A linear hexapeptide and cyclic peptides, compositions and uses thereof

Abstract

Disclosed are a linear hexapeptide and a cyclic peptide thereof, a composition and use, relating to the technical field of polypeptides, and the peptide or salt thereof has a structure shown in formula (I): R1-Pro-Leu-Trp-His-Val-Lys-R2 (I). Also disclosed is a cyclic peptide, and the structure of the cyclic peptide is Cyclo-[Pro-Leu-Trp-His-Val-Lys]. The compound of the disclosure has the effects of oil control, antioxidation, anti-glycation and the like, and can be used for nursing skin or mucosa.

Description

Technical Field

[0001] This disclosure relates to the field of polypeptide technology, and in particular to a linear hexapeptide and its cyclic peptides, compositions and uses. Background Technology

[0002] Oil control and anti-oxidation are two core directions in the field of skin health care. Under normal physiological conditions, sebum secreted by sebaceous glands is a core component of the skin's lipid film, maintaining skin health. However, an imbalance in sebum secretion can lead to problems such as oily skin, enlarged pores, and acne, which is one of the core pain points in skin care. Oxidative stress causes oxidative damage to skin cells and accelerates aging. Achieving antioxidant protection through exogenous means is a key step in basic skin care for all skin types. In the modern environment, the combined effects of multiple factors such as environmental pollution, ultraviolet radiation, life stress, and improper skin care not only directly lead to an imbalance in sebum secretion and the accumulation of oxidative stress, but also trigger a vicious cycle of "excessive sebum secretion - enhanced oxidative stress." For example, excessive sebum secretion not only leads to enlarged pores and frequent acne breakouts, but the lipid peroxides produced by sebum metabolism themselves exacerbate the skin's oxidative stress. Continuous oxidative stress is a key pathway that accelerates skin aging and also upregulates lipid synthesis-related signaling pathways, further aggravating abnormal sebum secretion. Therefore, for the health management of skin, especially oily skin, a comprehensive strategy must be adopted to simultaneously achieve precise regulation of sebum secretion and multiple defenses against oxidative damage.

[0003] However, current technological solutions in the skincare field have significant limitations. Most active ingredients focus on only a single functional dimension, such as only having cleansing and oil-controlling effects or only having antioxidant effects, making it difficult to synergistically intervene in the aforementioned multiple pathways, and therefore failing to meet people's multifaceted skincare needs. On the one hand, traditional oil-controlling ingredients mostly work by absorbing oil and regulating the sebum content on the skin surface, focusing only on the single dimension of sebum regulation, with a single level of action and target; on the other hand, commonly used antioxidants, although effective in scavenging free radicals, also focus only on the single functional dimension of antioxidant effects.

[0004] Therefore, further research and development of more active ingredients with multiple functions is still needed in this field. Summary of the Invention

[0005] This disclosure relates to a linear hexapeptide and its cyclic peptide, compositions and uses, wherein the linear hexapeptide, cyclic peptide, and compositions containing these compounds have multiple functions such as oil control and anti-oxidation, and can be used for skin 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-Pro-Leu-Trp-His-Val-Lys-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-C17 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-[Pro-Leu-Trp-His-Val-Lys], 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] Due to their application outside the mammalian body, the peptides of this disclosure can form 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 implementations...The adjuvants are selected from: agents that activate Clock expression, analgesics, agents that inhibit PAR-2 ​​activity, agents that regulate PGC-1α synthesis, agents that regulate PPARγ activity, agents that increase or decrease triglyceride content in 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 bleaching agents, pigmentation promoters, self-tanning agents, anti-aging agents, NO-synthesizers, 5α-reductase inhibitors, inhibitors of lysyl hydroxylase and / or prolyl hydroxylase, antioxidants, free radical scavengers, and other similar agents. Base scavengers 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 for the treatment and / or use of chaperone protein synthesis, cAMP synthesis, hyaluronic acid synthesis, fibronectin synthesis, deacetylase synthesis, lipid and stratum corneum component synthesis, ceramides, fatty acids, elastin degradation inhibitors, serine protease inhibitors, fibroblast proliferation stimulators, keratinocyte proliferation stimulators, adipocyte proliferation stimulators, melanocyte proliferation stimulators, keratinocyte differentiation stimulators, acetylcholinesterase inhibitors, skin relaxants, glycosaminoglycan synthesis stimulators, anti-hyperkeratosis agents, comedolytic agents, anti-psoriasis agents, anti-eczema agents, DNA repair agents, DNA protectants, stabilizers, antipruritic agents, for the treatment and / or use of chaperones. Agents for sensitive skin care, 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 acting on capillary circulation and / or microcirculation, agents that stimulate angiogenesis, agents that inhibit vascular permeability, venous tension agents, agents acting 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 protect against 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-oxidation, or anti-glycation.

