CN117164663B

CN117164663B - Polypeptide compound, composition and use thereof

Info

Publication number: CN117164663B
Application number: CN202310960266.XA
Authority: CN
Inventors: 张君革; 王崇杰; 尹翠娟
Original assignee: Qingdao Biopeptek Pharmaceutical Co ltd
Current assignee: Qingdao Biopeptek Pharmaceutical Co ltd
Priority date: 2023-08-01
Filing date: 2023-08-01
Publication date: 2024-05-10
Anticipated expiration: 2043-08-01
Also published as: CN117164663A

Abstract

A polypeptide compound or a cosmetically or pharmaceutically acceptable salt thereof, which is capable of combating skin ageing, preventing loss of skin elasticity and firmness, protecting the skin or its appendages from external damage. The polypeptide compounds may also prevent or treat diseases associated with mitochondrial dysfunction including neuromuscular or cardiac degeneration, type II diabetes, or aging.

Description

Polypeptide compound, composition and use thereof

Technical Field

The present invention relates to the field of cosmetic or pharmaceutical preparations, in particular to polypeptide compounds having a protective effect on skin cells, compositions thereof, and their use for combating skin ageing, preventing loss of skin elasticity and firmness, protecting the skin from external damage, etc.

Background

Mitochondria are organelles in eukaryotic cells that are dedicated to energy production, they are given their own unique DNA (DNAmt), and the energy produced by the respiratory chain is stored in the form of ATP. Under certain cell stress conditions, the respiratory chain generates free radicals by electrons released by oxidative phosphorylation, thereby disrupting mitochondrial structures. These stressors may be endogenous or exogenous and in the latter may include ultraviolet light, toxins, radiation and digestive oxidants. Thus, mitochondrial function gradually declines with age, which may be related to the accumulation of mutations at DNAmt (k.singh (2004), ann.ny acad.sci., 1019.) these DNAmt mutations may be induced by repeated exposure to ultraviolet light, and are also evidence of photoaging (w.berneburg et al (2004), j.invest.dermotol., 122 (5)).

Mitochondria also play a central role in apoptosis, and thus mitochondrial degradation may be a factor in initiating a series of reactions leading to apoptosis in a variety of cell types (g.kroemeral. (1995), FASEB j., 9:1277-87).

Disclosure of Invention

The present invention provides a polypeptide compound which can be used for protecting skin cells, against skin aging, preventing loss of skin elasticity and firmness, and protecting the skin or its accessory organs from external damage.

In one aspect of the invention there is provided a polypeptide compound, or a cosmetically or pharmaceutically acceptable salt thereof, the amino acid sequence of which is selected from the group consisting of:

