terminus or cleave them from the solid support.

[0029] The method for obtaining the cyclic peptide of this disclosure, in addition to the steps described above, further includes:

[0030] - The amino group at the N-terminus of the peptide chain is coupled and cyclized with the carboxyl group at the C-terminus;

[0031] - Eliminate groups that protect the side chains.

[0032] In some embodiments, the C-terminus is bound to a solid support and the method is carried out 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; removing the group protecting the N-terminus; and repeating this sequence a number of times as required to thus obtain a peptide of the desired length, followed by cleaving the synthesized peptide from the original polymer support and cyclizing the amino group at the N-terminus of the peptide chain to the carboxyl group at the C-terminus, followed by removing the group protecting the side chain.

[0033] Throughout the synthesis, the functional groups of the side chains of these amino acids are adequately protected by temporary or permanent protecting groups.

[0034] In some embodiments, solid-phase synthesis can be carried out using a convergent strategy, which involves coupling dipeptides or tripeptides to a polymer support or to dipeptides or amino acids previously bound to a polymer support.

[0035] For ease of application, the peptides of this disclosure can be included as part of various types of compositions. Therefore, another aspect of this disclosure provides a composition comprising an effective amount of the aforementioned peptide, or a stereoisomer thereof, 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.

[0036] In some embodiments, the adjuvant is selected from: analgesics, agents that inhibit PAR-2 ​​activity, 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, lipolytic agents, 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 promoters, self-tanning agents, anti-aging agents, NO-synthesizers, 5α-reductase inhibitors, inhibitors of lysyl hydroxylase and / or prolyl hydroxylase, antioxidants, and free radical scavengers. Agents and / or anti-air pollution agents, active carbonyl scavengers, anti-glycation agents, antihistamines, antiviral agents, antiparasitic agents, emulsifiers, emollients, organic solvents, liquid propellants, water-retaining substances, alpha-hydroxy acids, beta-hydroxy acids, humectants, epidermal hydrolases, vitamins, amino acids, proteins, pigments, dyes, biopolymers, gelling polymers, thickeners, surfactants, softeners, adhesives, preservatives, anti-wrinkle agents, agents that reduce or treat under-eye bags, keratolytic agents, antimicrobial agents, agents that stimulate the synthesis of dermal or epidermal macromolecules and / or inhibit or prevent their degradation, agents that stimulate elastin synthesis, agents that stimulate core proteoglycan synthesis, agents that stimulate laminin synthesis, and agents that stimulate defensin synthesis. Agents, agents stimulating chaperone protein synthesis, agents stimulating cAMP synthesis, agents stimulating hyaluronic acid synthesis, agents stimulating fibronectin synthesis, agents stimulating deacetylase synthesis, agents stimulating lipid and stratum corneum component synthesis, ceramides, fatty acids, agents inhibiting elastin degradation, agents inhibiting serine proteases, agents stimulating fibroblast proliferation, agents stimulating keratinocyte proliferation, agents stimulating adipocyte proliferation, agents stimulating melanocyte proliferation, agents stimulating keratinocyte differentiation, agents inhibiting acetylcholinesterase, skin relaxants, agents stimulating glycosaminoglycan synthesis, anti-hyperkeratosis agents, comedolytic agents, anti-psoriasis agents, anti-eczema agents, DNA repair agents, DNA protectants, stabilizers, antipruritic agents, for the treatment and / or protection of skin. Agents for sensitive skin, including hardening agents, firming agents, reconstructing agents, anti-stretch mark agents, agents that regulate sebum production, antiperspirants, agents that stimulate healing, agents that assist healing, agents that stimulate re-epithelialization, agents that assist re-epithelialization, cytokines, sedatives, anti-inflammatory agents, agents that act on capillary circulation and / or microcirculation, agents that stimulate angiogenesis, agents that inhibit vascular permeability, venous tension agents, agents that act on cell metabolism, agents for improving dermal-epidermal junction, agents that induce hair growth, agents that inhibit or delay hair growth, fragrances, chelating agents, plant extracts, essential oils, marine extracts, agents derived from bio-fermentation processes, inorganic salts, cell extracts, sunscreens, and organic or inorganic photoprotective agents or mixtures thereof that effectively resist UVA and / or UVB rays.

[0037] The effective amount of the disclosed peptides to be administered and their dosage will depend on many factors, including age, the user's condition, the severity of the condition, the route and frequency of administration, and the specific nature of the peptide to be used.

[0038] "Effective amount" means an amount of one or more peptides of this disclosure that is non-toxic but sufficient to provide the desired effect. The peptides of this disclosure are used in compositions of this disclosure at effective concentrations to obtain 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.

[0039] Another aspect of this disclosure provides a delivery system or sustained-release system for better penetration of the active ingredient, comprising an effective amount of the aforementioned peptide, or a stereoisomer thereof, or a mixture thereof, or a salt thereof, or a combination thereof.