[0047] In another aspect of this disclosure, there is a 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 a composition for reducing skin sebum synthesis or secretion; or in the preparation of a composition for scavenging free radicals or reactive oxygen species; or in the preparation of a composition for inhibiting the formation of advanced glycation end products.

[0048] Another aspect of this disclosure provides the use of the above-described peptide, or its stereoisomers, or mixtures thereof, or salts thereof, or the above-described compositions, or the above-described delivery systems or sustained-release systems in the preparation of cosmetics. In some embodiments, the cosmetics are used for oil control, anti-oxidation, or anti-glycation.

[0049] 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.

[0050] The term "skin care" refers to the maintenance and care of the skin to improve its condition, making it delicate, smooth, soft, and healthy.

[0051] This disclosure has the following advantages and effects:

[0052] 1. The compounds disclosed herein can inhibit the synthesis or secretion of sebum by sebaceous gland cells, slow down sebum deposition, and have an oil-controlling effect;

[0053] 2. The compounds disclosed herein can effectively scavenge DPPH, have antioxidant activity, and are beneficial in combating skin aging, thus having anti-aging and antioxidant effects;

[0054] 3. The compounds disclosed herein can effectively inhibit the formation of advanced glycation end products (AGEs), have anti-glycation activity, help combat skin aging, and have anti-aging and anti-glycation effects;

[0055] 4. The compounds disclosed herein have oil-controlling, antioxidant, and anti-glycation effects, and can be used for skin or mucous membrane care. Attached Figure Description

[0056] 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.

[0057] Figure 1 This is Example 1 of the present disclosure, Cyclohexapeptide A (molecular formula C). 39 H 56 N 10 The mass spectrum of O6.

[0058] Figure 2 This is Example 2 of the present disclosure, hexapeptide B (molecular formula C). 39 H 58 N 10 The mass spectrum of O7. Detailed Implementation

[0059] 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.

[0060] 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).

[0061] Unless otherwise specified, all experimental reagents and materials used in this disclosure are commercially available. The following are abbreviations for some reagents and materials:

[0062] 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; TFEA: 2,2,2-trifluoroethanol; TFA: trifluoroacetic acid; EDT: 1,2-ethylenedithiol; HATU: 2 -(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate; Tis: triisopropylsilane; Pro: proline; Leu: leucine; Trp: tryptophan; His: histidine; Val: valine; Lys: lysine; Fmoc: 9-fluorenylmethoxycarbonyl; Boc: tert-butoxycarbonyl; Trt: triphenylmethyl; Ac-: acetyl (CH3-CO-); Palm-: palmitoyl (CH3-(CH2)) 14 -CO-); Myr-: Myristoyl (CH3-(CH2) 12 -CO-); Lauroyl-: lauroyl (CH3-(CH2) 10 -CO-).

[0063] Example 1: Preparation of Cyclo-[Pro-Leu-Trp-His-Val-Lys]

[0064] Cyclo-[Pro-Leu-Trp-His-Val-Lys] is prepared through the following steps:

[0065] 1.1 Swelling of the resin

[0066] Weigh 20g of 2-CTC Resin into a solid-phase synthesis reaction column, swell it with DCM, wash the resin, and remove the solvent.

[0067] 1.2 Feeding and Reaction

[0068] Weigh 22.3 g of Fmoc-Lys(Boc)-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 it for 10 min. Add the activated Fmoc-Lys(Boc)-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 30 min. Wash the resin and remove the solvent to obtain Fmoc-Lys(Boc)-2-CTC Resin.

[0069] Fmoc-Lys(Boc)-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. 17.6 g of Fmoc-Val-OH and 8.4 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 in a -18°C refrigerator for 30 min. 12 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 indicated that the reaction was complete, yielding Fmoc-Val-Lys(Boc)-2-CTC Resin.