SEQ ID No.1：Ser-Cys-Thr-Gly-Pro-Arg-Gly-Asp-NH₂

SEQ ID No.2：Ser-Cys-Ile-Asn-Thr-Gly-Pro-Arg-Gly-Asp-NH₂

SEQ ID No.3：Ser-Cys-Ile-Gln-Gly-Pro-Arg-Gly-Asp-NH₂

SEQ ID No.4：Ser-Cys-Thr-Asn-Thr-Gly-Pro-Arg-Gly-Asp-NH₂

SEQ ID No.5：Ser-Cys-Ile-Asn-Ser-Gly-Pro-Arg-Gly-Asp-NH₂

SEQ ID No.6：Arg-Gly-Asp-Gly-Pro-Ser-Cys-Thr-NH₂

SEQ ID No.7：Arg-Gly-Asp-Gly-Pro-Ser-Cys-Ile-Asn-Thr-NH₂

SEQ ID No.8：Arg-Gly-Asp-Gly-Pro-Ser-Cys-Ile-Gln-NH₂

SEQ ID No.9：Arg-Gly-Asp-Gly-Pro-Ser-Cys-Thr-Asn-Thr-NH₂

SEQ ID No.10：Arg-Gly-Asp-Gly-Pro-Ser-Cys-Ile-Asn-Ser-NH₂

SEQ ID No.11：Ser-Cys-Thr-Pro-Gly-Arg-Gly-Asp-NH₂

SEQ ID No.12：Ser-Cys-Ile-Asn-Thr-Pro-Gly-Arg-Gly-Asp-NH₂

SEQ ID No.13：Ser-Cys-Ile-Gln-Pro-Gly-Arg-Gly-Asp-NH₂

SEQ ID No.14：Ser-Cys-Thr-Asn-Thr-Pro-Gly-Arg-Gly-Asp-NH₂

SEQ ID No.15：Ser-Cys-Ile-Asn-Ser-Pro-Gly-Arg-Gly-Asp-NH₂

SEQ ID No.16：Arg-Gly-Asp-Pro-Gly-Ser-Cys-Thr-NH₂

SEQ ID No.17：Arg-Gly-Asp-Pro-Gly-Ser-Cys-Ile-Asn-Thr-NH₂

SEQ ID No.18：Arg-Gly-Asp-Pro-Gly-Ser-Cys-Ile-Gln-NH₂

SEQ ID No.19：Arg-Gly-Asp-Pro-Gly-Ser-Cys-Thr-Asn-Thr-NH₂

SEQ ID No.20：Arg-Gly-Asp-Pro-Gly-Ser-Cys-Ile-Asn-Ser-NH₂

SEQ ID No.21：Ser-Cys-Gly-Arg-Gly-Asp-NH₂

SEQ ID No.22：Arg-Gly-Asp-Ser-Cys-Thr-NH₂

SEQ ID No.23：Arg-Gly-Asp-Pro-Ser-Cys-Thr-NH₂

SEQ ID No.24：Thr-Ser-Cys-Gly-Arg-Gly-Asp-NH₂

SEQ ID No.25：Thr-Ser-Cys-Gly-Pro-Arg-Gly-Asp-NH₂

SEQ ID No.26：Ser-Cys-Gly-Pro-Arg-Gly-Asp-NH₂。

Optionally, the polypeptide compound N-terminal is acylated, preferably wherein the acylating group is selected from acetyl, propionyl.

The polypeptide compound provided by the invention can be singly used or two or more of the polypeptide compounds can be combined for use.

In the context of the present invention, the term "peptide" refers to a chain between two or more amino acids connected to each other by peptide bonds or modified peptide bonds, and the term "polypeptide" refers to a peptide of larger size.

It will be appreciated that the "peptide" of the invention is a natural or synthetic peptide, or at least one fragment thereof, obtained by proteolysis or synthesis, or even any natural or synthetic peptide, the sequence of which may be complete or partial, containing the peptides of the invention as described previously. In order to increase the resistance to degradation, it may be necessary to use protected forms of the peptides according to the invention. The protected form should of course be in a biologically compatible form and should be compatible with use in the cosmetic or pharmaceutical field.

This can be accomplished by methods conventional in the art for synthesizing polypeptide amino acid sequences. For example, the peptides of the invention may be prepared by one skilled in the art using well known processes for the synthesis, extraction and purification of proteins and peptides, preferably by chemical synthesis.

The polypeptide compound of the present invention or a cosmetically or pharmaceutically acceptable salt thereof may be used alone, or in combination of two or more, or in combination with at least one other active polypeptide.

Preferably, the cosmetically acceptable salt of the polypeptide compound is a salt of the polypeptide compound with: hydrochloric acid, phosphoric acid, hydrobromic acid.

Preferably, the pharmaceutically acceptable salt of the polypeptide compound is a salt of the polypeptide compound with: hydrochloric acid, hydrobromic acid, trifluoroacetic acid.

In another aspect of the invention, a cosmetic composition is provided comprising the polypeptide compound or a cosmetically acceptable salt thereof, optionally together with a cosmetically acceptable carrier.

Preferably, the cosmetically acceptable carrier is selected from: water, glycerin, alcohols (e.g., ethanol, propylene glycol, butylene glycol, dipropylene glycol, ethoxylated diethylene glycol (ethoxylateddiglycols), propoxylated diethylene glycol (propoxylateddiglycols), cyclic polyols), petrolatum (petrolatum) and vegetable oils and mixtures of two or more thereof.