[0040] The term "delivery system" refers to a diluent, adjuvant, excipient, or carrier applied with the peptides of this disclosure, selected from water, oil, or surfactants, including those of petroleum, animal, plant, or synthetic origin, such as and not limited to peanut oil, soybean oil, mineral oil, sesame oil, castor oil, polysorbate, sorbitol ester, ether sulfate, sulfate, betaine, glucosinolate, maltodextrin, fatty alcohol, nonyl alcohol ether, poloxamer, polyoxyethylene, polyethylene glycol, dextran, glycerol, digitalis saponins, and the like. Those skilled in the art are familiar with various diluents, adjuvants, excipients, or carriers that can be used in different delivery systems for administering the peptides of this disclosure.

[0041] The term "sustained release" is used in its conventional sense to refer to a compound delivery system that provides the gradual release of a compound over a period of time. In some embodiments, the sustained release system maintains a relatively constant level of compound release throughout the entire time period.

[0042] Examples of delivery systems or sustained-release systems include, but are not limited to: liposomes, oil bodies, alcohol bodies, millimeter capsules, micrometer capsules, nanocapsules, nanostructured lipid carriers, sponges, inclusion complexes, lipid vesicles, micelles, millimeter spheres, micrometer spheres, nanospheres, lipid spheres, micrometer emulsions, nanoemulsions, millimeter particles, micrometer particles, or nanoparticles.

[0043] In another aspect of this disclosure, a cosmetic product is provided, comprising an effective amount of the aforementioned peptide, or a stereoisomer thereof, or a mixture of stereoisomers thereof, or a salt thereof, or a composition thereof, or a delivery system or sustained-release system thereof.

[0044] In some embodiments, the dosage form of the cosmetic includes ointment, cream, emulsion, aqueous solution, oil, gel, powder, tablet, mud, patch, film, aerosol, spray, lyophilized preparation or nano-preparation.

[0045] Another aspect of this disclosure provides the use of the above-described peptide, or a stereoisomer thereof, or a mixture thereof, or a salt thereof, or the above-described composition, or the above-described delivery system or sustained-release system in the preparation of a composition for the care of skin or mucous membranes.

[0046] Another aspect of this disclosure provides the use of the above-described peptide, or a stereoisomer thereof, or a mixture thereof, or a salt thereof, or the above-described composition, or the above-described delivery system or sustained-release system in the preparation of compositions for oil control, anti-aging, or anti-glycation.

[0047] In another aspect of this disclosure, there is provided the use of the above-described peptide, or its stereoisomer, or mixture of its stereoisomers, or its salt, or the above-described composition, or the above-described delivery system or sustained-release system in the preparation of a composition for reducing skin sebum synthesis or secretion; or in the preparation of a composition for preventing or reducing wrinkles; or in the preparation of a composition for inhibiting calcium ion influx; or in the preparation of a composition for inhibiting the formation of advanced glycation end products; or in the preparation of a composition for improving dull skin and / or brightening skin tone.

[0048] Another aspect of this disclosure provides the use of the above-described peptide, or its stereoisomer, or a mixture of its stereoisomers, or a salt thereof, or the above-described composition, or the above-described delivery system or sustained-release system in the preparation of cosmetics.

[0049] In some embodiments, the cosmetic is used for oil control, anti-aging, or anti-glycation.

[0050] In this disclosure, the term "skin" should be understood as comprising its multiple layers, from the uppermost layer or stratum corneum to the lowermost layer or subcutaneous tissue, including both ends. These layers are composed of different types of cells, such as keratinocytes, fibroblasts, melanocytes, and / or adipocytes. In this disclosure, the term "skin" includes the scalp.

[0051] The term "skin care" refers to the maintenance and care of the skin to improve its condition, making it delicate, smooth, soft, and healthy.

[0052] The term "prevention" refers to the ability of the peptides disclosed herein to prevent, delay, or hinder the occurrence or development of a disease or condition before it occurs.

[0053] This disclosure has the following advantages and effects:

[0054] The disclosed compound can effectively inhibit the synthesis or secretion of sebum by sebaceous gland cells, slow down sebum deposition, and has an oil-controlling effect.

[0055] The disclosed compound can effectively inhibit the influx of calcium ions, thereby inhibiting muscle contraction, and can be used to prevent or reduce wrinkles, thus having an anti-aging effect.

[0056] The compounds disclosed herein can effectively inhibit the formation of AGEs, reduce the damage of glycation reactions to the skin, improve the dull and sallow skin condition, thereby delaying skin aging, brightening the skin tone, and having anti-aging and anti-glycation effects.

[0057] The disclosed compounds have oil-controlling, anti-aging, and anti-glycation effects and can be used for skin or mucous membrane care. Attached Figure Description

[0058] To more clearly illustrate the technical solutions of this disclosure, the accompanying drawings used in the description of this disclosure will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of this disclosure. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0059] Figure 1 This is Example 1 of the present disclosure, Cyclohexapeptide A (molecular formula C). 39 H 53 N9O 12 The mass spectrum of ).

[0060] Figure 2 This is Example 2 of the present disclosure, hexapeptide B (molecular formula C). 39 H 55 N9O 13 The mass spectrum of ). Detailed Implementation

[0061] To make the objects, features, and advantages of this disclosure more apparent and understandable, the disclosure will be further described in detail below with reference to the accompanying drawings and embodiments. Obviously, the described embodiments are only some, not all, of the embodiments of this disclosure. All other embodiments obtained by those skilled in the art based on the embodiments of this disclosure without inventive effort are within the scope of protection of the appended claims.