[0070] The N-terminal Fmoc group was deprotected, and 31.7 g of activated Fmoc-His(Trt)-OH was coupled to a peptide resin in the presence of 8.4 g HOBt and 12 mL DIC using DMF as a solvent, with the reaction lasting 1 h. The resin was then washed, and the deprotection of the Fmoc group was repeated to couple the next amino acid. In each coupling, 27.3 g of Fmoc-Trp(Boc)-OH, 18.3 g of Fmoc-Leu-OH, and 17.5 g of Fmoc-Pro-OH were sequentially coupled in the presence of 8.4 g HOBt and 12 mL DIC using DMF as a solvent; after complete reaction, the resin was washed, the solvent was removed, and Fmoc-Pro-Leu-Trp(Boc)-His(Trt)-Val-Lys(Boc)-2-CTC Resin was obtained.

[0071] The N-terminal Fmoc group of the peptide resin was deprotected twice with 20% piperidine / DMF, 8 min each time. A sample was taken for K-test, and the color development was deep blue. The resin was washed 4 times with DMF and 3 times with DCM to remove the solvent. After processing, 41 g of H-Pro-Leu-Trp(Boc)-His(Trt)-Val-Lys(Boc)-2-CTC Resin was obtained.

[0072] 1.3 Resin removal

[0073] Measure 307 mL of TFEA and 307 mL of DCM, mix them thoroughly, and prepare the lysis buffer.

[0074] Weigh 41 g of H-Pro-Leu-Trp(Boc)-His(Trt)-Val-Lys(Boc)-2-CTC Resin and add it to a round-bottom flask. Add the above lysis buffer, stir and react for 4 h, filter, and collect the filtrate. Filter again, and dry by rotary evaporation to obtain 21 g of H-Pro-Leu-Trp(Boc)-His(Trt)-Val-Lys(Boc)-OH.

[0075] 1.4 Loop closure

[0076] 21g of H-Pro-Leu-Trp(Boc)-His(Trt)-Val-Lys(Boc)-OH and 1.6g of HOBt were added to a flask, followed by 2L of DMF and stirring. Then, 6.5g of HATU and 3.6g of DIPEA were added, and the reaction was allowed to proceed for 4 hours. After the reaction was complete, post-treatment was performed, yielding a fully protected cyclic peptide of Cyclo-[Pro-Leu-Trp(Boc)-His(Trt)-Val-Lys(Boc)] with a wet weight of 29g.

[0077] 1.5 Cleavage (deprotection)

[0078] Take 130.5 mL TFA, 3.6 mL Tis, 3.6 mL water, 3.6 mL EDT, and 3.6 mL anisole and mix well. Add 27 g of the above fully protected cyclic peptide, stir for 2 h, filter, and post-process to obtain a crude Cyclo-[Pro-Leu-Trp-His-Val-Lys] peptide with a wet weight of 15.8 g.

[0079] 1.6 Purification

[0080] 15.8 g of Cyclo-[Pro-Leu-Trp-His-Val-Lys] crude peptide (wet weight) was dissolved in purified water, filtered, and purified by reversed-phase HPLC. The purification gradient is shown in Table 1 below:

[0081] Table 1

[0082] Time (min) Flow rate (mL / min) A% (acetonitrile) B% (0.1% acetic acid + purified water) 0 40 5 95 10 40 15 85 30 40 18 82 45 40 20 80

[0083] The filtered sample was purified by injection, the fraction was collected, concentrated and lyophilized to obtain a cyclic peptide Cyclo-[Pro-Leu-Trp-His-Val-Lys] with a purity of 96.8%, denoted as cyclic hexapeptide A, with the chemical structure shown below:

[0084] .

[0085] 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 761.4481, and the molecular weight measured by mass spectrometry was 760.45, which is consistent with the theoretical precise molecular weight of cyclic hexapeptide A.

[0086] Example 2: Preparation of H-Pro-Leu-Trp-His-Val-Lys-OH

[0087] 2.1 Swelling of the resin

[0088] Weigh 20g of 2-CTC Resin into a solid-phase synthesis reaction column, swell it with DCM, wash the resin, and remove the solvent.

[0089] 2.2 Feeding and Reaction

[0090] Weigh 22.3 g of Fmoc-Lys(Boc)-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 it for 10 min. Add the activated Fmoc-Lys(Boc)-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 30 min. Wash the resin and remove the solvent to obtain Fmoc-Lys(Boc)-2-CTC Resin.

[0091] Fmoc-Lys(Boc)-2-CTC Resin was deprotected twice with 20% piperidine / DMF, 10 min each time. A K test was performed on the sample; a deep blue color was observed. The resin was washed 7 times with DMF, and the solvent was removed. 17.6 g of Fmoc-Val-OH and 8.4 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 in a -18°C refrigerator for 30 min. 12 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 indicated complete reaction, yielding Fmoc-Val-Lys(Boc)-2-CTC Resin.