In a preferred embodiment, the cosmetic composition may further comprise additives commonly used in the art, and adjuvants required for formulation. Such as solvents (preferably water, phenoxyethanol), thickeners (preferably glycerol, butylene glycol, carbomer, xanthan gum), diluents (preferably water), antioxidants (preferably triethanolamine, ubiquinone, tocopherol), humectants (preferably methyl glucitol polyether-10, glycerol, butylene glycol, squalane), colorants, solar filters (preferably Artemia (Artemia) extract), pigments, preservatives (preferably methyl benzoate, ethyl benzoate, butyl benzoate, propyl benzoate, jin Yi butyl benzoate), fragrances, other cosmetically or pharmaceutically active ingredients (preferably allantoin), essential oils, vitamins, essential fatty acids (preferably glyceryl stearate), surfactants (preferably lanolin alcohol, propylene glycol dipelargonate) or film-forming polymers (preferably PEG-75 stearate).

The adjuvant and the proportion of the adjuvant are chosen within a range which does not impair the desired advantageous properties of the cosmetic composition according to the invention. Preferably, the weight percentage of the adjuvant in the cosmetic composition is between 0.01 and 20% of the total weight of the composition.

In a preferred embodiment, when the cosmetic composition of the invention is an emulsion, the oil phase may be present in a proportion by weight of from 5 to 80%, preferably from 5 to 50%, relative to the total weight of the composition.

In a preferred embodiment, the cosmetic composition is in the form of a cream, oil-in-water emulsion, water-in-oil emulsion, or a multiple emulsion (multiple emulsions), solution (e.g., aqueous solution, hydroalcoholic solution, oily solution), suspension, gel, emulsion (mill), lotion (lotions), stick, aerosol, or powder that is applicable to the skin, mucous membranes (mucous membrane), lips, and/or their appendages.

In a preferred embodiment, the concentration of the polypeptide compound or cosmetically acceptable salt thereof in the cosmetic composition is from 0.005 to 5000ppm (ppm: parts per million) (preferably from 0.05 to 500ppm, more preferably from 0.01 to 100ppm, more preferably from 0.01 to 50 ppm).

In another aspect of the invention, there is provided the use of said polypeptide compound or a cosmetically acceptable salt thereof or a cosmetically acceptable composition comprising said polypeptide compound or a cosmetically acceptable salt thereof for the preparation of a cosmetic product for combating skin ageing, preventing loss of skin elasticity and firmness, protecting the skin or its appendages from external damage.

In a preferred embodiment, the polypeptide compound of the invention or a cosmetically acceptable salt thereof or a cosmetic composition comprising the polypeptide compound or a cosmetically acceptable salt thereof is used for the preparation of a cosmetic product for protection of skin cells against exposure to Ultraviolet (UVB) light.

In a preferred embodiment, the polypeptide compound of the invention or a cosmetically acceptable salt thereof or a cosmetic composition comprising the polypeptide compound or a cosmetically acceptable salt thereof is used for the preparation of a cosmetic product for the protection of skin cells under oxidative stress.

In a preferred embodiment, the polypeptide compound of the invention or a cosmetically acceptable salt thereof or the cosmetic composition comprising said polypeptide compound or a cosmetically acceptable salt thereof is used for the preparation of a cosmetic product for activating mitochondrial activity.

In another aspect of the invention, there is provided a pharmaceutical composition comprising the polypeptide compound or a pharmaceutically acceptable salt thereof, optionally including pharmaceutically acceptable excipients.

In another aspect of the invention there is provided the use of said polypeptide compound or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising said polypeptide compound or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention or treatment of a disease associated with mitochondrial dysfunction.

In another aspect of the invention, there is provided a method for preventing or treating a disease associated with mitochondrial dysfunction, comprising providing to an individual in need thereof a therapeutically or prophylactically required amount of the polypeptide compound or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the polypeptide compound or a pharmaceutically acceptable salt thereof.

Preferably, the disease associated with mitochondrial dysfunction includes neuromuscular or cardiac degeneration, type II diabetes or aging.