[0062] In this disclosure, the abbreviations used for amino acids follow the rules specified by the IUPAC-IUB Commission of Biochemical Nomenclature in the European Journal of Biochemistry (Eur. J. Biochem. 1984, 138: 9-37).

[0063] Unless otherwise specified, all experimental reagents and materials used in this disclosure are commercially available. The following are abbreviations for some reagents and materials:

[0064] 2-CTC Resin: A starting resin for polypeptide synthesis (2-chlorotriphenylmethyl chloride resin); DCM: dichloromethane; DMF: N,N-dimethylformamide; DIPEA: diisopropylethylamine; MeOH: methanol; piperidine: piperidine; HOBt: 1-hydroxybenzotriazole; DIC: diisopropylcarbodiimide; TFA: trifluoroacetic acid; HATU: 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate; NaHCO3: sodium bicarbonate; EA: ethyl acetate; Tis: triisopropylsilane; EDT: ethylenedithiol; Tyr: tyrosine; Arg: arginine; Nle: leucine; Glu: glutamic acid; Asp: aspartic acid; Fmoc: 9-fluorenylmethoxycarbonyl; tBu: tert-butyl; OtBu: tert-butoxy; Pbf: 2, 2, 4, 6, 7-Pentamethyldihydrobenzofuran-5-sulfonyl; Ac-: Acetyl (CH3-CO-); Palm-: Palmitoyl (CH3-(CH2) 14 -CO-); Myr-: Myristoyl (CH3-(CH2) 12 -CO-); Lauroyl-: lauroyl (CH3-(CH2) 10 -CO-).

[0065] Example 1: Preparation of Cyclo-[Tyr-Tyr-Arg-Nle-Glu-Asp]

[0066] Cyclo-[Tyr-Tyr-Arg-Nle-Glu-Asp] is prepared through the following steps:

[0067] 1.1 Swelling of the resin

[0068] Weigh 80g of 2-CTC Resin into a solid-phase synthesis reaction column, swell it with DCM, wash the resin, and remove the solvent.

[0069] 1.2 Feeding and Reaction

[0070] Weigh 78 g of Fmoc-Asp(OtBu)-OH into a dry Erlenmeyer flask, dissolve it in DMF, and cool it in an ice-water bath for 10 min. Add 90 mL of DIPEA and activate for 10 min. Add the activated Fmoc-Asp(OtBu)-OH to the swollen resin and react for 3 h. Remove the reaction solution, wash the resin, and remove the solvent. Continue to add DCM, MeOH, and DIPEA for end-capping treatment for 40 min. Wash the resin, remove the solvent, and obtain Fmoc-Asp(OtBu)-2-CTC Resin.

[0071] Fmoc-Asp(OtBu)-2-CTC Resin was deprotected twice with 20% piperidine / DMF, 5-10 min each time. A sample was tested with K (K+) and a deep blue color was observed. The resin was washed 7 times with DMF, and the solvent was removed. 63.8 g of Fmoc-Glu(OtBu)-OH and 24.3 g of HOBt were weighed and added to a dry Erlenmeyer flask. DMF was added to dissolve the amino acids, and the flask was sealed and placed at -18°C for 30 min. 34.6 mL of DIC was added for activation for 3 min. The activated amino acids were added to the deprotected resin and reacted for 1 h. The reaction solution was then removed. A colorless and transparent K-test indicates complete reaction, yielding Fmoc-Glu(OtBu)-Asp(OtBu)-2-CTC Resin.

[0072] The N-terminal Fmoc group was deprotected, and 53 g of the activated Fmoc-Nle-OH was coupled to a peptide resin in the presence of 24.3 g HOBt and 34.6 mL DIC, using DMF as a solvent, and the reaction was continued for 1 h. The resin was then washed, and the deprotection treatment of the Fmoc group was repeated to couple the next amino acid. In each coupling, 97.3 g of Fmoc-Arg(Pbf)-OH, 68.9 g of Fmoc-Tyr(tBu)-OH, and subsequently 68.9 g of Fmoc-Tyr(tBu)-OH were sequentially coupled using DMF as a solvent in the presence of 24.3 g of HOBt and 34.6 mL of DIC. After the reaction was complete, the resin was washed and the solvent was removed to obtain Fmoc-Tyr(tBu)-Tyr(tBu)-Arg(Pbf)-Nle-Glu(OtBu)-Asp(OtBu)-2-CTC Resin.

[0073] The N-terminal Fmoc group of the peptide resin was deprotected twice with 20% piperidine / DMF, 5-10 min each time. A sample was taken for K testing; the result was a deep blue color. The resin was washed six times with DMF, and the solvent was removed. After treatment, H-Tyr(tBu)-Tyr(tBu)-Arg(Pbf)-Nle-Glu(OtBu)-Asp(OtBu)-2-CTC Resin with a wet weight of 208 g was obtained.