[0092] The N-terminal Fmoc group was deprotected, and 31.7 g of activated Fmoc-His(Trt)-OH was coupled to a peptide resin in the presence of 8.4 g HOBt and 12 mL DIC using DMF as a solvent, with the reaction lasting 1 h. The resin was then washed, and the deprotection of the Fmoc group was repeated to couple the next amino acid. In each coupling, 31.2 g Fmoc-Trp(Boc)-OH, 21.0 g Fmoc-Leu-OH, and 20.1 g Fmoc-Pro-OH were sequentially coupled in the presence of 9.6 g HOBt and 13.7 mL DIC using DMF as a solvent; after complete reaction, the resin was washed, the solvent was removed, and Fmoc-Pro-Leu-Trp(Boc)-His(Trt)-Val-Lys(Boc)-2-CTC Resin was obtained.

[0093] 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 processing, 60 g of H-Pro-Leu-Trp(Boc)-His(Trt)-Val-Lys(Boc)-2-CTC Resin was obtained.

[0094] 2.3 Pyrolysis

[0095] Measure 162 mL TFA, 4.5 mL Tis, 4.5 mL water, 4.5 mL EDT, and 4.5 mL anisole, mix them thoroughly to prepare the lysis buffer, seal it and store it in a -18°C freezer for later use; store the isopropyl ether in a -18°C freezer for later use.

[0096] 30g of H-Pro-Leu-Trp(Boc)-His(Trt)-Val-Lys(Boc)-2-CTC Resin was weighed and added to a round-bottom flask. The frozen lysis buffer was added, and the mixture was stirred for 2 hours. The mixture was filtered, and the filtrate was collected. Isopropyl ether was added, and the mixture was stirred, centrifuged, and washed three times. After processing, 30g of crude H-Pro-Leu-Trp-His-Val-Lys-OH peptide with a wet weight was obtained.

[0097] 2.4 Purification

[0098] Weigh 30g of the above-mentioned H-Pro-Leu-Trp-His-Val-Lys-OH crude peptide and dissolve it in 300mL of purified water. Remove isopropyl ether by rotary evaporation. Filter the solution through a 0.45μm microporous membrane to obtain a clear solution. Purify the solution by reversed-phase HPLC. The purification gradient is shown in Table 2 below.

[0099] Table 2

[0100] Time (min) Flow rate (mL / min) A% (acetonitrile) B% (Purified Water) 0 40 10 90 10 40 15 85 30 40 20 80 45 40 25 75

[0101] The filtered sample was purified by injection, the fraction was collected, concentrated, filtered, rotary evaporated, and lyophilized to obtain peptide H-Pro-Leu-Trp-His-Val-Lys-OH with a purity of 99.5%, 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 [M+H] + The mass-to-charge ratio (m / z) of the quasi-molecular ion peak was 779.4469, and the molecular weight measured by mass spectrometry was 778.45, which is consistent with the theoretical precise molecular weight of hexapeptide B.

[0102] Other peptides disclosed herein, including but not limited to: H-Pro-Leu-Trp-His-Val-Lys-NH2, Ac-Pro-Leu-Trp-His-Val-Lys-OH, Ac-Pro-Leu-Trp-His-Val-Lys-NH2, Myr-Pro-Leu-Trp-His-Val-Lys-OH, Myr-Pro-Leu-Trp-His-Val-Lys-NH2, Palm-Pro-Leu-Trp-His-Val-Lys-OH, Palm-Pro-Leu-Trp-His-Val-Lys-NH2, Lauroyl-Pro-Leu-Trp-His-Val-Lys-OH, Lauroyl-Pro-Leu-Trp-His-Val-Lys-NH2, etc., can be prepared by similar peptide solid-phase synthesis methods.

[0103] Example 3: Oil Content Test

[0104] 3.1 Reagents and Materials

[0105] 0.25% trypsin digestion solution (prepared by mixing 0.25g trypsin with 100mL water), PBS, complete culture medium, FFA (prepared by mixing linoleic acid and palmitic acid in a molar ratio of 1:1), Oil Red O staining kit, and isopropanol.

[0106] 3.2 Instruments

[0107] Microscope, constant temperature CO2 incubator, ultra-clean workbench, microplate reader, air bath constant temperature shaker.

