CN113576941B

CN113576941B - New use of s-mu-conopeptide CnIIIC in preparing composition for skin repair and tightening

Info

Publication number: CN113576941B
Application number: CN202111034502.2A
Authority: CN
Inventors: 丁文锋; 赵文豪
Original assignee: Shenzhen Weiqi Technology Co ltd
Current assignee: Shenzhen Weiqi Technology Co ltd
Priority date: 2021-09-03
Filing date: 2021-09-03
Publication date: 2024-03-08
Anticipated expiration: 2041-09-03
Also published as: CN113576941A

Abstract

Use of s- μ -conopeptide CnIIIC or a salt thereof for the preparation of a composition for skin repair tightening comprising one or more of improving cell adhesion capacity, increasing skin elasticity or improving skin firmness.

Description

New use of s-mu-conopeptide CnIIIC in preparing composition for skin repair and tightening

Technical Field

The invention belongs to the technical field of active polypeptides, and particularly relates to a novel application of s-mu-conopeptide CnIIIC (great name: arginine/lysine polypeptide) in preparation of a composition for skin repair and tightening.

Background

Human skin can be divided into three layers, epidermis, dermis and subcutaneous tissue, with dermis consisting mainly of fibroblasts and extracellular matrix. There are various collagens (e.g., type I, type II, type III, etc.), elastin, non-collagenous glycoproteins, proteoglycans, aminoglycans, etc. in the extracellular matrix, which maintain the mechanical strength, elasticity, and normal physiological function of the skin. Wherein, collagen occupies 70% of all proteins in the extracellular matrix, and is the main component of the extracellular matrix. In addition, the presence of type IV collagen and type VI and VII collagen, respectively, at the junction of the basement membrane and dermis-epidermis, can provide skin with firmness and pressure resistance. The collagen content and distribution in the skin determine whether the skin is young or not, and when the collagen content is abnormally reduced, the dermis layer becomes thin, and the skin begins to become loose and lose elasticity, and wrinkles appear.

With age, metabolism of skin begins to slow, collagen production in skin decreases, collagen fiber structure also changes, skin gradually loses elasticity, and becomes loose. In addition, some exogenous factors such as ultraviolet radiation, air pollution or daily pressure can also accelerate skin aging, resulting in impaired skin barrier, dark complexion, rough skin, and reduced skin elasticity and firmness.

In this regard, many methods have been proposed to combat aging, such as activating cell regeneration, increasing extracellular matrix (collagen, elastin, etc.), protecting the body from ultraviolet radiation or environmental pollution, etc. Collagen is a major component of the extracellular matrix, and thus researchers have conducted extensive studies on peptide sequences that mimic the activity of collagen. Palmitoyl pentapeptide-4, for example, is a hydrolysate of procollagen alpha 1, which modulates cellular activity by interaction with specific receptors, activates certain genes involved in extracellular matrix turnover and cellular proliferation processes, promotes the production of type i and iii collagen, fibronectin, increases skin thickness and reduces wrinkles. Palmitoyl tetrapeptide-7 inhibits some unwanted and inappropriate inflammatory reactions and glycosylation damage, stimulates laminin V and collagen production, thereby increasing skin elasticity and firmness, preventing skin from wrinkling and sagging.

Recent studies have shown that keratinocyte adhesion at the dermis-epidermis junction plays an important role in the treatment of skin aging. By increasing cell adhesion and cell-extracellular matrix adhesion between them, skin laxity can be prevented or even treated. However, there is currently little research on cell adhesion to increase skin elasticity, prevent skin sagging, and combat aging. Therefore, it is necessary to study polypeptide sequences having skin cell adhesion promoting effects.

It has been reported that s-mu-conopeptide CnIIIC can target a variety of Voltage Sensitive Sodium Channels (VSSCs) and is useful for the treatment or prevention of pain and local anesthesia. Patent application WO2013/153236 describes that s- μ -conopeptide CnIIIC blocks mainly the nav1.4 channel for the cosmetic field to eliminate fine lines or wrinkles on the human face. Heretofore, the effect of s- μ -conopeptide CnIIIC on adhesion between skin cells has never been described in the prior art.