[0074] 1.3 Resin removal

[0075] Place TFA in a -18°C refrigerator for 1.5 hours.

[0076] Prepare 800 mL of 2% TFA / DCM lysis buffer. Add 208 g of H-Tyr(tBu)-Tyr(tBu)-Arg(Pbf)-Nle-Glu(OtBu)-Asp(OtBu)-2-CTC Resin under stirring at room temperature. A gel-like substance precipitates during the reaction. Add 100 mL of DMF to increase the solubility of the system. Stir the reaction for 30–40 min, filter, and collect the filtrate. Repeat once. Combine the filtrates, rotary evaporate until no dripping occurs, allow to settle, and precipitate the solid with 5–6 L of purified water. Filter and dry to obtain 135 g of H-Tyr(tBu)-Tyr(tBu)-Arg(Pbf)-Nle-Glu(OtBu)-Asp(OtBu)-OH.

[0077] 1.4 Loop closure

[0078] 135g of H-Tyr(tBu)-Tyr(tBu)-Arg(Pbf)-Nle-Glu(OtBu)-Asp(OtBu)-OH, 45g of HATU, 10.6g of HOBt, 25.5g of DIPEA, 7L of DCM, and 1L of DMF were reacted overnight. 0.3L of DMF and 25g of HATU were added, and the reaction was continued for 2 hours. The DCM was removed by concentration. Three volumes of NaHCO3 aqueous solution were added to the remaining DMF solution after concentration. Extraction was performed by EA, and the EA phase was concentrated to obtain 122g of Cyclo-[Tyr(tBu)-Tyr(tBu)-Arg(Pbf)-Nle-Glu(OtBu)-Asp(OtBu)] fully protected cyclic peptide.

[0079] 1.5 Cleavage (deprotection)

[0080] Take 594 mL TFA, 15.2 mL Tis, 15.2 mL water, 15.2 mL EDT, and 15.2 mL anisole and mix well. Add 122 g of the above fully protected cyclic peptide and lyse for 2.5 h. Precipitate with isopropyl ether and post-process to obtain a crude Cyclo-[Tyr-Tyr-Arg-Nle-Glu-Asp] peptide with a wet weight of 213 g.

[0081] 1.6 Purification

[0082] 213g of Cyclo-[Tyr-Tyr-Arg-Nle-Glu-Asp] crude peptide was dissolved in 1020mL of purified water, isopropyl ether was removed by rotary evaporation, ammonia was added to adjust the pH to 8, activated carbon was added, the mixture was filtered, and the sample was loaded for purification by reversed-phase HPLC. The purification gradient is shown in Table 1 below.

[0083] Table 1

[0084] Time (min) Flow rate (mL / min) A% (acetonitrile) B% (Purified Water) 0 40 5 95 10 40 15 85 30 40 18 82 45 40 18 82 60 40 22 78

[0085] The filtered sample was purified by injection, the fraction was collected, concentrated and lyophilized to obtain a cyclic peptide Cyclo-[Tyr-Tyr-Arg-Nle-Glu-Asp] with a purity of 98.1%, denoted as cyclic hexapeptide A, with the chemical structure shown below:

[0086] .

[0087] The molecular weight of cyclic hexapeptide A was determined, and the mass spectrum is shown below. Figure 1 As shown. The results show that [M+H] + The mass-to-charge ratio (m / z) of the quasi-molecular ion peak was 840.3927, and the molecular weight measured by mass spectrometry was 839.39, which is consistent with the theoretical precise molecular weight of cyclic hexapeptide A.

[0088] Example 2: Preparation of H-Tyr-Tyr-Arg-Nle-Glu-Asp-OH

[0089] 2.1 Swelling of the resin

[0090] Weigh 20g of 2-CTC Resin into a solid-phase synthesis reaction column, swell it with DCM, wash the resin, and remove the solvent.

[0091] 2.2 Feeding and Reaction

[0092] Weigh 19.5 g of Fmoc-Asp(OtBu)-OH into a dry Erlenmeyer flask, dissolve it in DMF, and cool it in an ice-water bath for 10 min. Add 22.6 mL of DIPEA and activate for 10 min. Add the activated Fmoc-Asp(OtBu)-OH to the swollen resin and react for 3 h. Remove the reaction solution, wash the resin, and remove the solvent. Continue adding DCM, MeOH, and DIPEA for end-capping treatment for 20 min. Wash the resin, remove the solvent, and obtain Fmoc-Asp(OtBu)-2-CTC Resin.

[0093] Fmoc-Asp(OtBu)-2-CTC Resin was deprotected twice with 20% piperidine / DMF, 10 min each time. A sample was tested for K, and a deep blue color was observed. The resin was washed 7 times with DMF, and the solvent was removed. 16.1 g of Fmoc-Glu(OtBu)-OH and 6.2 g of HOBt were weighed and added to a dry Erlenmeyer flask. DMF was added to dissolve the flask, and the flask was sealed and placed in a -18°C refrigerator for 30 min. 8.5 mL of DIC was added for activation for 3 min. The activated amino acid was added to the deprotected resin and reacted for 1 h. The reaction solution was then removed. A colorless and transparent K test of the resin indicated complete reaction, yielding Fmoc-Glu(OtBu)-Asp(OtBu)-2-CTC Resin.