[0108] 3.3 Cell lines

[0109] Human sebaceous gland cells (SZ-95).

[0110] 3.4 Samples to be tested and grouping

[0111] 3.4.1 Sample to be tested

[0112] Cyclic hexapeptide A and hexapeptide B were both dissolved in PBS, and the test concentration was 50 ppm.

[0113] 3.4.2 Grouping

[0114] Blank control group: PBS.

[0115] Model group: FFA induction + PBS.

[0116] Experimental group: FFA induction + test sample.

[0117] 3.5 Experimental Methods

[0118] 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 aspirated, and staining was performed according to the Oil Red O staining kit instructions.

[0119] 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.

[0120] Relative oil content = (OD value of test group / OD value of blank control group) × 100%

[0121] 3.6 Experimental Results

[0122] 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.

[0123] The results of the effects of the test samples on lipid secretion in SZ-95 cells are shown in Table 3.

[0124] Table 3. Relative lipid secretion of SZ-95 cells (n=4)

[0125] Group Relative sebum secretion (Mean±SD) Blank control group 100.00%±5.59% Model group <![CDATA[242.72%±1.32% ### ]]> Cyclic hexapeptide A group 88.89%±0.65%*** Hexapeptide B group 130.29%±1.37%***

[0126] Note: Compared with the blank control group ### P <0.001; compared with the model group, *** P <0.001.

[0127] 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.

[0128] Example 4 DPPH Test

[0129] 4.1 Reagents and Materials

[0130] DPPH, 95% methanol.

[0131] 4.2 Instruments

[0132] ELISA reader.

[0133] 4.3 Samples to be tested and grouping

[0134] 4.3.1 Sample to be tested

[0135] Cyclic hexapeptide A and hexapeptide B were dissolved in 95% methanol, and the test concentration was 100 ppm.

[0136] Vitamin C (positive control), tested at a concentration of 100 ppm.

[0137] 4.3.2 Grouping

[0138] Sample group: DPPH + test sample;

[0139] Blank group: DPPH + 95% methanol;

[0140] Sample control group: Test sample + 95% methanol;

[0141] Blank zeroing group: 95% methanol.

[0142] 4.4 Experimental Methods

[0143] Prepare a 200 μg / mL DPPH solution. Weigh the sample to be tested and dilute it to the required concentration with 95% methanol. Mix 100 μL of the sample solution with 100 μL of DPPH standard solution in a 1:1 ratio, react in the dark for 90 min, and then measure the absorbance S at 490 nm. Mix 95% methanol with the DPPH standard solution and measure the absorbance C at 490 nm. Use the sample to be tested and 95% methanol as a control and measure the absorbance S at 490 nm. b The absorbance C was measured at 490 nm using a 95% methanol solution. b The DPPH scavenging capacity of the sample to be tested is calculated using the following formula:

[0144] DPPH removal rate (%) =

[0145] 4.5 Experimental Results

[0146] DPPH is a stable nitrogen-centered free radical, and its alcoholic solution is purple. When DPPH pairs with a free radical scavenger using a single electron, the purple color of the alcoholic solution gradually fades. The degree of fading is quantitatively related to the number of electrons received, allowing for rapid quantitative analysis using an ELISA reader to evaluate the antioxidant capacity of the test substance. Vitamin C, by providing a hydrogen atom to pair with the nitrogen-centered DPPH free radical, has the effect of scavenging DPPH free radicals and is often used as a positive control in antioxidant activity experiments. In this experiment, DPPH is treated with test samples, and the color change of the methanolic solution of DPPH is detected to determine whether the peptide disclosed in this paper possesses antioxidant capacity.

[0147] The DPPH removal rate of the test samples is shown in Table 4.

[0148] Table 4. DPPH removal rate of the test samples (n=3)

[0149] Group DPPH clearance rate (Mean±SD) Blank control group (DPPH) 0.00%±1.77% Vitamin C group 65.40%±0.59%*** Cyclic hexapeptide A group 50.96%±0.63%*** Hexapeptide B group 22.90%±0.30%***

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

[0151] The results showed that both cyclic hexapeptide A and hexapeptide B of this disclosure significantly scavenged DPPH, exhibiting significant free radical and reactive oxygen species scavenging effects. Furthermore, compared to linear hexapeptide B, cyclic hexapeptide A, obtained by cyclocyclizing hexapeptide B end-to-end, showed a significantly enhanced DPPH scavenging ability. Cyclic hexapeptide A and hexapeptide B of this disclosure can effectively scavenge free radicals and reactive oxygen species, demonstrating antioxidant 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 and hexapeptide B were tested at a concentration of 10 ppm.