Disclosure of Invention

As a result of a great deal of experimental study, the inventors have found that, in a surprising and unexpected manner, s-mu-conopeptide CnIIIC has an effect on adhesion between skin cells, and can improve cell adhesion ability, increase skin elasticity and improve skin firmness.

The invention therefore aims to provide a novel use of s-mu-conopeptide CnIIIC or a salt thereof in the preparation of a composition for skin repair and tightening. The skin repair tightening includes one or more of improving cell adhesion, increasing skin elasticity, or improving skin firmness.

The term "cell adhesion" refers on the one hand to the adhesion between cells and extracellular matrix and on the other hand to the cell adhesion between cells. The term "adhesion between skin cells" refers on the one hand to adhesion between skin cells and extracellular matrix and on the other hand to adhesion between skin cells.

An increase in the ability of skin cells to adhere may indicate an increase in integrin expression. Integrins are ubiquitous on vertebrate cell surfaces and are involved in the adhesion of keratinocytes to the extracellular matrix, the attachment between cells, and the basal lamina cohesion of the skin, with a crucial impact on cell adhesion. Integrins interact with various molecules of the extracellular matrix such as collagen, fibronectin, laminin, or elastin, such as integrins of basal keratinocytes interact with laminin-5, allowing anchoring of the cells on a two-dimensional network of dermis-epidermis junctions. In addition, the enhancement of cell adhesion can protect the structure of collagen fibers and resist skin atrophy due to aging, particularly photoaging.

Alternatively, the sequence of the s-mu-conopeptide CnIIIC is pGlu-Gly-Cys-Cys-Asn-Gly-Pro-Lys-Gly-Cys-Ser-Ser-Lys-Trp-Cys-Arg-Asp-His-Ala-Arg-Cys-Cys-NH ₂ 。

Alternatively, the s- μ -conopeptide CnIIIC has a 3-pair disulfide bond located at Cys3-Cys15, cys4-Cys21, and Cys10-Cys22 positions.

The s-mu-conopeptide CnIIIC has the following structural sequence (i.e. peptide A):

the abbreviations for amino acids used in the present invention follow the biochemical nomenclature Committee of IUPAC-IUB at Eur J.biochem. (1984) 138:9-37 and J.chem (1989) 264: 633-673.

The peptides of the invention may exist as stereoisomers or as mixtures of stereoisomers; for example, the amino acids comprising them may have the configuration L-, D-, or be racemic independently of each other. Thus, it is possible to obtain isomeric mixtures as well as racemic mixtures or diastereomeric mixtures, or pure diastereomers or enantiomers, depending on the number of asymmetric carbons and what isomers or isomeric mixtures are present. The preferred structures of these peptides of the invention are pure isomers, i.e., enantiomers or diastereomers.

Optionally, the composition comprises 0.0001% -5% by mass of s- μ -conopeptide CnIIIC or a salt thereof;

optionally, the composition comprises 0.0005% -1% by mass of s- μ -conopeptide CnIIIC or a salt thereof;

optionally, the composition comprises s- μ -conopeptide CnIIIC or a salt thereof at a mass percentage concentration of 0.001% -0.1%;

optionally, the composition comprises s-mu-conopeptide CnIIIC or a salt thereof in a mass percentage concentration of 0.005% to 0.01%.

The s-mu-conopeptide CnIIIC or the salt thereof can improve the cell adhesion capability, increase the skin elasticity or improve the skin compactness.

The salt of s-mu-conopeptide CnIIIC comprises a metal salt of s-mu-conopeptide CnIIIC, the metal comprising: lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc or aluminum;

optionally, the salt of s- μ -conopeptide CnIIIC comprises a salt of s- μ -conopeptide CnIIIC with an organic base comprising: ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, arginine, lysine, histidine or piperazine;

alternatively, the salt of s- μ -conopeptide CnIIIC comprises a salt of s- μ -conopeptide CnIIIC with an inorganic or organic acid comprising: acetic acid, citric acid, lactic acid, malonic acid, maleic acid, tartaric acid, fumaric acid, benzoic acid, aspartic acid, glutamic acid, succinic acid, oleic acid, trifluoroacetic acid, oxalic acid, pamoic acid or gluconic acid;

optionally, the inorganic acid comprises: hydrochloric acid, sulfuric acid, boric acid or carbonic acid.