[0094] The N-terminal Fmoc group was deprotected, and 13.4 g of the activated Fmoc-Nle-OH was coupled to a peptide resin in the presence of 6.2 g HOBt and 8.5 mL DIC using DMF as a solvent, with the reaction lasting 1 h. The resin was then washed, and the deprotection treatment of the Fmoc group was repeated to couple the next amino acid. In each coupling, 32.7 g of Fmoc-Arg(Pbf)-OH was coupled using DMF as a solvent in the presence of 8.2 g HOBt and 11.7 mL DIC; 20.3 g of Fmoc-Tyr(tBu)-OH and subsequently 20.3 g of Fmoc-Tyr(tBu)-OH were coupled sequentially in the presence of 7.2 g HOBt and 10.2 mL DIC; after the reaction was complete, the resin was washed, the solvent was removed, and Fmoc-Tyr(tBu)-Tyr(tBu)-Arg(Pbf)-Nle-Glu(OtBu)-Asp(OtBu)-2-CTC Resin was obtained.

[0095] The N-terminal Fmoc group of the peptide resin was deprotected twice with 20% piperidine / DMF, 10 min each time. A sample was taken for K-test, and a deep blue color was observed. The resin was washed 6 times with DMF, and the solvent was removed. After shrinkage and drying, 46 g of H-Tyr(tBu)-Tyr(tBu)-Arg(Pbf)-Nle-Glu(OtBu)-Asp(OtBu)-2-CTC Resin was obtained.

[0096] 2.3 Pyrolysis

[0097] Measure 34.2 mL of TFA, 0.9 mL of Tis, and 0.9 mL of water, mix and stir well to obtain the lysis solution, seal and store at -18°C for later use; store isopropyl ether at -18°C for later use.

[0098] Weigh 5.7 g of H-Tyr(tBu)-Tyr(tBu)-Arg(Pbf)-Nle-Glu(OtBu)-Asp(OtBu)-2-CTCResin into a round-bottom flask, add the previously frozen lysis buffer, and stir for 2.5 h. Filter, collect the filtrate, add isopropyl ether, stir, centrifuge, wash three times, and vacuum dry to obtain 17.5 g of crude H-Tyr-Tyr-Arg-Nle-Glu-Asp-OH peptide.

[0099] 2.4 Purification

[0100] Weigh 17.5g of the above-mentioned H-Tyr-Tyr-Arg-Nle-Glu-Asp-OH crude peptide, dissolve it in 200mL of purified water, sonicate, filter, and purify by reversed-phase HPLC. The purification gradient is shown in Table 2 below:

[0101] Table 2

[0102] Time (min) Flow rate (mL / min) A% (acetonitrile) B% (Purified Water) 0 40 5 95 10 40 15 85 30 40 20 80 50 40 20 80

[0103] The filtered sample was purified by injection, the fraction was collected, concentrated, and lyophilized to obtain peptide H-Tyr-Tyr-Arg-Nle-Glu-Asp-OH with a purity of 96.8%, denoted as hexapeptide B. The molecular weight of hexapeptide B was determined, and the mass spectrum is shown below. Figure 2 As shown. The results show that [MH] - The mass-to-charge ratio (m / z) of the quasi-molecular ion peak was 856.3117, and the molecular weight measured by mass spectrometry was 857.31, which is consistent with the theoretical precise molecular weight of hexapeptide B.

[0104] Other peptides disclosed herein, including but not limited to: H-Tyr-Tyr-Arg-Nle-Glu-Asp-NH2, Ac-Tyr-Tyr-Arg-Nle-Glu-Asp-OH, Ac-Tyr-Tyr-Arg-Nle-Glu-Asp-NH2, Myr-Tyr-Tyr-Arg-Nle-Glu-Asp-OH, Myr-Tyr-Tyr-Arg-Nle-Glu-Asp-NH2, Palm-Tyr-Tyr-Arg-Nle-Glu-Asp-OH, Palm-Tyr-Tyr-Arg-Nle-Glu-Asp-NH2, Lauroyl-Tyr-Tyr-Arg-Nle-Glu-Asp-OH, Lauroyl-Tyr-Tyr-Arg-Nle-Glu-Asp-NH2, etc., can be prepared by similar peptide solid-phase synthesis methods.

[0105] Example 3: Oil Content Test

[0106] 3.1 Reagents and Materials

[0107] 0.25% trypsin digestion solution, PBS, complete culture medium, FFA (linoleic acid and palmitic acid mixed in a 1:1 molar ratio), Oil Red O staining kit, and isopropanol.

[0108] 3.2 Instruments

[0109] Constant temperature CO2 incubator, clean bench, microplate reader.

[0110] 3.3 Cell lines

[0111] Human sebaceous gland cells (SZ-95).

[0112] 3.4 Samples to be tested and grouping

[0113] 3.4.1 Sample to be tested

[0114] Cyclic hexapeptide A and hexapeptide B were both dissolved in PBS, and the test concentration was 50 ppm.