The compositions of the present invention may be used in any suitable manner, particularly orally, parenterally or by external use, and the formulations used may be adjusted by those skilled in the art, particularly as cosmetic or dermatological compositions. Preferably, the compositions of the present invention are for topical administration, transdermal administration.

In the present invention, the term "attachment organ" (appendages) includes keratinized attachments exposed on the body surface, such as body hair, eyelashes, eyebrows, nails, and hair.

Skin aging includes, among other things, wrinkled and fine wrinkled, atrophic skin, loose skin, thin skin, lack of elasticity and/or tension of the skin, lack of luster or pigmented spots on the skin, and any other change in the appearance of the skin and its corresponding internal changes, such as any internal degradation of the skin after exposure to Ultraviolet (UV).

Preferably, the cosmetic composition of the polypeptide compound or a cosmetically acceptable salt thereof is capable of combating the loss of elasticity and firmness of the skin.

The term "external damage" may include, among other things, external damage caused by contamination, ultraviolet light, products of irritating nature (such as surfactants, preservatives and perfumes). The pollution may be "outdoor" pollution, such as Diesel particulates (Diesel-fuel), ozone or heavy metals, or "indoor" pollution, such as emissions of paint, glue or wallpaper solvents (such as toluene, styrene, xylene or benzaldehyde), and pollution caused by cigarette smoke.

The polypeptide compounds of the invention may be synthesized by methods conventional in the art for synthesizing polypeptide amino acid sequences. For example, the preparation of the polypeptide is completed by soaking Rink resin in methylene chloride, washing with DMF and draining, adding piperidine/DMF mixed liquid, stirring for reaction, draining, washing with DMF and draining, mixing Fmoc-AA-OH, HOBt and DIC, adding to the resin, stirring for reaction, draining, washing with DMF and draining, and coupling the subsequent amino acids by repeating the above procedures.

Detailed Description

The polypeptide compounds of the present invention referred to in the following examples are synthesized by methods conventional in the art for synthesizing polypeptide amino acid sequences.

Example 1: protection of skin cells exposed to Ultraviolet (UVB) light by the peptide SEQ ID No. 1-peptide SEQ ID No.26

The protection effect of the SEQ ID No.1 peptide-SEQ ID No.26 peptide on skin fibroblasts irradiated by UVB rays was determined, and cell viability test was performed using MTT technique.

The test method is as follows: human dermal fibroblasts were treated with 50ppm of a PBS solution of the peptide SEQ ID No. 1-SEQ ID No.26 peptide for 24 hours, irradiated with UVB radiation (25-100 mJ/cm ²), and then cultured in the presence of the same concentration of the peptide SEQ ID No. 1-SEQ ID No.26 peptide for an additional 24 hours.

Under the same conditions, a control not treated with peptide and not irradiated, and a control not treated with peptide but irradiated were obtained.

At the end of the experiment, the cells were incubated in a solution containing 0.1mg/ml MTT (3- [4, 5-dimethylthiazolyl ] -2, 5-diphenyl-2H-tetrazolium bromide). MTT compound is absorbed by living cells and then metabolized by mitochondrial enzymes to formazan, a blue-violet compound, measured spectrophotometrically at 540 nm. Absorbance (OD) is proportional to mitochondrial enzyme activity and the number of living cells. The results are shown in table 1 below:

TABLE 1

MTT method evaluation of cell viability results show, on the one hand, that the SEQ ID No.1 peptide-SEQ ID No.26 peptide increases cell viability; on the other hand, human fibroblasts were subjected to cytotoxicity depending on the amount of UVB irradiation, but did not show such cytotoxicity effect after treatment with the peptide of SEQ ID No. 1-SEQ ID No. 26.

Conclusion: the SEQ ID No.1 peptide-SEQ ID No.26 peptide can increase the cell activity and can effectively protect skin cells from the cytotoxicity of UVB rays.