The s- μ -conopeptide CnIIIC or a salt thereof can be obtained intact using methods known per se in the field of peptide chemistry, such as solid phase synthesis, liquid phase synthesis or solid phase and liquid phase combination, and can also be prepared by biotechnological methods aimed at producing the desired sequence, or by controlled hydrolysis of proteins of animal, fungal or plant origin.

For example, one method of obtaining s- μ -conopeptides CnIIIC comprises the steps of:

-coupling an amino acid having a protected N-terminus and a free C-terminus with an amino acid having a free N-terminus and a protected or solid carrier-bound C-terminus;

-elimination of the group protecting the N-terminal end;

-repeating the coupling sequence and elimination of the N-terminal protecting group until the desired peptide sequence is obtained;

-elimination of the C-terminal protecting group or cleavage from the solid support.

Preferably, the C-terminus is bound to a solid support and the method is performed on a solid phase, comprising coupling an amino acid having a protected N-terminus and a free C-terminus with an amino acid having a free N-terminus and a C-terminus bound to a polymeric support; eliminating the group protecting the N-terminus; and repeating this sequence as many times as necessary to thereby obtain a peptide of the desired length, followed by cleavage of the synthesized peptide from the original polymer carrier.

The functional groups of the side chains of these amino acids remain fully protected with temporary or permanent protecting groups throughout the synthesis and may be deprotected simultaneously or orthogonally to the process of cleaving the peptide from the polymeric carrier.

The s- μ -conopeptide CnIIIC or salt thereof may be incorporated into a cosmetically or pharmaceutically acceptable delivery system or a slow release system.

The term "delivery system" refers to a diluent, adjuvant, excipient or carrier with which the peptides of the invention are administered, selected from the group consisting of: water, oils or surfactants, including those of petroleum origin, animal origin, vegetable origin, or synthetic origin, such as, and not limited to, peanut oil, soybean oil, mineral oil, sesame oil, castor oil, polysorbates, sorbitan esters, ether sulfates, betaines, glucosides, maltosides, fatty alcohols, nonoxynol, poloxamers, polyoxyethylene, polyethylene glycols, dextrose, glycerol, digitonin, and the like. Diluents which can be used in different delivery systems to which the peptides of the invention can be administered are known to those of ordinary skill in the art.

The term "sustained release" is used in a conventional sense to refer to a delivery system that provides a gradual release of a compound over a period of time, and preferably, but not necessarily, has a relatively constant level of release of the compound over the entire period of time.

Examples of delivery systems or slow release systems are liposomes, oleosomes, nonionic surfactant liposome vesicles, ethosomes, millimeter-capsules, microcapsules, nanocapsules, nanostructured lipid carriers, sponges, cyclodextrins, lipid vesicles, micelles, millimeter-spheres, microspheres, nanospheres, lipid spheres, microemulsions, nanoemulsions, millimeter-particles, microparticles or nanoparticles. Preferred delivery systems or slow release systems are liposomes and microemulsions, more preferably water-in-oil microemulsions having an internal structure of reverse micelles.

Sustained release systems can be prepared by methods known in the art and can be administered, for example, by: by topical or transdermal administration, including adhesive patches, non-adhesive patches, occlusive patches, and microelectronic patches; or by systemic administration, such as and without limitation, oral or parenteral routes, including nasal, rectal, subcutaneous implantation or injection, or direct implantation or injection into a particular body part, and preferably a relatively constant amount of these peptides of the invention should be released. The amount of peptide contained in the sustained release system will depend, for example, on the site where the composition is to be administered, the kinetics and duration of release of the peptide of the invention, and the nature of the condition, disorder and/or disease to be treated and/or cared for.

The s- μ -conopeptide CnIIIC or salt thereof may also be adsorbed on a solid organic polymer or solid inorganic support, such as, but not limited to, talc, bentonite, silica, starch, maltodextrin, or the like.