[0115] 3.4.2 Grouping

[0116] Experimental group: FFA, the sample to be tested.

[0117] Blank control group: PBS.

[0118] Model groups: FFA, PBS.

[0119] 3.5 Experimental Methods

[0120] Take one flask of SZ-95 cells in good exponential growth phase, add 0.25% trypsin digestion solution, digest to detach the adherent cells, and count (1~4)×10⁻⁶ cells. 5 Cells were cultured at a concentration of [number] cells / mL to prepare a cell suspension. An appropriate amount of the cell suspension was seeded into a 12-well plate containing complete culture medium and incubated in a CO2 incubator for 24 h. Except for the blank control group which received PBS, each well of the other plates received FFA to a final concentration of 225 μmol / L. Simultaneously with induction of cell modeling, the experimental groups received the corresponding test samples, while the model group received the same amount of PBS. The plates were incubated in a CO2 incubator for 48 h. The culture medium was then discarded, and staining was performed according to the Oil Red O staining kit instructions.

[0121] Discard the solution in the well plate, add isopropanol to dissolve the Oil Red O staining solution, and measure the absorbance at 490 nm using a microplate reader. Calculate the relative content of lipid secretion from the cells based on the absorbance values.

[0122] Relative oil content = (OD value of test group / OD value of blank control group) × 100%

[0123] 3.6 Experimental Results

[0124] Oil Red O is a fat-soluble dye that is highly soluble in fat. Its staining principle is that Oil Red O specifically adsorbs onto neutral triglycerides, lipids, and lipoproteins in tissues and cells, thus staining the fat. Free-floxacin (FFA) is an inducer; under FFA stimulation, SZ-95 cells secrete large amounts of oil that can be stained by Oil Red O. In this experiment, test samples were used to treat SZ-95 cells induced by FFA stimulation. By detecting the amount of oil produced by SZ-95 cells, the extent to which the disclosed peptide can inhibit sebum secretion by sebaceous gland cells was determined.

[0125] The results of the effects of the test samples on lipid secretion in SZ-95 cells are shown in Table 3.

[0126] Table 3. Relative lipid secretion in SZ-95 cells

[0127] Group Relative sebum secretion (Mean±SD) Blank control group 100.00%±5.59% Model group <![CDATA[242.72%±1.32% ### ]]> Cyclic hexapeptide A group 87.30%±0.65%*** Hexapeptide B group 146.03%±2.28%***

[0128] Note: Compared with the blank control group ### P <0.001; compared with the model group, *** P <0.001.

[0129] Experimental results show that both cyclic hexapeptide A and hexapeptide B can effectively inhibit the synthesis or secretion of sebum by sebaceous gland cells, slow down sebum deposition, and can be used to improve problems such as excessive oil production and water-oil imbalance in the skin, thus having an oil-controlling effect. Compared with linear hexapeptide B, cyclic hexapeptide A, obtained by cyclocyclizing hexapeptide B head-to-tail, has a significantly enhanced ability to inhibit sebum synthesis and secretion.

[0130] Example 4: Calcium ion influx test

[0131] 4.1 Reagents and Materials

[0132] 0.25% trypsin digestion solution, PBS, acetylcholine solution containing 1% fetal bovine serum, and Fluo-3AM calcium ion probe.

[0133] 4.2 Instruments

[0134] Fluorescence microscope, constant temperature CO2 incubator, ultra-clean workbench.

[0135] 4.3 Cell lines

[0136] Mouse neuroblastoma cells (Neuro-2a cells).

[0137] 4.4 Samples to be tested and grouping

[0138] 4.4.1 Sample to be tested

[0139] Cyclic hexapeptide A and hexapeptide B were tested at a concentration of 25 ppm.

[0140] 4.4.2 Grouping

[0141] Experimental group: The sample to be tested was an acetylcholine solution containing 1% fetal bovine serum.

[0142] Control group: PBS, acetylcholine solution containing 1% fetal bovine serum.

[0143] 4.5 Experimental Methods

[0144] Take one flask of Neuro-2a cells in good exponential growth phase, add 0.25% trypsin digestion solution, digest to detach the adherent cells, and count (1~4) × 10⁻⁶ cells. 5Cells were cultured at a density of [number] cells / mL to prepare a cell suspension. An appropriate amount of cell suspension was seeded into a 12-well plate containing complete culture medium and incubated in a CO2 incubator for 24 h. The complete culture medium was then removed from the wells. The experimental group received complete culture medium and the test sample, while the control group received complete culture medium and an equal volume of PBS. The plates were incubated in a CO2 incubator for 24 h. The supernatant was discarded, and the cells were washed twice with PBS. Fluo-3AM working solution was added to the 12-well plates and incubated at 37°C for 30 min. The Fluo-3AM working solution was discarded. The experimental group received the test sample and an acetylcholine solution containing 1% fetal bovine serum (FBS). The control group received an equal volume of PBS and an acetylcholine solution containing 1% FBS. The plates were incubated for 5 min. The supernatant was discarded, and the cells were washed twice with PBS. The cells were observed and photographed under a fluorescence microscope, and relative fluorescence intensity was analyzed using ImageJ software.