Example 2: protection of skin cells under oxidative stress by SEQ ID No.1 peptide-SEQ ID No.26 peptide

The protective effect of the peptide SEQ ID No. 1-SEQ ID No.26 on skin fibroblasts under oxidative stress caused by hydrogen peroxide (hydrogen peroxide) at a concentration of 4mM or 5mM was determined. For this purpose, cell viability tests were performed using the MTT technique.

The testing method comprises the following steps: human skin fibroblasts were treated with 1% of 50ppm SEQ ID No.1 peptide-SEQ ID No.26 peptide in PBS for 24 hours, oxidative stress was induced with 4mM or 5mM hydrogen peroxide for 30 minutes, and then incubated for 24 hours at the same concentration of SEQ ID No.1 peptide-SEQ ID No.26 peptide.

Under the same conditions, a control which was not treated with peptide and treated with hydrogen peroxide and a control which was treated with hydrogen peroxide alone were obtained.

At the end of the experiment, the cells were incubated in a solution containing 0.1mg/ml MTT (3- [4, 5-dimethylthiazolyl ] -2, 5-diphenyl-2H-tetrazolium bromide). MTT compound is absorbed by living cells and then metabolized by mitochondrial enzymes to formazan, a blue-violet compound, measured spectrophotometrically at 540 nm. Absorbance (OD) is proportional to mitochondrial enzyme activity and the number of living cells. The results are shown in Table 2 below:

TABLE 2

Assessment of cell viability by MTT technique showed that, on the one hand, the SEQ ID No.1 peptide-SEQ ID No.26 peptide increased cell viability and, on the other hand, human fibroblasts were subjected to cytotoxicity, depending on the amount of oxidative stress caused by 4mM or 5mM hydrogen peroxide, but did not show such cytotoxic effects after treatment with the SEQ ID No.1 peptide-SEQ ID No.26 peptide.

Conclusion: the SEQ ID No.1 peptide-SEQ ID No.26 peptide can increase the cell viability and effectively protect skin cells from the cytotoxicity of oxidative stress.

Example 3: protection of skin cell DNA by Ultraviolet (UVB) light

The protective effect of the peptide SEQ ID No. 1-SEQ ID No.26 on cells was investigated by evaluating the damage caused at the DNA level. This study was done by comet (or single cell gel electrophoresis) test, a rapid and sensitive micro-electrophoresis technique that allows visualization and quantification of breaks in DNA in single cells.

The test method is as follows: primary human fibroblasts were seeded in petri dishes. When the cells reached 70% aggregation, they were treated with 1% of the peptide SEQ ID No. 1-SEQ ID No.26 (starting from a 50ppm solution) in PBS for 24 hours. Cells were then subjected to UVB irradiation at 100mJ/cm ² and then incubated in the presence of the polypeptide for an additional 24 hours. Culture dishes that were not treated with the polypeptide served as controls.

10 Ten thousand cells/ml of cell suspension were obtained, 500. Mu.l was removed, and an agarose solution was inserted and run between the slide and cover glass. These cells were lysed from freezing. The DNA was then denatured with alkaline buffer and subjected to brief electrophoresis (250 mA,30 min) and stained with propidium iodate. The slides were then observed under a fluorescence microscope.

The altered cell, whose DNA can be seen to extend to the anode, forms a "comet" in proportion to the number of DNA breaks. This highly degraded DNA was found on the "tail" of the comet. The intact cell is still circular and its DNA is then packed into the "head" region of the comet. The test results are shown in table 3 below:

TABLE 3 Table 3

The results show that in the absence of the peptide SEQ ID No. 1-SEQ ID No.26 (UVB control), the cells under UVB irradiation show the greatest "tail moment", i.e.the DNA damage is the most severe. On the other hand, the "tail moment", i.e., DNA damage, of cells treated with the peptide SEQ ID No. 1-SEQ ID No.26 was reduced by 20% -25%.

Conclusion: the SEQ ID No.1 peptide-SEQ ID No.26 peptide has important protection function on DNA of skin cells under UVB irradiation.

Example 4: effect of SEQ ID No.1 peptide-SEQ ID No.26 peptide on mitochondrial ultrastructure

To determine the effect of the peptide SEQ ID No. 1-SEQ ID No.26 on mitochondria, the mitochondrial ultrastructure was observed with an electron microscope.