The composition of the invention is a cosmetic composition or a pharmaceutical composition.

The composition is present in a formulation selected from: cream, oil, milk, balm, foam, lotion, gel, liniment, serum, soap, shampoo, foundation, serum, ointment, mousse, pomade, powder, stick, pen, spray, aerosol, capsule, tablet, granule, chewing gum, solution, suspension, emulsion, syrup, elixir, polysaccharide film, jelly, or gelatin.

The composition of the invention further comprises at least one other active agent for enhancing the skin repair tightening effect of the invention, said other active agent being selected from peptides, natural plant ingredients, vitamin C and derivatives thereof or retinoids.

The beneficial effects obtained by the invention relative to the prior art include:

the s-mu-conopeptides CnIIIC or salts thereof according to the invention have never been described in the prior art as having an effect on the adhesion between skin cells. The present inventors have found, as a result of a large number of experimental studies, that s-mu-conopeptide CnIIIC or a salt thereof can improve cell adhesion ability in a surprising and unexpected manner, can prevent or even treat skin relaxation by increasing adhesion between skin cells and cell-extracellular matrix adhesion, increase skin elasticity, and improve skin firmness, thereby having a good skin repair tightening effect, and can be applied to a product of skin repair tightening.

Drawings

FIG. 1 is a graph showing the effect of peptide A on HaCaT cell activity. * Indicates that the difference was very significant compared to the blank, p <0.001 (n=4).

FIG. 2 is a graph showing the effect of peptide A on NIH3T3 cell activity. * Indicates that the difference was very significant compared to the blank, p <0.001 (n=4).

FIG. 3 is a graph showing the effect of peptide A on haCaT cell adhesion. * Indicating that the dosing group had a statistical difference compared to the blank group, p <0.05 (n=8). * Indicating significant differences between the dosing group and the blank group, p <0.01 (n=8).

FIG. 4 is an image of the effect of example 5 on improvement of facial skin elasticity.

FIG. 5 is a graph of the results of the test for improvement of facial skin elasticity in example 5.

Detailed Description

For a better understanding of the present invention, reference will now be made in detail to the present invention, examples of which are illustrated in the accompanying drawings, however, it being understood that the examples and the accompanying drawings are for illustrative purposes only and are not intended to limit the scope of the present invention.

Example 1 cell Activity assay

1.1 reagents and materials

Fetal bovine serum (Gibco), DMEM medium (Gibco), penicillin, streptomycin, MTT (Sigma).

1.2 instruments

Enzyme-labeled instrument (MD, CO) ₂ Incubator (Shanghai-constant), ultra clean bench (su zhou purification).

1.3 cell lines

Human keratinocytes (HaCaT) were purchased from the institute of chinese academy of sciences 'typical culture preservation committee kunming cell bank, and mouse skin fibroblasts (NIH 3T 3) were purchased from the institute of chinese academy of sciences' typical culture preservation committee Shanghai cell bank.

1.4 sample to be tested

Drug administration group: 0.1ppm peptide A, 1ppm peptide A, 10ppm peptide A, 50ppm peptide A, 100ppm peptide A, 500ppm peptide A, 1000ppm peptide A;

control group: PBS blank control, 2% dmso positive control.

1.5 purpose of experiment

The purpose of this experiment was to determine the effect of the peptides of the invention on cell activity by evaluating the cell activity 72h after administration using NIH3T3 fibroblasts and HaCaT keratinocytes as subjects.

1.6 Experimental methods

Frozen NIH3T3 and HaCaT cells were cultured according to 1: and (5) carrying out passage 2 to about 5 generations, and selecting cells with better growth vigor as experimental objects.

Inoculating 2000 cells/well into 96-well plate, adding administration group and control group samples according to multiple dilution method after cell adhesion, supplementing culture medium to 200 μl, placing at 37deg.C, 5% CO ₂ Incubate in incubator for 72h.

Thereafter 22. Mu.L of 5mg/ml MTT was added per well and the reaction was continued at 37℃with 5% CO ₂ Incubate in incubator for 4h. The original solution was discarded and 150. Mu.L/well DMSO was added. After 5min, the reference OD values at 490nm and 630nm wavelengths were read using a microplate reader.