[0145] 4.6 Experimental Results

[0146] Calcium ion influx plays a crucial role in skin and muscle contraction. Inhibiting calcium ion influx can reduce excessive muscle contraction, improve skin surface wrinkles, and reduce wrinkle depth, thereby achieving an anti-wrinkle effect. The calcium ion content in cells is directly proportional to the fluorescence staining intensity; that is, the stronger the fluorescence intensity, the higher the calcium ion content in the cells. This experiment determined whether the disclosed peptide could inhibit calcium ion influx by detecting the relative fluorescence intensity of calcium ions in Neuro-2a cells.

[0147] The results of the test samples on the calcium ion influx in Neuro-2a cells are shown in Table 4.

[0148] Table 4. Relative calcium ion content in Neuro-2a cells

[0149] Group Relative calcium ion content (Mean±SD) control group 100.00%±2.19% Cyclic hexapeptide A group 69.77%±1.88%*** Hexapeptide B group 82.73%±4.63%**

[0150] Note: Compared with the control group, ** P <0.01, *** P <0.001.

[0151] The results showed that, compared with the control group, both cyclic hexapeptide A and hexapeptide B of this disclosure significantly reduced calcium ion content in Neuro-2a cells and inhibited calcium ion influx. Compared with linear hexapeptide B, cyclic hexapeptide A, obtained by cyclocyclizing hexapeptide B head-to-tail, significantly enhanced its ability to inhibit calcium ion influx. Therefore, the compounds of this disclosure can effectively inhibit calcium ion influx, thereby inhibiting muscle contraction, and can be used to prevent or reduce wrinkles, exhibiting anti-aging effects.

[0152] Example 5 Anti-glycation test

[0153] 5.1 Reagents and Materials

[0154] PBS, MGO, bovine serum albumin (BSA), aminoguanidine hydrochloride, Proclin 300.

[0155] 5.2 Instruments

[0156] ELISA reader.

[0157] 5.3 Samples to be tested and grouping

[0158] 5.3.1 Sample to be tested

[0159] Cyclic hexapeptide A, hexapeptide B, and aminoguanidine hydrochloride (positive control) were all tested at a concentration of 1 ppm.

[0160] 5.3.2 Grouping

[0161] Blank control group: PBS was added.

[0162] Experimental group: Cyclic hexapeptide A, hexapeptide B, aminoguanidine hydrochloride.

[0163] 5.4 Experimental Methods

[0164] Prepare 5 mmol / L MGO solution, 10 mg / mL BSA solution, and 1 mg / mL aminoguanidine hydrochloride solution. Add a mixture of 10 mg / mL BSA, 5 mmol / L MGO, and Proclin 300 to 0.2 mol / L phosphate buffer (pH 7.4) to prepare AGEs. Add each group of test samples to the BSA-MGO model at a 1:1 volume ratio and shake well. Incubate all reaction mixtures at 37°C under sterile conditions for 7 days. The blank control group is prepared by replacing the test samples with the same volume of PBS, with the remaining procedures identical. Before determining the anti-glycation effect, each reaction mixture is diluted 5-fold with PBS and then transferred to a 96-well black plate to detect its fluorescence intensity at an excitation wavelength of 360 nm and an emission wavelength of 420 nm. The AGEs inhibition rate of the test samples is calculated using the following formula:

[0165] AGEs inhibition rate % = (1 - F1 / F0) × 100%

[0166] Where F1 is the fluorescence value of the test sample and F0 is the fluorescence value of the blank control.

[0167] 5.5 Experimental Results

[0168] Advanced glycation end products (AGEs) are stable end products formed by the non-enzymatic glycation reaction of proteins with reducing sugars. The amount of AGEs generated, which exhibits fluorescence properties, is positively correlated with their fluorescence intensity. In this experiment, an in vitro AGEs generation model was constructed using BSA and MGO. By detecting changes in fluorescence intensity in different samples, the anti-glycation activity of the peptide disclosed in this study was determined.

[0169] The inhibition rates of the test samples against AGEs are shown in Table 5.

[0170] Table 5. Inhibition rate of AGEs by the test samples

[0171] Group AGEs inhibition rate (Mean±SD) Blank control group 0.00%±0.81% aminoguanidine hydrochloride group 9.00%±1.05%*** Cyclic hexapeptide A group 14.24%±1.13%*** Hexapeptide B group 8.02%±2.00%**

[0172] Note: Compared with the blank control group, ** P <0.01, *** P <0.001.

[0173] Aminoguanidine hydrochloride can effectively inhibit the formation of advanced glycation end products (AGEs) and has anti-glycation effects, often used as a positive control in anti-glycation experiments. In this experiment, aminoguanidine hydrochloride showed anti-glycation effects even at low concentrations. The cyclic hexapeptide A and hexapeptide B disclosed herein can also inhibit the formation of advanced glycation end products to some extent at low concentrations. Compared to linear hexapeptide B, cyclic hexapeptide A, obtained by cyclocyclizing hexapeptide B end-to-end, further enhances its ability to inhibit AGE formation. The compounds disclosed herein can effectively inhibit AGE formation, reduce the damage of glycation reactions to the skin, improve dull and sallow skin, thereby delaying skin aging, brightening skin tone, and exhibiting anti-aging and anti-glycation effects.