The experimental method comprises the following steps: normal human keratinocytes were treated with 1% 50ppm SEQ ID No.1 peptide-SEQ ID No.26 peptide in PBS for 72 hours. Negative controls were obtained identically but without the peptide.

Cell fixation was performed using a Carnovsky fixative (Karnovsky's fixative,20 ml 16% paraformaldehyde/8 ml 50% glutaraldehyde/25 ml 0.2M sodium phosphate buffer/25 ml water) for 1 hour and then overnight at 4 ℃. The medium was scraped to the canola-fixative and the cells were centrifuged at 5000 rpm for 5 minutes. The supernatant was separated and the particles resuspended in 1ml of 0.1M calcium carbonate. The samples were then stored at 4 ℃ for observation by electron microscopy.

Results: the organelle of the cells treated with the peptide SEQ ID No. 1-SEQ ID No.26 shows ultrastructural features, indicating an increase in their metabolic activity. In particular, the characteristics of the mitochondrial population and the abundance of golgi elements are consistent with the stimulation of metabolic synthesis.

Conclusion: the peptide SEQ ID No. 1-SEQ ID No.26 has stimulatory effect on mitochondrial activity.

Preparation of the composition:

1. Sun cream

The components of phase A and phase B are heated to between 70 ℃ and 75 ℃ respectively, and phase B is emulsified in phase A under stirring. Add phase C at 45℃while stirring. When the temperature is lower than 40 ℃, adding the phase D again, and continuing to cool to 25 ℃ by gentle stirring.

2. Emulsion for spreading After Sun-drying (After-Sun Milk)

Phase A is stirred and mixed, xanthan gum and dispersing agent (polyethylene glycol and/or HPMA and/or glyceryl tristearate, etc.) are gradually added and stirred. After the gel has set, add phase C and phase D. Then adding E phase, pigment (mica and/or ultramarine) and essence (essential oil and/or musk and/or menthol) which are prepared to the perfect dissolution point of DHA in advance. The pH is adjusted to 4-4.5 as required.

3. Anti-aging agent

Phase A was prepared and melted at 65-75deg.C. Phase C was heated to 65-70 ℃. Phase B is added to phase a before phase a is emulsified in phase C, and carbomers are neutralized by the addition of phase D at about 45 ℃. Then phase E was added with light stirring and cooling continued to 25 ℃. If necessary, phase F is added.

4. Daytime protective cream

Phase a was prepared and heated to 75 ℃ with stirring. Preparing phase B, stirring and dispersingXanthan gum, and standing. Then heated to 75 ℃, at which temperature a is emulsified in B with rotor-stator stirring. Add phase C with rapid stirring to neutralize. After cooling to 40 ℃, phase D and phase E were added. Cooling was continued by gentle stirring and phase F was added.

The above description of the specific embodiments of the present invention has been given by way of example only, and the present invention is not limited to the above described specific embodiments. Any equivalent modifications and substitutions for the present invention will occur to those skilled in the art, and are also within the scope of the present invention. Accordingly, equivalent changes and modifications are intended to be included within the scope of the present invention without departing from the spirit and scope thereof.

Claims

1. A polypeptide compound or a cosmetically or pharmaceutically acceptable salt thereof, the amino acid sequence of which is selected from the group consisting of:

SEQ ID No.1：Ser-Cys-Thr-Gly-Pro-Arg-Gly-Asp-NH₂

SEQ ID No.2：Ser-Cys-Ile-Asn-Thr-Gly-Pro-Arg-Gly-Asp-NH₂

SEQ ID No.3：Ser-Cys-Ile-Gln-Gly-Pro-Arg-Gly-Asp-NH₂。

2. the polypeptide compound or a cosmetically or pharmaceutically acceptable salt thereof according to claim 1, wherein the cosmetically acceptable salt of the polypeptide compound is a salt of the polypeptide compound with: hydrochloric acid, phosphoric acid, hydrobromic acid.