1.7 results

The MTT method is a method for detecting the survival and growth of cells, and the measured OD value is proportional to the activity of the cells.

FIG. 1 shows the results of detection of peptide A on HaCaT cells, showing that the cell activity of the positive control group is greatly reduced under the action of 2% DMSO, and the difference is very significant compared with the blank control group. In contrast, no significant HaCaT cytotoxicity was observed for each dose of peptide a in the range of 0-1000 ppm.

FIG. 2 shows the results of the detection of peptide A on NIH3T3 cells, showing that the cell activity of the positive control group is greatly reduced under the action of 2% DMSO, and the difference is very significant compared with the blank control group. In contrast, peptide a at doses ranging from 0-1000ppm had no apparent NIH3T3 cytotoxicity.

Therefore, the s-mu-conopeptide CnIIIC provided by the invention has no obvious toxicity to keratinocytes and fibroblasts within the range of 1000 ppm.

Example 2 cell adhesion experiment

2.1 reagents and materials

2.2 instruments

2.3 cell lines

Human keratinocytes (HaCaT) were purchased from the kunming cell bank of the national academy of sciences typical culture collection committee.

2.4 sample to be tested

Drug administration group: 0.1ppm peptide A, 1ppm peptide A, 10ppm peptide A, 50ppm peptide A, 100ppm peptide A;

control group: PBS blank.

2.5 purpose of experiment

By selecting HaCaT keratinocytes, plating the HaCaT keratinocytes in a 96-well plate coated with the drug, incubating the HaCaT keratinocytes and evaluating the influence of the drug on cell adhesion after a period of external force action, thereby determining whether the peptide of the invention can improve cell elasticity.

2.6 Experimental methods

Frozen HaCaT cells were taken and cultured according to 1: and (5) carrying out passage 2 to about 5 generations, and selecting cells with better growth vigor as experimental objects.

Samples to be tested were added to 96-well plates at 20 μl/well and oven dried at 37 ℃ overnight. After the HaCaT cells with better growth vigor are digested on the next day, the plates are plated with the HaCaT cells with a density of 1 ten thousand per well, and the culture medium is supplemented to 200. Mu.L, and then the plates are plated with 5% CO at 37 DEG C ₂ Incubate in incubator for 3h. After the culture is finished, the culture plate is taken out and the culture medium is continuously supplemented until the liquid level just overflows, and the culture plate is sealed by a sealing film to ensure that no bubbles exist. The mixture was turned clockwise for 20min. The original medium was discarded, 90. Mu.L of fresh medium and 10. Mu.L of 5mg/mL MTT were added to each well, and the mixture was placed at 37℃in 5% CO ₂ Incubate in incubator for 3h. The solution was discarded and 150. Mu.L of DMSO was added. Reference OD values at 490nm and 630nm wavelengths were read using a microplate reader.

2.7 results

Cell adhesion experiments reflect the elasticity of cells by evaluating their ability to adhere. After three-dimensional force action, cells with strong adhesiveness can be kept on a 96-well plate, and the adhesion effect of the cells can be reflected by carrying out MTT quantitative analysis on living cells on the plate. The more viable cells that remain on the 96-well plate, the greater the OD values measured, indicating a stronger effect of the coated drug to promote cell adhesion, further indicating a greater effect of the drug to increase cell elasticity.

FIG. 3 is a graph showing the effect of peptide A on haCaT cell adhesion. The results show that peptide A at concentrations of 1ppm to 100ppm significantly improved cell adhesion, with statistical differences compared to the blank. Wherein, the effect of 50ppm of peptide A on promoting cell adhesion is more obvious, and the difference is obvious compared with a blank control group.

The above shows that the s-mu-conopeptide CnIIIC can promote the adhesion capability of HaCaT cells, thereby being beneficial to improving the elasticity of the HaCaT cells.