[0174] Example 6

[0175] A cream is prepared through the following steps, and the specific formula is shown in Table 6 below:

[0176] Table 6

[0177]

[0178] According to the formula, heat phase C in a suitable container to 55-60℃ until completely dissolved, then set aside. Add phase A to a mixing pot and heat to 80-85℃. Add phase B to an oil phase pot and heat to 75-80℃ until completely dissolved. Transfer phase B into phase A, apply vacuum, homogenize for 5 minutes, maintain stirring, and keep warm for 20 minutes. Begin cooling to 60-65℃, add phase C, and homogenize for 2 minutes. Cool to 35-40℃, add the pre-dissolved phase D, and stir for 10-15 minutes to obtain the final product.

[0179] Example 7.

[0180] An essence is prepared through the following steps, and the specific formula is shown in Table 7 below:

[0181] Table 7

[0182]

[0183] According to the formula dosage, add all materials of phase A to the mixing pot, stir and heat to 80-85℃; mix all materials of phase B evenly until there are no powder particles, add to the mixing pot, and continue stirring for 10-15 minutes; start cooling down, cool down to 60-65℃, add materials of phase C; cool down to 35-40℃, add materials of phases D and E, stir for 10-15 minutes, and the product is ready.

[0184] In this disclosure, relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or terminal device that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or terminal device. Without further limitation, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or terminal device that includes said element.

[0185] While specific embodiments of this disclosure have been described for illustrative purposes, various modifications or alterations can be made by those skilled in the art without departing from the spirit and scope of this disclosure. All such modifications or alterations should fall within the scope of the appended claims.

Claims

1. The peptide or its salt represented by formula (I), R1-Tyr-Tyr-Arg-Nle-Glu-Asp-R2(I) In formula (I), R1 is selected from H, acetyl, lauroyl, myristoyl, or palmitoyl; R2 is -OH or -NH2.

2. A peptide or a salt thereof, characterized in that, The peptide is a cyclic peptide with the structure Cyclo-[Tyr-Tyr-Arg-Nle-Glu-Asp].

3. The peptide or its salt according to claim 1 or 2, characterized in that, The salt includes a metal salt of the peptide, and the metal includes: lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc or aluminum; Alternatively, the salt may comprise a salt formed by the peptide and an organic base, wherein the organic base may be ethylenediamine, ethanolamine, arginine, lysine, histidine, or piperazine. Alternatively, the salt may comprise a salt formed by the peptide and an inorganic or 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, pyric acid, or gluconic acid; and the inorganic acid includes: hydrochloric acid, sulfuric acid, boric acid, or carbonic acid.

4. A composition, characterized in that, It includes an effective amount of the peptide or salt thereof as described in any one of claims 1-3, as well as at least one excipient and optional adjuvant.

5. A delivery system or sustained-release system, characterized in that, Contains an effective amount of the peptide or its salt as described in any one of claims 1-3, or the composition as described in claim 4.

6. The delivery system or sustained-release system according to claim 5, characterized in that, The delivery system or sustained-release system includes: liposomes, oil bodies, alcohol bodies, millimeter capsules, micrometer capsules, nanocapsules, nanostructured lipid carriers, sponges, inclusion complexes, lipid vesicles, micelles, micrometer emulsions, nanoemulsions, millimeter particles, micrometer particles, or nanoparticles.

7. A cosmetic product, characterized in that, The present invention comprises an effective amount of the peptide or salt thereof as described in any one of claims 1-3, or the composition as described in claim 4, or the delivery system or sustained-release system as described in claim 5 or 6.

8. The cosmetic product according to claim 7, characterized in that, The dosage forms of the cosmetics include ointments, creams, emulsions, liquids, oils, gels, powders, tablets, muds, patches, films, aerosols, sprays, freeze-dried preparations, or nano-preparations.

9. Use of the peptide or salt thereof according to any one of claims 1-3, or the composition according to claim 4, or the delivery system or sustained-release system according to claim 5 or 6 in the preparation of compositions for oil control, anti-aging or anti-glycation.

10. The use according to claim 9, characterized in that, Oil control includes reducing the synthesis or secretion of sebum in the skin.

11. The use according to claim 9, characterized in that, The anti-aging measures include inhibiting the influx of calcium ions.

12. The use according to claim 9, characterized in that, The anti-glycation includes inhibiting the formation of advanced glycation end products (AGEs).

13. Use of the peptide or salt thereof according to any one of claims 1-3, or the composition according to claim 4, or the delivery system or sustained-release system according to claim 5 or 6 in the preparation of a composition for preventing or reducing wrinkles; or in the preparation of a composition for improving dull skin and / or brightening skin tone.

14. Use of the peptide or salt thereof according to any one of claims 1-3, or the composition according to claim 4, or the delivery system or sustained-release system according to claim 5 or 6 in the preparation of cosmetics for oil control, anti-aging, or anti-glycation.

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