3. The polypeptide compound or a cosmetically or pharmaceutically acceptable salt thereof according to claim 1, wherein the pharmaceutically acceptable salt of the polypeptide compound is a salt of the polypeptide compound with: hydrochloric acid, hydrobromic acid, trifluoroacetic acid and acetic acid.

4. A cosmetic composition comprising a polypeptide compound of any one of claims 1-3 or a cosmetically acceptable salt thereof, optionally together with a cosmetically acceptable medium.

5. The cosmetic composition of claim 4, wherein the cosmetically acceptable medium is selected from the group consisting of: water, glycerin, alcohols, vaseline, vegetable oil or a mixture of two or more thereof.

6. The cosmetic composition of claim 5, wherein the alcohol is selected from the group consisting of ethanol, propylene glycol, butylene glycol, dipropylene glycol, ethoxydiglycol, and cyclic polyols.

7. The cosmetic composition according to claim 4, characterized in that it further comprises solvents, thickeners, diluents, antioxidants, moisturizers, colorants, solar filters, pigments, preservatives, fragrances, other cosmetic or pharmaceutical active ingredients, essential oils, vitamins, essential fatty acids, surfactants or film forming polymers.

8. The cosmetic composition according to claim 7, characterized in that said solvent is selected from water, phenoxyethanol; the thickener is selected from glycerol, butanediol, carbomer and xanthan gum; the diluent is water; the antioxidant is selected from triethanolamine, ubiquinone, and tocopherol; the humectant is selected from methyl glucitol polyether-10, glycerol, butanediol, and squalane; the sunlight filtering agent is selected from artemia salina extract; the preservative is selected from methyl benzoate, ethyl benzoate, butyl benzoate, propyl benzoate and Jin Yi butyl benzoate; the other cosmetic or pharmaceutical active ingredient is allantoin; the essential fatty acid is glyceryl stearate; the surfactant is selected from lanonol and propylene glycol dipelargonate; the film-forming polymer is selected from PEG-75 stearate.

9. Cosmetic composition according to any one of claims 4 to 8, characterized in that it is in a dosage form selected from: paste, oil-in-water emulsion, water-in-oil emulsion, composite emulsion, solution, suspension, gel, emulsion.

10. The cosmetic composition according to claim 9, wherein said solution is selected from the group consisting of aqueous solutions, hydroalcoholic solutions, oily solutions.

11. Cosmetic composition according to any one of claims 4 to 8, characterized in that the concentration of the polypeptide compound or a cosmetically acceptable salt thereof in the cosmetic composition is between 0.005 and 5000ppm.

12. Cosmetic composition according to any one of claims 4 to 8, characterized in that the concentration of the polypeptide compound or a cosmetically acceptable salt thereof in the cosmetic composition is between 0.05 and 500ppm.

13. Cosmetic composition according to any one of claims 4 to 8, characterized in that the concentration of the polypeptide compound or a cosmetically acceptable salt thereof in the cosmetic composition is between 0.01 and 100ppm.

14. Cosmetic composition according to any one of claims 4 to 8, characterized in that the concentration of the polypeptide compound or a cosmetically acceptable salt thereof in the cosmetic composition is between 0.01 and 50ppm.

15. Use of a polypeptide compound according to any one of claims 1 to 3 or a cosmetically acceptable salt thereof, or a cosmetic composition according to any one of claims 4 to 14, for the preparation of a cosmetic product against skin ageing, against loss of skin elasticity and firmness, protecting the skin or its appendages from external damage;

The skin accessory is selected from body hair, eyelashes, eyebrows, nails, or hair;

The external damage includes external damage caused by products of contaminating, ultraviolet, irritating nature;

The irritating product comprises a surfactant, a preservative or perfume;

the pollution is the pollution caused by the emission of diesel oil particles, ozone, heavy metals, paint, glue, wallpaper solvents and cigarette smoke;

The wallpaper solvent emissions include toluene, styrene, xylene or benzaldehyde emissions.

16. A pharmaceutical composition comprising a polypeptide compound of any one of claims 1-3, or a pharmaceutically acceptable salt thereof, optionally together with pharmaceutically acceptable excipients.