EXAMPLE 3 preparation of liposomes containing peptide A

Phosphatidylcholine was weighed and dissolved in chloroform. Evaporating the solvent under vacuum until a thin layer of phospholipid is obtained, and hydrating the layer by treating it with an aqueous peptide solution of the desired concentration at 55℃to obtain a multilamellar liposome. The multi-chamber liposome is subjected to high-pressure homogenization treatment to obtain single-chamber liposome with smaller and uniform size.

Example 4 preparation of a microemulsion composition containing peptide A

Weighing the component of phase B according to the dosage of the prescription, and adding the component into a container. Then, phase D was added to phase B and homogenized with continuous stirring. Phase a was then added to the mixture. Finally, phase C is added to obtain the micron emulsion composition containing peptide A.

Example 5 preparation of essence containing peptide A

Weighing glycerol, butanediol and hyaluronic acid according to the prescription amount, and mixing uniformly in a proper container in advance; adding water into a batching pot, starting stirring, heating to 80-85 ℃, and preserving heat for 30min; cooling the batching pan to about 65 ℃, adding pentanediol and hexanediol, and stirring for 10min until uniform; continuously cooling to about 40deg.C, sequentially adding betaine and peptide A, stirring for 20-30min, and dispersing completely.

Comparative example 1 preparation of essence without peptide A

Weighing glycerol, butanediol and hyaluronic acid according to the prescription amount, and mixing uniformly in a proper container in advance; adding water into a batching pot, starting stirring, heating to 80-85 ℃, and preserving heat for 30min; cooling the batching pan to about 65 ℃, adding pentanediol and hexanediol, and stirring for 10min until uniform; continuously cooling to about 40deg.C, adding betaine, stirring for 20-30min, and dispersing completely.

Example 6 functional test to increase skin elasticity

6.1 subject

20 subjects aged 30-50 years old, with unlimited sexuality.

6.2 sample to be measured

Taking example 5 as a sample to be tested, and observing and detecting the improvement effect of facial skin elasticity by photographing before using the sample and after using the sample for 15 min.

6.3 test instrument

Skin elasticity tester MPA580 (CK, germany).

6.4 purpose

The better the skin elasticity, the more relaxed the skin is after suction, the greater the rebound value, and the greater the fall between the suction phase and the relaxation phase. The improvement of elasticity by the peptides of the invention was evaluated by testing the skin elasticity of the face of the subject before and after the use of the sample.

6.5 method

The subject applied his face for 15 minutes using example 5, and photographed his face skin before and after 15 minutes of use and tested for facial skin elasticity using a skin elasticity tester.

When elastic testing was performed, the skin 3s (suction phase) was aspirated, and the bullet 3s (relaxation phase) was replaced to monitor the skin state change throughout the process.

6.6 results

Example 5 sample images for improving facial skin elasticity and test results are shown in fig. 4 and 5, respectively.

The results in FIG. 4 show that the subject had no rough face or sagging face after 15 minutes of application of the sample, and the skin was more firm, plump, fine and shiny, relative to the sample of example 5.

The skin elasticity test results of fig. 5 show that the drop between the suction phase and the relaxation phase is greater after 15 minutes using the sample of example 5, compared to before using the sample, indicating that the rebound value of the skin is greater and the skin elasticity is improved.

Therefore, the s-mu-conopeptide CnIIIC can improve the adhesion capability of keratinocytes, improve the skin quality from the source, obviously increase the elasticity of facial skin after acting for 15min and improve the skin compactness under the condition of low dosage of 0.00125 percent, and has good skin repairing and compacting effects, thus being applicable to products with skin repairing and compacting.

Example 7 face tightening efficacy test

7.1 subject

40 female subjects aged 30-50.

7.2 sample to be tested

Comparative example 1 was used as placebo with example 5 as the sample to be tested.

7.3 test instrument

VISIA facial image analyzer (USA).

7.4 purpose

The effect of the peptides of the invention on facial tightening was evaluated by testing the change in chin width of the subjects before and after the use of the samples.

7.5 method

The 40 subjects were randomized into two groups of 20 subjects each, blind tested using example 5, comparative example 1.

After face cleaning, photographs were tested using a VISIA facial image analyzer as 0 day data. The subjects applied the test samples to their faces once a day in the morning and evening for 4 weeks before taking a photograph of the faces. The reduced chin width after sample application was analyzed for each group of subjects by comparing the photographed data for day 0 and 4 weeks.