[0160] Aminoguanidine hydrochloride (positive control), test concentration 10 ppm.

[0161] 5.3.2 Grouping

[0162] Blank control group: PBS added;

[0163] Experimental group: Cyclic hexapeptide A, hexapeptide B, aminoguanidine hydrochloride.

[0164] 5.4 Experimental Methods

[0165] 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 other procedures remaining the same. 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.

[0166] The AGEs inhibition rate of the sample to be tested is calculated using the following formula:

[0167] AGEs inhibition rate (%) = (1-F1 / F0) × 100%

[0168] Where F1 is the fluorescence value of the test sample and F0 is the fluorescence value of the blank control.

[0169] 5.5 Experimental Results

[0170] Glycation is a crucial mechanism of skin aging, occurring between reducing sugars and matrix proteins within the skin. Non-enzymatic glycation is a complex series of non-enzymatic reactions in which reducing sugars such as proteins and glucose undergo non-enzymatic reactions to form early glycation products such as Schiff bases and Amadori products. These products then undergo oxidation, rearrangement, and cross-linking processes to form irreversible advanced glycation end products (AGEs). AGEs can bind to the receptor for advanced glycation end products (RAGEs) to exert biological effects, leading to skin aging. Aminoguanidine hydrochloride can effectively inhibit the formation of AGEs and has anti-glycation activity, often used as a positive control in anti-glycation experiments. Based on the autofluorescence properties of AGEs, this experiment determined whether the disclosed peptide has anti-glycation activity by measuring the fluorescence intensity at a specific wavelength.

[0171] The inhibition rates of AGEs by the test samples are shown in Table 5.

[0172] Table 5. Inhibition rate of AGEs by the test samples (n=3)

[0173] Group AGEs inhibition rate (Mean±SD) Blank control group (AGEs) 0.00%±0.81% aminoguanidine hydrochloride group 8.31%±1.62%** Cyclic hexapeptide A group 9.08%±0.28%*** Hexapeptide B group 7.96%±1.26%**

[0174] Note: Compared with the blank control group, ** P <0.01, *** P <0.001.

[0175] The results showed that the peptide disclosed herein exhibited an anti-glycation effect similar to that of aminoguanidine hydrochloride, and was able to inhibit the formation of advanced glycation end products to a certain extent even at low concentrations.

[0176] Example 6

[0177] A cream is prepared through the following steps, and the specific formula is shown in Table 6 below:

[0178] Table 6

[0179]

[0180] 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.

[0181] Example 7

[0182] An essence is prepared through the following steps, and the specific formula is shown in Table 7 below:

[0183] Table 7

[0184]

[0185] 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.

[0186] 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.

[0187] 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-Pro-Leu-Trp-His-Val-Lys-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-[Pro-Leu-Trp-His-Val-Lys].

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, and at least one excipient.

5. The composition according to claim 4, characterized in that, It also includes adjuvants.

6. 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 or 5.

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

8. 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 5, or the delivery system or sustained-release system as described in claim 6 or 7.

9. The cosmetic product according to claim 8, 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.

10. Use of the peptide or salt thereof according to any one of claims 1-3, or the composition according to claim 4 or 5, or the delivery system or sustained-release system according to claim 6 or 7 in the preparation of compositions for oil control, anti-oxidation or anti-glycation.

11. Use of the peptide or salt thereof according to any one of claims 1-3, or the composition according to claim 4 or 5, or the delivery system or sustained-release system according to claim 6 or 7 in the preparation of a composition for reducing skin sebum synthesis or secretion.

12. Use of the peptide or salt thereof according to any one of claims 1-3, or the composition according to claim 4 or 5, or the delivery system or sustained-release system according to claim 6 or 7 in the preparation of a composition for scavenging free radicals or reactive oxygen species.

13. Use of the peptide or salt thereof according to any one of claims 1-3, or the composition according to claim 4 or 5, or the delivery system or sustained-release system according to claim 6 or 7 in the preparation of a composition for inhibiting the formation of advanced glycation end products.

14. Use of the peptide or salt thereof according to any one of claims 1-3, or the composition according to claim 4 or 5, or the delivery system or sustained-release system according to claim 6 or 7 in the preparation of cosmetics.

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