7.6 results

The average of the chin width reduction dimensions for the two groups of subjects after 4 weeks using the samples of example 5 and comparative example 1 are shown in table 1 below.

Table 1 facial tightening effects of example 5 and comparative example 1

The results in table 1 show that the chin width of the subjects in the administration group of example 5 is significantly reduced after 4 weeks of use, which indicates that the s-mu-conopeptide CnIIIC of the present invention can improve the adhesion ability of skin cells, has excellent facial tightening efficacy, and can be applied to products for skin repair tightening.

The foregoing is a further detailed description of the invention in connection with the preferred embodiments, but is not intended to limit the practice of the invention to such description. It will be apparent to those skilled in the art that several simple deductions or substitutions can be made without departing from the spirit of the invention, and the invention is not limited to the above-mentioned embodiments.

Claims

Use of 1.s-mu-conopeptide CnIIIC or a salt thereof for the preparation of a composition for skin repair tightening to reduce chin width, the sequence of s-mu-conopeptide CnIIICIs pGlu-Gly-Cys-Cys-Asn-Gly-Pro-Lys-Gly-Cys-Ser-Ser-Lys-Trp-Cys-Arg-Asp-His-Ala-Arg-Cys-Cys-NH ₂ The s- μ -conopeptide CnIIIC has a 3-pair disulfide bond located at Cys3-Cys15, cys4-Cys21 and Cys10-Cys22 positions.
2. The use according to claim 1, characterized in that the composition comprises s- μ -conopeptide CnIIIC or a salt thereof in a concentration of 0.0001% to 5% by mass.
3. The use according to any one of claims 1-2, characterized in that the salt of s- μ -conopeptide CnIIIC comprises a metal salt of s- μ -conopeptide CnIIIC, the metal comprising: lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc or aluminum;

the salt of s-mu-conopeptide CnIIIC comprises a salt of s-mu-conopeptide CnIIIC with an organic base comprising: ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, arginine, lysine, histidine or piperazine;

the salt of s-mu-conopeptide CnIIIC comprises a salt of s-mu-conopeptide CnIIIC with an inorganic or organic acid, the organic acid comprising: acetic acid, citric acid, lactic acid, malonic acid, maleic acid, tartaric acid, fumaric acid, benzoic acid, aspartic acid, glutamic acid, succinic acid, oleic acid, trifluoroacetic acid, oxalic acid, pamoic acid or gluconic acid;

the inorganic acid includes: hydrochloric acid, sulfuric acid, boric acid or carbonic acid.
4. The use according to any one of claims 1-2, characterized in that the s- μ -conopeptide CnIIIC or a salt thereof is incorporated into a cosmetically or pharmaceutically acceptable delivery system or a slow release system, or is adsorbed onto a cosmetically or pharmaceutically acceptable solid organic polymer or solid inorganic support;

the cosmetically or pharmaceutically acceptable delivery system or slow release system is selected from: liposomes, nonionic surfactant liposome vesicles, ethosomes, millimeter capsules, micron capsules, nanocapsules, nanostructure lipid carriers, sponges, cyclodextrins, lipid vesicles, micelles, millimeter spheres, microspheres, nanospheres, lipid spheres, microemulsions, nanoemulsions, millimeter particles, microparticles, and nanoparticles;

the cosmetically or pharmaceutically acceptable solid organic polymer or solid inorganic support is selected from: talc, bentonite, silica, starch or maltodextrin.
5. The use according to claim 1, characterized in that said composition is a cosmetic or pharmaceutical composition, the formulation of which is selected from: cream, balm, foam, lotion, gel, liniment, slurry, soap, shampoo, foundation, ointment, mousse, pomade, powder, pen, spray, aerosol, solution, suspension, emulsion, elixir, polysaccharide film or jelly.
6. The use according to claim 1, wherein the composition further comprises at least one other active agent for enhancing the tightening of skin repair, said other active agent being selected from peptides, natural plant ingredients, vitamin C and derivatives thereof or retinoids.